MME -303 Child Health Indira Gandhi National Open University School of Health Sciences

Block 6 CHILDHOOD MORBIDITY UNIT 28 Common Paediatric Problems 5 UNIT 29 Cardiovascular, Haematological and Renal Disorders 24 UNIT 30 Gastrointestinal, Parasitic and Neurological Disorders 61 UNIT 31 Tuberculosis 90 UNIT 32 HIV/AIDS 106 UNIT 33 Common Paediatric Emergencies 119 UNIT 34 Common Paediatric Surgical Problems 130 PROGRAMMECORE TEAM

Dr. I.C. Tiwari Dr. (Mrs.) Kamala Ganesh Dr. L.N. Balaji Dr. S.B. Arora Dr. Ruchika Kuba Sr. Consultant, UNICEF Director Professor and Head of Chief, Planning Division Course Coordinator Course Coordinator New Delhi O&G Deptt., MAMC, New Delhi UNICEF, New Delhi SOHS, IGNOU, New Delhi SOHS, IGNOU, New Delhi

Dr. S.C. Chawla Dr. Sidharth Ramji Prof. (Col.) P.K. Dutta Dr. T.K. Jena Director Professor and Head of Professor, Deptt. of Paediatrics Programme Coordinator Course Coordinator PSM Deptt., LHMC, New Delhi MAMC, New Delhi SOHS, IGNOU, New Delhi SOHS, IGNOU, New Delhi COURSE REVISION TEAM (1st Revision)

Dr. Neena Raina Dr. Harish Kumar Dr. M.S. Prasad Prof. A.K. Agarwal Dr. Ruchika Kuba Technical Officer, WHO Consultant Paediatrics, Head, Deptt. of Paediatrics Director, SOHS Sr. Lecturer and Course SEARO Office, New Delhi D.D.U. Hospital, New Delhi Safdarjang Hospital, IGNOU, New Delhi Coordinator New Delhi SOHS, IGNOU, New Delhi Dr. Siddharth Ramji Dr. A.K. Patwari Dr. T.K. Jena Professor, Deptt. of Peadiatrics National Professional Officer, Dr. Piyush Gupta Reader and Programme LNJP and MAMC, Delhi WHO Nirman Bhawan, Reader, Deptt. of Paediatrics Coordinator New Delhi GTB Hospital and UCMS SOHS, IGNOU, New Delhi New Delhi COURSE REVISION TEAM (2nd Revision) Dr. Siddharth Ramji Dr. M.S. Prasad Dr. (Mrs.) Lalitha Kailash Dr. (Mrs.) Jayam Subramanium Dr. A.K. Agarwal Professor, Deptt. of Peadiatrics Head, Deptt. of Paediatrics Professor, Deptt. of Peadiatrics Ex. Professor, Professor, SOHS, IGNOU, LNJP and MAMC, Safdarjang Hospital, GMC, Thiruvananthapuram, Deptt. of Peadiatrics New Delhi New Delhi New Delhi Kerala Madras Medical College, Chennai Dr. T.K. Jena Dr. S. Aneja Dr. Vinod Anand Dr. B.D. Bhatia Professor and Programme Professor, Deptt. of Peadiatrics Professor, Deptt. of Peadiatrics Professor, Deptt. of Peadiatrics Dr. S. B. Arora Coordinator LHMC, New Delhi LHMC, New Delhi IMS,BHU, Varanashi, U.P. Professor & Director, SOHS SOHS, IGNOU, New Delhi IGNOU, New Delhi COURSE REVISION TEAM (3rd Revision)

Dr. Harish Chellani Dr. Anju Seth Dr. Neelam Verma Dr. A. P. Dubey Dr. T.K. Jena Professor and Head Director Professor, Professor and Head, Professor and Head, Professor, Deptt. of Paediatrics Deptt. of Peadiatrics Deptt. of Peadiatrics Deptt. of Peadiatrics School of Health Sciences VMMC & Safdarjung Hospital, LHMC, New Delhi Patna Medical College & LNJP and MAMC, IGNOU, New Delhi New Delhi-110029 Hospital, Patna, New Delhi Bihar-800004 BLOCKPREPARATIONTEAM Writers Unit 28 Unit 29-31 Unit 32 Format Editor Dr. Satinder Aneja Dr. Satinder Aneja Dr. Jagdish Chandra Dr. T.K. Jena Director Professor, Director Professor, Director Professor, Deptt of Paediatrics, Professor and Deptt of Paediatrics, Deptt of Paediatrics, LHMC, New Delhi Programme Coordinator LHMC, New Delhi LHMC, New Delhi Dr. Lalitha Kailash (Pre-revised) SOHS, IGNOU, New Delhi Dr. Jagdish Chandra (Pre-revised) Prof. Deptt of Paediatrics, Director Professor, Thiruvananthapuram Deptt of Paediatrics, LHMC, New Delhi Unit 33 Dr. Rajiv Chadha Director Professor, Deptt of Paediatric Surgery, LHMC, New Delhi CO-ORDINATION

Dr. S. B. Arora Dr. T.K. Jena Professor & Director, SOHS Professor and Programme Coordinator IGNOU, New Delhi SOHS, IGNOU, New Delhi PRINTPRODUCTION Mr. Ajit Kumar Section Officer (Pub.), SOHS IGNOU, New Delhi

March, 2019 © Indira Gandhi National Open University, 2019 ISBN- All rights reserved. No part of this work may be reproduced in any form, by mimeograph or any other means, without permission in writing from the Indira Gandhi National Open University. Further information about the School of Health Sciences and the Indira Gandhi National Open University courses may be obtained from the University’s office at Maidan Garhi, New Delhi-110 068, India. Printed and published on behalf of the Indira Gandhi National Open University, New Delhi, by Prof. S. B. Arora, Director, School of Health Sciences. Lasertypeset by : Rajshree Computers, V-166A, Bhagwati Vihar, (Near Sec. 2, Dwarka), Uttam Nagar, New Delhi-110059 Printed at: BLOCK 6 INTRODUCTION

This block provides you an overview of common paediatric systemic illnesses and emergencies. Unit 28 will take you through the evaluation of common childhood problems. Cardiovascular, haematologic and renal disorders are discussed in Unit 29, while gastrointestinal, liver and neurologic problems are presented in Unit 30. Tuberculosis and HIV are emerging childhood problems which are discussed in Unit 31 and Unit 32. Paediatric emergencies such as resuscitation, poisoning, accidents, etc. are reviewed in Unit 33 of this block. Finally, the Unit 34 on common paediatric surgical problems gives you an insight about the possible surgical procedures. ChildhoodMorbidity

4 UNIT 28 COMMON PAEDIATRIC PROBLEMS Structure 28.0 Objectives 28.1 Introduction 28.2 Child with Fever 28.2.1 Common Causes of Fever 28.2.2 Acute Fever 28.2.3 Fever of Unknown Origin (FUO) 28.3 Child with Rash 28.4 Child with Jaundice 28.5 Child with Sore Throat 28.6 Child with Ear Infection 28.7 Common Skin Disorders 28.7.1 Bacterial Infections 28.7.2 Fungal Infections 28.7.3 Parasitic Infections 28.8 Let Us Sum Up 28.9 Key Words 28.10 Answers to Check Your Progress

28.0 OBJECTIVES After reading this unit, you will be able to:  diagnose and treat various types of viral exanthematous illnesses;  diagnose common febrile illnesses and plan investigations of a patient with fever of unknown origin;  manage a child with jaundice;  differentiate self-limiting benign causes of sore throat from potentially serious infections such as diphtheria; and  identify and manage common skin disorders in children.

28.1 INTRODUCTION In clinical practice, a child presents with a symptom rather than a disease. Therefore, a step wise approach is required to make differential diagnosis and plan investigations. In this unit, a symptom-wise approach is used to enable you to make a clinical diagnosis of some common problems. Other common conditions are. described in brief. You are required to refer to standard text books for the detailed discussion of these disorders. 5 ChildhoodMorbidity 28.2 CHILD WITH FEVER Fever is the commonest presenting symptom in children. Fever is defined as elevation of body temperature in response to a pathological stimulus. Conventionally temperature >38°C is called fever. Fever greater than 41.5°C is called hyperpyrexia and warrants aggressive antipyretic treatment because of risk of irreversible organ damage, Children presenting with fever can be di\!ided into three groups: (i) acute fever with obvious focus such as tonsillitis or pneumonia etc. (ii) acute fever with no localizing sign or non-specific signs and (iii) prolonged fever of unknown origin. It is the latter two groups which pose diagnostic problem. While evaluating the patient with fever the first important thing to consider is the age of the patient. Acute fever in an infant less than 2 months should always arouse suspicion of serious bacterial infection presence of petechial haemorrhages at any age is also indicative of serious illness and necessitates hospitalization. The other important consideration is duration of fever. Important causes of fever of short duration (2 weeks) and prolonged fever are listed in Table 28.1. The common causes of acute fever are malaria, viral illness( may also cause upper respiratory infection and diarrhea) and bacterial infections such as typhoid fever. . 28.2.1 Common Causes of Fever The common causes of fever are given in Table 28.1. We shall learn more about these causes in the subsequent sub-sections. Table 28.1: Common Causes of Fever in Children Causes of fever of short duration Prolonged fever ( <2 weeks) ( >2 weeks)

Infections  Malaria  Typhoid.  Respiratory infection e.g.  Kala-azar Tonsillitis  Malaria Pneumonia  Tuberculosis Otitis Media  UTI  Viral Exanthem  Bacterial endocarditis  Typhoid fever  Abscess in liver  Urinary Tract Infection (UTI)  Brucellosis  Heat hyperpyrexia  Infectious mononucleosis  Occult pyogenic infection Connective tissue disorders e.g. abscess  Rheumatoid arthritis

6 Common Paediatric  Meningitis  SLE, Kawasaki disease Problems Neoplastic Condition e.g. Leukaemia, lymphoma Others Drug fever Thyrotoxicosis Immune deficiency-HIV Diabetes Insipidus

28.2.2 Acute Fever Evaluate for any focus of infection. Determine whether the child is seriously ill? A sick child has one or more of following symptoms and signs: Symptoms Signs Lethargy “sick” or toxic look Inability to suck lethargy/poor tone Irrititability weak cry Drowsiness tachypnoea poor peripheral perfusion The fundamental basis of diagnosis is to localize the infection by careful history and clinical examination. It should also be remembered that in children disease develops over hours and days and a single examination may not provide the diagnosis. Where there is a doubt, the child should be hospitalized and reexamined. In a small but significant proportion of children no identifiable cause of fever is found even after detailed examination. This problem is more common in infants and toddlers. The common causes of acute fever without obvious focus are viral illness, malaria, otitis media, typhoid fever, occult bacteremia. The diagnosis can be then established by (i) obvious focus such as tonsillitis or pneumonia etc. (ii) acute fever with no localizing sign or non-specific signs and (iii) prolonged fever of unknown origin. It is the latter two groups which pose diagnostic problem. In areas endemic for malaria, empirical therapy for malaria may be started. In case laboratory investigations are not available treatment is often based on clinical diagnosis. Occult bacteremia implies presence of bacteria in the blood stream with minimal clinical signs. This condition commonly occurs in infants (3-24 months). The organisms frequently implicated are S. pneumoniae, Hemophilus influenzae. Salmonella species and Staphylococcus aureus. Depending on the age, host factors and bacterial virulence, bacteremia can be self-limited, spread with localizing infection or result in overwhelming sepsis. 7 ChildhoodMorbidity The challenge for the clinician is to differentiate children with bacteremia from those with fever due to other causes. Clinical feature of bacteremia inelude sick and toxic look, reduced level of alertness and poor feeding. The WBC count >15,000/cu mm, in a child who has fever> 39°C is highly suggestive of bacteremia. All children with high risk for bacteremia (particularly if <3months) should be hospitalized. Blood culture should be drawn and empiric antibiotic therapy started with ceftriaxone or cefotaxime. The patient should be closely observed for any metastatic infection like meningitis or arthritis. The possibility of meningitis should be always considered in young infants and spinal tap performed if suspected. 28.2.3 Fever of Unknown Origin (FUO) This term is reserved for fever for more than 2 weeks duration with no localizing signs. The principal causes of FUO are infections, connective tissue disorders and neoplastic disorders. Most fevers of unknown origin result from the a typical presentation of common diseases. Diagnostic Clues Bacterial infections are common in younger children and auto-immune diseases should be considered in adolescents. The type of fever whether intermittent or remittent provides a vital clue. Intermittent fever is seen in malaria, kala-azar, brucellosis and lymphoma. Remittant fever is seen in typhoid, bacterial endocarditis, pyogenic abscess, infectious mononucleosis. Fever with chills and rigors is suggestive of septicaemia, pyelonephritis, liver abscess besides malaria. The place of residence if endemic to certain infectious diseases should always be borne in mind. Kala-azar is endemic in Bihar, some areas of eastern UP and West Bengal. History of similar illness in neighbours and family members point to the endemicity of the disease.Scrub typhus is common in rural areas and hilly areas. History of blood transfusion or blood products should alert the physician to hepatitis B and HIV infection. History of exposure to animal (e.g. leptosprosis) and history of contact with a case of tuberculosis should be sought in all patients with prolonged fever. Examination The general appearance of the patient whether toxic or well looking gives an indication of severity of the disease. Physical examination is done to look for any focus of infection. A complete physical examination with special reference to examination of bones and joints, lymph nodes, ear, nose and throat is mandatory. The presence of physical signs provide clue to the type of infection. Skin rash may be seen in meningococcemia. viral haemorrhagic fever. leptospirosis or collagen disorders. Similarly, presence of anaemia (malaria); jaundice (hepatitis. infectious mononuclosis. malaria, typhoid, leptospirosis), lymphadenopathy (tuberculosis. infectious mononucleus, AIDS. kawasaki. leukemia) and hepatosplenomegaly (typhoid. malaria, kala-azar.TB, brucellosis), oral thrush (AIDS) help in narrowing down the diagnosis.

8 After the history and examination, the physician can make a reasonable Common Paediatric working diagnosis and decide if the patient is suffering from life threatening Problems infection and requires hospitalization or can be observed at home. Investigation Investigations include , absolute neutrophil count (>10,000 suggestive of bacterial infection; neutropenia is seen in viral infection and typhoid fever); peripheral smear for malarial parasite and ESR. Blood culture and urine culture should be sent in all cases. A mantoux test and X-ray chest is required in all cases of FUO in countries with high prevalence of tuberculosis. The serological tests including widal for typhoid provides additional information. In patients with suspected pyogenic infection an ultrasound of abdomen should be done to exclude deep abscess e.g., subdiaphragmatic abscess, liver abscess. A child having fever for more than one month should be tested for HIV after pretest counselling. If the above investigations do not yield any information, further haematological and radiological investigations are required. Bone marrow aspiration provides the diagnosis of parasitic diseases like Kala-azar, malaria, haematological disorders. CT Scan of chest and bronchoscopic lavage for AFB should be done if tuberculosis is a major diagnostic consideration. When bone and joint infection is a probability, a bone scan should be done since plain radiograph is not informative in early cases of osteomyelitis. Management 1) Specific treatment: It can be started after a working diagnosis is made. 2) Supportive treatment: Patients with fever should receive adequate fluids and nutrition. Children should not be overclothed. Loose and light clothing is best suited. 3) Antipyretic: Acetaminoplen (paracetamol) 15 mg/kg/dose is the drug of choice for bringing down temperature. Give paracetamol if fever is more O than 38 C. Other alternative drugs are ibuprofen and nimesulide.

28.3 CHILD WITH RASH Skin rash is a common complaint in children. The skin rash may reflect effect of toxin (scarlet fever); bacteria (meningococcal); inflammation (drug rash) or vasculitis (kawasaki). Occasionally, the clinical picture is diagnostic but more often the rash is non-specific and careful history and examination is necessary to make a diagnosis. A brief diagnostic approach to a child presenting with rash is outlined below. History History should include the onset of rash relative to the course of underlying illness if any and associated problems. The parents should be asked for details of associated fever, and the temporal relationship of fever with rash. Other associated features should be looked e.g. diarrhoea (enteroviral) and 9 ChildhoodMorbidity severe illness (meningococcal). The location of rash to begin with and how it developed and spread and the subsequent course helps in making diagnosis. Parents should be enquired about the history of similar illness in neighbourhood or siblings. All medications taken prior to the onset of rash must be noted. A note should be made about the immunization history. Examination The first step is to distinguish the rash associated with life threatening conditions e.g., meningococcemia or which require immediate treatment from benign conditions that can simply be observed. The general appearance, pulse, BP, respiration and temperature help in deciding the severity of illness. Next the characteristics of the rash are noted whether macular/maculopapular or vesicular/pustular. Secondary manifestations e.g., superadded infection or itch marks should also be noted. The mucosal surfaces should be inspected particularly conjunctivae and oral cavity. In children with suspected viral exanthema, koplik spots should be looked for. Mucosits is prominent in Steven Johnson syndrome. Diagnosis Thc involvement of other organs and systems can give a clue to diagnosis e.g. lymph node (rubella), arthritis and renal (connective tissue disorder). By careful history and examination of the patient a clinical diagnosis can be made in most cases. In cases in which there is suspicion of serious illness e.g. dengue or meningococcemia, the patient should be hospitalized and diagnosis confirmed by relevant investigations. Immpiric antibiotics should be started after taking blood culture when sepsis is probable diagnosis. The different diagnosis of fever with rash is given in Table 28.2. Many viral exanthema can present with fever with rash. The salient features of various viral exanthema is given in Table 28.3. Table 28.2: Diagnosis of Rash with Fever

10 Table 28.3: Differential Diagnosis of Viral Exanthema Common Paediatric Problems

Check Your Progress 1 1) An ill looking thud with history of headache, vomiting and tense fontanelle is brought to emergency. On examination the child looks sick, has rapid pulse and apurpurie rash. The most probable diagnosis is...... 2) A 1 year old fully immunized child has history of coryza and high grade fever for last 4 days and developed a maculopapular rash. The fever subsided immediately after the appearanceofthcrash. The most probable diagnosis is ...... 3) Enumerate the conditions associated with maculopapular rash...... 4) Chickenpox is caused by ...... 11 ChildhoodMorbidity 28.4 CHILD WITH JAUNDICE Definition Jaundice (or icterus) can be defilled as yellowish discoloration of sclera (seen through bulbar conjunctives), skin and mucous membranes due to elevation of serum bilirubin level (hypeerbilirubinemia). Causes Jaundice can occur in variety of clinical conditions. The causes vary by age . Present discussion w’ill focus on causes of jaundice beyond neonatal period (Table 27.4). However in early part of infancy some conditions causing neonatal jaundice may be encountered. Table28.4: Causes of Jaundice in Children (beyond neonatal period) Group A : Unconjugated hyperbilirubinemia i) Congenital hemolytic anaemia: a) Thalassemia b) Hereditary spherocytosis c) d) G-6-PD and other RUC enzyme deficiency. ii) Acquired hemolytic states: a) Infections-acute bacterial infection, malaria b) Immune hemolYtic anaemia. iii) Miscellaneous: a) Criggler-Najjar syndrome b) Gilbertsyndrome c) Drugs-Vitamin.K. Group B : Hepatocellular jaundice and conjugated hyperbilirubinemia (cholestasis syndromes) i) Infections: a) Hepatitis — A, B, C, D, E. b) Other viruses—cytomegalovirus, E.B. virus. c) Malaria d) Bactetial infections-septicemia, typhoid fever. ii) Extrahepatic biliary obstruction-(may present in post neonatal period): a) Congenital extrahepatic biliary atresia. b) Choledochal cyst c) Gall stones — haemolytic anaemia, idiopathic d) Bile duct stenosis e) Extraneous compressiol1 e,g. lymph node enlargement at porta hepatis. 12 Common Paediatric iii) Intrahepatic cholestasis: Problems a) Idiopathic neonatal hepatitiS b) Alagelle syndrome c) Intrahepatic biliary hypoplasia d) Congenital hepatic fibrosis iv) Metabolic: a) Disorders of carbohydrate metabolism — galactosemia, Fructosemia, glyeogen storage disease. b) Disorder of amino acid metabolism — Tyrosinemia c) Disorders of lipid metabolism-Gaucher disease — Niemann-Pick disease, Wolman disease d) Miscellaneous — :-l antitrypsin deficiency, Indian childhood Cirrhosis, cystic fibrosis, Wilson disease.

Three basic pathological states can cause hyperbilirubinemia: 1) Over production of bilirubin due to excess RBC breakdown, which will result in unconjugated hyperbilirubinemia (hemolytic jaundice), 2) Diseases of liver resulting in defects in metabolism of bilirubin, leading to hyperbilirubinemia of mixed type (hepatocellular jaundice), and 3) Intrahepatic or extra hepatic lesions resulting in obstruction to the free flow of bile leading to conjugated hyperbilirubinemia (obstructive jaundice). Diseases leading to over production of bilirubin will cause unconjugated hyperbilirubinemia while those due to disease of liver and obstruction to bile flow result in conjugated hyperbilirubinemia. Approach to a Child with Jaundice The commonest cause of jaundice in children is viral hepatitis. Cases with viral hepatitis have fever, anorexia, abdominal discomfort and nausea, along with yellow discolouration of eyes and urine. In the initial phase, patient may have acholic stools. Usually liver is palpable, soft and tender. Patients with hemolytic anemias have anemia and usually only mild jaundice. Spleen and liver both are enlarged as a result of and extramedullary hematopoeisis. Patients with cholastatic jaundice have intense urinary discolouration and acholic stools. Pruritis is a feature of obstructive jaundice Patients with choledochal cyst present with fever, abdominal pain and abdominal lump in association with jaundice. Investigations Liver functions tests including levels of total and differential serum bilirubin, AL T, AST, alkaline phosphatase, serum proteins, albumin and globulin are the initial investigations. Significant increase of conjugated bilirubin (> 20% of total) reflects decreased excretion and is usually associated with increased levels of alkaline phosphatase. 13 ChildhoodMorbidity In the neonatal period and early infancy, obstructive jaundice due to hepatitis and biliary atresia poses a specific clinical problem due to overlapping clinical signs and results of investigations. Their early differentiation is of utmost importance as for biliary atresia, surgical intervention is required results of which are better if done early (before 8 weeks of age). Both conditions are equally common and present with jaundice., acholic stools and hepatosplenomegaly. These patients should be promptly referred to a specialized center for investigation and early surgery if required. In older children having hepatitis like clinical picture, markers for various viruses should be’ looked for. After appearance of jaundice in cases with viral hepatitis, fever subsides. Its persistence should make one look for typhoid or malaria as etiology. In younger infants even UTI can present as hepatitis/ obstructive cholangiopathy. Hematological investigations including peripheral smear examination for RBC morphology, and reticulocyte count should be ordered. When hemolytic anemia is a strong possibility, confirmation of the diagnosis can be done by specific tests: Ultrasonographic and CT examination of abdomen is required to outline the anatomic defects leading to obstructive jaundice. Liver biopsy is resorted to in cases where etiology of jaundice is unclear. Management The management of patient with jaundice will depend upon the cause. The occurrence of jaundice with prior febrile episode with acute onset and history of vomiting and pain abdomen should make you suspect viral hepatitis. The most common cause of jaundice in children is infection with hepatitis A virus which is generally a benign disease in this age group. Hepatitis B, C and D infectiops are more likely to progress to chronic liver disease, hence should be excluded in children with history of blood transfusion or if jaundice is prolonged. Treatment is supportive and symptomatic. Bed rest is recommended in acute stage of the disease. There is no dietary restriction and diet should be regulated by the patient’s appetite. Since most drugs are metabolized in the liver, any medicine given for symptomatic treatment e.g. pain or fever should be used judiciously, avoiding hepatotoxic drugs. There is no specific treatment for acute viral hepatitis. Interferon is used for treatment of chronic hepatitis B. Chronic hepatitis B requires close follow up and should be treated in tertiary care centers. Prevention of hepatitis due to hepatitis virus A and b can be achieved by safe water supply, personal hygiene and environmental sanitation since these are transmitted by oro-fecal route. Control measures for hepatitis B are different since this is spread by blood and blood products or by vertical transmission or by sexual contact. There is a strong need for incorporation of immunization against hepatitis B in the national immunization programe (see theory Block 5, Unit 21). Immunization against hepatitis A is also available but this strategy remains of unproven benefit.

14 Check Your Progress 2 Common Paediatric Problems 1) Enumerate common-causes of unconjugated hyperbilirubinemia in a 3 year old child...... 2) Enumerate the infections which can cause jaundice...... 3) A 4 weeks old imant has presented with history of passing clay coloured stools and dark coloured urin-e since birth. On examination he is found to be having jaundice and hepatosplenomegaly. What will you do if you see such a patient in a PHC? ......

28.5 CHILDWITH SORE THROAT Acute infection of the upper respiratory tract, particularly the tonsils, fauces and pharynx (sore throat) is common in children, and usually occurs as a part of diffuse upper respiratory tract imection accompanied with obvious coryza and cough. This infection can be caused by many common respiratory viruses and this condition is generally self limiting and benign and does not require any treatment. However, bacterial pathogens such as Group A. Streptococci are the causative agents in nearly 10-20% of cases, and these require specific antibiotic therapy. In unimmunised population, diphtheria is a life threatening infection which can cause similar clinical picture. It is important for the attending physician to be able to differentiate benign causes from those requiring referral and immediate treatment. Viral Pharyngitis Etiology Pharyngitis, tonsillitis and tonsillopharyngitis are common manifestations of adenoviruses, coxsackie, echoviruses ,influenza and parainfluenzae viruses. Viral pharyngitis is the most common cause of sore throat. Clinical Features Pharyngitis due to viral origin has a gradual.-onset with fever, malaise, anorexia and mild throat pain. The soreness and pain in throat begins a day or two after the onset of illness. Hoarseness of voice, cough and rhinitis are other common features. The pharyngeal inflammation is generally less intense 15 ChildhoodMorbidity than streptococcal sore throat though often the two conditions are clinically indistinguishable. The cervical lymph nodes may be enlarged but are not tender. The entire illness is brief generally lasting for less than 5 days. Laboratory leatures Total leucocyte count is elevated with neutrophilic predominanace and is therefore of not much significance in differentiating bacterial from viral etiology. The specific virus causing the sore throat is not important except from epidemiological point of view and cannot be made out clinically except in certain cases. Thus adenoviral infection can cause exudative pharyngitis with high grade fever. The type 3 adenovirus causes a distinct clinical syndrome - pharyngoconjunctival fever which is characterised by high fever, pharyngitis, conjunctivitis and cervical lymphadenopathy. Mucopurulent conjunctivitis in this infection often persists after the fever has resolved. In sore throat with influenzae and para-influnzae viruses the systemic symptoms are much more prominent. Treatment Treatment of viral pharyngitis is symptomatic. Antibiotics are of no use and should not be given. Streptococcal Pharyngitis Epiderlnology Group A streptococcus is the most common bacterial cause of acute pharycngitis. Otber pathogens like Staph aureus, H.injlunzae, M catarrhalis can also cause sore throat but are infrequent causative pathogens. Streptococcal infection is specially common in chil.dren between the ages of 5-15 years. The infection may spread by person to person or by droplet. Clinical Features The condition often begins with acute onset of headache, vomiting, along with high grade fever. The throat may feel sore with tonsillar enlargement, exudation and pharyngeal erythema. There is pain during swallowing. Anterior cervical group of lymph nodes are enlarged and tender early in the disease. On examination there is diffuse redness of tonsil.s and their pillars with follicular exudates. Suspect streptococcal. sore throat in a child:  Sore throat without coryza  Enlarged tender cervical lymph node and  Whitish exudate on tonsils or pharynx . Laboratory Diagnosis Diagnosis is made by detection of streptococl:al antigen or by culture of streptococcus from throat swab. However since a small percentage of patients may b¥ asymptomatic carriers the cause and effect relationship cannot be proved even in presence of positive. culture. Treatment Because of potentially harmful sequelae such as acute rheumatic fever and 16 glomerulonephritis all suspected streptococcal throat infections should be treated with oral penicillin or amoxicillin (50mg/kg/day) or erythromycin Common Paediatric (30-50mg/kg/day in 4 divided doses) for ten days. A single intramuscular Problems injection of Benzathine penicillin in a dose of 600,000 units for children under 5 years of age and 1,20,000 units intramuscular for chidren above 5 years of age is sufficient to prevent rheumatic fever. There is prompt clinical response to antibiotics with defervescence within 24-36 hours. If there is Severe pain in throat, acetaminophen and warm saline gargles (in co-operative children) provide symptomatic relief.

28.6 CHILD WITH EAR INFECTION Ear infections rarely cause death. However, they cause significant morbidity. Ear infections are the main cause of deafness in developing countries. Acute otitis media (AOM) is caused by S. pneumoniae, non-typable H. influenzae and M. catarrhalis. When a child has an acute ear infection, pus collects behind the tympanic membrane in the middle ear and causes pain and often fever. The fever and pain subsides if there is perforation, but the child suffers from conductive hearing loss. These infections may extend and spread to the head and neck structures and to the brain. i) Acute Otitis Media (AOM) usually present with a history of rapid onset of such as pain in ear, irritability (especially in infants), otorrhea, and/or fever. These findings other than otorrhea, are nonspecific and frequently overlap those of an uncomplicated viral upper respiratory infection. Middle ear infection is suggested by presence of ear discharge or fullness or bulging of the tympanic membrane on otoscopy. Pain is prominent in acute phase but subsides if there is perforation of tympanic membrane. The diagnosis of acute otitis media can be made on otoscopy. In the field situation, the assessment of a child with ear problem can be based on clinical examination without use of otoscopy. It takes into account the following three key features:  Ear pain  Ear discharge and duration of discharge.  Swelling and tenderness of mastoid which indicates mastoiditis Treatment:  Oral amoxicillin should be given for 7 days.  Fever and pain usually subsides with Paracetamol  The ear should be dried by wicking with clean cloth if there is pus draining from the ear. ii) Chronic otitis media: An ear discharge that has been present for 2 weeks or more is treated as a chronic ear infection and is usually caused by Pseudomonas sp. and Staph. aureus. Topical quinolone ear drops should be instilled after wicking the ear dry. Systemic antibiotics are not required for chronic ear infection. There is no role of antihistaminics or decongestants in treatment of acute /chronic ear infections iii) Mastoiditis : Children with mastoiditis need specialized care and should be admitted in a hospital which has ENT specialist. Mastoiditis 17 ChildhoodMorbidity may be complicated by meningitis or brain abscess and such patients should be assessed and treated for these complications.

28.7 COMMON SKIN DISORDERS Skin is composed of 3 layers the outer epidermis (ectodermal in origin), and inner dermis; and subcutaneous tissue (mesodermal in origin). The skin appendages hair and nails arc vestigeal structures with no physiological function. Skin disorders may be primary in nature affecting only the skin or may be a marker of systemic or neurocutaneous disorder. To diagnose a skin disorder a careful and detailed history is essential. History should also include past history, family history of atopy/allergy, and prior treatments. Examination should be done after undressing in a good light. General health, nutrition and other systems should be examined. Accurate morphological description of skin lesions and their distribution is critical for making diagnosis. Macules are flat small le9ions identified because of a difference in color from surrounding skin. Large macules > 1 cm are called patches. Papules are small palpable circumscribed lesions, raised above the surface. Large papules (> I cm) are called nodules. Vesicles are fluid filled elevated lesions while pustules contain purulent material. The primary lesion can evolve into secondary lesions such as ulcer, erosion, or scale. While examining the skin you should also see the relationship of the lesion to appendages such as hair follicles and examine the mucus membrane. The common skin problems encountered in paediatrics are infections and infestations of skin. developmental disorders and allergic disorders. Some of the important conditions are described below. Developmental Disorders a) Congenital Melanocytic Nevi: These are very common seen in nearly 1-2% of populations. These are small hyperpigmented nevi. With small lesions the risk of malignant transformation is low. With large lesions the risk is higher (4.6%). A large melanocytic nevus over the back should arouse suspicion of spinal dysraphism. b) Hemangioma: This is the most common benign tumour of childhood. Hemangioma are composed of capillaries and are characterised by proliferation of endothelial cells. These generally appear in the first week of life as an area of pallor followed by a tetengiectatic patch. The lesion proliferates rapidly in the 1 st 6 months of life growing upto a well demarcated reddish tumour. There is phase of slow growth followed by a stationery phase, after which the lesion involutes. 90% of cases involute by 9 years leaving residual changes such as hypopigmentation. Management Most hemangiomas do not need any treatment. Large disfiguring lesions or one tl}at is interfering with vital organs require treatment. During the period of rapid growth, bleeding, ulceration and infection can occur. Steroids (oral arid intralesional) slow the gro~th of the hemangioma. Superficial hemangiomas can be effectively treated with use of laser. 18 28.7.1 Bacterial Infections Common Paediatric Problems Pyoderma The cutaneous bacterial infections are commonly caused by Staphylococus aureus and beta hemolytic streptococci. Impetigo This is a common skin infection of children living in overcrowded, not and humid conditions. Following colonisation of the skin with beta hemolytic streptococci, the bacteria invade around areas of trauma or scabies and form small vesicles and pustules which rupture and dry .leaving crusts. Scratching helps to spread the lesion to other parts of body. Bullous impetigo is due to Staph aureus and appears as large fluid filled blisters.. Non bullous impetigo may be due to staphylococci or group A beta-hemolytic streptococci. Potential complications of impetigo include cellulitis, osteomyelitis, pneumonia and septicemia. Infection with nephritogenic strains can cause post- streptococcal glomerulonephritis. Furunculosis Furunculosis or boils are small abscesses around the hair follicles caused by staphylococci. Infection is deeper and there is erythema, pain and edema of the surrounding skin. Trca.tmcnt of pyodcnna Minor and superficial infections heal by themselves. In infants however they may lead to septicemia. Topical antibiotic mupirocin which is bactericidal .can be applied to superficial lesions. In seyere and deep infections systemic antibiotics such as erythromycin, cloxacillin or cephlexin may be used. Cellulitis Bacteria! skin infection may spread rapidly to the &ubcutaneous tissue causing redness, swelling, pain and regional lymphadenopathy. The causative bacteria are streptococci and staphylococci but invasive H. influenzae may also cause cellulitis in children which is usually seen in the area of head and neck and is often associated with septicemia. All forms of cellulitis should be treated early with antibiotics that cover stephylococci and streptococci. 28.7.2 Fungal Infections Fungal infection of keratinised tissues are especially common in tropical countries due to ideal growth conditions provided by heat and sweat. Superficial mycoses include dermatophyte infections and candidiasis. Dermatophytoses These are infections caused by ringworm fungi-aerobic filamentous fungi- ‘Minosporum, Trichophyton and Epidermophyton. The infections are confined to superficial keratinised layer of the skin. The body reacts to the infection by increased cell turnovcr leading to scaling aI1d hair loss. Tinea Capitis presents as patchy or diffuse dermatosis with scaling with variable loss of hair. There may be secondary infection with pustule formation. 19 ChildhoodMorbidity Topical antifungal agents such as clotrimazole are effective. Tinea pedis is characterized by infection of interdigital cleft of feet with maceration, secondary infection and marked itching. Candidiasis Infection of the skin or mucosa with candida albicans may present as oral thrush, diaper rash, or vulvovaginitis. In children who are immunocompromised! condidial infection may be severe with widespread systemic involvement. Local Nystatin or clotrimazole preparations are effective for local infection. 28.7.3 Parasitic Infections Scabies Scabies is a skin infection caused by the mite Sarcoptes scabeii. Mites are not free living and die within 1-2 days away from the host body. Transmission is usually by direct contact with infected person. After fertilization in the skin surface, the female mite burrows into the skin where she lays eggs for a few days before dying. The body’s response to the mite, eggs, and faeces (scybala) cause the inflammation and intense itching. Hands, feet, axillae and neck are commonly infected but in person with poor hygiene children may be completely covered with excoriating lesions. The head, neck, palms and soles are generally spared in older children and adults. The lesions are extremely pruritic especially at night. There may be secondary bacterial infection which may in turn lead to acute glomerulonephritis. Diagnosis is mainly clinical but confirmed by microscopic identification of eggs and scybala of the mite from skin scrapings. Treatment: The best treatment is 5% pyrethroid (permethrin topical cream). A single application cures 9011/0 of cases. The entire family should be treated simultaneously. Clothing and bed linen should also be laundered simultaneously. 1 % gamma benzene hexachloride is another alternative but has a danger of neurotoxicity. Pediculosis Capitis (Head lice) It is an intensely pruritic infestation of lice on scalp hair. It is caused by Pediculus capitis an obligate parasite ,of human host. The adult louse is 2-4 mm in length. The louse is transmitted most commonly by head to head contact. Shared combs and brushes can also transmit the louse. The adult female lays 0.5 mm translucent eggs near the proximal end of the hair shaft which is cemented to one side of the shaft. Symptoms do not appear immediately but develop as the individual gets sensitized. Intense pruritis with scratching is the main symptom. Secondary pyoderma after trauma due to scratching may result in matting of hair and cervical lymphadenopathy. Dermatitis may be noted in neck and behind the pinnae. Treatment: The treatment of choice is permethrin 1 % which is applied for 10 minutes and then washed off. Application is repeated after 7-10 days. Mites should be removed with a fine toothed comb. Brushes and combs should be thoroughly cleaned with. boiling water or else discarded. 20 Check Your Progress 3 Common Paediatric Problems 1) Enumerate the microbes which can cause sore throat...... 2) The potentially harmful sequele of acute streptococcal sore throat are ...... and...... 3) Outline the treatment of a patient with a) scabies and b) pediculosis capitis...... 4} Name two cutaneous fungal infections......

28.8 LET US SUM UP Fever is the commonest presenting symptom in children. Acute fever in infants < 2 months should arouse the suspicion of bacterial infection. In older infants and children fever of short duration with no localizing features is. most commonly due to malaria, viral infections and upper respiratory infections. Fever for more than 2 weeks duration with no localizing feature requires investigation. Typhoid fever, Tuberculosis, malaria, kala-azar and urinary tract infections are common causes of prolonged fever. Skin rash can be due to a potentially life threatening condition like meningococcemia or a self-limited viral exanthem. You should be able to make a probable diagnosis with the diagnostic approach outlined. Jaundice can be due to variety of disorders. The most common cause of acute onset of jaundice in a child is infective hepatitis due to hepatitis A virus. Hepatitis A is mild in childrcn with a short clinical course. The treatment is mainly symptomatic. Hepatitis due to hapatitis B, C and D are more likely to progress to chronic liver disease. Sore throat is most commonly caused by respiratory viruses and is self-limited infection. Streptococcal pharyngitis should be considered if the patient is having high grade fever, tonsillar enlargement with exudation and cervicai lymphadenopathy, Becausc of potentially harmful complications such as rheumatic fever all suspected streptococcal infection should be treated with penicillin, In un immunized patients phaiyngeal diphtheria should be excluded in patients with sore throat who have unilateral or bilateral tonsillar membrane. Skin infections, both pyogenic and fungal are common in tropical countries because of heat and humidity. Poor personal hygiene is the predisposing factor for parasitic infestations such as scabies and pediculosis. Skin infections can be diagnosed easily by their characteristic appearance and you should treat them appropriately.

21 ChildhoodMorbidity 28.9 KEY WORDS Bullae : Large blisters> 0.5 cm Dermatophytosis : Infection of the skin caused by ringworm fungi- Minosporum, Trichophyton and Epidermophyton. Enanthema : Eruptions of the skin accompanied by inflammation Enteric fever : Systemic infection due to S typhi, S. paratyphi A, B Exanthema : Eruptions of mucus membranes Macule : Flat lesion on skin not raised above surface Papule : Small palpable lesion elevated above the skin surface. A large papule (> 1 cm) is called Nodule Pustule : Vesicles containing pus Typhoid fever : Systemic bacterial infection due to Salmonella typhi Vesicles : Fluid filled blisters

28.10 ANSWERS TO CHECK YOUR PROGRESS Check Your Progress 1 1) meningococcemia 2) exanthema subitum 3) measles, rubella, enteroviruses, typhoid fever, leptospirosis, kawasaki disease 4) varicella zoster virus Check Your Progress 2 1) Unconjugated hyperbilirubinemia is due to hemolytic anaemia-<:ongenital (sickle cell disease, hereditary spherocytosis) or acquired (auto-iI1)mune hemolytic anaemia) and infections and drugs causing hemolysis. 2) Infective causes of jaundice are -hepatitis virus A, B, C, D and E, Cytomegalovirus,. Epstein-barr virus, malar~, typhoid fever etc. 3) The infant requires urgent evaluation for extra hepatic biliary atresia; and should be referred to higher centre.

Check Your Progress 3 1) Viruses such as adenovirus, coxsackie, EB virus; bacteria -Strept pyogenes, C.diphtheria. 2) acute rheumatic fever, post-streptococcal glomerulonephritis. 3) a) The best treatment is 5% pyrethroid (permethrin topical cream). A single application cures 90% of cases. The entire family should be treated simultaneously. Clothing and bed linen should also be 22 laundered simultaneously. 1 % gamma benzene hexachloride is Common Paediatric another alternative but has a danger of neurotoxicity. Problems b) The treatment of choice is permethrin 1 % which is applied for 10 minutes and then washed off. Application is repeated after 7-10 days. Mites should be removed with a fine toothed comb. Brushes and combs should be thoroughly cleaned with boiling water or else discarded. 4) Ring worm fungi and candida albicans.

23 ChildhoodMorbidity UNIT 29 CARDIOVASCULAR, HEMATOLOGICAL & RENAL DISORDERS Structure 29.0 Objectives 29.1 Introduction 29.2 Common Cardiac Problems in Childhood 29.2.1 Indicators of Heart Disease 29.2.2 Congenital Heart Disease 29.2.3 Acute Rheumatic Fever 29.2.4 Congestive Heart Failure 29.2.5 Benign Murmurs 29.3 Hematological Disorders in Childhood 29.3.1 Approach to a Child with Anemia 29.3.2 Iron Deficiency Anemia 29.3.3 Megaloblastic Anemia 29.3.4 Beta Thalassemia 29.3.5 Hemorrhagic Disorders - Diagnostic Approach 29.4 Common Renal Disorders 29.4.1 Evaluation of a Child with Common Renal Problems including Hematuria 29.4.2 Urinary Tract Infections 29.4.3 Oedema in Children 29.4.4 Nephrotic Syndrome 29.5 Let Us Sum Up 29.6 Answers to Check Your Progress 29.7 Further Readings

29.0 OBJECTIVES After reading this unit you should be able to:

l identify common congenital heart diseases;

l identify and treat acute rheumatic fever;

l diagnose the cause of anemia and treat iron and other deficiency anemia;

l diagnose and treat urinary tract infection;

l evaluate cases presenting with hematuria and oedema; and

l to diagnose and manage cases of nephrotic syndrome. 24 Cardiovascular, 29.1 INTRODUCTION Haematological and Renal Disorders In the previous unit infections and common febrile illnesses affecting children have been discussed. This and subsequent unit is devoted to systemic diseases in pediatric age group. In this unit common cardiovascular, hematological and renal / genitourinary diseases are discussed. Section on cardiovascular diseases describes the management of congestive cardiac failure and acute rheumatic fever. In addition, recognition of common congenital heart diseases has been discussed. Iron and other deficiency anemias are still the major health problems in developing countries. Sections on hematological disorders discuss these anemias alongwith diagnostic approach to children with anemia. Congenital and acquired / bleeding disorders are also briefly discussed. Sections on genitourinary / renal diseases describes management of Urinary Tract Infection in children in details.

29.2 COMMON CARDIAC PROBLEMS IN CHILDHOOD 29.2.1 Indicators of Heart Disease Heart disease in the young is often suspected due to presence of a cardiac murmur on routine evaluation; or because of presence of excessive precordial activity, breathlessness and sweating during feeding (equivalent to exertional dyspnea in older children). Resting heart rate above 140/mt and respiratory rate above 60/mt are abnormal in the term neonates. Frequent lower respiratory tract infections are commonly seen in patients with cardiac lesions that cause increase pulmonary blood flow e.g. ventricular septal defect. (It is very important to differentiate this increase in lower respiratory tract infection from reactive airway disease which is also characterized by frequent episodes of fast breathing with cough and fever). Presence of central cyanosis in the absence of lung disease generally indicates a serious underlying cardiac disorder. In older children exertional dyspnea, palpitation, or chest pain are presenting features. A child with history of joint pains needs cardiac evaluation for rheumatic heart disease. Uncommonly, fast or slow pulse, high blood pressure, missing femoral pulse, or cardiac enlargement on chest x-ray are the pointers to an underlying cardiac abnormality. 29.2.2 Congenital Heart Disease Congenital Heart Disease (CHD) occurs in 6-8/1000 live births throughout the world. The common CHD in order of prevalence are ventricular septal defect (VSD), patent ductus arteriosus (PDA), tetralogy of fallot (TOF), and atrial septal defect (ASD). Aetiology The aetiology of CHD largely remains unknown. Exposure to an environmental teratogen within first trimester is responsible for CHD in less than 5% of instances. Rubella infection in first trimester, maternal alcohol intake, drugs like thalidomide and exposure to radiation are known teratogens. Another 5% of CHD result from genetic disorders like Down’s syndrome etc.

25 ChildhoodMorbidity But most of the congenital heart diseases are considered to be multifactorial and occur as a result of poorly understood genetic and environmental interactions. The chances of recurrence of CHD (not necessarily the same defect) in the siblings is about 3-5%. CHD can be broadly grouped as follows : i) Left to right shunts like VSD, PDA, ASD, ii) Right to left shunts like TOF, TGA (transposition of great vessel), and iii) Lesions causing valvular obstruction. Left to Right Shunts Under normal circumstances the amount of blood flow to the lungs and to the rest of the body is equal. In disorders where part of systemic blood gets into pulmonary circulation in excess are called as LR shunts. This occurs as a result of presence of VSD, ASD or PDA. Consequences of LR Shunts i) No Symptoms : If the communication between two systems is small, such patients have little or no symptoms. ii) Recurrent Lower Respiratory Tract Infections : Increased blood flow to lungs predispose to frequent chest infections like acute bronchitis and pneumonia. iii) Congestive Heart Failure (CHF) : Moderate to large communication usually result in CHF due to volume loading of the left ventricle iv) Failure to Thrive : In some cases feeding difficulties, recurrent chest infections and congestive heart failure combine to cause failure to thrive resulting in an irritable infant (a state of cardiac cachexia). v) Pulmonary Hypertension : Because of increase in pulmonary blood flow, pulmonary hypertension develops. It may be hyperkinetic pulmonary hypertension or obstructive pulmonary hypertension. Pulmonary hypertension of the severity that leads to reversal of shunt makes the patient inoperable. vi) Infective Endocarditis : The jet of the blood stream through the defect traumatizes the endothelium. Any transient bacteremia colonises the aggregate formed at the jet lesions and forms vegetations. The risks of endocarditis are higher in smaller ventricular septal defects than larger ones. Endocarditis rarely occurs in patients with atrial septal defect or Eisenmenger’s Syndrome as pressure difference between heart chamber is small. Clinical Recognition Clinically you must learn to recognize left to right shunts. The neonates with LR shunts do not have an audible murmur in first few days of life. This is because the pulmonary vascular resistance is high initially. In normal babies, pulmonary vascular resistance falls within 24 hours to nearly half the systemic levels. In children with CHD, this fall is more delayed. Neonates with LR shunt do not develop symptoms in first two weeks of life. As the pulmonary 26 vascular resistance falls, the shunt increases more and more; by 8 weeks these infants manifest symptoms and signs of congestive heart failure, Cardiovascular, Haematological and Renal tachycardia, tachypnoea and excessive seating. The infant is unable to Disorders complete a feed, tires out easily, is hungry and irritable. Orthopnoea is reported by sensitive mothers as the baby is more comfortable when held against the shoulder. Elevated jugular venous pressure is difficult to appreciate in neonates but hepatomegaly is a good indicator of congestive heart failure. Gallop rhythm is a comon auscultory finding. The recognition of exact site of shunt is whether the patient has VSD, PDA, ASD (ostium secundum or endocardial cushion defect type), depends largely on precordial examination findings. Patients with VSD have a panasystolic murmur at left lower sternal border. P2 is loud if pulmonary hypertension has developed. Patients with PDA are characterized by presence of a continuous machinary murmur at the second left interspace and below the left claicle. Second sound is paradoxically split in patients with large shunts. The hallmark of ASD is presence of fixed and wide second sound along with an ejection type systolic murmur at the base of the heart. The shunt across the interatrial defect does not lead to audible murmur, due to narrow pressure gradient. Indications for Surgery in Acynotic CHD All patients with VSD or PDA in congestive heart failure should be operated after stabilization with medical therapy. Patients of VSD are usually operated around 6 months of age or even earlier if required. In older children VSD with LR shunt which is large pulmonary blood flow more than twice of systemic blood flow or one which is associated with pulmonary hypertension should be closed. Severe PAH in absence of significant shunt suggest that patient has developed obstructive changes in the lung vasculature and surgery is not indicated, if the calculated pulmonary vascular resistence is higher than 8-10 units by cardiac catheterization. Surgery for VSD caries less than 1% mortality. All patients with PDA require closure as the risks of infective endocarditis is very high. The closure can be accomplished by transcatheter procedure or surgery. A patient with ASD and substantial shunt is operated by 4 - 5 years age. Early surgery is required only if there is CCF refractory to medical treatment. Children with congenital heart disease should be evaluated by pediatric cardiologist and cardiac surgeon. RIGHT TO LEFT SHUNTS Cyanotic Heart Disease The cardiac disease, wherein part of systemic venous return circulated into aorta (without undergoing oxygenation in lungs) results in cyanosis. These are known as right to left shunt lesions. Tetralogy of Fallot, transposition of great vessels, tricuspid atresia, total anomalous pulmonary venous return, single ventricle etc are some of the common cyanotic CHD. Tetralogy of Fallot (TOF) TOF is the commonest congenital cyanotic heart disease which is a constellation of (i) large VSD, (ii) pulmonic stenosis (or right ventricular 27 ChildhoodMorbidity outflow tract obstruction), (iii) overriding of aorta, and (iv) right ventricular hypertrophy. Patients with TOF may not have cyanosis in early weeks of life. Initial presentation may be with hypercyanotic spells (also called anoxic blue spells) characterized by irritability and crying resulting in accentuation of cyanosis at rest. There is fast breathing on account of hypoxia and acidosis. The episode is terminated by either treatment or when the patient is exhausted. At times, the patients may have convulsions or may lose consciousness. Another characteristic feature of TOF is history of ‘squatting’ – patients assume squatting posture on becoming dyspneic. Physical examination reveals a relatively quiet precordium with single P and 2 an ejection systolic murmur in left second and third intercostal spaces. Systolic murmer decreases in intensity or disappears during hypercyanotic spell. ECG in cases with TOF shows right ventricular hypertrophy. Chest X-ray shows decreased vascular markings in the lungs typical cardiac shadow (wooden boot appearance or “Cor-en sabot”). Management of Hypercyanotic Spells Hypercyanotic spell is a medical emergency and needs urgent medical attention. The patient should be put in knee chest position. Clothes around chest are loosened and humidified oxygen is administered. Injection morphine 0.1 to 0.2 mg/kg subcutaneously is given Propranolol at 0.1-0.2 mg/kg IV helps reduce the infundibular spasm. Acidosis needs correction. Occasional patient not responding to this management may require administration of general anaestheria. For prevention of further episodes of hypercyanotic spells, propranolol is used orally in a dose of 0.5-1 mg / kg 6 hourly. Prevention and treatment of iron deficiency anemia also helps preventing hypercyanotic spells. Definitive treatment is surgery. Check Your Progress 1 Fill in the blanks : 1. ASD is characterised by: a. Loud first heart sound b. Fourth heart sound c. Wide and fixed second heart sound 2. VSD is characterized by: a. Loud first heart sound b. Pansystolic murmer c. Cyanosis of nails d. Low pulse volume 3. TOF is characterized by: a. Increased frequency of chest infections. 28 b. Hypercyanotic spells Cardiovascular, Haematological and Renal c. Loud first heart sound Disorders d. Pansystolic murmer Rheumatic Heart Disease Rheumatic Heart Disease (RHD) is still a major cardiac problem in India and other developing countries. About 6-11 per 1000 school children suffer from RHD. Poverty, overcrowding, lower socio-economic status are linked with RHD. All chronic RHD is believed to result from episodes of acute rheumatic fever, but only half of the patients give a history suggestive of acute rheumatic fever (ARF). Recurrent episodes of ARF increase the severity of cardiac lesion and consequently increase morbidity and mortality of RHD. 29.2.3 Acute Rheumatic Fever Aetiology ARF results from a hemolytic streptococcal infection of the throat in the susceptible individuals, however, only in 0.3-3% of the people with streptococcal sore throat, the infection results in ARF. Susceptible individuals mount an exaggerated immune response to streptococcal throat infection. The antibodies seem to cross react with their myocardial, synovial and other tissue antigens resulting in the occurrence of ARF. Any subsequent streptococcal sore throat is highly likely (nearly 50% of the times) to result in another episodes of ARF. Clinical Features After 7-10 days of an episode of apparent or inapparent streptococcal throat infection, patient develops the syndrome of ARF. The major manifestations of ARF viz. arthritis, carditis, rheumatic nodules, chorea and erythema marginatum are outlined below: Arthritis : ARF involves large joints. Most commonly involved joints are knee, elbow, ankle, and hip. Small joints of hand are infrequently involved. Spine, sacroiliac, temporomandibular, and sternoclavicular joints are very rarely involved. The involved joint is tender and often obviously swollen. The arthritis lasts for few days in one joint (rarely more than 2-3 days) and picks up another (migratory arthritis). There are no lasting deformities. Arthralgia alone, without swelling is also frequently seen in ARF. Carditis : It affects all layers of heart but the occurrence of valvulitis is the most important cause of morbidity. Tachycardia, gallop sounds, cardiomegaly or murmurs suggest presence of carditis. The pansystolic murmur of mitral regurgitation is commonest. Short diastolic murmur of mitral stenosis may occur due to inflammed mitral valve (Carey Coombs’ murmur). Aortic regurgitation causes high pitched diastolic murmur in 3rd left intercostal space. Congestive heart failure may occur due to valvular involvement. Cardiac enlargement may result from these lesions or pericardial effusion. Pericardial friction produces a scratchy triphasic noise. Rheumatic Nodules : These small to moderate sized non-tender nodules are of diagnostic importance. They occur over bony prominences like elbow, 29 ChildhoodMorbidity knuckles, spine, knees. The skin over them is freely mobile. These nodules occur in crops and they are invariably associated with carditis. Rheumatic Chorea : This is a late manifestation occurring about 3 months after the onset of ARF. There may not be any other manifestation of ARF at that time. Chorea consists of purposeless, jerky movements of the body associated with hypotonia and emotional lability. There is inability to sustain a voluntary effort like protruding the tongue for sometime. Deteriorating hand writing, dropping things may be a clue to an unidentified mild attack of chorea. Untreated, it has a self limited course of 2 to 6 weeks. However, secondary prophylaxis is required in all patients with rheumatic chorea. Erythema Marginatum : This geographic rash is rarely seen in Indians. It is a spreading rash with clear center, often brought out by sunlight or hot bath in fair people. It suggests ARF, but not necessarily carditis. Other Manifestations : Fever occurs in initial stages of ARF, is usually not high grade and is self limited. Arthralgia is a minor criteria if arthritis is not taken as major criteria. Prolonged PR interval on ECG, leucocytosis, raised ESR, and C-reactive protein are other minor manifestations. Diagnosis It is essential to establish the presence of recent antecedant streptococcal infection for the diagnosis of ARF. A throat culture growing B hemolytic streptococci would clinch the issue. More commonly, raised antibody titre to streptococci (Antistreptolysin – 0) is used to establish this. Revised Jones Jones criteria for diagnosis of acute rheumatic fever are shown in Table-1. Table 29.1: Revised Jones Criteria*( 2015) for Diagnosis of Initial attack of Rheumatic Fever Major Criteria Minor Criteria

1. clinical /subclinical Carditis# 1. Fever 2. Polyarthritis/monoarthritis 2. Arthralgia 3. Erythema marginatum 3. Elevated acute-phase reactants (ESR, CRP) 4. Chorea 4. Prolonged PR interval on ECG 5. Subcutaneous nodule plus

Evidence of preceding group A streptococcal infection (culture, rapid antigen, antibody rise / elevation).

* Presence of two major criteria or of one major and two minor criteria supported by evidence of preceding streptococcal infection indicates high probability of rheumatic fever.

# Subclinical carditis indicates echocardiographic valvlitis

@ ESR > 30 and CRP > 3mg/dl Differential Diagnosis : Diagnosis of ARF is often straight forward. In patients with a previously known RHD, recurrent episodes often typically 30 produce similar clinical pattern. However, in these patients bacterial Cardiovascular, Haematological and Renal endocarditis poses some difficulty when fever and arthralgia occurs. In Disorders healthy children, growing pains, other causes of joint pains like septic arthritis, viral infections, leukemia etc. should be considered in differential diagnosis. In general population, mitral regurgitation from mitral valve prolapse is common. The presence of click and late systolic murmur help to differentiate it from rheumatic MR. Judicious interpretation of laboratory tests including echocardiography would distinguish these clinical problems. Treatment Treatment of ARF includes : i) Treatment of streptococcal infection, ii) Anti-nflammatory therapy for arthritis and/or carditis, iii) Drug treatment of chorea, and iv) Treatment of congestive cardiac failure if present. All patients with ARF should be treated with 10 day course of oral penicillin or a single intramuscular injection of benzathine penicillin. Anti-inflammatory therapy consists of salicylates or corticosteroids. Patients without carditis or with carditis but not in cardiac failure are treated with salicylates. More sick patients with severe carditis and failure are usually treated with corticosteroids Oral corticosteroids are given as Prednisolone 2 mg/kg/day for 2-3 weeks, after which they can be tapered. When the tapering doses start, salicylates are added (usually 100mg/Kg/day for 3-5 days followed by 75 mg/kg/day). Duration of anti-inflammatory therapy is 8 weeks. However, a longer duration – upto 12 weeks is recommended in our country. For mild chorea, phenobarbitone is prescribed. Severe cases are usually managed with haloperidol or chlorpromazine. Prognosis In 90% of patients, the episode of ARF would be over by 12 weeks and one-third of patients with mitral regurgitation would lose the murmur in future, if no recurrence follows. Aortic regurgitation rarely disappears. The severity of carditis is ifluenced by recurrent attacks, hence prevention of ARF is vital. Prevention of ARF Primary Prevention : Identification and treatment of streptococcal sore throat would prevent the first attack of ARF. About 3% of patients with streptococcal throat infection result in ARF. Clinically yellow exudates on the throat, presence of anterior cervical lymph nodes are quite suggestive of streptococcal infection. Proper treatment of sore throat would prevent the first attack of ARF. Secondary Prophylaxis In patients of established RHD, streptococcal infection results in recurrence of ARF and thus 3 weekly injection of benzathine penicillin 1.2 mega units is used to prevent streptococcal sore throat. For patients with ARF without carditis, prophylaxis should be given for a minimum of 5 years after an attack of ARF or until 21 years of age, whichever is later. Longer duration upto 10 years or well into adulthood is 31 ChildhoodMorbidity recommended for patients having carditis. In patients with severe heart lesions, some recommend life long prophylaxis. In persons allergic to penicillin, erythromycin 250 mg twice daily, or a sulphonamide 500 mg daily is recommended. 29.2.4 Congestive Heart Failure Heart failure occurs when the heart can not deliver adequate cardiac output to meet the metabolic needs of the body. In the early stages of heart failure, various compensatory physiological mechanisms try to maintain normal metabolic functions. When these mechanisms start falling short, increasingly severe clinical manifestations start appearing. Clinical features The symptoms resulting from heart failure include effort intolerance and fatigue, dyspnea, cough, anorexia and abdominal pain. Physical examination reveals tachypnea and tachcardia. Jugular venous pressure is elevated though it may be difficult to appreciate in young children. Basal crepitations are audible on examination of chest and liver is characteristically enlarged and tender. Management Prudent management of patient with CHF includes: i) Drugs aimed at reducing preload, afterload and improving contractility. ii) Management of precipitating factors, and iii) Surgical treatment of anatomic defects. Management of Precipitating Factors Anemia, chest infection, cardiac arrhythmias etc. worsen the circulatory state and should be appropriately managed. General Measures You must administer oxygen to sick patients in pulmonary edema. Rest with pillow elevating the head end is helpful. Infants with severe distress should temporarily be denied oral feeds to avoid aspiration. Diet in patients with chronic CHF should have less salts as far as possible. Drugs: i) Digoxin : Digoxin is the mainstay of medical treatment of CHF. Regular maintenance digoxin is administered in two divided doses and is adequate for most situations. The dosages are given in Table 29.1. Digoxin has a narrow therapeutic to toxic margin and overdose results in nausea, vomiting and cardiac arrhythmias (brady or tachy arrhythmias). Digoxin toxicity can be fatal. It is potentiated by hypokalemia, hypomagnesemia. Patients with myocarditis are sensitive to digoxin and may require very small dosages. ii) Diuretics : Intravenous diuretics quickly relieve symptoms of pulmonary congestion. Oral diuretics are required for treatment of chronic CHF. It is important to guard against overzealous use to prevent electrolyte 32 disturbances with these drugs. Potassium sparing diuretics are supplemented with furosemide or thiazides. Low dose intravenous Cardiovascular, Haematological and Renal dopamine serves as a diuretic by its renal vasodilatory actions Disorders iii) Vasodilators : In patients with CHF there is disproportionate elevation of afterload, i.e., disproportionate vasoconstriction aimed at maintaining organ perfusion. Vasodilators reduce myocardial work load and are very useful drugs in CHF in patients with primary myocardial disease or valvular regurgitation. Even in patients with shunt lesions, vasodilators like ACE inhibitors and hydralazine are found useful. ACE inhibitors like enalapril, captopril have revolutionized the medical management of CHF. These drugs inhibit the converting enzyme responsible for generation of angiotensin and are both arteriolar and venodilators. iv) Phosphodiesterase inhibitors: Milirone and amrinone are excellent afterload reducing agents. They are useful in treating low output CHF refractory to standard therapy. However, their administration needs to be carefully supervised. 29.2.5 Benign Murmurs Sometimes a cardiac murmur is present without any significant structural abnormality. The one commonly heard in children is Still’s murmur. It is a typical soft, vibratory, systolic murmur at the third-fourth left intercostal space. The benign murmurs could also occur because of a straight back, kyphoscoliosis etc. In newborn soft systolic murmur is thought to occur due to angulation of pulmonary artery origin (which subsequently disappears). Systolic murmur in the pulmonary area could occur due to anemia. This would be the commonest cause of a benign murmur. As a rule, diastolic murmurs are not benign. Systolic benign murmurs usually are of short duration, low intensity (grade I or II, rarely grade III), heard in early systole, are ejection type and poorly transmitted in other areas . They are associated with no symptoms, normal second heard sound and normal ECG. It is important to be aware of these murmurs to avoid undue anxiety in the parents. Check Your Progress 2 1. State whether True/False : a) During an episode of sore throat, presence of anterior cervical lymph nodes favours a viral cause. (True/False) b) Dose of prednisolone in cases with ARF is 0.5 mg/kg/day. (True/ False) c) Erythema margenatum is commonly not seen in Indians. (True/False) d) Carey Coomb’s murmer is a pansystolic murmer. (True/False) 2. List all major criteria of ARF : (a) ...... (b) ...... (c) ...... (d) ...... (e) ...... 33 ChildhoodMorbidity Table 29.2: Commonly used drugs for CHF Drug Dosage Side effects

Digoxin Digitalising dose Nausea, vomiting Oral-premature 20 mcg/kg arrhythmias higher Neonate 30 mcg/kg toxicity during Infants 30 mcg/kg hypokalemia Child 40 mcg/kg (in 3 doses over 24 hrs) Maintenance dose 10 mcg/kg/day given in two divided dose. Captopril 0.5-6.0 mg/kg/day in Cough, angioedema 3 doses (Oral) hypotension, worseningrenalfailure Enalapril 0.1-0.3 mg/kg/day in As above One or two doses (oral) Hydrallazine 0.75-3 mg/kg/day in Headache tachycardia 2-4 doses (Oral) hypotension Furesamide I/V 1 mg/kg/dose Electrolyte Oral 1-4 mg/kg/day in disturbances, volume 2-4 doses. Depletion, rashes

29.3 HAEMATOLOGICAL DISORDERS IN CHILDHOOD The Anemias - Definition and Classification Anemia is defined as a condition where the (Hb) concentration or (Hct) of an individual is below normal. The World Health Organization (WHO) criteria for the diagnosis of anemia is listed in Table I. Anemia is considered to be mild, when Hb concentrations are above 10 g/dl but below the cut-off value for age, moderate when the concentration is between 7 and 10 g/dl and severe when it is below 7 g/dl. Table 29.3 : WHO Criteria for Diagnosis of Anemia Age/Sex Group Hb (g/dl) Children 6 months – 6yrs <11 Children 6 – 14 yrs <12 Adult males <13 Adult females (non pregnant) <12 Adult females (pregnant) <11 34 29.3.1 Approach To Child With Anemia Cardiovascular, Haematological and Renal Let us first understand important cause of anemia. Tables II and III describe Disorders the classification of anemia based on etiology and morphology of RBC which helps in arriving at a diagnosis. Table 29.4: Classification of Anemia Based on Etiology A. Disorders of red cell production and maturation 1. Deficiency anemias : (a) Iron deficiency anemia. (b) Megaloblastic anemia (B12 and folate deficiency) (c) Protein deficiency. 2. Marrow aplasia : (a) Aplastic anemia – acquired and congenital – (Fanconis pancytopenia) (b) Pure red cell aplasia – congenital (Diamond-Blackfan syndrome) and acquired. (c) Marrow infiltration. (i) Leukemia (ii) Disseminated malignancies – lymphona etc. (iii) Myelofibrosis (iv) Kala-azar. 3. Impaired erythropoeitin production : (a) Chronic Renal Failure. (b) Anemia of chronic inflammation. (c) Hypothyroidism, hypopituitarism. B. Disorders of excess red cell destruction 1. Congenital / Hereditary : (a) Quantitative Defects - Thalassemia (beta, alpha etc) (b) Qualitative Defects - Sickle cell disease. (c) Red cell membrane defects - Hereditary spherocytosis. (d) Red cell enzymatic defects - G-6-PD deficiency, pyruvate kinase deficiency. 2. Acquired : (a) Infections - malaria, acute bacterial infections. (b) Antibody mediated - Immune hemolytic anemias.

Table 29.5: Classification of Anemias Based on Red Cell Size A. Microcytic anemias : (i) Iron deficiency anemia (ii) Thalassemia syndrome (i) Chronic lead poisoning (ii) Chronic inflammation (iii) Sideroblastic anemias. 35 ChildhoodMorbidity B. Macrocytic anemia : I. With megaloblastic marrow : (i) Folic Acid deficiency

(ii) B12 deficiency II. Without megaloblastic marrow : (i) Aplastic anemia (ii) Pure red cell aplasia (iii) Hypothyroidism (iv) Liver diseases. C. Normocytic anemia : I. Hemolytic anemias : (i) G-6-PD deficiency (ii) Hereditary spherocytosis. (iii) Immune hemolytic anemias. (iv) Malaria. II. Anemia due to acute blood loss. III. Anemia of chronic inflammation

Clinical Approach to a Child with Anemia Careful history and physical examination are extremely useful for short listing the causes of anemia in the given case. This helps in selecting the laboratory tests required to avoid unnecessary delay and expense in diagnosis. Age of onset, dietary history, family history are very important in some cases. Geographical area to which the patient belongs and ethnic origin may be useful in others. Following are some important clues in history and physical examination –

a. In a child born at term with normal birth weight, nutritional iron deficiency anemia (IDA) does not occur below 6 months of age. However, in preterm and low birth weight babies, IDA can appear earlier but usually only after they have doubled their birth weight.

b. Children with thalassemia major (TM) are normal at birth and in initial few months. They usually start becoming anemic between 6 – 18 months age.

c. Patients with constitutional aplastic anemia (Fanconi pancytopenia) usually present between 5 – 10 years, while cases with congenital pure red aplasia manifest in first few months.

d. Prolonged exclusive breast feeding by undernourished mothers may cause 36 megaloblastic anemia in infants and preschool children. e. Thalassemia is more commonly seen in cases from Sindhi, Punjabi and Cardiovascular, Haematological and Renal Gujrati families. Disorders In the physical examination, presence of hepatosplenomegoly and bleeding manifestations should be specifically looked for : a. Presence of splenomegaly and hepatomegaly suggests the diagnosis of –

i) Infections – Malaria, Kala-azar

ii) Hemolytic anemia.

iii) Leukemias (usually there is associated lymphadenopathy)

iv) Anemia of chronic infection/ inflammation. b. Presence of petechial and / or purpuric spots is suggestive of concomitant thrombocytopenia and will point towards the diagnosis of –

i) Acute leukemias.

ii) Aplastic anemia.

iii) Megaloblastic anemia.

Investigations

Following should be the initial investigations in cases with anemia : i) Estimation of Hb %. ii) TLC, DLC and platelet count. iii) Examination of peripheral blood smear for RBC size and shapes, anisopoikilocytosis, presence of immature cells and hemoparasites. iv) Reticulocyte count.

Currently, most of the laboratories use electronic cell counters for hematological investigations which give additional useful information such as MCV, MCH, MCHC etc.

Following important information can be gathered from the above investigations : a. Type of anemia – on the basis of cell size – such as microcytic (MCV < 80 fl), normocytic and macrocytic (MCV > 90 fl) – and on the basis of Hb content i.e. hypochromic or normochromic. b. Associated thrombocytopenia and/ or neutropenia. (It is advisable to calculate absolute neutrophil count from TLC and neutrophil percentage) Presence of bicytopenia / pancytopenia points towards very specific causes of anemia such as asplastic anemia, megaloblastic anemia, leukemia and other causes of bone marrow infiltration. c. Increased, normal or decreased reticulocyte count will suggest whether anemia is due to decreased production (aplastic anemia, leukemia, etc) or 37 ChildhoodMorbidity increased destruction of RBCs (e.g. thalassemia, other hemolytic anemias, acute blood loss).

Following section describes the differential diagnosis of cases of anemia according to preliminary investigation results :

a. Microcytic hypochromic anemia – Two important causes of microcytic hyprochromic anemia are – IDA and thalassemia major (TM). In IDA, the reticulocyte count is normal or mildly elevated. In TM, reticulocyte count is usually 4-6 % (TM patients also have target cells and numerous nucleated RBCs, on smear examination). Other causes of microcytic anemia such as lead poisoning and pyridoxine responsive anemia, sideroblastic anemia and copper deficiency are rare. The diagnosis of TM is confirmed by demonstrating elevated fetal Hb and hemoglobin electrophoresis.

b. Macrocytic normochromic anemia – Most common cause in this category is megaloblastic anemia of B12 and folate deficiency. These patients may have associated neutropenia and / or thrombocytopenia, Reticulocyte count is usually low. Bone marrow examination for demonstration of megaloblastic changes in nucleated RBCs is required for confirmation of diagnosis. Other causes of macrocytic anemia are liver diseases, hypothyroidism, thiamine deficiency and aplastic anemia.

c. Normocytic normochromic anemia – This group comprises a large number of causes:

(i) Hemolytic anemia such as immune hemolysis, hereditary spherocytosis, G-6PD def. etc..are usually normocytic normochronic. Reticulocyte count will be increased because of increased RBC production.

(ii) Bone marrow infiltration such as leukemia and other neoplarms storage disorders, myelofibrosis etc. In leukemias, leucocytosis thrombocytopenia and / or neutropenia is usually present. Peripheral smear examination also show immature cells. Diagnosis is confirmed by bone marrow examination.

(iii) Congenital or acquired aplastic anemia may have normocytic anemia – these patients will have bicytopenia or pancytopenia and decreased reticulocyte count. Bone marrow aspiration or biopsy examination is required for confirmation of diagnosis.

(iv) Anemia resulting from acute blood loss also will be normocytic normochromic.

29.3.2 Iron Deficiency Anemia

Iron deficiency Anemia (IDA) is the most widespread clinical nutritional deficiency and accounts for 90 % of all anemias.

Causes of Iron Deficiency

(i) Inadequate Iron Supply – Low dietary intake and poor bioavailability 38 of iron in cereal – based diets (2-5%) appears to be the important factor. Breast milk , though low in iron, meets the requirement due to Cardiovascular, Haematological and Renal high bioavailability. Diminished absorption of iron occurs in presence of Disorders bacterial, viral and parasitic infection particularly giardiasis and malabsorption syndromes. ii) Increased Iron Losses – An important cause of iron loss is infestation with parasites including the hookworms and possibly trichuris trichura. Bleeding from gums, hiatus hernia, reflux espohagitis, esophageal varices, peptic ulcer and Meckel’s diverticulum are some of the known causes of GI bleed.

Clinical Features

Children with iron deficiency anemia usually have malnutrition of varying severity. However, cases receiving large quantity of milk alone may have iron deficiency and normal weight for age.

Usually the onset of symptoms is insidious. Initially pallor, anorexia and irritability may be noticed. Hyperdynamic circulation may lead to palpitation, fatigue, shortness of breath, decreased exercise intolerance and congestive heart failure. Pallor is best appreciated by examination of palmer surface of hands, conjunctiva, tongue and nails. Tongue may become smooth; the so- called bald tongue. With long standing anemia, there is flattening or spooning of nails (koilonychias). Nails also become thin and brittle. Glossitis, stomatitis, angular cheilosis may be observed. Rarely, mucosal webs may form the pharyngo-esophageal junction resulting in dysphagia. Mild degree of hepatosplenomegaly is also not uncommon. Pedal edema may be due to congestive heart failure or associated protein deficiency. Pica is a well documented feature of anemia in children. Craving to eat unusual substances such as dirt, clay, ice, laundry starch, salt, card board, etc. are seen in almost 70-80% of patients. Iron deficiency has also been associated with breath holding spells.

Other important adverse effects of iron deficiency are poor physical performance, growth retardation, impaired immune response, impaired mental and psychomotor functions. Impaired cognitive functions have been observed in children with iron deficiency with or without anemia. Such changes may be irreversible if iron deficiency occurs at a young age (infancy and preschool years).

Laboratory Evaluation of Iron Status and Diagnosis:

Both Hb and Hct are equally useful tests and are interpreted similarly. On an average, hematocrit values are roughly equivalent to three times the Hb concentration. There is fall in MCV, MCH and MCHC values. Red Cell Distribution Width (RDW) is increased Peripheral smear examination will show anisocytosis, poikilocytosis and microcytic hypochromic RBCs. Reticulocyte count is normal . Mild degree of leucocytosis and thrombocytosis may be observed.

Serum ferritin concentration is reduced (< 12 mcg/l), serum iron level is low and iron binding capacity is increased.

39 ChildhoodMorbidity Management

Cause of Iron deficiency should be identified and corrected . Hookworm infeststaion and poor dietary intake are the common causes in our country.

Cases with severe anemia with heart failure will require hospitalization. Packed cell transfusion is indicated for children with Hb level < 4 g/dl. Case having Hb 4-6 gm/dl and signs of cardiorespiratory decompensation or acute infections may also need blood transfusion.

Therapeutic approach must rely on medicinal iron. Ferrous sulphate, gluconate and fumarate are the compounds commonly used. Preparations containing iron polymaltose complex or iron polysucrose complex do not show better response and are much more expensive.

For infants and children, the recommended dose is 3-4 mg/kg/day, in 2-3 divided doses given between meals. Duration of therapy is upto 8 weeks after normal Hb, for age is achieved. Elemental iron content of various salts is as follows–

· Ferrous sulphate 20%

· Ferrous gluconate 12%

· Ferrous fumarate 33%,

· Colloidal iron 50%

Rapid response can be confidently predicted in iron deficiency. Subjective well being is noticeable within a day due to replacement of iron containing enzymes. Reticulocytosis is seen within 2-3 days and rise of Hb is observed between 5-7 days. Rate of rise of Hb is 0.25gms/day. Usually normal Hb is achieved between 8-12 weeks of adequate therapy. Hence total duration of therapy is 5 months. If there is no response within 2 weeks following causes should be looked for – inadequate dose prescribed / actually taken, presence of diarrhea, malabsorption, infections (UTI, TB), occult blood loss and incorrect diagnosis.

In addition to medicinal iron, dietary modification should be advised. Cases who are receiving largely milk bases diet should be advised appropriate complementary feeding. 29.3.3 Megaloblastic Anemia

Megaloblastic anemia represents an abnormal line of development of red cells, i.e. megaloblasts in the bone marrow. It is due to deficiency in the body of folic acid and/or Vit. B129. Infants with malnutrition, chronic diarrhoea and infection are more prone to develop megaloblastic Anemia. Goat’s milk is a poor source of folic acid. Strict vegetarians are prone to Vit. B12 deficiency over the years. As Vit. B12 is absorbed from the ileum, diseases involving this part of the intestine will lead to B12 malabsorption. Deficiency of B12 is more common in infants and young children while in older children folate deficiency is more common cause of megaloblastic anemia. 40 Clinical Features Cardiovascular, Haematological and Renal The onset is usually gradual. Hyperpigmentation of the hands particularly over Disorders knuckles, feet, face is characteristic. Gastrointestinal disturbances, mild to moderate hepatosplenomegaly, bleeding tendency, glossistis are more common. Infants may have slow mental development and tremors. Bleeding manifestations are not uncommon and these cases may mimic aplastic anemia or acute leukemia.

Laboratory Diagnosis

A peripheral blood smear examination will show anisocytosis and poikilocytosis. Characteristic finding is macrocytosis, many of the macrocytes being oval (macrovalocytes). Concomitant iron deficiency leads to dimorphic anemia-presence of microcytes as well as macrocytes. RBC count is low and MCV is raised (usually above 100 fl.) with normal MCHC. Neutropenia and/or thrombocytopenia are observed in 50-80% cases. In some of them neutropenia and thrombocytopenia may be severe. Megaloblastic reaction of red cell precursors in the marrow is diagnostic. Serum vitamin B12 level of less than 100 pg/ml and a serum folate level of less than 5 ng/ml are diagnostic of their respective deficiency.

Treatment

Folic acid is effective by oral route even with a small dose of 100-200 mg daily. Usual recommended dose is 1 mg per day. Vitamin B12 100 mg to 500 mg weekly for 6-8 weeks is sufficient to correct any deficiency. Larger doses (1mg) are usually not required. Response to the treatment is usually fast. 29.3.4 Beta Thalassemia (Cooley’s Anemia or Mediterranean Anemia)

Thalassemia are a group of hemolytic anemia resulting from diminished synthesis of one or the other globin chain of hemoglobin. a chain suppression leads to a thalassemia. Like wise in b thalassemia -which is commonest type of thalassemia the world over, synthesis of b chain is suppressed. b thalassemia is transmitted as autosomal recessive trait. Homozygous state results in most severe clinical form (thalassemia major) when suppression of B chain synthesis is complete or severe. Thalassemia intermedia is also homozygous state but suppression of B chain synthesis is not complete resulting in only mild clinical presentation. Individuals with heterozygous state are carrier of the disease. They have only mild or no anemia.

Clinical Features

Thalassemia major manifests with pallor usually by the age of 4-6 months, and splenohepatomegaly. Children usually also have recurrent episodes of fever and growth failure. At this stage, often they are diagnosed as iron deficiency anemia but failure to respond to hematinics arouses suspicion. Excessive erythropoiesis resulting from chronic anoxia leads to bone changes which may manifest by second year, though it may be delayed in some cases. Typical thalassemic facies include prominent cheeks, and a receding lower jaw with widely spaced teeth, globular enlargement of the head depressed bridge of the 41 ChildhoodMorbidity nose, and a mongoloid slant of the eyes. Thalassemia traits are clinically normal.

If left untreated, children with thalassemia major die of anemia and its consequences by late first decade or early second decade of life. With appropriate treatment (see below) the life expectancy of thalassemics has th th considerably improved most patients now survive upto 4 and 5 decade. Older patients develop complications due to iron deposition in various organs of body. Most affected organs are skin, liver, heart and endocrine glands.

Laboratory Investigations

Peripheral blood smear examination of thalassemia traits will show microcytic hypochromic Anemia with disproportionately high red cell count. Large number of target cells, basophilic stipplings, and normoblastemia in peripheral smear will suggest thalassemia major. Diagnosis is confirmed by Hb electrophoresis or alkali denaturation tests showing elevated Hb F (40%- 90%). Parents of thalassemics will show elevated Hb A2 level (>3.5%), characteristic of traits. Due to widening of medullary cavity, X-rays will show rectangular appearance of metacarpals and widening of diploic spaces in the skulls.

Management

With appropriate management thalassemics can lead normal life. Definitive treatment for thalassemia is bone marrow transplantation from a matched sibling donor. This is curative but very expensive and not easily available. Blood transfusions and iron chelation are the key components of management. ‘Hypertransfusion’ to maintain Hb level above a minimum of 10 g/dl with a mean of 12 g/dl are ideal to prevent anoxia and allow normal growth and development. Properly cross matched and stringently screened (for HIV, hepatitis B and C) blood should be transfused usually at 3-4 weeks interval to maintain pretransfusion Hb 9-10.5 gm/dl.

Repeated blood transfusion leads to hemosiderosis which causes multiorgan dysfunction including cirrhosis and cardiomyopathy. Removal of excess iron is essential. Desferrioxamine is the best iron chelator available but needs to be given parenterally. An oral iron chelator, 1-2, dimethyl 1-3-hydroxypyrid- 4-one (also known as L1 or deferiprone) has been found useful for iron chelation .Deferasirox is another oral chelating agent which chelates both intracellular and extracellular deposits excess in liver and heart. .Splenctomy may be required in cases receiving irregular transfusions where massive splenomegaly leads to hypersplenism. Hematopoetic stem cell transplantation is the only known curative treatment.

Birth of thalassemia major cases can be prevented by genetic counseling. Carrier detection (traits) is advised as a part of marriage counseling. In case of married couples if both are traits, antenatal diagnosis by chronic villous sampling and DNA studies during first trimester of is necessary to prevent birth of thalassemia major.

42 Check Your Progress 3 Cardiovascular, Haematological and Renal 1. Fill in the blanks : Disorders

(a) In boys above 14 years, Hb concentration under ______gm/dl is considered anemia.

(b) In beta thalassemia, peripheral film shows ______, ______RBC (morphology).

(c) Hereditary spherocytosis results from defect in ______of RBC.

(d) In patients with ______anemias, enlargement of liver and spleen is usually observed.

(e) Hyperpigmentation of knuckles and terminal phalanges is observed in ______anemias.

(f) Dose of medicinal iron for treating iron deficiency anemia is ______mg/kg/day.

(g) Carriers of beta thalassemia will show elevated ______levels on Hb electrophoresis. 29.3.5 Hemorrahagic Disorders

Patients with hemorrhagic disorders present with spontaneous hemorrhages, easy bruising, bleeding from multiple sites, prolonged bleeding from minor trauma or tooth extraction, hemarthrosis and family history of such symptoms. These clinical problems can arise from defects of coagulation, thrombocytopenias and defects of platelet functions.

Diagnostic Approach

It is important to differentiate the bleeding resulting from abnormal number and function of or defects of coagulation. Following are important clues in history and physical examination which help in diagnosis: l Disorders of coagulation are very often inherited and hence family history is helpful. Hemophilia is an X- linked recessive disease – family history in male siblings, male children of maternal aunt and maternal uncle may be obtained. l Cases with congenital coagulation defects may have history of bleeding from umbilical cord and cephalhematoma l Platelet defects result in superficial skin bleeds – petechiae and echymosis. Bleeding from cuts starts immediately and responds well to pressure applied over the site. l Coagulation defects result in deep spontaneous hematoma. Bleeding from cuts is slightly delayed and responds very little to pressure. l Bleeding into joints (hemarthrosis) is typically seen in patients with hemophilia. 43 ChildhoodMorbidity l Patients having bleeding due to disseminated intravascular coagulation (DIC) are usually very sick because of underlying disease.

l Presence of significant anemia, hepatosplenomegaly and / or lymphedenopathy in patient with thrombocytopenic bleed may point towards lymphoreticular malignancy as a cause of thrombocytopenia.

Laboratory Diagnosis

Initial investigations in a case with hemorrhagic manifestations include – platelet count, (PT) and activated partial thromboplastin time (with kaolin) – PTTK. Clotting time (CT) tests entire coagulation cascade but for this test to be abnormal, severe deficiencies of clotting factors are required. Thus patients with mild or moderate deficiency of clotting factor may have normal clotting time. is not routinely performed and is reserved for patients having significant bleeding but normal PT, PTTK and platelet counts.

PT and PTTK are found to be abnormal in deficiency of many clotting factors. To arrive at definite diagnosis, mixing studies with normal plasma and serum are done. More accurate are the assays of clotting factors.

Presumptive diagnosis of bleeding disorders can be made with the help of the following table :

Platelet count BT PT PTTK Presumptive Diagnosis

D I N N Thrombocytopenia

N N N I VIII, IX, XI, XII factor deficiency

N N I N Fibrionogen, Prothrmbrin, V, X deficiency, fibrionlysis, liver diseases

D I I I DIC

N N I I Vit. K deficiency

N I N I Von Willebrand’s disease

N I N N Platelet function disorder

N N N I VII deficiency

Note : N = Normal, I = Increased, D = Decreased, DIC = Disseminated Intravasular Coagulation

Idiopathic Thromocytopenic Purpura

Idiopathic thrombocytopenic purpura (ITP) is usually seen between 2 to 10 years of age and commonly follows an infection, usually viral by 2-3 weeks.

Petechiae, ecchymoses and easy bruisability are the main features. Nose bleeding may be severe. CNS bleeding occurs rarely but may be fatal. Anemia is proportionate to bleeding. There may be mild splenomegaly. Lymphadenopathy is absent. Other than bleeding, children appear well. 44 Most obvious laboratory finding is reduced platelet count. Peripheral smear Cardiovascular, may show giant forms and deeply stained platelets. Bone marrow examination Haematological and Renal Disorders is not diagnostic but is required to exclude other common causes of thrombocytopenia in children particularly aplastic anemia and acute leukemia. Bone marrow examination in ITP will show normal or increased number of megakaryocytes.

In most patients ITP runs a self limited course with 90% children recovering within a few weeks. Patients’ treatment should be based more on severity of bleeding manifestations rather than platelet counts alone. Patients having only skin bleeds may be left untreated. For children with significant mucosal bleeds 3 or severe thrombocytopenia (platelet count <20,000/mm ), currently treatment with Intravenous immunoglobulins (IVIg), intravenous anti-D or methyl prednisolone is recommended. IVIg is used in a total dose of 1-2 gm/kg given over 2-5 days. Anti-D can only be used in patients having Rh positive blood group who do not have significant anemia. Intravenous administration of methyl prednisolone is an alternative. Children requiring such treatments should be managed under supervision of a pediatrician. Treatment with oral prednisolone used in milder cases is of questionable value. Transfusion of platelets does not help increase the platelet count. However, large dose of platelet concentrates may be helpful in cases with severe bleeding. Patients/ parents should be advised to avoid drugs like aspirin, ibuprofen and antihistaminics, which interfere with platelet aggregation.

When platelet counts persist to be low for six months or more after onset, they are labeled as chronic ITP. Such cases need evaluation and should be referred to pediatrician.

Hemophilia

Hemophilia is an X-linked disorder transmitted by females to their male offspring. Hemophilia A (factor VIII deficiency or classic hemophilia) accounts for three-fourth cases of hemophilia. Hemophilia B (factor IX deficiency or Christmas disease) is less common.

Clinical Features

Cases are designated as mild, moderate and severe hemophilia if the factor levels is less than 1%, 1 - 5% and 6 - 30% of the normal respectively. In mild cases, prolonged bleeding follows severe injury. In severe cases, prolonged bleeding may follow separation of umbilical stump and circumcision, dental eruption or may occur even spontaneously. Hemarthrosis (knees, ankles or hips) is hallmark of this condition. Bleeding in the oral cavity and deep muscle hematoma are also bothersome. Laboratory findings include prolonged PTT and decreased levels of specific factor VIII or IX.

Management

Efforts should be made to decrease the risks of injury by control of behaviour and providing safe environment. Drugs like aspirin, ibuprofen and antihistaminics, which interfere with platelet aggregation should be avoided. Local measures to stop bleeding include icepack, application of pressure (5- 15 minutes), immobilizing and elevating the joints.

45 ChildhoodMorbidity Specific therapy includes replacement of deficient factors. Factor VIII concentrate (lyophilized factor VIII ) is currently recommended form of therapy. It is infused in dose of 20 to 50 unit per kg depending on severity. The dosage may have to be repeated 12-24 hourly.

In our country, hemophiliacs are still treated with blood products providing factor VIII. Fresh frozen plasma (FFP) provides one unit of factor VIII per ml. FFP is used for mild cases only as only 10-15 ml/kg can be given without causing volume overload. Cryoprecipitate has higher concentration and is available as 100 units per bag. A dosage of one bag per 5 kg usually gives a factor VIII level of 40% (20% is the minimum hemostatic level). Whole blood transfusions are not recommended.

For hemophilia B, Factor IX concentrates are ideal to use.

Check Your Progress 4

True or False: (i) Hemarthrosis is classically seen in patients with hemophilia. (True/False) (ii) Bleeding from cuts is slightly delayed in cases with coagulation defects compared to thrombocytopenia. (True/False) (iii) In vitamin K deficiency bleeding, PT is prolonged and PTTK is normal. (True/False) (iv) In factor VIII deficiency, PT is prolonged and PTTK is normal. (True/False)

29.4 COMMON RENAL PROBLEMS 29.4.1 Evaluation of a Child with Renal Problems Including Haematuria Evaluation A child with a renal problem may present with scanty urine (oliguria), difficulty in urination (dysuria), bloody urine (hematuria) or oedema due to excretion of protein in urine (proteinuria). Sometimes symptoms are totally unrelated for example, a case of acute post streplococcal glomerutomephritis presenting with convulsions due to hypertensive encephalopathy. In the history, onset, duration and pattern of symptoms is to be determined. Any precipitating factors like trauma, toxins, medications, diarrhoea, sore throat should be ascertained. There may be some predisposing factors like bleeding disorders, hemolytic Anemias or collagen vascular disorders. Dysuria, frequency and fever suggest UTI. Polyuria, polydypsia, weight loss indicates diabetes mellitus. Diarrhoea / dysentery may precede HUS (haemolytic uremic syndrome). Dark coloured urine (brown or cola), oliguria, oedema suggest glomerular disease. Bright red blood with or without clots and without oedema and hypertension suggest a non-glomerular pattern. Headache, vomiting, visual disturbances, convulsion suggest hypertensive encephalopathy. Dyspnoea and orthopnoea indicates circulatory overload. Lymphadenopathy, hepatosplenomegaly, abdominal mass, rash, arthritis suggest 46 malignancy or collagen vascular disease. Thus it is obvious that in children Cardiovascular, Haematological and Renal suspected to have primarily genitourinary or renal disease, complete general Disorders physical and systemic examination is essential. Following section describes the approach to a child with hematuria , oedema and diagnosis and treatment of a case with UTI. Evaluation of a child with hematuria Presence of blood is urine is an alarming symptom in a child. Hematuria, may be gross or it can be microscopic that is detected on routine urine microscopic examination. Blood in urine may originate in the kidneys (cola coloured or brown urine) or from lower urinary tract (bright red or pink in colour). Following table presents a comprehensive list of causes of hematuria. Hematuria should always be differentiated from other causes of discoloration of urine i.e. ingestion of beets, berries and drugs (vifampicin etc). Causes of Hematuria Glomerular diseases : Glomerulonephritis Systemic Lupus Erythematosis(SLE) Hemolytic Uremic Syndrome (HUS) Anaphylactoid purpura Recurrent gross hematuria syndrome e.g. IgA nephropathy idiopathic hematuria Alport’s syndrome Infections : Bacterial (TB), viral Hematologic : Coagulopathies Thrombocytopenia Sickle cell Anemia Renal vein thrombosis Ureteric and Vesical Calculus Anatomic abnormalities : Congenital anomalies Polycystic kidneys Vascular abnormalities Tumors Miscellaneous : Exercise Drugs While evaluating a child with hematuria, details history, physical examination and screening tests will usually indicate towards diagnosis. Preceding history of sore throat or skin infection may indicate post streptococcal glomerulonephritis, preceding diarrhoeal illness may point towards HUS, associated increased frequency of micturition and dysuria may point towards UTI Presence of a renal mass will suggest the diagnosis of a renal tumour, renal vein thrombosis, hydronephrosis or polycystic kidney. Concomitant joint involvement may point towards SLE and anaphylactoid purpura. Initial investigations in a child with hematuria includes a detailed urine examination for RBCs, pus cells, casts and crystals. Urine culture and sensitivity is always required. Alongwith, a complete hemogram to look for anemia, (e.g. HUS) and thromboytopenia (e.g. HUS, other thromboytopenias) 47 ChildhoodMorbidity should be done. Blood urea and creatinine values are helpful to assess the kidney functions. Ultrasonography, DMSA scan and/or IVP are used for further assessment in selected cases. Serum C3 levels, if decreased will suggest the possibility of certain forms of glomerulonephritis e.g. post streptococcal, lupus, membranoproliferative and chronic infection. Renal biopsy is a rarely required investigation, in situations such as persistent high grade microscopic hematuria, persistent hematuria with deranged KFT and/or hypertension and/or proteinuria >150 mg/24 hrs. Biopsy is also indicated with second episode of gross hematuria. 29.4.2 Urinary Tract Infection (UTI) UTI are common infections in children. The incidence of UTI varies with age and sex of the patients. The risk of getting UTI before 14 years is 1% in boys and 3-5% in girls. In the new borns and first year, there is male predominance (M:F=3-5:1) while beyond 1-2 years there is marked female preponderance (M:F=1:10). Ascending infection is more common, E.Coli, Klebsiella, and Proteus being the common organisms. Risk factors for UTI in children include urinary stasis, vesicoureteric reflux (VUR) and bladder distension. UTI is also common in cases with PEM, constipation and chronic diarrhoea. Asymptomatic infections also are common and they are more dangerous because late detection may cause irreversible renal damage. Conventionally UTI have been described as upper and lower UTI. The distinction between the two is usually not possible and not even necessary. The management is based on clinical severity of illness. All febrile UTI are considered to involve upper urinary tract with potential for renal scarring. History In older children, dysuria, frequency, urgency, recent onset enuresis abdominal pain, flank pain, foul smelling and cloudy urine and fever with chills and rigors are common. Information regarding frequency of recurrent episodes should be ascertained. Sometimes possible predisposing factors like poor hygiene, trauma, pinworms, vaginitis, infrequent voiding, tight clothing might be identified. In neonates UTI is a part of septicemia and presents with fever, lethargy, jaundice, vomiting etc. Physical Examination Child should be examined for fever, toxemia and dehydration. External genitalia should be examined for presence of vulvovaginitis, urethral discharge, labial fusion, phimosis or tight prepuce. Abdominal examination should be carried out to see for suprapubic or renal angle tenderness and renal masses. Recording of blood pressure is essential. Diagnosis and laboratory Investigations: Diagnosis is based on urine culture. A clean catch midstream urine or suprapubic aspiration or a catheterized urine specimen are desirable for culture and sensitivity. Culture of urine collected from bag applied to perineum are not recommended. While collecting midstream specimen, contamination by periurethral and prepucial organisms can be minimized by washing the genitalia with soap and water. Antiseptic washes and forced prepucial retraction are not advised. The specimen should be directly collected in a sterile glass or plastic bottle. Prompt plating of the urine specimen, within one hour of 48 collection, is important. If delay is anticipated, the sample can be stored in a Cardiovascular, Haematological and Renal refrigerator at 4ºC for up to 24 hours. Urine culture should be repeated if Disorders UTI is strongly suspected and the colony count is equivocal. Culture should also be repeated in case contamination is suspected, e.g., mixed growth of two or more pathogens, or growth of organisms that normally constitute the periurethral flora. Table 29.6 shows interpretation of culture reports of various urinary specimen. Urinalysis shows presence of leucocytes (>5 leukocytes/high power field in a centrifuged sample or >10 leukocytes/mm3 in an uncentrifuged sample), proteinuria, RBCs and bacteria on Gram staining. Total and differential blood counts and blood culture should be done. Blood urea and creatinine levels should be estimated. If there is clinical evidence of obstruction, ultrasonographic (USG) examination of abdomen should be obtained. Table 29.6: Interpretation of Urine Culture Method of collection Colony count indicative of UTI

1. Midscreem clean catch > 105 organisms/ml 2. Suprapubic aspiration Urinary pathogens in any number 3. Urethral catheterization > 50x103 organisms/ml Treatment Treatment of UTI depends upon age and general condition of the patient. Whether the UTI is simple or complicated, first or recurrent will also determine the therapy. A simple UTI can be defined as UTI with low grade fever, dysuria, frequency, urgency but none of the symptoms of complicated UTI. UTI is said to be complicated in presence of fever >38.5OC, toxemia, persistent vomiting, and renal angle tenderness. Second attacks of UTI are defined as recurrent UTI. New borns, infants younger than 3 months of age and children with complicated UTI should receive parenteral antibiotics. Combination of ampicillin and gentamicin (or cefotaxime/ceftriaxone) is usually preferred. Older infants and children with simple UTI may be treated with oral antibiotics. Amoxicillin, cotrimoxazole and oral cephalosporin are preferred. Nalidixic acid and nitrofurantion are currently not recommended as the concentrations achieved by them in renal parenchyma are believed to be inadequate. Usual duration of therapy for simple infection is 7-10 days while 10-14 day therapy is recommended for children with complicated UTI. Table 29.7 gives the doses of antibiotics used for UTI. Children with recurrent UTI should be put on long term antibiotic prophylaxis using cotrimoxazole or nitrofurantoin in one third therapeutic dose given once a day. Child should be investigated for underlying cause for recurrence (e.g. constipation, urinary obstruction, voiding dysfunction etc.) and should be treated.

49 ChildhoodMorbidity Table 29.7: Antimicrobials for treatment of UTI Oral Parenteral

Drug mg/kg/day No. of Drug mg/kg/day No. of Doses/day doses/day

Cotrimoxazole 6-10 mg 2 Ampicillin 100 3 (trimethoprim) Cefotaxime 100-150 3 Cephalexin 50-70 3 Ceftriaxone 75-100 1 or 2 Ciprofloxacin 10-20 2 Gentamicin 5-6 2 Norfloxacin 12-15 2 Amikacin 15-20 2 Amoxicillin 30-35 3 Co-amoxiclav 30-35 3 (amoxicillin)

Post-Treatment Evaluation All children even with first UTI occurring at any age should undergo evaluation to identify cases having underlying urogenital abnormality. An ultra sound (USG) examination is the first investigation. It it is found to be abnormal, the patient needs further evaluation with micturiting cystourethrogram (MCU) and renal scintigraphy using 99mTc-radiolabelled dimercaptosuccinic acid (DMSA) which is an excellent technique for detecting renal cortical scarring. Children younger than 2 years even with normal. USG should undergo DMSA scan and MCU to detect cases with or at risk of vesicoureteric reflux. For children between 2-5 years with normal USG, DMSA Scan is recommended. MCU is recommended only if DMSA Scan is not available or is found to be abnormal. Children with normal USG and above 5 years do not need immediate further evaluation. Children with recurrent UTI are recommended to undergo a USG, DMSA Scan and MCU irrespective of their age. 29.4.3 Oedema in Children Common causes of generalized oedema in children are as follows : 1. Nephrotic Syndrome and Nephritis (with mixed nephritic – nephrotic presentation) 2. Nutritional – (Kwashiorkar) and other causes of hypoproteinemia 3. Chronic Liver Disease 4. Congestive Heart Failure (CHF) 5. Angioedema Nephrotic syndrome is one of the commonest causes of anasarca in children. The swelling is related to urinary protein loss leading to hypoalbuminemia and decreased oncotic pressure. Typically swelling starts in periorbital soft tissues and descends down to involve whole body. Another characteristic feature of renal oedema is that it is most marked in the early morning hours (on getting up) and then gradually decreases as the day progresses. Usually, the patients also have decreased urinary output. Patients with nephritis commonly have only facial puffiners, occasionally the oedema may be generalized (nephritic- 50 nephrotic presentation). Most cases of nephritis have associated hematuria, Cardiovascular, Haematological and Renal oliguria and hypertension. Disorders Oedema due to nutritional protein deficiency usually first appears on lower limbs and advances to involve whole body including face. It does not have diurnal variation. Cases with nutritional protein deficiency (Kwashiorkar) will have other associated clinical features such as growth retardation, skin and hair changes and mental apathy. Hypoproteineuria resulting from protein losing enteropathy and other causes will also have similar pattern of oedema. Oedema associated with chronic liver disease is more complex. While hypoproteinemria, is an important determinant, portal hypertension and sodium retention due to poor metabolism of aldosterone also contribute to development of edema. Oedema appears on legs first if hypoproteineuria is pronounced, but if portal hypertension is significant, ascites may be the first manifestation. Other features of portal hypertension e.g. splenomegaly, dilated veins over abdominal wall and history of hemetemesis and melena are helpful in diagnosis. Oedema due to CHF first appears on dependent parts. In young infants, this may be first noticed on face (as they keep lying most of the time) and will need to be differentiated from oedema of renal cause. Only rarely, the oedema of CHF will progress to involve whole body. Cases with cardiac edema will have other clinical features suggestive of CHF (e.g. tachypnea, tachycardia, effort intolerance elevated JVP, basal crepitation and tender hepatomegaly). While the edema due to nutritional hypoproteineuria, nephrotic syndrome, hepatic causes and CHF is classically ‘pitting’, type, the swelling associated with angioedema is ‘non-pitting’. Pruritis is associated. Differential Diagnosis For making an appropriate diagnosis in a case of anasarca, a careful history and physical examination are important. Oedema associated with renal, hepatic, cardiac or nutritional cause can usually be recognized on the basis of their characteristic patterns and associated clinical findings as discussed above. Usual initial investigations required in such cases include estimation of total serum proteins, serum albumin and urinary proteins. Nephrotic syndrome is diagnosed by demonstrating nephrotic range proteinuria (more than 0.1 gm/kg/ day, +++ to ++++ on random urine examination) and hypoalbuminemia (less than 29.5 gm/dl) in a case with anasarca. Hyperlipidemia is a usual accompanying feature. Cases with hepatic causes in addition to hypoalbuminemia have increased globulin levels and deranged LFTs. Proteinuria is absent. Nutritional deficiency cases also do not have proteinuria. Hypoalbuminemia is usually accompanied by various degrees of anemia. 29.4.4 Nephrotic Syndrome Nephrotic syndrome (NS) is characterized by massive proteinuria, hypoalbuminemeia (serum albumin < 29.5 gm/dl), hyperlipidemia (serum cholesterol > 200 mg/ dl) and edema. Proteinuria is considered massive or “ nephrotic range” when the urine protein is 3+/4+ on a dipstick test or more 2 2 than 1 gm/ m /day or more than 40 mg/m /hour on timed sample. 51 ChildhoodMorbidity The interistitial edema of NS is primarily due to decreased plasma oncotic pressure resulting from hypoalbuminemia. Hypoalbuminemia also leads to hypovolemia resulting in stimulation of renin-angiotensin-aldosterone axis and antidiuretic hormone secretion leading to increased water and sodium retention which further increases the edema. Figure I explains pathogenesis of edema in NS. Hypoalbuminemia also induces synthesis of beta-lipoproteins in the liver resulting in hypercholesteremia. Etiology: More than 90 % of childhood NS is primary or idiopathic. Causes of secondary NS in children include systemic lupus erythematosus, Henoch- Schonlein purpura, hepatitis B, amyloidosis and postinfectious glomerulonephritis. Of the idiopathic or primary NS, 75-80 % are due to minimal change nephrotic syndrome (MCNS). Other histological lesions observed in pediatric NS include mesangial proliferation, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis and membranous nephropathy (sometimes collectively referred as NS with significant lesions). Minimal Change Nephrotic Syndrome (MCNS): In MCNS the light microscopy does not show any significant histological change. Electrom microscopy shows obliteration of foot processes in the glomerular basement membrane. Pathogenesis of MCNS is unclear though there is indirect evidence of T cell dysfunction. Clinical Features: becomes generalized. Ascites and edema of external genitalia & hydrocele is common when edema becomes severe. Occasionally pleural effusion may occur. Edema is usually more marked in the morning when the child gets up. Urine output is decreased particularly when edema is marked. Infections of the skin, peritonitis and pneumonia may be present at the onset and at the time of relapse. Blood pressure is usually normal and gross hematuria is absent. In some cases history of a viral illness in preceding 1-2 weeks is obtained. Laboratory findings Urine examination shows massive proteinuria (3+/4+). On microscopic examination, hyaline and granular casts may be present. Some cases may have microscopic hematuria. Serum albumin is low (< 29.5 gm/dl) and serum cholesterol level is increased. Blood urea and creatinine values are normal except in cases with massive edema when they may be elevated due to decreased renal perfusion resulting from hypovolemia. Blood levels of IgG are low and IgM are elevated. C 3 level is normal. Managemant Diagnosis and initial evaluation In a child with generalized edema diagnosis of nephrotic syndrome is confirmed by demonstration of massive proteinuria, hypoalbuminemia and raised serum cholesterol level. Quantitative 24 hour urinary protein estimation is not routinely required. Weight of the child and blood pressure should be recorded. Blood counts and blood levels of urea and creatinine should be obtained. Microscopic examination of urine should be performed and urine 52 culture should be done if UTI is suspected. X-ray chest and Mantoux test should be done to look for/ exclude tuberculosis as these cases will require Cardiovascular, Haematological and Renal treatment with corticosteroids. Indications of kidney biopsy are shown in Disorders Table I. A child is likely to have MCNS if he/she is between 2-6 years, does not have hypertension, hematuria, persistent elevation of blood urea and creatinine. Initial good response to corticosteroid therapy further supports the diagnosis of MCNS. Treatment Treatment of NS includes corticosteroid therapy and supportive treatment which includes dietary therapy, treatment of infections, edema and hypertension and patient and parents education. Corticosteroid therapy Adequate treatment of the initial episode is extremely important. The intensity of initial treatment may decrease the rate of subsequent relapses. It is necessary to treat infections before starting treatment with prednisolone. Initial episode of NS should be treated with prednisolone administered in a dose of 2 mg/kg (maximum 60 mg) in two-three divided doses daily for six weeks, followed by 1.5 mg/kg (maximum 40 mg) as a single morning dose on alternate days for the next six weeks. Treatment with prednisolone is then discontinued. Corticosteroids should preferably be administered after meals. For treatment of relapse, prednisolone is administered in a dose of 2 mg/kg/ day (single or two divided doses) until urine protein is trace or nil for 3 consecutive days, or for two weeks. Subsequently, prednisolone is given in a dose of 1.5 mg/kg on alternate days for 4 weeks, and then discontinued. Patients requiring daily corticosteroid therapy for more than 2 weeks, to induce remission, should be referred to a pediatric nephrologist for evaluation. The usual duration of treatment for a relapse is thus 5-6 weeks. In case the patient is not in remission despite two weeks treatment with daily prednisolone, such treatment might be extended for two more weeks. The patient with relapse should be examined for infections, which are treated before initiating corticosteroid therapy. Criteria for defining remission and relapse are in Table II. Patients not adequately responding to steroid therapy, having frequent relapses should be referred to pediatric nephrologist for evaluation. Treatment of frequent relapses or steroid dependence Treatment of child with NS having frequent relapses or steroid dependence is complex and should be undertaken in consultation with pediatric nephrologist. The treatment options MCNS occurs in children between 2-6 years of age. Boys are affected slightly more commonly than girls. The onset is insidious with edema of the eyelids. Gradually edema becomes generalized. Ascites and edema of external genitalia & hydrocele is common when edema becomes severe. Occasionally pleural effusion may occur. Edema is usually more marked in the morning when the child gets up. Urine output is decreased particularly when edema is marked. Infections of the skin, peritonitis and pneumonia may be present at the onset and at the time of relapse. Blood pressure is usually normal and 53 ChildhoodMorbidity gross hematuria is absent. In some cases history of a viral illness in preceding 1-2 weeks is obtained. Laboratory findings Urine examination shows massive proteinuria (3+/4+). On microscopic examination, hyaline and granular casts may be present. Some cases may have microscopic hematuria. Serum albumin is low (< 29.5 gm/dl) and serum cholesterol level is increased. Blood urea and creatinine values are normal except in cases with massive edema when they may be elevated due to decreased renal perfusion resulting from hypovolemia. Blood levels of IgG are low and IgM are elevated. C 3 level is normal. Managemant Diagnosis and initial evaluation In a child with generalized edema diagnosis of nephrotic syndrome is confirmed by demonstration of massive proteinuria, hypoalbuminemia and raised serum cholesterol level. Quantitative 24 hour urinary protein estimation is not routinely required. Weight of the child and blood pressure should be recorded. Blood counts and blood levels of urea and creatinine should be obtained. Microscopic examination of urine should be performed and urine culture should be done if UTI is suspected. X-ray chest and Mantoux test should be done to look for/ exclude tuberculosis as these cases will require treatment with corticosteroids. Indications of kidney biopsy are shown in Table I. A child is likely to have MCNS if he/she is between 2-6 years, does not have hypertension, hematuria, persistent elevation of blood urea and creatinine. Initial good response to corticosteroid therapy further supports the diagnosis of MCNS. Treatment Treatment of NS includes corticosteroid therapy and supportive treatment which includes dietary therapy, treatment of infections, edema and hypertension and patient and parents education. Corticosteroid therapy Adequate treatment of the initial episode is extremely important. The intensity of initial treatment may decrease the rate of subsequent relapses. It is necessary to treat infections before starting treatment with prednisolone. Initial episode of NS should be treated with prednisolone administered in a dose of 2 mg/kg (maximum 60 mg) in two-three divided doses daily for six weeks, followed by 1.5 mg/kg (maximum 40 mg) as a single morning dose on alternate days for the next six weeks. Treatment with prednisolone is then discontinued. Corticosteroids should preferably be administered after meals. For treatment of relapse, prednisolone is administered in a dose of 2 mg/kg/ day (single or two divided doses) until urine protein is trace or nil for 3 consecutive days, or for two weeks. Subsequently, prednisolone is given in a dose of 1.5 mg/kg on alternate days for 4 weeks, and then discontinued. Patients requiring daily corticosteroid therapy for more than 2 weeks, to induce remission, should be referred to a pediatric nephrologist for evaluation. 54 The usual duration of treatment for a relapse is thus 5-6 weeks. In case the Cardiovascular, Haematological and Renal patient is not in remission despite two weeks treatment with daily Disorders prednisolone, such treatment might be extended for two more weeks. The patient with relapse should be examined for infections, which are treated before initiating corticosteroid therapy. Criteria for defining remission and relapse are in Table II. Patients not adequately responding to steroid therapy, having frequent relapses should be referred to pediatric nephrologist for evaluation. Treatment of frequent relapses or steroid dependence Treatment of child with NS having frequent relapses or steroid dependence is complex and should be undertaken in consultation with pediatric nephrologist. The treatment options for such cases include long term steroid therapy, levamisol, cyclophosphamide, cyclosporine and pulse administration of high dose methyl prednisolone or dexamethasone. Treatment of Edema: Edema management is an integral part of management of NS. Corticosteroids usually induce diuresis within 48-72 hours of initiating therapy. However, therapy with diuretics is required in cases with moderate, massive or persistent edema. Management of edema should begin with salt restriction. Salt used in cooking is allowed. Salty snacks or sprinkled over salad etc should be avoided. Salt restriction is continued only till steroid therapy is being given. When diuretics are required, therapy is begun with oral furosemide 1-3 mg/ kg/day. Spironolactone 2 mg/kg/day may be added if response is not adequate.. Administration of 20% Albumin (1gm/kg) followed by administration of furosemide may be required for cases having very low serum albumin. Ascitic tap may be required if ascites is massive and interfering with diaphragmatic movements. Blood pressure and serum potassium should be monitored in children requiring large doses of diuretics. Diuretics should not be used in children having diarrhea, vomiting or hypovolemia. Diet: Child should be advised to take a balanced diet adequate in protein and calories. The child should receive 1.5-2 gm/kg/day proteins. A higher protein intake is recommended for children having persistent proteinuria. Carbohydrates in complex forms (starch and maltodextrin) are advised. Not more than 30 % calories should be provided by fats and saturated fats should be avoided. Patient/ Parent Education: Adequate information about the disease particularly relapsing course and associated complications should be provided. Reassurance should be given that progression to end stage renal failure is extremely rare. Parental motivation and involvement is essential in management of a child with NS. The following measures are emphasized. (a) Urine examination for protein at home using a dipstick or boiling test. Urine is examined once or twice a week during remission. The examination should be done daily during a relapse, during intercurrent 55 ChildhoodMorbidity infections or if the child has even mild periorbital puffiness. (b) Maintain a diary showing proteinuria, medications received and intercurrent infections. (c) Ensure normal activity and school attendance. It is important that the child participates in all activities and sports. (d) Infections are an important cause of morbidity and mortality and parents need to be explained the need for ensuring appropriate immunization and other measures for protection against serious infections. Immunization Patients should be advised to complete the primary immunization if not already completed. Patients receiving daily prednisolone 2mg/ kg or total 20 mg/day for more than 14 days are considered immunocompromized and should not be given live vaccines. These vaccines should be given when the patient is off steroid for 6 weeks or more. Children receiving alternate day steroid at 0.5 mg/kg/day or less can be given these vaccines. Pneumococcal vaccination is recommended for all children with NS particularly those who already have had an episode of peritonitis. Vaccine should be given when the patient is in remission and not receiving steroids. Varicella vaccination is also recommended for patients with NS when they are in remission and not receiving corticosteroids. Prognosis: NS runs a relapsing course in most cases. In a small number of patients there are no relapses after initial episode. Of the patients who respond to steroids, 25-40 % have infrequent relapses. Frequent relapsing course occurs in as many as 40 % cases and remainders show steroid dependence. There are no predictors for the subsequent course but younger children at onset are more likely to have relapsing course. Relapses usually stop after second decade. Progression to end stage renal disease is very rare. NS with Significant Lesions: In 10-15 % children with NS, significant glomerular histological changes are seen. There are various causes including mesangial proliferation, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis and membranous nephropathy. Depending upon histology, the course is variable. The children with significant lesion NS tend be older. They are more likely to have hematuria, hypertension and azotemia. C 3 levels are low in certain variety. The response to steroids is variable. Such cases should be managed in consultation with a pediatric nephrologist. Fig. 29.7: Pathogenesis of Edema in Nephrotic Syndrome Massive Proteinuria  Hypoalbuminemia  56 Decreased plasma oncotic pressure  Cardiovascular, Haematological and Renal Extravasation of intravascular fluid Disorders  Hypovolemia Renin – angiotensin axis volume receptors             Aldosterone Antidiuretic Hormone (ADH)         Sodium and water retention  Edema Table 29.8: Indications for Kidney Biopsy At onset

l Age <1 year or >15 years

l Persistent microscopic or gross hematuria, low serum C3

l Sustained hypertension

l Renal failure not attributable to hypovolemia

l Suspected secondary causes of nephrotic syndrome After initial treatment

l Proteinuria persisting despite 4 weeks of daily corticosteroid therapy

l Before starting treatment with cyclosporin A

l Frequently relapsing or steroid dependant nephrotic syndrome (discretion of the pediatric nephrologist)

Table 29.9: Definitions of remission and relapse in nephritic syndrome. Remission : Urine albumin nil or trace (or proteinuria <4 mg/ m2/h) for 3 consecutive days Relapse : Urine albumin 3+ or 4+ (or proteinuria >40 mg/ m2/h) for 3 consecutive days, having been in remission previously Frequent relapses : Two or more relapses in six months of initial response, or more than three relapses in any twelve months Steroid dependence : Two consecutive relapses when on alternate day steroids or within 14 days of its discontinuation Steroid resistance : Absence of remission despite therapy with 4 weeks of daily prednisolone in a dose of 2 mg/kg per day. 57 ChildhoodMorbidity Check Your Progress 5 1. Fill in the blanks : (a) In neonatal period ...... children are more prone to develop UTI. (b) Passage of cola coloured urine usually suggests presence of ...... disease. (c) Presence of urinary pathogens in suprapubic sample in ...... (number) is suggestive of UTI. (d) In cases with nephrotic syndrome ...... is usually present in addition to oedema, oliguria, proteinuria and hypoalbuminemia. (e) Oedema due to CHF first appears on ...... parts of the body.

29.5 LET US SUM UP In this unit we discussed the pathophysiology, clinical recognition and principles of management of common congenital and acquired heart diseases in children. The treatment of common problems like congestive heart failure and cyanotic spells was outlined. The indications, optimal age for surgery for various lesions were discussed thus allowing for proper referral of these patients. The preventive aspects of acute rheumatic fever were also stressed. We hope that after reading this unit, you will feel interested to acquire more detailed knowledge of the cardiac problems. In the section on hematological diseases we learnt that nutritional anemias are still very common in developing countries. Cases with megaloblastic anemia can have bleeding due to thrombocytopenia and hepatosplenomegaly and thus they may minic cases of eukemia and aplastic anemia. However, if properly diagnosed and treated with deficient micronutrient, they will respond extremely well. Management of thalassemia with adequate blood transfusion and iron chelation not only unproves their survival but quality of life as well. In diagnostic approach to bleeding in children we learnt that careful clinical history and basic investigations including complete blood counts and PT and PTTK will clinch the diagnosis in most of the cases. Section on renal diseases describes approach to cases with hematuria and anasarca. One realises that most cases of hematuria are diagnosed with careful history, urine analysis and KFT. Kidney biopsy is only rarely required. Urinary tract infection need to be treated adequately as they may lead to renal scarring. These cases should be evaluated for underlying genitourinary abnormalities and complications of UTI.

29.6 ANSWERS TO CHECK YOUR PROGRESS Check Your Progress I 1. (a) wide and fixed (b) respiratory 58 (a) squatting Cardiovascular, Haematological and Renal (b) knee-chest Disorders Check Your Progress 2 1) a) False b) False c) True d) False 2) a) Arthritis b) Carditis c) Sabcutaneous nodules d) Chorea e) Erythemamarginatum Check Your Progress 3 1) a) 13 b) Microcytichypochromic c) Cell membrane d) Hemolytic e) Megaloblastic f) 3-6

g) HbA2 Check Your Progress 4 1) a) True b) True h) False i) False Check Your Progress 5 1) a) Male b) Glomerulardisease c) Any d) Hyperlipidemia e) Dependent

59 ChildhoodMorbidity 29.7 FURTHER READINGS 1) Nelson’s Textbook of Pediatrics (volume 1 and 2) Sr. Editor : Nelson WE, eds: Behrman RE, Kliegman RM,ArvinAM. 15th Edition, 1999 (Indian Edition). 2) Essential Pediatrics. Editors : Ghai OP,Gupta P,Paul VK. Edition : 3) IAPTextbook of Pediatrics.

60 UNIT 30 GASTROINTESTINAL, PARASITIC AND NEUROLOGICAL DISORDERS Structure 30.0 Objectives 30.1 Introduction 30.2 Gastrointestinal and Hepatic Disorders 30.2.1 Signs of Liver Dysfunction 30.2.2 Ascites - Clinical approach 30.2.3 Hepatomegaly - Causes 30.2.4 Upper Gastoinestinal Hemorrhage 30.3 Central Nervous System 30.3.1 Acute Bacterial Meningitis 30.3.2 Encephalitis 30.3.2.1 Japanese Encephalitis 30.3.3 Seizure in Children 30.3.3.1 Febrile seizures (FS) 30.3.3.2 Epilepsy 30.3.4 Neurocysticercosis 30.3.5 Acute Flaccid Paralysis 30.4 Parasitic Infections 30.5 Let Us Sum Up 30.6 Answer to Check Your Progress 30.7 Further Readings 30.0 OBJECTIVES After reading this unit you should be able to :

 diagnose and treat acute bacterial meningitis;

 investigate and treat cases with seizure disorders;

 investigate and treat cases with acute flaccid paralysis;

 evaluate cases presenting with ascites;

 evaluate and treat cases with hepatomegaly and/or hepatic dysfunction; and

 diagnose and treat common parasitic infections/infestations.

30.1 INTRODUCTION This unit describes common neurological, gastrointestinal, hepatic and parasitic infestations affecting children. Acute gastroenteritis and persistent diarrhoea has already been discussed in the unit on IMNCI. This section 61 ChildhoodMorbidity describes clinical features of liver dysfunction alongwith clinical approach to cases with ascites and hepatomegaly. Enlargement of liver in children results from a variety of causes including intrauterine and other infections, metabolic diseases, congestive and hematological causes. In the section on hepatic diseases, the differential diagnosis of hepatomegaly is outlined alongwith diagnostic approach to a case of ascites.

Most of the convulsive disorders have their onset in childhood. Recognition of exact type of seizures is of utmost importance for their proper management. Neurocysticercosis has emerged as an important cause of secondary epilepsy which has been dealt with in this section. India has become polio free but there is need for continued surveillance.. In the section on neurological diseases, the differential diagnosis of AFP is discussed.

30.2 GASTROINTESTINAL & HEPATIC DISORDERS

30.2.1 Clinical Features of Liver Dysfunction

Liver serves diverse metabolic functions in the body, hence abnormalities of hepatic function give rise to protean clinical manifestations. Some common features of liver dysfunction are as follows :

1) Jaundice : Increased serum bilirubin levels in the blood lead to yellowish discolouration of mucous membranes, skin and most commonly of sclera which is seen through the bulbar conjunctiva. In children, as in adults, clinically evident jaundice occurs once the serum bilirubin is above 2-3 mg/dl but in neonates jaundice usually appears with bilirubin levels above 5 mg/dl. Whether the yellowish discolouration is reflected in the urine (as in conjugated hyperbilirubinemia or mixed typed) or not (as in unconjugated hyperbilirubinemia) serves as an important clue to the differential diagnosis.

2) Pruritis : Patients having hepatic diseases associated with conjugated hyperbilirubinemia sometimes have intense pruritis which is believed to be due to retention of bile acids in the blood. However, its presence and severity does not correlate with severity of hyperbilirubinemia.

3) Bleeding manifestations : Liver is the site of synthesis of various coagulation factors – II, VII, IX, & X – the vitamin K dependent factors. Coagulation defects are one of the earliest manifestations of liver diseases. PT and PTTK are usually prolonged in patients with liver disease.

4) Spider angiomas : Small dilated arterioles from which many smaller vessels radiate are seen in patients with chronic liver diseases particularly over the face and upper part of trunk. Their presence reflects altered hepatic metabolism of estrogen. 62 5) Palmar erythema : This finding is also more commonly observed in Gastrointestinal, Parasitic and Neurological patients with chronic hepatic disorders. The thenar & hypothenar Disorders eminence and finger tips and later whole of palms become erythematous which can be blanched on pressure.

6) Ascites : Ascites is a common feature of liver diseases. In chronic liver diseases, sinusoidal block leads to increased hydrostatic pressure leading to transudation of fluid into peritoneal cavity. Hypoalbuminemia also contributes to development of ascites.

7) Pedal oedema : Oedema in cases with liver disease results from hypoalbuminemia and presence of massive ascites.

8) Portal Hypertension : Pressure in the portal system increases as a consequence of increased sinusoidal pressure in liver diseases. The manifestations of portal hypertension include splenomegaly, ascites, esophageal varices and dilated veins over anterior abdominal wall – the last mentioned may take the form of caput medusae.

9) Xanthomata : Chronic cholestatic disorders may be associated with hyperlipidemia which at times may manifest as lipid deposition - Xanthomata into the dermis and subcutaneous tissues.

10) Hepatic encephalopathy : Metabolic abnormalities in acute and chronic liver diseases may lead to altered neuromuscular functions and altered consciousness. The constellation of signs and symptoms is called hepatic encephalopathy. Hepatorenal syndrome is a late manifestation and is characterized by azotemia and progressive oliguria in a patient with hepatic encephalopathy.

11) General Symptoms : Mild fever, abdominal discomfort and marked anorexia are common clinical features in cases with liver diseases.

30.2.2 Ascites - Clinical Approach

Presence of free fluid in the peritoneal cavity is called ascites. Abdominal distension due to ascites needs to be differentiated from other causes of generalized abdominal distension e.g. presence of gas, fecal retention, pregnancy, large tumor masses and obesity. Classic signs of fluid accumulation are – bulging of flanks, flank dullness, shifting dullness and fluid thrill. Small amounts of fluid are demonstrated by keeping the patient on knees and hands and using the Puddle sign. However, this maneuver is usually not required as ultrasonography can detect even smaller quantities of fluid.

Ascitic fluid may accumulate as a part of anasarca, as a manifestation of portal hypertension or as a result of reaction to diseases of various abdominal viscera, Table 30.1 describes common causes of ascites in children :

63 ChildhoodMorbidity Table 30.1 : Causes of ascites in children A. Portal Hypertension 1. Chronic liver diseases 2. Fulminant hepatic failure 3. Portal vein obstruction. B. Congestive 1. Budd-Chiari Syndrome 2. Constrictive pericarditis 3. Chronic congestive cardiac failure C. Infections 1. Tuberculosis 2. Pyogenic infections 3. Schistosomiasis D. Hypoproteinemia 1. Nephrotic syndrome 2. Kwashiorkor 3. Anemia with hypoproteinemia (e.g. malabsorption syndrome). E. Neoplastic 1. Lymphoma. 2. Other abdominal tumors F. Diseases of Abdominal Viscera 1. Pancreatitis and rupture of pancreatic duct 2. Bowel perforation. 3. Perforation of urinary tract. G. Miscellaneous 1. Chylous ascites. 2. Hypothyroidism. 3. Ventriculoperitoneal shunt

Approach to a child with ascites Detailed clinical history and physical examination provide important clues to the diagnosis of a case with ascites. Though Table I provides a comprehensive list of causes, commonly encountered causes of ascites include portal hypertension with chronic liver disease, nephrotic syndrome, tuberculous 64 ascites, pyogenic infections etc. Following are certain important clues in history Gastrointestinal, Parasitic and Neurological and physical examination in cases with ascites : Disorders 1) Patients with chronic liver disease will usually have history suggestive of hepatitis in the past. History of variceal bleed causing hemetemesis and/or melena may indicate portal hypertension. Presence of dilated abdominal veins and splenomegaly and features of hepatic dysfunction further support the diagnosis. Ascitic tap will reveal it to be transudative (see below).

2) In patients with nephrotic syndrome having ascites, history suggestive of renal cause of oedema will be obtained (oedema starting from face and then progressing downwards, more pronounced in early morning hours) alongwith history of oliguria.

3) Patients with kwashiorkor and hypoproteinemia will be undernourished. Dependent oedema will be more pronounced. Clinical features of deficiencies of other nutrients may be evident.

4) Congestive cardiac failure and constrictive pericarditis patients may have prominent cardiorespiratory symptoms. Jugular venous pressure will be elevated.

5) Patients with tuberculous ascites will be cachexic and may have other features of tubercular toxemia e.g. fever, anorexia, weight loss etc. Features of tuberculosis elsewhere in the body may be present.

6) History of abdominal blunt injury or acute abdominal pain preceding development of ascites will point towards pancreatitis as a cause.

7) Hepatomegaly/hepatosplenomegaly, if present, will point towards chronic liver diseases or congestive causes of ascites. Patients with nephrotic syndrome and hypoproteinemia will not have hepatomegaly / hepatosplenomegaly.

8) In patients with malignancies, abdominal lymph nodes or primary tumours may be palpable.

Investigations in a case with ascites

In some cases with ascites, diagnosis will be clinically apparent , investigations will be required only for confirmation or documentation. In others, the diagnosis may not be straight forward.

LFT and serum levels of total proteins, albumin and globulin levels are almost always required. Deranged LFT will point towards hepatic cause. Diagnostic paracentesis is often required and may clinch the diagnosis. Ascitic fluid should be examined for proteins (or albumin), presence and type of cells and microbiological examination if clinically warranted. Typically the fluid is described as exudative when fluid has more than 3.5 gm/dl proteins and transudative if the proteins are less than 2.5 gm/dl. Transudative ascites is characteristically seen in cases with portal hypertension, nephrotic syndrome, hypoproteinemia etc. Tuberculosis and pyogenic infection typically lead to exudative ascites. Pancreatic ascites and that associated with constrictive pericarditis may have variable amount of protein. Some authors recommend 65 ChildhoodMorbidity using serum-ascites albumin gradient (SAG) to characterize ascites. A high gradient (>1.1 gm/dL) is typically associated with cirrhosis and Budd Chiari syndrome. Low gradient (<1.1 gm/dL) is seen in cases with nephrotic syndrome, tuberculous ascites, pancreatic and pyogenic peritonitis. Chylous ascites refers to a turbid, milky or creamy peritoneal fluid due to presence of lymph. Fluid often has fat globules and increased triglyceride levels. The cause of chylous ascites is lymphatic obstruction due to causes like congenital abnormalities, tuberculosis, tumors, filariasis and trauma. Ultrasonographic and CT evaluation of liver and other abdominal viscera may be required. Doppler studies will be required to evaluate for suspected vena caval or hepatic vein obstruction. X-ray chest and Mx test should be done in cases with suspected tuberculosis. Constrictive pericarditis will be diagnosed by x-ray, ECG and echocardiography. Serum and / or ascitic fluid amylase levels will be useful for pancreatic diseases. Liver biopsy and peritoneal biopsy may be required in some cases.

The treatment of ascitis depends upon the the underlying cause. Small amounts of fluid does not cause any symptoms. Large amount of fluid may cause tense ascitis causing respiratory compromise and require abdominal paracentesis along with diuretics such as spironolactone 30.2.3 Hepatomegaly – Clinical Approach

Hepatomegaly i.e. enlarged liver is a common symptom of many illnesses. Causes vary with age. It is important to remember that in children liver margin upto 2 cms below right costal margin is normal. Similarly, in neonates a liver border beyond 3.5 cms below right costal margin in mid clavicular line is taken as abnormal. You would see apparent hepatomegaly in following conditions which needs to be differentiated from true hepatomegaly –

1) Visceroptosis due to laxity of segments e.g. rickets, PEM.

2) Increased intrathoracic pressure “pushed down liver” most commonly seen in acute respiratory conditions associated with air trapping e.g. bronchial asthma, foreign body, emphysema, empyema, pleural effusion, subphrenic abscess, post viral infection.

3) Thoracic deformity.

A palpable nonpathological liver has the following characteristics: Liver span is normal, borders are round, surface is smooth, consistency is soft, no pulsations or bruit, not tender. Following table describes causes of hepatomegaly in children : Table 30.2: Causes of Hepatomegaly A) In Newborn Infections either intrauterine or postnatal septicemia and neonatal hepatitis cause hepatomegaly. Other causes are congestive cardiac failure, cellular infiltration, hepatobiliary obstruction, alpha-1-antitrypsin deficiency, hemolytic disease of new born (Rh and ABO incompatibility).

66 Gastrointestinal, Parasitic B) Infants and Children and Neurological Disorders 1) Infections - i) Viral - Hepatitis A, B, C, D, E. Infectious mononucleosis, AIDS, - ii) Bacterial– septicemia, tuberculosis, syphilis cholangitis, liver abscess - iii) Parasitic – Malaria, Kala-azar, Amoebic abscess, toxoplasmosis 2) Hemolytic Anemias - Thalassaemia Major, Sickle Cell Anemia 3) Fatty Infiltration - PEM, severe infections, Diabetes mellitus, Cystic Fibrosis, Anemias 4) Hepatic Congestion - CCF, Constrictive Pericarditis, Veno- occlusive Disease, Budd-Chiari syndrome 5) Storage disorders - Glycogen storage disease, Galactosemia, Lipidosis, Wilson’s disease etc. 6) Malignancies - i) Primary – Hepatoblastoma, Hepatoma, hemangioma, lymphoma - ii) Secondary – Leukemia, lymphoma, histiocytosis, neuroblastoma 7) Miscellaneous - Indian childhood cirrhosis, Cysts, neonatal hepatitis, Biliary atresia Evaluation Detailed medical history, thorough physical examination and interpretation assisted by laboratory investigations and ultrasonography help in evaluation. Examination of liver should include size, consistency, margin, tenderness, surface of liver, its span and auscultation for bruit. Presence of following clinical signs indicate: 1) Tender hepatomegaly : congestive cardiac failure, acute viral hepatitis, cholangitis, liver abscess. 2) Anemia : Infections, Tuberculosis, Syphilis, 3) Anemia and Splenomegaly : Hemolytic Anemias, Malaria, Kala azar, Leukemias, Infectious Mononucleosis, TB, Brucellosis, Histiocytosis. 4) Ascites : Infections such as tuberculosis, portal hypertension, cirrhosis, veno-occlusive disease. 5) Jaundice : Intrauterine infection, Neonatal Hepatitis, Biliary Atresia, Septicaemia in new borns and in older children – viral hepatitis, terminal stages of cirrhosis, overwhelming infections

67 ChildhoodMorbidity 6) Engorged Neck Veins and Raised Jugular Venous Pressure : Constrictive pericarditis, congestive cardiac failure. 7) Microcephaly / Macrocephaly : Intrauterine TORCH Infections, 8) Cataract and Mental Retardation : Galactosemia 9) KF Ring and Neurological Manifestations : Wilson’s disease. 10) Rickets : Nutritional rickets with visceroptosis, Cystinosis, Tyrosinosis Investigations Initial investigations in a case of hepatomegaly / hepatosplenomegaly should include LFT (Serum bilirubin – total, unconjugated and conjugated, liver enzymes – serum alanine aminotransferase – ALT or SGPT, aspartate aminotransferase – AST or SGOT, serum alkaline phosphatase, serum proteins – total, albumin and globulin, coagulation profile – Prothrombin time and partial thromboplastin time); complete hemogram including Hb, TLC, DLC, platelet count, smear examination for type of anemia, hemoparasites and ultrasonographic examination of abdomen. Based on the results of preliminary investigation, confirmatory tests may be planned. A liver biopsy is indicated for histological diagnosis of primary liver disease. Mx test, X-ray chest and other investigations may be required to confirm or exclude tubercular etiology. Endoscopic examination may be required for esophageal varices. Ascites, if present, may need to be aspirated for biochemical and cytological examination. Check Your Progress 1 1) Fill in the blanks : a) In cases with cholestatic jaundice pruritis occurs due to retention of ...... b) Presence of spider angioma in cases with chronic liver diseases is believed to reflect altered metabolism of...... c) Ascitic fluid is described to be exudative if it contains proteins more than ...... gm/dl. d) Filariasis may cause ...... ascites. 2) State whether true or false : a) Palpable non-pathological liver is usually soft with round border, smooth surface and it is non-tender. (True / False) b) Prolongation of prothrombin time is usually observed in cases with hepatic dysfunction. (True / False) c) In tuberculous ascites, protein content of the ascitic fluid usually is less than 1gm/dl. (True / False) d) In acute viral hepatitis, palpable liver is usually nodular and non-tender. (True / False) e) In a patient with hepatic encephalopathy presence of renal failure is termed as hepato renal syndrome. (True / False)

68 30.2.4 Upper Gastrointestinal Hemorrhage Gastrointestinal, Parasitic and Neurological Bleeding arising in upper gastrointestinal tract proximal to the ligament of Disorders Treitz in the distal duodenum is referred to as upper GI bleeding. It commonly presents with hematemesis (vomiting of blood or coffee ground-like material) and/or melena (black, tarry stools). In comparison, hematochezia (bright red or maroon-colored blood or fresh clots per rectum) is usually a sign of a lower GI source (defined as distal to the ligament of Treitz). The most common causes of GI bleeding in children vary depending upon age .The common causes are gastric and duodenal ulcers, esophagitis, gastritis and varices. The age specific causes of GI bleeding in children are shown in Table 3. Clinical Features : Clinical features depend upon the onset and amount of blood lost. If the bleeding is acute in onset and voluminous, the patient will present with features of hypovolemic shock with overt bleeding. Patients who have chronic blood loss may present with iron deficiency anemia. In some disorders features of the primary underlying cause e.g. liver disease are prominent. Evaluation History: GI hemorrhage due to stress ulcers is common in course of illness in intensive care settings. In such cases the bleeding is not the main presentation. Dengue fever is another common cause but fever and petechial rash are prominent in dengue fever. A complete history is taken especially for intake of any NSAIDs, pain epigastrium, and history of bleeding from another site. Variceal bleeding is painless whereas bleeding due to GERD or peptic ulcer is accompanied with pain in abdomen. History of regurgitation and failure to gain weight is suggestive of GERD. Examination: Examination is directed towards checking for any evidence of acute blood loss by checking pulse and blood pressure as in this case correction of hypovolemia is the main priority. You should look for pallor, petechial rash , jaundice , abdominal tenderness , ascitis, hepatosplenomegaly and signs of liver dysfunction. A rectal examination is essential part of clinical examination. . Investigation You should undertake a complete blood count, coagulation studies, and a biochemistry panel in patients with substantial upper or lower GI bleeding, Anemia is usually present but in patients with large blood loss a normal hematocrit may be seen in children who present with hypovolemia and hemoconcentration. In patients with dengue hemorrhagic fever thrombocytopenia is present. Elevated abnormal prothrombin time indicates coagulopathy (ie, disseminated intravascular coagulation) or impairment of liver function. A high BUN level, points to an upper GI source that has had time to allow the body to reabsorb blood leading to a higher BUN level compared with a lower GI source.

69 ChildhoodMorbidity Management

One should first determine the amount of blood loss, and the site of bleeding.

The first thing is to determine if bleeding is truly gastrointestinal . Sometimes, the source can be naso-or oropharyngeal. The presence of “coffee ground emesis represents blood altered by gastric contents and usually means that there has been slow bleeding from the region between the esophagus and the duodenum.

The measurement of vital signs provides the only accurate assessment of blood loss. Orthostatic hypotension, tachycardia complaints of weakness or dizziness are pointers of hypovolemia. Such patients are resuscitated with saline or Ringer lactate infusion .Whole blood transfusion is required if there is major hemorrhage.

A positive NG tube aspirate for blood usually signifies that the site of bleeding is proximal to the ligament of Treitz. Other characteristics of upper GI bleeding are elevated BUN and hyperactive bowel sounds.

After initial stabilization, upper endoscopy is the preferred diagnostic and therapeutic tool for upper GI bleeding. The source of bleeding can be identified in 90% of cases if endoscopy is done within the first 24 hours. The common causes usually identified are gastritis, esophagitis, duodenal ulcers, and esophageal varices. Gastric varices are most commonly found in the fundus. Colonoscopy should be done after the acute bleeding has stopped in children with lower GI bleeding. In children with massive lower GI bleeding after neonatal period, Meckel’s diverticulum should be suspected. Technetium scan is investigation of choice for suspected Meckel diverticulum.

Further treatment depends upon the cause of GI bleeding .H2 antagonists e.g. ranitidine are used to treat bleeding due to stress gastritis. If the diagnosis of gastric or esophageal varices is confirmed, specific treatment is initiated. Drug therapy is directed at reducing the portal venous blood flow. Vasopressin, somatostatin, and beta-blockers have been used systemically to control bleeding varices. Endoscopic sclerotherapy controls bleeding with a success rate of 90-95%. Generally, endoscopic sclerotherapy is repeated in 2- to 4-week intervals after the acute bleed to prevent recurrence. Variceal banding is the other alternative but is more difficult to perform in children because of the smaller size of the esophagus. Surgical portosystemic shunts are reserved only for refractory cases .

Table 30.3: Causes of Gastro-intestinal Bleeding Neonatal age - Swallowed maternal blood Hemorrhagic disease of Newborn Stress gastritis Necrotizing enterocolitis

70 Gastrointestinal, Parasitic Bleeding diathesis e.g. DIC and Neurological Disorders Infants upto Gastroesophageal reflux disease 2 years Gastritis – primary and secondary to systemic disease Infective Colitis Vitamin K deficiency ( e.g. secondary to liver disease) Peptic ulcer disease Liver disease Anal fissure Meckel’s diverticulum

Age >2 years Esophageal varices Chronic liver disease Peptic ulcer disease Stress gastritis Dengue hemorrhagic fever Polyps Colitis Meckel’s diverticulum Inflammatory boel disease

30.3 CENTRAL NERVOUS SYSTEM 30.3.1 Acute Bacterial Meningitis Acute bacterial meningitis (ABM) remains a common life threatening condition in children Even though the mortality on account of this formidable disease has decreased over the years with the availability of potent antibiotics, a significant number of patients are left with neurological sequelae. Epidemiology ABM is essentially a disease of young children, mainly due to attenuated immunologic response in this age group. Nearly 95% of cases occur between 1 month and 5 years of age.. Etiology of ABM is related to the age of the patient with the background of several host factors. During the first 2 months of life, Escherichia coli K1 and other Gram negative enteric bacilli, group B Streptococcus and Listeria monocytogenes are the usual offending organisms. In children between 2 months to 12 years, bacterial meningitis is primarily due to H. influenzae type b, Streptococcus pneumoniae and Neisseria meningitides. The incidence and relative frequency of these bacteria differ markedly depending on 71 ChildhoodMorbidity geographic areas, genetic factors and usage of H. Influenzae type b vaccine and Pneumococcal vaccination.. The inclusion of Pentavalent vaccine in universal immunization programme and introduction of 13valent pneumococcal vaccine in phased manner is expected to lead to decline in number of cases of meningitis in this age group.. In children with severe malnutrition, compromised immunity or anatomical defects, infection can occur with other microbes like Staphylococcus, Salmonella, Pseudomonas, etc. Clinical Features Early symptoms of meningitis in young children are often vague and ill defined. In general, younger the infant the more non-specific are the symptoms. The main symptoms which are highly suggestive of a diagnosis of ABM in infants are fever (with or without vomiting), alteration of behavior (infant becomes lethargic or drowsy, irritable, feeds poorly), a high pitched cry, seizures and a full or tense anterior fontanelle. Specific signs of meningeal irritation are hardly ever present in infants below the age of 2 years. In older children, classical signs and symptoms of meningitis like fever, headache, vomiting, photophobia, neck stiffness and the meningeal signs are likely to be present. Neck stiffness is the most important of all meningeal signs and earliest to appear. It becomes more marked if tested while the patient sits up with knees extended. Kernig sign and Brudzinski sign are other meningeal signs. The meningeal signs are due to reflex muscle spasm in reaction to pain on stretching of contents of spinal cord. These signs may be absent in comatose patients. The second mode of presentation is acute and fulminant in which manifestations of sepsis and meningitis develop rapidly associated with severe brain edema and raised ICP. This type of presentation is seen most often with N. meningitidies. Petechial hemorrhages appearing on the skin which rapidly coalesce producing areas of purpura are considered hallmark of this disease. Profound hypotension and fatal shock may occur. Seizures occur in about 30 - 40% cases of ABM. Alterations of mental status and reduced level of consciousness is common and is due to increased intra- cranial pressure (ICP), cerebritis or hypotension. Focal neurologic signs may be due to vascular occlusion, abscess formation or cortical infarction. Complications of ABM can develop early in the course of illness or later after several days of therapy or may be noticed on follow up. Increased intracranial tension is present in almost all cases of ABM initially though only 1-3% of cases have persistent hydrocephalus. Seizures occur in about 30-40 of children with meningitis. Generalized seizures occurring within first four days are of no prognostic significance. Children with focal convulsions are more likely to have neurologic sequelae of meningitis. Causes of late onset seizures include cerebritis, subdural effusion, vascular thrombosis and abscess formation. Subdural effusion develops in 10-30% of patients with meningitis and are more common in H. influenzae meningitis. These effusions are asymptomic in 85-90%.

72 Effusions usually resolve during therapy and aspiration is required only in of Gastrointestinal, Parasitic increased ICP or a depressed consciousness. Subdural empyema more and Neurological Disorders aggressive treatment in tapping or operative treatment. Diagnosis Since the clinical features of ABM are non-specific specially in infants lumbar puncture should be performed at earliest suspicion of meningitis. Occasionally, LP may have to be deferred due to clinical signs of increased intracranial pressure or shock. In case it is deferred, empirical anti-meningitic treatment should be started immediately. CSF Examination: CSF examination includes a naked eye examination, pressure, microscopy-total and differential leukocyte count, Gram’s stain, estimation of proteins and glucose and CSF culture. The CSF should be examined immediately after doing the LP since the cell count tends to fall over a period of time. Polymorphonuclear response is the hallmark of ABM.Prior antibiotic therapy may results in lymphocytosis. Protein in CSF is raised (normal value 40 mg/dl after 2nd month of life) in all cases of ABM. In patients of ABM, CSF glucose and ratio of CSF to blood glucose (normally about 66%) are low. Gram stain of the smear is useful for detection of organisms and positivity depends on the number of organisms present. CSF culture provides a confirmatory evidence of ABM and is essential for selecting appropriate antibiotic for the etiological organisms. The rate of bacterial isolation is affected by antibiotic use prior to lumbar puncture. Rapid diagnostic tests such as latex particle agglutination test or PCR can provide specific diagnosis by detecting bacterial antigen/bacterial RNA in CSF, but these are expensive and should be reserved in cases where gram stain is negative. Treatment Treatment can be broadly categorized into: (1) Antibiotic therapy; (2) Supportive care and (3) Adjuvant therapy. Antibiotic Therapy The antibiotic regimen should be such that covers all the likely pathogens anticipated according to the age of the child, combination should not be antagonistic and it should achieve bactericidal concentrations in the CSF. Later the treatment can be modified depending upon the result of Gram stain and CSF culture. Various antibiotics used in initial therapy and subsequent treatment are shown in Table II. Third generation cephalosporins are the preferred initial antibiotics for meningitis as they are effective against most bacteria causing meningitis including resistant. H. influenzae type b and penicillin resistant strains of S. pneumoniae For penicillin resistant pneumococci, combination of vancomycin with cephalosporins should be used. The duration of antimicrobial therapy is based on the causative agent, and clinical response (Table II). Longer duration of treatment is required in cases of complications such as subdural empyema, prolonged fever, persistence of meningeal signs or development of nosocomial infections. In such cases discontinuation of antimicrobial therapy is individualized. 73 ChildhoodMorbidity Supportive Therapy

The first 3-4 days of treatment are critical because life threatening complications of meningitis occur most frequently during this period. Vital signs of patients should be monitored regularly during the first 24 - 28 hours of treatment. Neurological examination should be performed initially and daily throughout hospitalization .

Fluid and electrolyte balance is maintained. Intracranial pressure can be reduced by elevating the head end of the bed by 300 to maximize venous drainage. Mannitol (0.5-1 g/kg) is used to reduce ICP.Seizures are common during the course of bacterial meningitis. Metabolic complications like hyponatremia, and hypoglycemia must be excluded and specific therapy instituted if present. Immediate management of seizures include intravenous diazepam (0.1-0.2 mg/kg/dose) or lorazepam (0.05 mg/kg/dose). This is followed by a loading dose of phenytoin (20 mg/kg) and the maintenance dose of 5 mg/kg/24 h for further control of seizures. Phenytoin is preferred over phenobarbitone because it causes less CNS depression and allows assessment of sensorium. Anticonvulsants can be discontinued after a few days unless there is evidence of persistent seizure activity. Corticosteroids (Dexamethasone) have been shown to reduce the complications particularly Sensorineural hearing loss. To be effective it is given as Dexamethasone for first 48 hours of treatment and started along with the first dose of antibiotics. It is not recommended in patients who have been pretreated with antibiotics or in neonates and if diagnosis is not certain.

Prognosis: The prognosis of a patient with pyogenic meningitis depends on many factors including age, causative micro-organism, bacterial density, and intensity of host’s inflammatory response. Case fatality is reported to be 3 - 6% in developed countries but higher mortality is reported from developing countries. Neurodevelopmental sequelae are seen in 10 - 20% of patients. The sequelae of bacterial meningitis may improve with time and even resolve completely. The potential for recovery is attributed to the plasticity of brain

Prevention: Prevention of ABM is possible with (i) prevention of secondary cases with antibiotic chemoprophylaxis of index case and close contacts, and (ii) vaccination of susceptible population with specific vaccines.For N. meningitides, chemoprophylaxis is recommended for all close contacts .Rifampicin (10 mg/kg every 12 hours for 2 days) should be given to all close contacts. Vaccination against H. influenzae type b and Pneumococci has been recommended in national immunization programme..

74 Table 30.4:Initial and Subsequent Therapy in Cases of Bacterial Gastrointestinal, Parasitic and Neurological Meningitis Disorders

[A] Initial Empiric Therapy Age Pathogens Drug of Choice 0-2 months gram negative Ampicillin Cefotaxime enteric bacilli + + Group B strept Cefotaxime gentamicin

2 months to Hib, S.pneumoniae Ceftriaxone 12 years N.meningitidi or Cefotaxime l [B] Subsequent Antibiotic Therapy in children 2-12 months Pathogen Drug of choice Duration of therapy (days) Pathogen Ceftriaxon 14 Unknown H.influenzae Ceftriaxone 10 Type b Penicillin Ceftriaxone 14 resistant + Strep pneumoniae Vancomycin

N. meningitids Crystalline penicillin 7-10 Staphylococci Vancomycin 2-3 weeks

* Dosage Schedule (All drugs to be given intravenously) Ampicillin (300 mg/kg/24 hours, in 4 divided doses) Ceftriaxone (100 mg/kg/24 hours, in 2 divided doses) Cefotaxime (200 mg/kg/24 hours, in 4 divided doses) C. penicillin (300,000 units/kg/24 hour, in 4-6 divided doses) Vancomycin (60 mg/kg/24 hours, in 3-4 divided doses) 30.3.2 Encephalitis Encephalitis is defined as an inflammatory process of the brain with dysfunction of the brain. Etiology: Table 30.5 defines common pathogens causing encephalitis in children. Herpes encephalitis is particularly important to diagnose, because of therapeutic implications and severe complications, if left untreated in the early stages of the disease. Table 30.5: Common Pathogens for Encephalitis Viruses Non Viral 1. RNA viruses (mumps, measles, 1. Rickettsia rubella, enteroviruses) 2. DNA viruses (herpes simplex, come 2. Fungi alovirus, Epstein Barr, pox group) 3. Arthropod borne (Japanese B, 3. Protozoa West Nile, Equine Viruses) (Toxoplasma gondii) 4. Rabies 4. Bacteria (TB)

5. Dengue 5. Spirochetal 75 ChildhoodMorbidity Clinical Manifestations

The onset is usually sudden with fever, headache, vomiting, altered sensorium, seizures and variable neurological or motor symptoms. The neurological deficits may have a static or quickly progressive course and features of raised intracranial pressure may supervene. Clinical picture is variable and often difficult to distinguish from acute bacterial meningitis. Recent illness may provide due to the possible cause. A careful examination ef CSF is essential. The CSF is generally under raised pressure, clear with a cell count varying from zero to several hundred, with no significant elevation of protein and normal sugar. Virological work up is essential on CSF, stool, blood and throat samples. Serological work up should include ELISA for IgM on CSF /serum for arbo/enteroviruses. PCR is an important test, especially for herpes. If neuro- imaging studies (CT/MRI) and EEG suggest focal involvement, then herpes shotud be suspected as etiology. ‘ Treatment Treatment is essentially symptomatic and supportive. Raised intracranial pressure is managed by IV infusion of20% mannitol (lg of mannitol/kg body weight) given in 30 minutes and dexamethasone in a dose of 0.4 mg/kg IV as initial dose followed by 0.1 mg/kg IV every 6 hours. Specific therapy for herpes infection should be given early, if the diagnosis is suspected. Herpes should be suspected and identified if there are focal clinical and EEG signs or imaging is suggestive of focal involvement or CSF has RBCs. A virological confirmation should not be awaited as early therapy is mandatory. Treatment on suspicion of herpes is justifiable in view of the sequelae that ensure from delay in therapy. Acyclovir in a dose of 10 mg/kg/ dose IV, every 8 hourly for 10 days is given. 30.3.2.1 Japanese Encephalitis Japanese encephalitis is a disease caused by mosquito-borne virus from the family Flaviviridae. Domestic pigs and wild birds are reservoirs of the virus; transmission to humans may cause severe symptoms. This disease is most prevalent in South East Asia and the Far East.

Epidemiology Japanese encephalitis is a leading cause of viral encephalitis in Asia, with 30,000 -50,000 cases reported annually. Case fatality rates range from 0.3% to 60% and depend on population and on age. Residents of rural areas in endemic locations are at highest risk; Japanese encephalitis usually does not occur in urban areas. Countries which had major epidemics in the past, but which have controlled the disease primarily by vaccination, include China, Korea, Japan, Taiwan and Thailand. Other countries which still have periodic epidemics include Vietnam, Cambodia, India, Nepal and Malaysia. Human, cattle and horses are dead-end hosts and disease manifests as fetal encephalitis. The most important vector is Culex tritaeniorhynchus, which feeds on cattle in preference to humans. The natural host of the Japanese encephalitis virus is bird and not human and the virus will therefore never be 76 completely eliminated. Clinical features Gastrointestinal, Parasitic and Neurological Japanese encephalitis has an incubation period of 5 to 15 days and the vast Disorders majority of infections are asymptomatic. only 1 in 250 infections develop into encephalitis.

Severe rigors mark the onset of this disease in humans. Fever, headache and malaise are other non-specific symptoms of this disease which may last for a period between 1 and 6 days. Signs which develop during the acute encephalitic stage include neck rigidity, hemiparesis, and convulsions and raised body temperature. The symptoms may progress to coma. Mortality of this disease is generally higher in children. Life long neurological deficits such as deafness, emotional liability and hemiparesis may occur.

Treatment

There is no specific treatment for Japanese encephalitis and treatment is supportive. There is no transmission from person to person and therefore patients do not need to be isolated.

Prevention

I The widespread use of vaccine and urbanization has led to control of the disease in Japan, Korea, Taiwan and Singapore. The inclusion of JE vaccine in routine UIP in India (endemic areas) is expected to reduce the morbidity and mortality due to JE 30.3.3 Seizures in Children

Seizure are the most common neurological problem encountered in children. Although the word seizure and convulsions are used interchangeably it is the motor manifestation of seizure which is called a convulsion

Definitions

Seizure is defined as sudden, transitory, abnormal phenomenon of motor, sensory or psychic nature resulting from transient dysfunction of part or all of the brain. Epilepsy is defined as recurrent unprovoked seizures due to excessive discharge of hyper excitable neurons. It must be remembered that seizure is a symptom of underlying CNS disorder and does not constitute a diagnosis. The CNS disorder has to be defined and managed appropriately

The common clinical situation encountered in practice are – seizures in a newborn, febrile seizures, seizures occurring with underlying acute CNS insult, and as recurrent unprovoked seizures (epilepsy). Another clinical situation which may occur in association with any of these is status epilepticus in which the patient has prolonged seizure with life threatening complications.

Non Epileptic paroxysmal events : A variety of paroxysmal events can mimic a seizure and if labelled incorrectly as seizure can result in unnecessary treatment with potentially harmful medical and social consequences. The common nonepileptic events are breath holding spells, shuddering attcks, syncopal attacks, night terror , hyperventilation attacks and hysterical fits. 77 ChildhoodMorbidity Breath-holding spells : This is the commonest entity misdiagnosed as seizure in infants.

BHS are of 2 types- cyanotiic spells and pallid spells. In the cyanotic variety the patient after a provocation or tantrum cries ,hold his breath in expiration and becomes blue and may then have clonic movements of limbs and even incontinence. In the pallid variety the infant gasps ,becomes apneic followed by pallor and unresponsiveness in response to an unpleasant or painful stimulus. Bradycardia is present since there in increased vagal tone.

Oral iron therapy is effective in treatment of BHS. Parents should be reassured regarding the benign nature of the disorder.

Syncopal attacks: In childhood and adolescence syncopal attacks form the major diagnostic confusion. Syncope results from vasovagal stimulation and is ppted by fear ,pain, heat ,or standing in erect posture for a long time. Onset of symptoms is slower than in a seizure and the patient experiences faintness, giddiness and visual blurring. The patient may fall down but the duration is brief with complete orientation following the event.

30.3.3.1 Febrile seizures (FS)

In the young children febrile seizure is the commonest cause of seizure. FS are defined as event in infancy or childhood occurring between 6 months to 5 years, associated with fever but without evidence of intracranial infection or a defined cause. It is to be noted that in a child who has had a afebrile seizure or epilepsy, seizure may be precipitated by fever, but these are not FS. Febrile seizure is not a type of epilepsy as it is provoked by fever.

FS is a common disorder affecting about 3-5% of children below the age of 5 years. A typical or simple FS is brief generalized, clonic or tonic seizure which occurs during the first 48 hours of a febrile illness (mostly viral). The fever is generally >390 C. The seizures are brief lasting for 2 –5 minutes and there is no post-ictal manifestation like todd’s palsy. The FS may occur following vaccination also. There is a strong genetic predisposition for FS and the risk of a child having FS is 10-25% if one of the parents had FS . Nearly 85% of patients have simple or typical FS. The rest 15% have one or more complex features e.g. focal seizures, multiple seizures during a febrile illness or duration > 15 min.

Outcome : Nearly 2/3rd of the patients may have a single episode of FS. Around 1/3rd will have recurrent FS. The risk of recurrence is higher in children who are younger at onset (age < 9 months), have delayed development , those who have family history of FS and children who have FS at mild fever. Long term outcome of FS is very good and there is no risk of intellectual impairment or neurological deficit as a result of FS.

The risk of subsequent epilepsy after a simple febrile seizure is 2-3 times higher than in general population but is still negligible( 0.5% in general population and 1.5% in simple FS)

78 Management Gastrointestinal, Parasitic and Neurological Exclude intrcranial infection and determine the cause of fever: The Disorders child who presents with fever and seizures for the first time requires a detailed history and thorough check up to exclude possible CNS infection. In a tropical country like India a child with fever and convulsions may be suffering from meningitis or cerebral malaria or even metabolic derangement which may occur along with systemic illnesses e.g. hyponatremia with diarrhoea. Hence it is important to exclude CNS infections or any other cause of seizure. In infants the signs of meningitis are hardly ever seen so LP should be done in children younger than 18 months who are brought with fever and convulsions. It should also be considered in patients who have received anticonvulsant drugs and those getting antibiotics.

Treatment of convulsion: In most cases of FS the duration of seizure is brief and the child is well by the time he/she is brought to a physician .In such children nothing much needs to be done except to confirm that there is no CNS infection and to give antipyretics and tell the parents about the benign prognosis of this disorder. Children with prolonged seizure or those brought convulsing should receive intravenous diazepam/lorezepam on arrival. Since administration of these drugs is likely to interfere with watching of sensorium these children need to be hospitalized and observed.

EEG and neuroimaging is not required in children with FS. Routine blood chemistry is done only if there a suspicion of these derangement.

Teach parents about home management of seizures and how to give midazolam nasal spray if the seizures are prolonged. ( see box page no..)

Reduction of body temperature : This is done by giving antipyretics e.g. Paracetamol 10-15mg/kg every 6 hours or ibuprofen 5-7 mg/kg every 8 hr. Aspirin should not be used in children .

Most children with FS will not have recurrence. The risk of recurrence is high if the first seizure occurred at age < 9 months, there is family history of FS; or if the patient has neurodevelopmental delay.

Continuous prophylaxis with phenobarbitone and valproic acid is efficacious in preventing FS but is not recommended in view of the benign nature of FS and unacceptable side effects (hepatotoxicity in valproic acid and cognitive effects of phenobarb).Similarly there is no role of oral clobazam or rectal diazepam to prevent recurrence.

Check Your Progress 2

1. (a) Write three common pathogens causing acute bacterial meningitis beyond 3 months of age.

(i)

(ii)

(iii) 79 ChildhoodMorbidity (b) Name three signs of meningeal irritation.

(i)

(ii)

(iii)

2. State whether true or false :

(a) E.coli is a common pathogen causing menintgitis in neonatal period. (True / False) (b) In large majority of cases, subdural effusion are asymptomatic. (True / False) (c) Lymphocytic cellular response in CSF is diagnostic of bacterial meningitis. (True / False) (d) Third generation cephalosprin are preferred initial antibiotics in cases of pyogenic meningitis beyond 3 months of age. (True / False) (e) There is no role of continuous prophylaxis with antiepileptic drugs to prevent recurrence of Febrile seizures (True / False) 3. Fill in the blanks : (a) Children having first seizure at ______months of age or earlier. Have higher chances of recurrence. (b) Risk of subsequent epilepsy in case with simple febrile seizure is ______. (c) LP should be done in all children aged less than ——— with frist febrile seizure and those who have received ——— —— or —————————- 30.3.3.2 Epilepsy Epilepsy is defined as occurrence of 2 or more unprovoked seizures. Epilepsy is a common condition with a prevalence of 4-8/1000. The international league against epilepsy in 1981 classified epileptic seizure based on seizure description and EEG into 3 types – generalized, partial and unclassified( inadequate data) . Partial Generalized Simple partial Absence- typical Complex partial Atypical absence Atonic Partial with Myoclonic Secondary Clonic Generalization Tonic Tonic clonic 80 Evaluation of a child with epilepsy Gastrointestinal, Parasitic and Neurological Establish the diagnosis : The diagnosis of epilepsy is based on meticulous Disorders history which should elicit the description of seizures , the pre-ictal and post- ictal period, and any triggering events. A variety of non-epileptic events can mimic epileptic fits. The first step in diagnosis is to determine whether the event is truly a seizure or not. These may be Breath holding spells, syncopal attacks , shuddering attacks, hyperventilation attacks ,hysterical seizures , tetany and tetanus. The circumstances in which the event occurs and the observation of the ‘fit” can help in diagnosing these conditions. Determine the seizure type : To classify the seizure a proper history of onset of seizure is essential. Partial seizures may start with brief focal features like adversive movement or conjugate deviation of eyes to one side and get quickly generalized and it is only by getting a good history that proper classification can be made. EEG is recommended since it helps in classifying the epileptic seizures. However an absence of abnormality on EEG does not exclude epilepsy. Determine the cause : This may be found by history of perinatal events or head trauma. Clinical examination may reveal neurocutaneous stigmata of neurofibromatosis or tuberous sclerosis . Considering that neurocysticercosis is common in our country the patient should be specially inspected for subcutaneous nodule . Any focal neurological deficit or presence of papilledema is suggestive of a space occupying lesion and requires imaging and appropriate treatment. Imaging is indicated in all cases that have raised ICP, partial epilepsy, abnormal EEG, age less than 2 yrs , poorly controlled epilepsy. Anti-Epileptic Drug therapy : A single episode of seizure is not designated as epilepsy. Anti-epileptic drugs (AED) are not required for the first generalized seizure. The patient should be evaluated by EEG and CT scan / MRI and AED started if required. The choice of AED is based on type of seizure and cost factors and life style of the patient. The first line AED i.e. carbamazepine(CBZ), phenytoin, phenobarbitone and sodium valproate(VPA) are all equally effective in the management of common epileptic disorder. VPA is drug of choice for primary generalized epilepy such as absences and myoclonic epilepsy. CBZ can sometimes worsen absences. Phenytoin is not preferred in girls because it can cause hirsuitism and coarse facies. Generally carbamazepine oxcarbazepine is preferred drug for partial epilepsy and generalized tonic clonic epilepsy, while VPA is drug of choice for absences, myoclonic, atonic and polymorphic epilepsy. The AED drugs are started on a lower dose and then slowly increased to minimum effective dose so as to reduce the chances of CNS side effects. The dosages and side effects of the first line AEDs are shown in table I. Duration of treatment : AED therapy is continued for a total of 2 years of seizure free period after which it is tapered off slowly over 6-12 weeks. Parent education : Parents should be educated regarding the nature of disease, drug therapy, side effects and compliance, injury prevention and home management of seizure. 81 ChildhoodMorbidity Table 30.6: Comparison of first line AED

Phenytoin Valproate Carbamazepine Daily dose 5-8 mg/kg 10-50mg/kg 10-30mg/kg No of doses OD or BD BD BD or TID Available Tab-50mg,, Tab – 200mg, Tab – 100mg, Preparations 100mg 300 mg , 500mg 200 mg, retard Syrups- 2 (Chrono form also form available formulations] also 30mg/5 ml available Syrup-100mkg in 5ml & Syrup-200 mg 125mg/5ml in 5ml Side effects Hirsuitism, gum Increase in apetite, Somnolence, diplopia, hyperplasia, Hair loss, Bone marrow Cognitive effect Hepatotoxicity in suppression, young children

Table 30.7: Domiciliary treatment of seizures

l Recovery position

l Clear the mouth

l In seizure lasting >5 minutes give - Nasal midazolam spray one spray in each nostril - Take the patient to the nearest hospital if seizure persist

30.3.4 Neurocysticercosis Neurocysticercosis is an important health issue of many developing countries in Asia, South America. In India it is a common cause of epilepsy. In children nearly 1/3rd of partial unprovoked seizure are due to inflammatory granulomas which are most commonly due to NCC. Eating of infected pork can cause NCC but eating of cyst infected raw vegetables is perhaps the most important cause of the infestation. Clinical features : The live larva after lodging in brain excites little reaction. But as the larva dies the lesion causes host inflammatory reaction with perilesional edema . The larva lodges most commonly in the parenchyma but may lodge in meninges, subarachnoid space or ventricle. CNS involvement in NCC is variable depending upon the site, number of cysts and the host 82 reaction. Cysticercosis may remain asymptomatic and be picked on routine neuroimaging. Seizures are the most common presenting symptoms and these Gastrointestinal, Parasitic and Neurological are commonly partial onset seizures. Other manifestations are raised Disorders intracranial pressure, encephalopathy, meningitis like symptoms and extracranial manifestations such as subcutaneous nodules and ocular involvement. Diagnosis : Diagnosis is made by neuroimaging. On a CT scan live cysts are seen as hypodense cystic lesions while the dying cyst is seen as contrast enhancing ring lesion. A scolex may be seen as an eccentric nodule inside the ring in nearly 1/3rd cases. Old healed cysts may be seen as calcified lesions. Tuberculoma is another cause of inflammatory granuloma but the tubercular granulomas are generally larger (>20mm) with irregular margins, and a thick ring with greater perilesional edema.. MRI is superior in identifying active cysts, intraventricular lesions and cysts in posterior fossa . MRI is better in differentiating other causes of granuloma notably Tuberculoma from NCC but being more expensive should be reserved for cases in whom diagnosis is not clear. Serodiagnosis (serum IgG by ELISA) is commonly done but has a limited role as it is generally negative in patients with a single cyst.. Treatment : Treatment consists of treatment of seizures by AEDs . Raised intracranial tension is treated by osmotic diuretis and steroids Cysticidal therapy is conventionally used with the premise that live cysts will be destroyed and to prevent the long term sequeale and risk of epilepsy.Cysticidal therapy is not indicated in calcified or inactive lesions. All single/multiple cysts and live cysts are given cysticidal treatment unless contraindicated. The cysticidal treatment is contraindicated in encephalitic form of NCC , ventricular form and ocular cysticercosis . Albendazole is the drug of choice and is administered in the dose of 15mg/kg/day for 2-3weeks. Oral dexamethsone (0.5mg/kg/day) or prednisolone should be started 2 days prior to starting Albendazole and continued for 5 days . Neurosurgical intervention in form of VP shunt is rarely required for ventricular cysts and hydrocephalus. Prevention : Health education to discourage open field defecation and proper disposal of excreta is required to interrupt the infestation. Community awareness regarding proper food hygiene, peeling and washing of raw vegetables before eating can reduce the burden of this disease. 30.3.5 Acute Flaccid Paralysis .The global incidence of polio has reduced by more than 99% and only 3 countries are reported to have endemic polio at present . India reported the last case of wild poliovirus in 2011 and has been declared polio free since 2014. However since there can be importation of virus from the endemic countries , there is need for continued efforts to keep the country polio free. Ongoing endemic transmission in three countries will continue to threaten polio-free areas everywhere, unless it is eradicated entirely. To achieve poliomyelitis eradication, the World Health Organization recommends that countries conduct surveillance for cases of acute flaccid paralysis (AFP). Acute flaccid paralysis (AFP) is defined as a sudden onset of paralysis/weakness in any part of the body of a child less than 15 years of age. This syndromic reporting strategy, of investigating all AFP cases rather than just “suspected poliomyelitis”, serves many purposes. First, it increases the sensitivity of the surveillance system and allows it to detect a possible paralytic poliomyelitis due to wild poliovirus transmission in the population. 83 ChildhoodMorbidity AFP surveillance is also an indicator of the quality of surveillance in an individual country or large population group. AFP Surveillance also helps to monitor progress in polio eradication .. Since there can be several causes of AFP, so each AFP needs to be evaluated to find out if the paralysis is due to polio or not. Polio is only one out of the many causes of AFP. All cases of AFP should be reported to Surveillance medical officer of National Polio Surveillance Programme. For the purpose of reporting any case of AFP within last 6 months has to be reported. . Cases are immediately investigated within 48hours of notification by a trained Medical officer. After examining the case and confirming that the case is of AFP 2 stool samples are collected 24 hours apart preferably within 14 days of onset of paralysis. These are sent to reference laboratories for testing for wild polio virus. A case is classified as polio if wild polio virus is isolated from a case of AFP. Differential Diagnosis of AFP As polio causes acute flaccid paralysis (AFP), physician has to differentiate this condition from other causes leading to AFP so that diagnosis of the specific condition is not missed. This may affect treatment which is quite different in each case and misdiagnosis may lead to disastrous consequences, Table 2 below shows the points of differentiation of important diagnostic conditions. Guillian barre syndrome (GBS ) : an acquired demyelinating disease of peripheral nervous system is a common cause of AFP in childhood .Children with GBS may have sensory complaints in form of hypoanasthesia in a glove stocking distribution or tingling and burning sensation .GBS is differentiated from polio by the following features GBS is common in children >2 years while polio is common in children <3 years. Fever is present in polio just before onset of paralysis, in GBS there may be history of fever 2-3 weeks prior to paralysis . Symmetric ascending paralysis involving distal muscles is seen in GBS while in polio paresis is patchy involving proximal muscles. CSF shows albumino-cytological disassociation in GBS . Traumatic neuritis and transverse myelitis are other common causes of AFP which are differentiated by clinical features (Table I) Pseudoparalysis : Certain conditions may present with pseudoparalysis due to local inflammatory conditions of hip or knee and can be confused with other causes of AFP. These are not to reported as AFP. Common causes of pseudoparalysis are hypokalaemia, inflammtory condition of femur, hip & knee such as toxic synovitis, arthritis, osteomyelitis; scurvy; and congenital syphilitis Other Non- Polio Enteroviruses : A number of other non- polioenteroviruses(NPEV) are known to cause AFP. Coxsackie A, coxsackie B ,echovirus ,enteroviruses types 70 and 71 have been associated with polio like illness. Most of cases of infection with NPEV show complete recovery within 60 days of of onset. The paralytic sequelae of polio are more severe and permanent leading to atrophy of muscles and shortening of limb. Other condition which can cause confusion are peripheral neuropathies due to toxins such as lead and organophosphorous compounds and post diphtheria paralysis. The clinical picture of post diphtheratic paralysis is similar to GBS 84 but there is a history of sore throat, nasal twang and nasal regurgitation of Gastrointestinal, Parasitic and Neurological fluids 2-5 weeks prior to paralysis. Disorders Table 30.8: Differential Diagnosis of Acute Flaccid Paralysis

Signs & Polio GBS* TM** TN*** Symptoms

Progression 24-48 Hours HOURS- Hours - 4 Hours – 4 Of paralysis 10 Days days days

Fever High, Always Not common Rarely often present Present at onset present before, during of and after FP FP, disappears next Day

Flaccid Acute Acute Acute Lower Acute Paralysis Asymmetrical Symmetric Limbs Asymmetrical, (FP) Mainly Distal Symmetrical only one limb. proximal.

Tone Decreased or Diminished Hyptonia of Decreased or absent lower limbs absent in in affected limb affected limb.

Deep Tendon Decreased to Global Absent in Decreased to Reflexes absent Areflexia lower limbs absent

Sensation Severe myalgia Cramps, Anaesthesia Pain in No sensory Tingling Hypo/ of lower Gluteus changes anaesthesia limbs with a Hypothermia. Palms & sensory Only in Bulbar Soles level. form Often Absent Absent Present

Cranial Nerve Mainly in cases In severe If lesion is Not Present Involvement with respiratory Cases Cervical or paralysis thoracic

Respiratory Increased <10WBC Normal Normal Insufficiency Normal High N or mild é

CSF:WBC: Generally Sometimes Present Never Protein: Absent Transient

Bladder Abnormal : Ant. Abnormal: No. Abnormal Dysfunction Horn Cell Demyelination diagnostic in sciatic nerve Disease value normal in 1st 2 weeks

Nerve Abnormal Normal Normal Normal Conduction Denervation Velocity : 3rd Week

EMG –3weeks Severe Mild, Flaccid Moderate asymmetric Symmetric diplegia atrophy only Atrophy, Atrophy of in affected Sequel at 3 skeletal distal muscles limb Months Deformities later *GBS : Guillain Barre Syndrome, *TM : Transverse Myelitis, *TN : Traumatic Neuritis 85 ChildhoodMorbidity Check Your Progress 3

1. Fill in the blanks :

(a) Dose of carbamazapine in children is _____ mg/kg/day.

(b) Hirsutism and gum hyperplasia are known side effects of _____.

(c) In cases with neurocysticercosis, daily dose of albendazole is ______/kg.

(d) For differentiating granuloma due to NCC from tuberculoma, ______is a better neurouriaging technique.

2. State whether true or false :

(a) Poliomyelitis is characterised by paralysis which is pure motor, flaccid and asymmetrical. (True / False)

(b) Albumino-cytological dissociation is a characteristic feature of transverse myelitis. (True / False)

(c) Transverse myelitis results from involvement of anterior hour cells in spina cord. (True / False)

(d) Isolated facial nerve palsy should also be reported to surveillance medical officer as a part of AFP surveillance (True / False)

30.4 PARASITES INFECTIONS

Parasitic infections are still very common in our country the reason for acquiring most of these parasites are—poor sanitary conditions, poverty and lack of health education. Intesrinal parasites mostly cause abdominal pain, diarrboea, vomitting, abdominal distension etc. Large parasites like ascaris and pinworms are visible to naked eye. Table 30.9 describes common parasites, their clinical manifestations in brief and their therapy.

86 Table 30.9: Intestinal Parasites Gastrointestinal, Parasitic and Neurological S. Parasite Route of Clinical Drug Disorders No. (Other names) infection symptoms therapy and signs 1. Entamoeba Histolytica Ingestion of Intestinal Intestinal (Amoeblasis) cysts dysentry. Hepatic (Dysentry): Amoebic, liver Mctronidazol 30-50 abscess mg/kg day for 10 day followed by diloxanide furoate 10 mg/kgz day or 10 days. Amoebic liver abscess Metronidazol initially I.V. for 10 days alternative drugs: dehydr. line. Chloroquin 2. GIardia lamblia Ingestion of Diarrhoea, weight Metronidazole cysts loss, abdominal 15 mg/kg/day for 5 pain, failure to Furazolidine thrive (sprue like 5 mg/kg/day for 10 symptoms) days. 3. Ascaris lumbricoides Ingestion of Pulmonary:Loeffer Albendazole400 mg (Ascariasis, round- which contain live syndromes: single dose, or worm infestation) mature larvae cough fever Mebendazol hemoptysis, twice daily 100 mg intestinal abdomi- for 3 days abdomi- or Pyraniel pamoate nal pain and II mg/kg single dose distention, worms in or Piperazine citrate stool/vomitus, 50-75 mg/kg/day aciopic migration, for 2 days intestinal obstruction 4. Ankylosioma duodo- Penetration Prunius and Albendazole, nale (hookworm) of skin eruption at the site 400 mg single of feel by 400 mg single dose, or Larvae of entry, Anemia Mebendazole oedema twice daily for Pyrantel abdominal 3 days, 11 mg/kg single pain, reduced appetite. dose. or, pamoate 5. Etercoius vermicularis Ingestion of Nocturnal perianal Albendazole embryensied pturitis, single dose, repeat 400 mg Sleeplessness, after 2 weeks or Passage of worms. Mebendazol 100 mg twice daily for 3 days or Pyrantal pamoate, 11 mg/kg single dose 6. Strongyloides Penetration if Proitis, rash of the Thiabendazol Stercora1is skin by site of entry 50 mgikg/day in 2 (Strongylodiasis) filariform abdominal pain, divided doses for 2 larvae diarrhoea, days. vomitting.

87 ChildhoodMorbidity 30.5 LET US SUM UP

In this unit you have learnt about diseases affecting liver and CNS. In the section on diseases of liver, it is stressed that palpable liver in all instances is not pathological. True hepatomegaly may occur due to variety of causes. For proper management the cause needs to be identified based on clinical observations and laboratory investigations. Common causes of ascites and their differentiation have been outlined.

Acute bacterial meningitis is still a common potentially serious childhood morbidity in developing countries. It is important that it is diagnosed early and promptly treated so that the complications can be immunizes. Most of the seizure disorders have their onset in pediatric age group. Their proper management rests on recognizing the exact type of seizures. You have also learnt that most cases with febrile seizure do not require long term anticonvulsant therapy.

India has been declared polio free but AFP surveillance need to be continued . All AFP cases should be promptly notified to medical officer of National Polio Surveillance Programme ..

30.6 ANSWERS TO CHECK YOUR PROGRESS

Check Your Progress 1

1. (a) bile salts

(b) estrogen

(c) 3.5

(a) chylous

2. (a) True

(b) True

(c) False

(d) False

(e) True

Check Your Progress 2

1. (a) (i) H. influenzae type b

(ii) S. pneumoniae

(iii) Neisseria meningitis

(b) (i) Neck rigidity

(ii) Kernig sign

(iii) Brundzinski sign 88 2. (a) True Gastrointestinal, Parasitic and Neurological (b) True Disorders (c) False (d) True (e) False 3. (a) Diazepam (b) Nine (c) 1.5% Check Your Progress 3 1. (a) 10-30 (b) Phenytoin (c) 15 mg (d) MRI 2. (a) True (b) False (c) False (d) True

30.7 FURTHER READINGS 1. Nelson’s Textbook of Pediatrics eds: Kliegman RM,Bonita Stanton, Joseph St Geme and Nina F Schor . 20th Edition, 2015 2. Ghai Essential Pediatrics. Editors : Vinod K Paul , Arvind Bagga 8th Edition 2017 3. Field Guide :Surveillance for of Acute Flaccid paralysis 3rd Edition 2005 Child health division Ministry Of health & Family

89 ChildhoodMorbidity UNIT 31 TUBERCULOSIS Structure 31.0 Objectives 31.1 Introduction 31.2 Pathogenesis 31.3 Clinical Manifestations 31.4 Case Finding and Evaluation 31.5 Diagnosis 31.6 Treatment 31.7 General Measures 31.8 Control of Tuberculosis 31.9 Let Us Sum Up 31.10 Answer to Check Your Progress 31.11 Further Readings 31.0 OBJECTIVES After completing this unit you will be able to : l explain the pathogenesis of tuberculosis in brief; l identify the clinical manifestations of tuberculosis in children; and l diagnose and treat various clinical forms of tuberculosis in children. 31.1 INTRODUCTION In the previous units of this block you have learnt about acute infectious illnesses. By now it is also clear that infections are still a very common cause of morbidity and mortality in children of developing countries. In this unit you will learn about tuberculosis which is a major cause of morbidity and mortality in children. It is the commonest cause of death from a single infectious disease. Tuberculosis elimination is now getting renewed thrust as Government of India has formulated a national strategic plan to end TB. The National Strategic Plan is aiming to achieve elimination of TB, by 2025. Key strategies adopted by strategic plan are 1. Private sector engagement 2. Active Case finding 3. Drug resistant TB case management 4. Addressing social determinants including nutrition 5. Robust Surveillance system 6. Community engagement 6 Multi-sectoral approach

90 As per the Global TB report 2017 the estimated incidence of TB in India Tuberculosis was approximately 28,00,000 accounting for about a quarter of the world’s TB cases. Nearly 4 lakh people die of TB per year in India . The incidence of MDR Tuberculosis ia also alarming – 146,000 Cases per year… TB in paediatric age group often go undetected due to nonspecific symptoms and non-uniformity of diagnostic modalities in public and private sector. In year 2015, Paediatric TB contributed (6-7%) of total TB cases. The mortality is maximum in children below five years of age, due to high incidence of severe form of tuberculosis such as meningeal or disseminated. Rapid emergence of resistance in mycobacteria to various chemotherapeutic agents is posing a challenge. In India, as many as 20% of the organisms, show primary resistance to one or other antitubercular drug.

31.2 PATHOGENESIS Tuberculosis is caused by acid fast bacilli-Mycobacterium tuberculosis. In more than 98% cases, portal of entry and thus the site of primary focus is the lung. Following section describes the formation of primary focus and its course and outcome. Formation of Primary Complex When a ‘sputum positive’ (infective) case coughs, large number of live bacilli are coughed in the air where they remain suspended. Process of primary focus formation sets in when inhaled aerosolized particles, containing bacilli are lodged into the alveoli. Alveolar macrophages kill most of the bacilli but if the organism is virulent and immunity is low, these bacilli may continue to multiply intracellularly. Inflammatory mononuclear cells are attracted to the site of infection and as tissue hypersensitivity develops, this inflammatory response intensifies over 2-12 weeks. The bacilli and surrounding cellular response leads to formation of tubercle which contains the macrophages, epitheloid cells, lymphocytes and Langerhans giant cells. This focus is usually located in sub- pleural areas and is called primary focus or Ghon’s focus. From the primary focus, the bacilli are taken to the regional lymphnodes (in case of pulmonary primary focus, these are hilar or paratracheal lymphnodes) via the lymphatics. In the lymph nodes also similar tissue reaction occurs leading to tubercle formation and glandular enlargement. The primary focus, draining lymphatics and infected regional lymphnodes are collectively called Primary Complex. The parenchymal portion of primary focus usually heals completely by fibrosis and calcification after undergoing caseous necrosis and encapsulation. Regional lymphnode lesion also undergoes some degree of encapsulation and fibrosis but healing is usually incomplete. Course and Outcome of Primary Complex Bacterial virulence, quantum of infection and host immunity are major determinants of course and outcome of primary complex. In cases with incomplete natural healing the parenchymal infection may persist or increase. Increasing of inflammation at parenchymal lesion, lymphatics and lymph nodes may lead to fusion of parenchymal lesion and regional lymph nodes – progressive primary tuberculosis. The parenchymal lesion may go on to develop pneumonia or consolidation. Further contiguous spread may cause pleural involvement leading to pleurisy, effusion or empyema. Persistence of parenchymal lesion and subsequent coughing of liquified caseum leads to 91 ChildhoodMorbidity cavitation. Enlarged lymph node may cause complete or partial occlusion of the bronchus causing collapse or air trapping (distal emphysema). Endobronchial tuberculosis is the result of erosion of bronchus by enlarging lymph node and subsequent spread of infected caseous material to both lungs. Tubercular bronchiectasis is caused by persistent infection and occlusion of the bronchus. Frequently the tubercular pulmonary lesion has a combination of segmental or lobar consolidation and collapse. Disseminated, Miliary and Extrapulmonary disease During the development of primary complex bacilli are carried to most tissues of the body via the blood and lymphatic vessels. This spread may manifest as disseminated tuberculosis if the number of circulating bacilli is large and host response is inadequate. Miliary tuberculosis is characterized by presence of small millet seed like shadows of 1-3 mm size in all parts of lung. Frequently, liver, spleen and other organs are also involved. Miliary tuberculosis develops due to tubercle bacilli traversing the thoracic duct from involved lymph nodes and entering venous system and lung parenchyma. Development of disease in various organs appears to follow the Wallegran’s “Time table of tuberculosis”. TBM usually occurs 3-6 months, pleuritis 3-9 months, bone and joint disease 1-3 years and renal disease in 5-25 years following primary infection.

31.3 CLINICAL MANIFESTATIONS The clinical manifestations in primary tuberculosis in children are variable and depend upon on the type of illness, severity organ involvement and associated problems. The common manifestations include fever, failure to gain weight or weight loss and poor appetite. In the following paragraphs you will learn about more manifestations in different types of tuberculosis. Asymptomatic Mantoux Positive In most instances, 6-8 weeks after introduction of tuberculosis bacilli in the body, the Mantoux test becomes positive. If the resistance is strong there may be no symptoms. Such patients are commonly detected during family survey for tuberculosis. Pulmonary Primary Complex Children with pulmonary primary complex may have non specific symptoms described above along with cough. Progressive Primary Disease Progressive primary disease is the result of progression of primary disease and includes tubercular consolidation with or without collapse, bronchopneumonia, cavitation, bronchiectasis, pleural involvement etc. Children with this type of disease may have high grade fever along with cough and expectoration .. In addition there may be pain chest, respiratory distress and toxic appearance. Respiratory system examination will reveal findings depending upon pathological lesion as described above. Children with endobronchial TB may present with fever and troublesome cough. Dyspnea and wheeze may be prominent leading to misdiagnosis of asthma. 92 Disseminated Tuberculosis Tuberculosis Children with this illness may have all the clinical manifestations described under progressive primary disease. In addition these children have generalized lymphadenopathy, hepatosplenomegaly and evidence of organ dysfunction of involved organs. Miliary Tuberculosis In children with miliary TB, features of toxemia are prominent. Fever, cough and dyspnea are usually present. Examination of chest reveals generalized crepitations and/or rhonchi. Hepatosplenomegaly is a common association. Some children may also have associated tuberculous meningitis. Pleural effusion :It follows rupture of subpleural focus into pleural cavity . The effusion usually occurs due to hypersensitivity of to Tubrcular protein Onset may be insidious or acute with fever, cough, dyspnoea, and pleuritic pain on the affected side. Abdominal Tuberculosis In children with abdominal TB, enlarged mesenteric lymphnodes may be palpable. Peritoneal involvement will manifest as ascites. Intestinal involvement presents with recurrent diarrhoea, at times with present of blood in stools, and recurrent abdominal pain. Subacute intestinal obstruction results from stricture formation and hypertrophic ileocecal tuberculosis. Tuberculosis Meningitis/ Meningo- encephalitis (TBM) CNS tuberculosis is one of the most common cause of death attributed to tuberculosis in children. All parts of CNS may be involved but more common is the involvement of meninges and cerebral hemisphere. Clinical features of TBM can be described in three stages – Stage I – is characterized by fever, irritability, malaise and drowsiness. Focal neurological signs and signs of meningeal irritation are absent. Stage II – is characterized by signs of meningeal irritation (nuchal rigidity, Kernig’s and Brudzinski signs), cranial nerve and other focal neurological deficits and features of raised intracranial pressure. Stage III – is marked by deepening coma, decerebrate posturing and deterioration of vital signs. Diagnosis of TBM is based on CSF examination, evidence of tuberculosis elsewhere in the body and CT scan findings. Tuberculosis of Lymphnodes Lymphnodes may be involved by hematogenous, or lymphatic dissemination of tubercule bacilli, and may affect superficial and deep lymphnodes. Cervical region is the commonest site to be involved. Nodes involved are multiple, may show matting and ultimately may form chronically discharging sinuses. Diagnosis is based on demonstration of typical granulomatous lesion or by the presence of Acid Fast Bacilli (AFB) by fine needle aspiration cytology (FNAC) or by biopsy. When clinically not palpable, abdominal lymphadenopathy may be demonstrated by ultrasonography. Congenital Tuberculosis Maternal illness maybe transmitted to the baby transplacentally or by aspiration, or ingestion of amniotic fluid in the presence of tubercular 93 ChildhoodMorbidity amnionitis. Symptoms and signs of this rare illness may be present at birth but more commonly begin by second or third week of life. Clinical manifestations include respiratory distress, fever, hepatosplenomegaly, failure to thrive, skin lesions, jaundice and meningitis. The diagnosis is based on demonstration of tuberculous infection in the infant and mother, with exclusion of postnatal exposure. HIV and Tuberculosis Co-infection An HIV infected individual is at 5-10 times increased risk of developing TB. In Indian series on HIV/AIDS in children 30-65% cases were found to have associated tuberculosis. Disseminated and extra-pulmonary tuberculosis are relatively more common as are the chances of having disease with multidrug resistant or atypical mycobacteria. In presence of HIV/AIDS, response to tuberculin is poor. Anti-tubercular chemotherapy is same in HIV positive individuals. Corticosteroids, if otherwise indicated, can also be used. . Progressive BCG Disease BCG may result in a local non-healing ulcer or abscess, and sometimes lymphadenopathy in axillary, supraclavicular or cervical group of nodes. Rarely there may be generalised illness in immunocompromised hosts. The BCG associated complications may increase due to inappropriate techniques of administration (e.g. sub-cutaneous in place of intradermal), higher doses or use of more reactogenic bacterial strains (Japanese strain of BCG). Check Your Progress 1 1. Identify following statement as true / false : (a) Poor cell mediated immunity leads to more severe illness. (True/ False) (b) Primary pulmonary focus is usually subpleural. (True/False) 2. List the nonspecific clinical manifestations of tuberculosis in children. 3. Fill in the blanks : (a) Peritoneal involvement in tubercular infection may give rise to ______. (b) In ______% cases of HIV/AIDS associated tuberculosis is found.

31.4 CASE FINDING AND DIAGNOSTIC EVALUATION Early identification of children with high probability of having active TB ( presumptive TB) is the most important method of case finding. Presumptive TB refers to children with persistent fever and/or cough for more than 2 weeks , loss of weight/ no weight gain and /or history of contact with infectious TB case. Children with suggestive symptoms attending health facilities need to be screened by the physicians with appropriate evaluation as outlined below. High risk groups such as children with severe malnutrition and those with HIV and contacts with adults with TB should be evaluated even if asymptomatic. 94 Principles of diagnosis Tuberculosis All efforts should be made to demonstrate microbiological evidence [AFB smear, Mycobacterium tuberculosis culture or Cartridge based nucleic acid amplification technique (CBNAAT)] in the diagnosis of pediatric TB. In cases where sputum is not available for examination or sputum microscopy fails to demonstrate AFB, alternative specimens (Gastric lavage, Induced sputum, broncho-alveolar lavage) should be collected, depending upon the feasibility, under the supervision of a pediatrician) for procedure to obtain gastric lavage and induced sputum). There is no role for serology (IgM, IgG, IgA antibodies against MTB antigens), various in-house or non-validated commercial PCR tests and BCG test. There is no role of IGRAs in clinical practice for the diagnosis of TB. i) Intradermal Skin Test Intradermal tuberculin testing is the first immunodiagnostic test. These tests are cheap, easy to perform with varying sensitivity and specificity. The tests consists of an intradermal administration of antigen preparation. A positive response is indicated by the appearance of induration, which results from migration of activated lymphocytes and macrophages to the site of antigen desposition. Purified protein derivative (PPD) derived from old tuberculin is used these days. There are several ways for testing tuberculin hypersensitivity. These include Mantoux test, Tine test, Heaf’s test etc. Of these only the Mantoux test is described, as this is the one in common use in India. MANTOUX TEST The test consists of intradermal injection of 2 TU PPD by using a 26 gauge needle and tuberculin syringe. The test is read after 48-72 hours. The induration (and not erythema) at the site of injection is measured, and the maximum length and width of induration is expressed in millimeters. The interpretation of Mantoux test is described in Table I. A positive Tuberculin skin test/Mantoux positive is defined as 10 mm or more induration. False negative Mantoux test : A negative Mantoux test does not rule out presence of active tuberculosis. False negative response may be present in upto 20-50% of patients suffering from tuberculosis. The various reasons for a negative test include, (a) loss of potency of PPD due to improper storage, contamination, improper administration, i.e. leakage from the site of injection, and (b) factors interfering with the lymphocytic activation and delayed hypersensitivity reaction, i.e. extremes of age (congenital tuberculosis), overwhelming infection (eg miliary TB and TBM), concommitant viral infection such as HIV, measles, influenza etc, immunization with a live viral vaccine, treatment with immunosuppressive agents, severe degree of malnutrition, neoplastic diseases such as lymphoma, other diseases like sarcoidosis, renal failure etc. Mantoux test may be negative in first 2-8 weeks of acquiring infection. False positive Mantoux test : Positive Mantoux test does not always indicate presence of active disease. In some circumstances it may be falsely positive such as, (a) repeated skin testing with PPD or old tuberculin, or (b) 95 ChildhoodMorbidity prior BCG vaccination or infection with atypical mycobacteria. Positive Mantoux following BCG vaccine rarely exceeds 10mm, and is strongest in the first few years following immunization, so any reaction that exceeds 10mm with 2 Tuberculin Unit should be considered as indicative of presence of tubercular infection. It must be kept in mind that higher strengths of Tuberculin give more false positive tests and the cutoff of 10mm may not be valid with them. Table 31.1: Interpretation of Mantoux Test Size of Induration Interpretation Remarks

Less than 5 mm Negative Absence of active infection, unless false negative

5-10 mm Borderline In HIV +ve cases, it is taken as positive

More than 10 mm Positive Indicates infection, patient needs further evaluation for active infection

ii) Demonstration of Mycobacteria Demonstartion of Mycobacteria by smear or culture or Nucleic acid amplification is the gold standard for diagnosis of PulmonaryTuberculosis. Currently NAAT are recommended to be used for Pediatric pulmonary TB wherever available. Collection of sputum is difficult in children because they fail to bring it out. Whenever possible, an early morning specimen is preferred. In older children sputum production can be induced with hypertonic saline aerosols. AFB can be demonstrated in gastric aspirate, or bronchial aspirates obtained by bronchoalveolar lavage. Gastric aspirate yield for the organism is 30-40% in cases with pulmonary tuberculosis. In infants with extensive disease, the yield may be as high as 80-90%. The gastric fluid is aspirated early in the morning as the child awakens, before the stomach empties itself of the overnight accumulation of secretions swallowed from the respiratory tract. The aspirated material is kept in a sterile container, stomach is washed with 30 ml of water and is added to the aspirated material. This should be transported to laboratory immediately. If delay in transport is expected, the pH should be neutralised immediately with sodabicarb till it is just pink with phenol red. The same procedure should be repeated on three consecutive days. AFB can be demonstrated from lymphnode aspirates in tubercular adenitis, pleural pericardial and ascitic fluid and from CSF in tubercular meningitis. Histological sections from lymphnode or liver biopsy can also be examined for presence of the mycobacteria. The Zeil Neilson’s (ZN) staining technique is still used extensively because of its low cost. Methods suggested for better yield of AFB are: (a) Floatation of material containing AFB with commercial bleach and xylol, and subsequent staining of creamy upper layer with ZN stain. (b) Fluorescent staining. Use of fluorescent dyes such as auramin-O, 96 rhodamin etc give a better yield of mycobacteria than ZN stain. (c) Improvement in culture techniques. Use of liquid media in place of LJ Tuberculosis media, and use of Bactec radiometric system yields better and quicker results. Bactec System is an automated radiometric culture method. The system uses a liquid medium containing radiometric palmitic acid labeled with radioactive carbon 14C. Growth of mycobacteria within the system is 14 measured as a daily growth index that detects the production of CO2 by the growing organisms. CBNAAT: Currently Cartridge based Nucleic Acid Amplification technique (CBNAAT) is the recommended test for demonstration of Mycobacterium tuberculosis.. The main advantages of CBNAAT is rapid availability of result indicates presence or absence of tuberculosis within 2 hours; Besides it indicates presence or absence of resistance to Rifampicin. Being cartridge based, it has an inherent built in system of quality control, obviating risk of contamination. Presently its use is recommended in all children with pulmonary and/or extra pulmonary tuberculosis for respiratory (sputum, gastric lavage, induced sputum) and non-respiratory (lymph node aspirates, CSF, pleural fluid, and other body fluids) specimens. However a negative result does not definitively rule out the diagnosis of tuberculosis.. iii) Radiology Investigations l X-ray film of the chest provide valuable information suggestive of tubercular infection. These include, (a) adenitis - hilar, paratracheal, subcarinal; (b) parenchymal lesion; (c) miliary mottling; (d) pleural effusion; (e) collapse; and (f) evidence of bronchogenic spread. l In skeletal tuberculosis X-ray of bones may demonstrate lytic lesions.. l USG abdomen is useful for abdominal tuberculosis. It may show mesenteric lymphadenopathy and ascitis. l Computerized tomography scan and magnetic resonance imaging. These sophisticated investigations are helpful in demonstration of tuberculomas in the brain. These also help in demonstration of exudates in basal cisterns of brain, ventricular dilatation with or without peri-ventricular ooze. CT scan of brain is essential in cases of suspected tubercular meningitis for determining the degree of exudates, and the recognition of severity of hydrocephalus, as early surgical decompression of ventricles improve outcome, especially the onset of optic atrophy. CT abdomen and chest have been occasionally used to demonstrate the lymphnode enlargement and other tubercular lesions.

31.5 DIAGNOSIS The diagnosis of tuberculosis is simpler when the disease is florid. However, diagnosis in the early stage of illness is often difficult. In a presumptive case of tuberculosis, Mantoux test and X-ray film of the chest and Sputum/ for AFB/ CBNAAT should be obtained. The algorithm for pediatric pulmonary TB is shown in Figure 31.1 If Mantoux test is negative but radiographs of chest show parenchymal lesions, the child should be treated with broad spectrum antibiotics for 10-14 days. However, all feasible attempts to isolate or demonstrate to organism by CBNAAT from Gastric aspirates/ induced sputum / borncho-alveolar lavage 97 should be made. ChildhoodMorbidity

GA-gastric aspirate, IS-Induced Sputum * Highlysuggestive Chest X-rays include Miliary Lymphadenopathy (hilar or mediastinal) or chronic fibro-cavitatorylesions. l Speutum forAFB smear should be done twice but sputum for CBNAATshould be done once only. l Sputum positive on smear or CBNAATshould be referred to as bacteriologicallyconfirmed case. l Antibiotics like Linesolid and Fhroroquinolones should not be used as theyhaveantitubercularactivitity. l All TB cases should be offered testing for HIV.

98 If the child is symptomatic but X-ray and sputum test is negative and the possibility of tuberculosis is high, then a focus of tubercular infection elsewhere in the body should be looked for. Various other investigations including FNAC, biopsies ultrasonography, CT Scan can be used for this purpose. Check Your Progress 2 1. Fill in the blanks : (a) Induration in Mantoux test is dependent on ______cell function. (b) The stain used for mycobacteria is called ______stain. 2. Lists the conditions which can cause false positive mantoux test.

31.6 TREATMENT Goal of TB Treatment-The goal of Tuberculosis treatment are: l To decrease case fatality and morbidity by ensuring relapse free cure l To minimize and prevent development of drug resistance l To render patient non-infectious, break the chain of transmission and do decrease the pool of infection Case definitions I. Microbiologically confirmed TB case refers to a presumptive TB patient with biological specimen positive for acid fast bacilli, or positive for Mycobacterium tuberculosis on culture, or positive for tuberculosis through Quality Assured Rapid Diagnostic molecular test. II. Clinically diagnosed TB case refer to a presumptive TB patient who is not microbiologically confirmed, but has been diagnosed with active TB by a clinician on the basis of X-ray abnormalities, histopathology or clinical signs with a decision to treat the patient with a full course of Anti-TB treatment. In children, clinically diagnosed TB case is diagnosed based on the presence of abnormalities consistent with TB on radiography, a history of exposure to an infectious case, evidence of TB infection (positive TST) and clinical findings suggestive of TB in children in event of negative or unavailable microbiological results Microbiologically confirmed or clinically diagnosed cases of TB are also classified according to: l Anatomical site of disease; l History of previous treatment; l Drug resistance; Classification based on anatomical site of disease a) Pulmonary tuberculosis (PTB) refers to any microbiologically confirmed or clinically diagnosed case of TB involving the lung parenchyma or the trachea-bronchial tree. 99 ChildhoodMorbidity b) Extra Pulmonary tuberculosis (EPTB) refers to any microbiologically confirmed or clinically diagnosed case of TB involving organs other than the lungs such as pleura, lymph nodes, intestine, genitourinary tract, joint and bones, meninges of the brain etc. Miliary TB is classified as PTB because there are lesions in the lungs. A patient with both pulmonary and extrapulmonary TB should be classified as a case of PTB. Classification based on history of TB treatment a) New case - A TB patient who has never had treatment for TB or has taken anti-TB drugs for less than one month is considered as new case. b) Previously treated patients have received 1 month or more of anti-TB drugs in the past. I. Recurrent TB case – A TB Patients previously declared as successfully treated (cured/treatment completed) and is subsequently found to be microbiologically confirmed TB case is a recurrent TB case II. Treatment After failure patients are those who have previously been treated for TB and whose treatment failed at the end of their most recent course of treatment. III. Treatment after loss to follow-up A TB patient previously treated for TB for 1 month or more and was declared lost to follow-up in their most recent course of treatment and subsequently found microbiologically confirmed TB case IV. Other previously treated patients are those who have previously been treated for TB but whose outcome after their most recent course of treatment is unknown or undocumented. The programme is now introducing daily regimen fir treatment of drug sensitive Tuberculosis among Pediatric TB patients in the entire country.The principle of treatment for tuberculosis (other than confirmed Drug Resistant forms of TB) with daily regimens is to administer daily fixed dose combinations of first – line anti-tuberculosis drugs in appropriate weight bands. For new TB cases, the treatment in intensive phase (IP) will consist of eight weeks of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol in daily dosages as per four weight band categories. There will be no need for extension of IP. Only Pyrazinamide will be stopped in the Continuation Phase (CP), while the other three drugs will be continued for another 16 weeks as daily dosages. For previously treated cases of TB, the IP will be of 12 weeks, where injection Streptomycin will be stopped after 8 weeks and the remaining four drugs (INH, Rifampicin, Pyrazinamide and Ethambutol) in daily dosages as per wight bands will continued for another 4 weeks The CP in both new and previously treated cases may be extended by 12-24 weeks in certain forms of TB like CNS TB, Skeletal TB, Disseminated TB etc. based on clinical decision of the treating physician. Extension beyond 12 weeks should only be on recommendation of experts of the concerned field. Loose Drugs would be needed as substitutions in case of adverse drug reaction or with co-morbid conditions. 100 Tuberculosis Table 31.2: Treatment of drug sensitive TB Type of TB Treatment regimen Treatment regimen Cate in IP CP New (2) HRZE (4) HRE

Previously treated (2) HRZES + (1) HRZE (5) HRE

Number in parentheses is for number of months The aim of therapy in tuberculosis is to cure all patients with a regimen of antitubercular drugs with minimal relapse rate, least side effects, acceptable cost and compliance. For achieving these objectives antitubercular regimen should have rapid bactericidal action, should prevent emergence of drug resistance and should have good sterilizing action. The Revised National Tuberculosis Control Program (RNTCP) of the Government of India recommends directly observed treatment for all cases of TB irrespective of their age. As per revised RNTCP guidelines the drugs are given on daily basis to children ..A daily fixed dose combination of 1st line antitubercular drugs as per the weight band is given to the patient ( Table no 31-3 ) The added essential component of the direct observation fi.e. where the drugs are swallowed in the presence of the health worker or a community volunteer or a responsible family member ) makes it a current standard of care for managing TB. The Table 31.4 details the categorization as used under the revised strategy . All patients should be put on the suggested regimens of fixed drug combinations. Under RNTCP, the patient after the diagnosis is categorized as per the standardized protocol and is registered at the area DOTS center. Every patient who is registered under the program is provided with a box of drugs needed for their complete course which is kept at the center labeled with the patient’s name. This ensures an uninterrupted availability of drugs. Table 31.3: Drug Dosage for Pediatrics TB Weight Number of tablets Inj. category (dispersible FDCs) Streptomycin Intensive phase Continuation phase HRZ E HRE 50/75/150 100 50/75/100 Mg 4 – 7 kg 1 1 1 100 8 – 11 kg 2 2 2 150 12 – 15 kg 3 3 3 200 16 – 24 kg 4 3 4 300 25 – 29 kg 3 + 1A* 4 3 + 1A* 400 30 – 39 kg 2 + 2A* 2 2 + 2A* 500 A = Adult FDC (HRZE = 75/150/400/275; HRE = 75/150/275) 101 ChildhoodMorbidity III)SPECIFIC ISSUES IN TREATMENT Infant of a Mother with Tuberculosis Infant of a mother who has active tuberculosis should be screened for disease by doing a Mantoux test, radiograph of chest and gastric aspirate for AFB on three consecutive days. The infant who is symptomatic, and/or has evidence of tuberculous disease on other investigations should be treated with standard regime of antitubercular therapy .The infant who is asymptomatic, and who has no evidence of disease on investigations, should be given isoniazid 10 mg/ kg/day for 3 months. Mantoux test is repeated at the end of 3 months. If Mantoux test is negative, isoniazid is stopped and the infant is immunized with BCG. If Mantoux test is positive, isoniazid is continued for another 3 months. Asymptomatic Children with Positive Mantoux Test A healthy child who is non-immunocompromised, with no clinical or radiological evidence of illness, but who has a positive Mantoux test requires no therapeutic intervention, except when the child is below 5 years of age and is severely malnourished. In the later case, a 6 months chemoprophylaxis with isoniazid is recommended. Corticosteriod Therapy in Tuberculosis Corticosterios have been used as an adjunct to anti-TB therapy. It is useful to know that corticosteriod therapy is beneficial only in certain cases and should not be prescribed injudiciously. Following are the specific indication for corticosteriod use –

l Neurotuberculosis

l Severely ill patients with military TB.

l Genitourinary tuberculosis

l Bilateral or massive pleural effusion or tubercular empyema. For most cases, prednisolone 1-2 mg/kg/day for initial four weeks with tapering over next 2-4 weeks is sufficient. BCG Associated Adenitis If there is periadenitis, fluctuation in the lymphnode with size more than 1.5 cm or impending rupture of the node, surgical removal or drainage of node is indicated. Lymph nodes smaller than 1.5 cms usually do not require active intervention. Generally antitubercular drugs are not required. V. MANAGEMENT OF CONTACTS Apparently Healthy non-vaccinated Children (i) Mantoux-negative with known sputum positive contact : These children should receive INH until 10-12 weeks after contact has been broken. The Mantoux test should be repeated at that time. If it is “positive”, INH should be continued for a total of 6 months. If it is “negative”, INH can be discontinued and BCG vaccination administered. Under RNTP, all such patients are put on INH prophylaxis provided the disease has been ruled out.

102 (ii) Mantoux positive (without previous BCG vaccination) with known Tuberculosis contact : Approximately 5% of those converting their skin tests will develop clinical disease within the first 2-5 years following infection if they are not treated. These children should receive INH or 6 months. (iii) Children apparently healthy, BCG vaccinated with contact : Whether INH preventive therapy should be used will depend upon the clinical circumstances including whether the source case was infectious, the age of the contact and the closeness of the contact. Children with Tuberculosis who have Developed Jaundice during Course of Treatment Hepatotoxicity is one of the important untoward reaction to antitubercular drugs. Overall incidence of clinically significant hepatotoxicity is very low. In children with severe malnutrition and severe illness in term of disseminated illness the risk of hepatotoxicity is relatively high and hence a routine monitoring of liver function tests in these children is required. If clinically evident jaundice is detected or the value of transaminases is more than four times the normal, such patients require discontinuation of antitubercular drugs. The child should be monitored for clinical recovery. Liver function test should be repeated once a week and when the transaminase values are less than twice the normal values, rifampicin, INH and pyrazinamide are reintroduced in sequence. If the illness is severe and child is unstable a combination of streptomycin and ethambutol which are non-hepatotoxic may be continued till the other drugs are added.

31.7 GENERAL MEASURES A proper explanation of the nature of illness and therapy, health education, advice regarding nutrition, diet and screening other members for tuberculosis should be carried out. The patient should be followed every month for compliance. Liver function tests are not required routinely. However, in patients with pre-existing hepatic disorder baseline and periodic liver function test should be monitored. Routine supplementation with vitamin B6 along with Isoniazid is not required.

31.8 CONTROL OF TUBERCULOSIS Early diagnosis and treatment of cases of tuberculosis, investigations of all adult contacts for childhood tuberculosis, and BCG vaccination of all infants form the mainstay for control of tuberculosis. . Household contacts and other close contacts will be systematically screened for active TB Roll out of paediatric new guideline and its rigorous implementation has been done . Adequate and regular supply of paediatric Fixed Drug Combinations which will be provided to Public as well as Private paediatric TB patient’s free of cost will help improve adherence and bring down the number of new cases.

103 ChildhoodMorbidity Check Your Progress 3 1. Identity true and false statements (a) Nephrotoxicity is one of the common side effect of isoniazid. (True/False) (b) Routine monitoring of liver function test is not recommended in a child suffering from tuberculosis. (True/False) (c) In tuberculosis meningitis a 4-6 weeks course of corticosteroids is recommended. (True/False) (d) In a relapse of tuberculosis if a good regimen is given with good compliance the same regimen should be continued for longer period. (True/False)

31.9 LET US SUM UP In this unit we have learnt that tuberculosis is a major public health problem in India. The disease is caused by mycobacterium tuberculosis. The bacteria enter the body by aerosoles. If native resistance is poor then it progresses. The non specific manifestations of TB in children include fever, failure to thrive, cough, and weight loss. Other manifestations depend on the type of illness. Any child with cough for more than 2 weeks and/or fever and /or contact with case of TB should be investigated with Xray chest and Mantoux test and Sputum for Mycobacteria by CBNAAT> .All efforts should be made to demonstrate AFB by microscopy or CBNAAT from gastric aspirate or induced sputum. All cases of TB should be notified to health authorities . The daily treatment as recommended by RNTCP guidelines should be administered.. The preventive aspects include BCG vaccination, contact tracing and chemoprophylaxis.

31.10 ANSWER TO CHECK YOUR PROGRESS Check Your Progress I 1. (a) True (b) True 2. List the nonspecific clinical manifestations of tuberculosis in children : Fever Failure to thrive Weight loss Cough 3. Fill in the blanks : (a) Peritoneal involvement in tubercular infection may give rise to ascites. (b) In 30-65% cases of HIV / AIDS, associated tuberculosis is found. 104 Check Your Progress 2 Tuberculosis 1. Fill in the blanks : (a) Induration in Mantoux test is dependent on T cell function. (b) The stain used for mycobacteria is called Zeil Neilson stain. 2. List the conditions which can cause false positive mantoux test. (a) Previous BCG vaccination (b) Repeated testing with PPD Check Your Progress 3 (a) False (b) True (c) True (d) False

31.11 FURTHER READINGS 1. Ghai’s Essential Pediatrics. Editors : Paul VK. & Arvind Bagga CBS publishers 8th Edition Delhi 2. Technical and operational guidelines for RNTCP 2016. Central TB division MOHFW 3. India TB report 2018 RNTCP Annual status report Central TB Divsion, Ministry of Health & family welfare Govt of India Nirman Bhawan Delhi

105 ChildhoodMorbidity UNIT 32 HIV/AIDS Structure 32.0 Objectives 32.1 Introduction 32.2 Etiology and Transmission 32.3 Clinical Manifestation 32.4 Diagnosis 32.5 Management 32.6 Let Us Sum Up 32.7 Answers to Check Your Progress

32.0 OBJECTIVES After going through this Unit, you will able to:  describe the epidemiology of HIV infection in children;  discuss clinical features and clinical staging of HIV infection in children;  enumerate methods of diagnosis of HIV infection in infants and children;  outline ART regimens in various age group; and  explain strategies for prevention of HIV infection in children.

32.1 INTRODUCTION As per 2016 UNAIDS estimates 36.7 million (30.8-42.9 million) people were estimated to be living with HIV globally.Approximately1.8 million new infections occurred in 2016 worldwide and approximately 1.0 million people died of AIDS-related illnesses. In India, currently adult seroprevalence is estimated to be 0.3 %. However, due to its large population size, even with this low prevalence India has the third largest number of HIV infected people in the world. According to 2016 estimates by UNAID, there are 2.1 million people with HIV in India. Although HIV infection is reported from all parts of the country, 6 states are considered as high prevalence states. (Maharashtra, Karnataka, Tamil Nadu, Andhra Pradesh, Manipur and Nagaland). Overall, India’s HIV epidemic is slowing down, with a 32% decline in new HIV infections (80,000 in 2016), and a 54% decline in AIDS-related deaths between 2007 and 2015. At the present time, there are approximately 80, 000 new infections and 60,000 HIV related deaths every year. Children under 15 years constitute approximately 5 % of all HIV infections. While currently 50 % of adult patients are receiving ART, only one third of HIV infected children are receivingART. 106 Apart from this staggering figures about infection, more than 11.2 million HIV/AIDS children have been rendered ‘AIDS orphan’ which describes a child under 15 yrs who has lost his/her mother due to HIV/AIDS.

32.2 ETIOLOGYAND TRANSMISSION HIV (Human immunodeficiency Virus) is a lentivirus, one of the subfamily of retroviruses. There are two types, HIV -1 and HIV – 2, with HIV -1 infection being responsible for more than 95% infections in our country. Unlike in adults where more than 90% of HIV occurs through sexual route, in children 95% cases occur due to vertical transmission. Another common mode of transmission is through transfusion of contaminated blood and blood products. Sexual abuse is responsible for 1-2% of pediatric HIV infections Not all children born to HIV infected mothers are infected with HIV. Without any intervention, overall vertical transmission rates range from 16-20% in developed countries and 25-45% in developing countries. Vertical transmission (mother/parent to child; MTCT/PTCT) of HIV can occur during pregnancy (in utero), labour and delivery (intrapartum) or through breast feeding (post partum). Prematurity, advanced maternal HIV disease, exposure to maternal blood , firstborn twin, rupture of membranes of >4 hrs, high maternal viral load etc are associated with higher risks for HIV transmission. Breast feeding leads to additional risk of transmission by approximately 14-16%. Transmission can take place at any point during breast feeding; however about 7% transmission occurs during the first 4-6 months. Delivery by elective Caesarian section (before the onset of labour) and administration of antiretroviral drugs to the infant for initial few weeks decrease the risk of vertical transmission. Currently, anti-retroviral drug administration to mother and infants is in practice for prevention of PTCT. Delivery by is recommended unless it is indicated due to obstetrical reasons. 32.3 CLINICAL MANIFESTATION The clinical course differs in children as compared to adults. Children with HIV progress rapidly, develop more bacterial infections than opportunistic infections, suffer from neurological developmental problems and have higher mortality than adults. Lymphoid interstitial pneumonia (LIP) is characteristically seen in children while Kaposi’s sarcoma is rare in children. Mycobacterium avium complex and cryptococcal infection are more frequent in HIV infected adults than in HIV infected children. Patterns of clinical progression: On the basis of age of presentation and disease progression, three patterns have been described. a). Rapid progressors : Manifestations in the form of opportunistic infections and neurological features are apparent within the first few months of life. These are seen in 20-30% of cases and they undergo a rapid natural 107 downhill progression. ChildhoodMorbidity b) Gradual progressors : These children usually develop manifestations after the age of one year and they usually display failure to thrive, recurrent bacterial infections and lymphoid interstitial pneumonitis.

c) Slow progressors : This group comprises of children who manifest later in childhood. The disease often manifests in infancy as microcephaly, low birth weight and failure to thrive. Towards the end of the first year, children start developing repeated episodes of bacterial infections, diarrhea, Pneumocystis carinii pneumonia, persistent oral candidiasis etc. Other common findings are generalized lymphadenopathy and parotid swelling. CNS manifestations include loss or plateau of developmental mile stones, spasticity, hyperreflexia and gait disturbances. TB is the most common opportunistic infection encountered in children. Lymphoid interstitial pneumonia(LIP) is a chronic respiratory disease seen in children with HIV infection. Patients usually also have hepatomegaly, splenomegaly, dermatitis, anemia and neutropenia. Based on clinical manifestations, stage of HIV infection and associated immunosuppression is usually classified in 4 different stages. Table 1 describes Clinical staging in children using clinical and immunological criteria. Table 32.1: WHO Revised clinical staging

Classification of HIV-associated clinical disease WHO Clinical Stage

Asymptomatic Stage 1

Mild Stage 2

Advanced Stage 3

Severe Stage 4 (It should be emphasized that WHO clinical staging of HIV disease can only be applied where HIV infection has been established) Clinical Stage 1 Asymptomatic Persistent generalized lymphadenopathy Clinical Stage 2

l Unexplained persistent hepatosplenomegaly l Recurrent or chronic upper respiratory tract infections (otitis media, otorrhoea, sinusitis, tonsillitis) l Herpes zoster l Lineal gingival erythema l Recurrent oral ulceration l Papular pruritic eruption l Fungal nail infections l Extensive wart virus infection 108 l Extensive molluscum contagiosum HIV/AIDS l Unexplained persistent parotid enlargement Clinical Stage 3 l Unexplained moderate malnutritiona not adequately responding to standard therapy l Unexplained persistent diarrhoea (14 days or more) l Unexplained persistent fever (above 37.5°C, intermittent or constant, for longer than one 1 month) l Persistent oral candidiasis (after first 6 weeks of life) l Oral hairy leucoplakia l Lymph node tuberculosis l Pulmonary tuberculosis l Severe recurrent bacterial pneumonia l Acute necrotizing ulcerative gingivitis orperiodontitis l Unexplained anaemia (<8 g/dl), neutropoenia (<0.5 x 109/l) or chronic thrombocytopaenia (<50 x 109/l) l Symptomatic lymphoid interstitial pneumonitis l Chronic HIV-associated lung disease, including bronchiectasis Clinical Stage 4 l Unexplained severe wasting, stunting or severe malnutritionb not responding to standard therapy l Pneumocystis (jiroveci) pneumonia l Recurrent severe bacterial infections (such as empyema, pyomyositis, bone or joint infection, meningitis, but excluding pneumonia) l Chronic herpes simplex infection (orolabial or cutaneous of more than 1 month’s duration or visceral at any site) l Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs) l Extrapulmonary tuberculosis l Kaposi sarcoma l Cytomegalovirus infection (retinitis or infection of other organs with onset at age more than 1 month) l Central nervous system toxoplasmosis (after the neonatal period) l HIV encephalopathy l Extrapulmonary cryptococcosis, including meningitis l Disseminated nontuberculous mycobacterial infection 109 ChildhoodMorbidity l Progressive multifocal leukoencephalopathy

l Chronic cryptosporidiosis (with diarrhoea)

l Chronic isosporiasis

l Disseminated endemic mycosis (extrapulmonary histoplasmosis, coccidioidomycosis, penicilliosis)

l Cerebral or B-cell non-Hodgkin lymphoma

l HIV-associated nephropathy or cardiomyopathy

32.4 DIAGNOSIS In children over 18 months of age the diagnosis of HIV infection is made by demonstration of IgG antibody against HIV by ELISA. Usually more than one ELISA based on different antigens are used. Western blot or viral demonstration by PCR are other tests used. In children born to HIV +ve mothers and younger than 18 months, IgG antibody acquired transplacentally may give positive result, even though the infant may not be infected. In 74% and 96% of HIV-uninfected exposed children, HIV antibody test will be negative at age 9 and 12 months respectively. Viral detection by PCR is the test recommended under 18 months age. As per the Early Infant Diagnosis (EID) protocol of NACO, HIV exposed infants are tested for HIV infection status as follows: The first HIV DNA PCR test for HIV-1 infection using a Dried blood spot (DBS) is conducted at 6 weeks of age. If the DBS test is positive for HIV, the test is repeated on another DBS sample as early as possible for confirmation. In case the second DBS tests negative for HIV, the test is repeated on third DBS sample for a second confirmatory HIV -1 DNA PCR test and rely on the result of this test for final diagnosis. If the first PCR is negative, the child is screened for HIV antibodies (Rapid test) at 6 months age or earlier if the infant becomes symptomatic. Infants testing positive on rapid test are tested with a PCR test using DBS. If the child is breastfed and initial PCR tests are negative, re-testing is carried out 6 weeks after cessation of breastfeeding (however, breastfeeding is not stopped just for purpose of HIV testing). If the infant is seen for the first time after 6 months of age, an HIV serology is performed as a screening test. A PCR on a DBS sample is performed only if serology for HIV is positive. If the child is HIV positive by DNA PCR before 18 months age, antibody testing at 18 months is now not recommended. All HIV positive infants initiated on ART should continue to receive ART. Presumptive diagnosis where there is no virologic testing (DNA PCR) available: If the child is aged <18 months and has symptoms and signs that are suggestive of HIV infection and there is no virologic testing available, it is possible to make a “presumptive diagnosis” using clinical criteria, infants HIV antibody test results and mother’s HIV status. 110 Box below shows the clinical criteria for presumptive diagnosis of HIV HIV/AIDS infection in children aged <18 months when virological tests are not available. In a child meeting the presumptive criteria, ART is initiated as soon as possible without waiting for virological tests that, nevertheless, should be performed at the earliest.

Box : Clinical criteria for presumptive diagnosis of severe HIV disease in infants and children less than 18 months of age requiring ART in situations where virological testing is not available A presumptive diagnosis of severe HIV disease should be made if: The infant’s HIV antibody test is reactive and Diagnosis of any AIDS-indicator condition(s) can be made or The infant is symptomatic with two or more of the following *: l Oral thrush; l Severe pneumonia; l Severe sepsis. Other factors that support the diagnosis of severe HIV disease in an HIV seropositive infant include: Recent HIV-related maternal death; or advanced HIV disease in the mother; CD4 in the child <20%. Confirmation of the diagnosis of HIV infection should be sought as soon as possible. Notes: * As per IMCI definition: 1. Oral thrush: Creamy white to yellow soft small plaques on red or normally coloured mucosa which can often be scraped off (pseudo membranous), or red patches on tongue, palate or lining of mouth, usually painful or tender. 2. Severe pneumonia: Cough or difficult breathing in a child with chest in-drawing, stridor or any of the IMCI general danger signs; i.e., lethargic or unconscious, not able to drink or breast-feed, vomiting, and presence or history of convulsions during current illness; responding to antibiotics 3. Severe sepsis: Fever or low body temperature in a young infant with any severe sign such as fast breathing, chest in-drawing, bulging fontanelle, lethargy, reduced movement, not feeding or sucking breast milk, convulsions, etc. Diagnosis of HIV infection in children > 18 months

Children aged ?18 months are tested according to the national adult testing strategies:

111 ChildhoodMorbidity Two positive HIV antibody test results (done sequentially) in a clinically symptomatic child (symptoms suggestive of HIV infection) more than 18 months indicate HIV infection in the child. Other investigations routinely done for assessment of clinical status, prognosis and response to therapy include CD4 counts, complete blood counts and immunoglobulin levels. CD 4+ cell count is performed to define immune status of the patients.

Table 32.2: Immunologic categories based on age-specific CD4+ T-lymphocyte counts and percent of total lymphocytes

Immunologic Category Age of the Infant / Child 12 months 1-5 years 6-12 years uL % uL % uL % 1 No evidence of suppression >=1500 >=25 >=1000 >=25 >=500 >=25 2 Evidence of Moderate suppression 750-1499 15-24 500-999 15-24 200-499 15-24 3 Severe suppression <750 <15 <500 <15 <200 <15

32.5 MANAGEMENT

Management of HIV children includes general and supportive care, prophylaxis against infections , proper management of infections, immunization and antiretroviral therapy.

Apart from appropriate treatment of infections and nutritional rehabilitation, two issues are of particular importance for paediatric patients, 1. Feeding, and 2. prophylactic immunization. In developed countries since safe alternative feeding can easily be managed, HIV infected mothers are advised not to breastfeed their babies.

WHO recommendations on feeding of HIV exposed infants have undergone rapid changes in recent years based on accumulating evidences on child survival in the absence of breastfeeding and HIV transmission while infants receive breastfeeding. While not giving breastfeeding protects infants from getting HIV infection, it renders them vulnerable to undernutrition, gastroenteritis, pneumonia and other infections and succumbing to these complications. With the almost universal availability of ART to mother during pregnancy and to infants during period of breastfeeding has minimized the chances of HIV infection to less than 2 %. Taking into consideration the above facts, according to WHO, currently mothers are advised to breastfeed their infants explaining them well advantages of breastfeeding and very low risk of infection with use of ARVs. If the mother still wants to know other feeding options, exclusive replacement feeding is considered and the criteria

112 for replacement feeding are assessed. The current national guidelines for HIV/AIDS feeding of HIV-exposed and infected infants <6 months age are- Exclusive breastfeeding for at least 6 months and continued breastfeeding till 12 months and beyond. Exclusive Replacement feeding is considered only in situations where breastfeeding cannot be done or upon individual mother’s choice, only if all the 6 criteria for replacement feeding are met: i) Affordability ii) can prepare frequently in a clean manner iii) Availability of safe water and sanitation iv) sustainability for six months v) family is supportive and vi) Access to health care in case need arises. Mixed feeding was not recommended earlier as in absence of ARV interventions it increased the risk of HIV transmission compared to exclusive breastfeeding. With ART to pregnant women and ARV prophylaxis to infants, mixed feeding (or partial breastfeeding) can be permitted in situations when mother cannot give exclusive breastfeeding because of joining the job etc.

For immunizations WHO recommends that infants born to HIV +ve mothers whose HIV status is not determined or who are HIV positive but asymptomatic can be given all EPI vaccines including live attenuated BCG, measles and OPV. Measles and MMR are recommended even in symptomatic patients except in severely immunosupressed children (CD <15%). HIB vaccine should be given to all infants according to the 4 recommended immunization schedule for healthy children. Hepatitis B vaccine should also be given as per the recommended schedule; it is also recommended to double the dose of vaccine or give additional dose if there is no seroconversion. Varicella vaccine can be given to HIV infected children who have CD4 lymphocyte counts of 25% or more and it is recommended to give 2 doses even in children less than 13 years of age.

Prophylaxis against infection decreases the possibility of acquiring infections and consequent morbidity. The best example is administration of Co- trimoxazole for prevention of PCP in the dose of 5 mg/kg/day.

Antiretroviral therapy:

Antiretroviral drugs are potent inhibitors of viral replication, there by suppressing the viral burden. It is important to remember that HIV infection is treatable but not curable; hence once the treatment is started it has to continue life long. Combination therapy with 3 drugs from different groups is usually started.

Currently, many antiviral drugs are available, which are classified into following categories (Table 3): Table 32.3: Anti Retroviral Drugs I: NRTI: Zidovudine (ZDV, AZT) Lamivudine (3TC) Stavudine (d4T) Didanosine (ddI) Abacavir (ABC) 113 ChildhoodMorbidity Zalcitabine (ddC) Emtricetabine

II : Non nucleoside revise transcriptase inhibitors (NNRTI) Nevirapine (NVP) Efavirenz (EFV) Delavirdine Rilpivirdine

III : Protease Inhibitors (PI) Nelfinavir Ritonavir Indinavir Lopinavir Saquenavir Atazanavir

IV: Nucleotide Reverse trascriptase inhibitor (NtRTI) Tenofovir

V: Integrase inhibitor: Raltegravir Elvitegravir Dolutegravir

VI: Fusion Inhibitors: Enfuvirtide

VII: CCR5 Entry inhibitor: Maraviroc

At present all cases diagnosed as having HIV infection are started on ART regardless of their age, clinical stage or CD 4+ counts. Regimens are chosen based on age and earlier exposure to ARVs as a part of PPTCT interventions. Most regimens combine 2 NRTIs and one NNRTI or PI. First-line regimen for infants and children <3 years of age are described in the following table. There is a need for a potent first-line regimen in young children in the context of high viral load and rapid disease progression. Evidence is suggestive of the superiority of LPV/r-based regimen for children less than 3 years regardless of PMTCT exposure

114 Table 32.4: First line ART regimens for infants and children aged HIV/AIDS <3 years Particulars Recommended Regimen Hb >9 g/dl and not on Zidovudine + Lamivudine + concomitant Rifampicin Lopinavir/ritonavir containingATT Hb <9 g/dl and not on Abacavir + Lamivudine + concomitant Rifampicin Lopinavir/ritonavir containingATT

Hb >9 g/dl and on Zidovudine + Lamivudine + concomitant Rifampicin Lopinavir/ritonavir as per weight; containingATT In addition, super boosting with Ritonavir If super boosting is not possible, use NVP as per body surface area

Hb <9 g/dl and on Abacavir + Lamivudine + concomitant Rifampicin Lopinavir/ritonavir as per weight; containingATT In addition, super boosting with Ritonavir

If super boosting is not Those with intolerance or possible, use NVP as per contraindication to both Zidovudine body surface area and Abacavir Stavudine based regimen can be used as alternative after e-approval by p-CoE / CoE / ART plus SACEP Please note: Any regimen initiated for an infant or child must be based on the bodyweight First-line regimen for children >3 years – upto 10 years of age given in Table 5. Table 32.5 : First line ART regimens for children aged 3 to 10 years Particulars Recommended Regimen Hb >9 g/dl (regardless of Zidovudine + Lamivudine + Efavirenz concomitant Rifampicin containing ATT or not) Hb <9 g/dl (regardless of Abacavir + Lamivudine + Efavirenz concomitant Rifampicin containing ATT or not) For children with intolerance Stavudine based regimen can b or contraindication to both used as alternative after e-approval Zidovudine and Abacavir by CoE / PCoE / ART plus SACEP Please note: Any regimen initiated to an infant or child must be based on bodyweight 115 ChildhoodMorbidity Table 6 describes first-line regimen for adolescent >10 years and weighing >30 kg. The guiding principles remain the same i.e. use fixed dose combination of three antiretroviral drugs (Tenofovir + Lamivudine + Efavirenz); use simplified, less toxic and more convenient regimen. Table 32.6: First line ART regimens for adolescents (aged >10 years) ART Regimen Recommended For Tenofovir+Lamivudine First-lineARTRegimen for: All new + Efavirenz children aged above 10 years and weighing >30 kg except those with known renal disease OR those with confirmed HIV-2 or HIV-1 & 2 infections Zidovudine + 1. First-lineART Regimen for:All children Lamivudine +Efavirenz aged above 10 years and weighing >30 kg with Hb >9 g/dl with known renal disease 2. First-lineARTRegimen for:All children aged above 10 years and weighing <30 kg with Hb >9 g/dl Abacavir+Lamivudine +Efavirenz 1. First-lineARTRegimen for:All children aged above 10 years and weighing >30 kg with Hb <9 g/dlwith known renal disease 2. First-lineARTRegimen for:All children above 10 years and weighing <30 kg with Hb <9 g/ dl Tenofovir+Lamivudine First-lineARTregimen for:All children + Lopinavir/ritonavir above 10 years and weighing >30 kg with confirmed HIV-2 or HIV- 1 & 2 infections, except those with known renal disease ART in HIV-TB co-infection:

In TB co-infected HIV children, initiation of anti-TB treatment is priority. ART should be initiated after 2 to 8 weeks of anti TB treatment. This guideline is to enable the patient to get adjusted to the effects and side- effects of anti-TB drugs. It also helps to reduce the antigenic load of M. tuberculosis as much as possible at the time of ART initiation so as to reduce ART related complications, including IRIS. However, in moribund patients and in children aged >5 years of age with CD4 less than 50 cells/ cmm, ART can be initiated earlier than two weeks of ATT initiation with strict clinical monitoring. Efavirenz containing regimen are used with concomitant rifampicin containing ATT regimens. In children less than 3 years, efavirenz is not recommended. In such situation, super boosted Lopinavir is used. All CLHIV with all forms of TB shall be initiated on Efavirenz based first- line ART, if the children are aged >3 years and >10 kg. In children <3years and/or <10 kg, receiving TB treatment, Nevirapine may not be an optimal choice because of drug interactions with Rifampicin. Similarly, Efavirenz is not recommended in children less than 3 years and less than 116 10 kg. Also, paediatric formulations of Rifabutin are non-available. HIV/AIDS Hence, the preferred regimen is super-boosted LPV/r based regimen in children less than 3 years and/or less than 10 kg with TB co-infection and on Rifampicin based ATT. The ART should be initiated at least after two weeks of starting anti-TB treatment. Prevention of HIV infection in children: Most HIV infections in children can be prevented by addressing vertical transmission as most of HIV infection in children is acquired through this route. The National PPTCT programme recognizes the 4 elements integral to preventing HIV transmission among women and children. These include: 1: Primary prevention of HIV, especially among women of childbearing age ; 2: Prevention of unintended among women living with HIV; 3: Prevention of HIV transmission from pregnant women infected with HIV to their children; and 4: Provide care, support and treatment to women living with HIV and to their children and families. The National PPTCT programme adopts a public health approach to provide these services to pregnant women. The objective is capture 90 % HIV infected women and to provide ART to 100% infected pregnant women and prophylactic ARV to all HIV exposed infants. Pregnant women are started at diagnosis on ART (three drug regimen containing Tenofvir, lamivudine and Efavirenz). The mothers are counselled regarding feeding to their infants. The infant is started on Nevirapine. The duration of NVP given to infant is a minimum of 6 weeks, regardless of whether the infant is exclusively breast fed or exclusive replacement fed. Duration of Nevirapine prophylaxis should be increased to 12 weeks (for breastfeeding infants only), if ART to the mother has been started in late pregnancy, during or after delivery and she has not been on ART for an adequate period as to be effective to achieve optimal viral suppression (which is at least 24 weeks- 6 months). Infants of women with prior exposure to NVP should get syrup Zidovudine (AZT) in place of syrup Nevirapine. Check Your Progress 1 1. Fill in the blanks a) ……………………..people are infected with HIV in India of which ………. are children b) 90% of cases of HIV in children occur due to ……………………transmission c) In the absence of ARV intervenation, additional risk of transmission through breast feeding is……………..

d) An infant with more than …………….absolute CD4 count will be described as having no immunosuppression. 2. List the factors increasing the risk of MTCT a) …………………………… b) ………………………… 117 c) ………………………….. ChildhoodMorbidity d) …………………………… 3. Mark true (T) or false (F) a) HIB Vaccine is contraindicated in HIV +ve children (T/F) b) Nevirapine is a NNRTI (T/F) c) Mixed feeding is the ideal feeding practice in babies exposed to HIV infection (T/F) d) A positive HIV ELISA is considered as diagnosis of infection in a 6 month old baby (T/F) e) Presence of pneumocystitis carinni pneumonia indicates clinical stage 3 (T/F) 32.6 LET US SUM UP About 85 -90% of paediatric HIV infections occur as the result of maternal to child transmission (MTCT). The rate of vertical transmission in developed countries is 16-20% whereas in developing countries, including India this is 25-45%. ART to the mother during pregnancy and labour and to the infant for initial few weeks decreases the chance of maternal to child transmission (MTCT). Children with HIV infection have varied clinical presentations and high index of suspicion is required to diagnose them. Breast feeding and safe alternative feeding options should be discussed with the family. HIV infected asymptomatic and mildly symptomatic children can be and should be given all EPI vaccines. At present all children diagnosed as having HIV infection, should be initiated on ART. 32.7 ANSWERS TO CHECK YOUR PROGRESS Check Your Progress 1 1. a) i. 2.1 million, ii. 5% b) MTCT c) 14 – 16% d) 1500 2. a) Active maternal disease b) Prematurity c) Prolonged rupture of membranes d) First born twin 3. a) F b) T c) F d) F e) F

118 UNIT 33 COMMON PAEDIATRIC EMERGENCIES Structure 33.0 Objectives 33.1 Introduction 33.2 Accidental Poisoning 33.2.1 Principles of Management of Acute Poisoning 33.2.2 Common Poisons 33.2.3 Prevention of Poisoning 33.3 Accidents 33.3.1 Treatment of a Child with Injury 33.3.2 Prevention of Accidents 33.4 Anaphylaxis 33.5 Bites and Stings 33.5.1 Snake Bite 33.5.2 Scorpion sting 33.6 Let Us Sum Up 33.7 Answers to Check Your Progress

33.0 OBJECTIVES After reading this unit, you should be able to:

 outline the management of accidental poisoning;

 enumerate ways of prevention of accidents; and

 manage a case of anaphylaxis

33.1 INTRODUCTION Most emergencies in children are because of severe intercurrent infection such as diarrhoea, respiratory infections and CNS infections. Early recognition of illness and treatment can prevent the need of emergency care. These emergencies have been dealt in the earlier units. Other life threatening conditions like , anaphylaxis, poisoning and injury prevention has been described in this unit. Any of these conditions can cause physiological instability and if not treated, may terminate in cardiopulmonary arrest. Evaluation of a sick child by quick assessment of airway , breathing, circulation, coma and convulsions has been described elsewhere . You should be equipped with essential resuscitation equipment and medication to give the basic care. Once the child’s condition has been stabilized the child should be transported to a facility capable of providing definitive care. In this unit, you will learn to diagnose and manage certain common pediatric emergencies. 119 ChildhoodMorbidity 33.2 ACCIDENTAL POISONING A poison is a substance that causes harm if it gets in the body. A poison may get into the body through ingestion, inhalation (gas) or skin contact (pesticides). Most of the poisoning in children is accidental although intentional intake for suicides may be seen in adolescents. Accidental poisoning in children is a global problem. It is most common in the todd1ers when they start exploring the environment. The incidence of poisoning in children in hospital admissions in India ranges from 1-2%. It is commoner in poor, large families living in small houses. The pattern of poisoning varies amongst rural or urban areas due to exposure to different types of potential poisons. The ingestion of common household poisons can be either a non-toxic ingestion (product that does not produce symptoms such as ink, chalk etc.) or toxic ingestion (soaps, detergents, medicines etc.). Ingestion of non-toxic substances is more common than toxic ingestion. A child may be brought with history of ingestion of a known poison. You should suspect poisoning in a child brought with unexplained coma/ multisystem involvement and unexplained metabolic acidosis and if a child on chronic medication has unexplained symptoms. Kerosene oil poisoning is the most commonly reported poison followed by drugs and chemicals. The principles of management of acute poisoning are outlined below. 33.2.1 Principles of Management of Acute Poisoning 1) Initial stabilization: The first step in management is evaluation of the airway, breathing and circulation. Resuscitate if there is respiratory or circulatory compromise. 2) Identification of the poison: This can be done by careful history and examination. Besides finding about the nature of poison, try to determine the amount of poison consumed and the time elapsed since the event. 3) Removal of poison: This is achieved by reducing the absorption of the poison from various sites depending on the nature of poison. The skin and eyes can be decontaminated by irrigating with saline. Remove all contaminated clothes. This is especially important for organophosphorous poisons which are absorbed through the skin and mucosa. The absorption through gut can be reduced by inducing emesis and gastric lavage. In conscious children vomiting can be induced by tickling the mucosa of posterior pharyngeal wall with finger. Gastric lavage can be performed with tap water (aliquots 10- l5ml/kg each) in the stomach which is then removed by gravity or suction. Both emesis and gastric lavage are contraindicated in kerosene oil and corrosives poisoning. Activated charcoal is an adsorbent which can reduce the systemic absorption of the poison. Cathartics can also reduce absorption but can not be given in poisoning by agents with corrosive action on the gut. Specific antidotes are available for very few poisons. When specific antidote is available it must be given without delay for maximum action (Table 30.1). Increasing excretion of poison: The excretion or elimination of poison can be increased if the pharmacokinetics of the substance are known. Forced 120 diuresis is useful in poisoning by phenobarbitone and salicylates. This is Common Paediatric achieved by increasing the urine excretion and raising the pH for weak acids Emergencies (salicylates and phenobarbitone). For substances which are weak bases, the pH can be reduced with ammonium chloride. Forced diuresis needs to be done with caution as it can cause water intoxication and congestive heart failure. In many poisons hemodialysis is required to remove the poison from circulation. e.g., ethylene glycol, carbamazepine and phenobarbitone etc. Supportive therapy: The supportive therapy is as important as specific treatment. This consists of maintenance of airway, oxygenation, fluids and electrolytes and monitoring for complications. 33.2.2 Common Poisons The clinical features and treatment of common childhood poisons is given in Table 32.1.

Table 33.1: Clinical Features of Common Poisons and their Antidotes Agent Features Antidote Dose and Route of administration

Organo- Bronchospasm, sweating. Atropine Atropine- 0.05 mg/kg IV phosphorous hypotension, miosis, every 5 min till signs of abdominal pain, atropinization paralysis and coma Pralidoxime PAM -IV 25-50 mg/kg every 12 hours

Iron Vomiting, abdominal Desferrioxamine IV 15 mg/kg/hr in 10% pain Gastrointestinal dextrose hemorrhage, circulatory IM 50 mg/kg 4 hourly failure, hepatic damage

Phenothiazine Extrapyramidal signs, Diphenhydramine 1-5 mg/kg/day per oral arrythmias in 4 divided doses Acetamino- Vomiting, jaundice, N-acetylcysteine 140 mg/kg oral loading phen hepatic fai1ure dose then 70 mg/kg 4 hourly for 3 days

Datura Tachycardia, fever, Physostigmine 0.5 mg IV over 5 min visual disturbance, may be repeated every delirium, dilated pupils, 10 mins (total 2 mg) thirst

Salicylate Acidosis, hyperpnoea, None vomiting, bleeding, pulmonary edema, renal failure Kerosene Oil Poisoning Accidental kerosene oil poisoning is the most common poisoning in developing countries. This is because of extensive use of this agent as fuel and for lamps. Besides since it is widely available without special packing it is not stored in special containers and often kept in mineral water bottles. The inadvertent intake of kerosene oil by the child leads to vomiting and aspiration into respiratory passages. The clinical feature are predominantly respiratory and include dyspnea, cough, fever and acidosis. In severe cases coma and convulsions may occur. Radiological signs may appear within an hour and consist of basal infiltration particularly in the right lung. 121 ChildhoodMorbidity Treatment of kerosene oil poisoning is mainly supportive and consists of oxygenation and control of fever. Emesis and gastric lavage are contraindicated. Antibiotics are generally prescribed to prevent secondary infection. 33.2.3 Prevention of Poisoning Most of childhood poisoning can be prevented by making the environment safe for children. Parents should be told that all common drugs (e.g., iron tablets) are potential poisons. This can be done by:  Keeping all potential poisons out of reach for the child.  Keeping the drugs and agents in original containers which should be child proof.  Stringent regulations for dispensing medicines e.g. not to dispense more than the required amount of drug.  Good supervision of children i.e., not leaving children unattended.  Parent education.

33.3 ACCIDENTS Injuries represent another important cause of preventable pediatric morbidity and mortality. The term accident is being replaced by the ‘injury’ since the former implies an event occurring by chance without any pattern. Common accidents in children are burns, falls, drowning, foreign body inhalation and road traffic accidents. Risk factors that increase the risk of injuries to children include toddler age group, male sex, poor socio-economic status and poor housing conditions. A definite trend is also seen in association with festivals e.g. burns and eye injuries are common during Diwali while falls from rooftops are seen during Kite-flying season. Burns are common in adolescent girls since they are expected to help in cooking. With rapid urbanization and increase in stress and academic pressure there has been an increase in self inflicted injuries and suicides. 33.3.1 Treatment of a Child with Injury If a child is brought with an injury, manage with the following steps: 1) Elicit complete history from the parents and attendants. 2) Examine and check vital signs for airway, breathing and circulation. Observe for any evidence of blood loss or internal hemorrhage. 3) Apply local pressure or pressure bandage for external bleeding. 4) Examine for external and internal injuries. 5) In case of suspected fracture immobilize the limb with a splint. In case of suspicion of spinal injury, immobilize with head in a neutral position and arrange for transfer of the patient to higher centre. 6) Consider what the most serious diagnosis could be and refer accordingly. 122 33.3.2 Prevention of Accidents Common Paediatric Emergencies  Educate parents regarding age related accidents and ways to avoid them. Burns can be prevented by discouraging use of easily inflammable synthetic fabrics for clothes, and if parents would not cook or take hot drinks while holding children.  Change in product designs e.g., toys which do not have removable parts which can be inhaled or have sharp edges.  Modification of environment to make it safe for children.  dummy plugs in sockets to prevent electric burns  cooking areas to be beyond the reach of small children  use of railings and side walls to prevent falls from roof tops and stairs  closing of open drains and tanks to prevent drowning. Check Your Progress 1 1) Name the antidotes of the following: (i) paracetamol ; (ii) Iron; and (iii)organophophorus compounds...... 2) Name the poisonings in which gastric lavage is contra-indicated? ...... 3) Enumerate the ways by which you can prevent accidents in toddlers......

33.4 ANAPHYLAXIS Anaphylaxis is a potentially fatal condition caused by immediate type I hypersensitivity reaction that occurs soon after an antigen exposure. It is IgE mediated and occurs in hypersensitive individuals on re-exposure to antigen. Anaphylaxis should be suspected Iin any person with acute onset illness with typical skin features (urticarial rash or erythema/flushing, and/or angioedema), PLUS involvement of respiratory and/or cardiovascular and/or persistent severe gastrointestinal symptoms Common important causes of anaphylactic reactions are administration of penicillins and related drugs, contrast media, blood products particularly animal serum preparations, and insect/snake bite, vaccines and sometimes even food products like eggs and nuts. Penicillin is the commonest drug to which hypersensitivity has been observed. This can be prevented by performing the sensitivity test for penicillin, prior to its administration. 123 ChildhoodMorbidity Clinical Features The first symptom is the sense of impending doom that the patient feels. This may be followed by fainting, palpitations, an itching rash, vomiting, and difficulty in breathing. On examination patient has tachycardia, and hypotension with warm skin. There may be an urticarial rash and stridor. Untreated, the patient may deteriorate and go into shock. Syncope due to the pain of injection needs to be differentiated from anaphylaxis. Syncope occurs immediately after injection and the child has cold skin with bradycardia in contrast to anaphylaxis which occurs usually within minutes to a few hours and is accompanied by tachycardia, skin rash and respiratory symptoms.. Besides it is transitory and patient gets better on laying down. Management 1) Adrenaline is the mainstay of therapy. It is given in dose of 0.01 ml/kg of 1:1000 solution (maximum of 0.3 ml) given I/M. Remove the offending agent if known . 2) Call Ambulance and Transfer the patient to a health facility . 3) Administer oxygen at high flow rate 4) In case the child is hypotensive, IV fluids should be pushed in the dose of 20 ml/kg of Ringer lactate solution. Inotropic support in form of vasopressors like dopamine (5-10 microgram/kg/min) may be required in case of hypotension. 5) Hydrocortisone 5-10 mg/kg IV stat dose should be given . This prevents the biphasic reaction often seen .. 6) Educate the patient and the family regarding avoidance of the antigen and regarding immediate treatment.

33.5 BITES AND STINGS 33.5.1 Snake Bite Snake bite is a preventable public health hazard in tropical and subtropical countries. Snake bite should be considered in any severe pain or swelling of a limb or in any unexplained illness presenting with bleeding or abnormal neurological signs. Some cobras spit venom into the eyes of victims causing pain and inflammation. Common venomous snakes species seen in India are: Cobra, Krait, Russel’s viper and Saw scaled viper. Clinical features You must distinguish signs and symptoms due to envenoming, from those due to fear and anxiety . Since most of the suspected bites are due to non- venomous snakes, injudicious use of anti-snake venom can be avoided by examining the snake if it has been killed or captured and proper clinical evaluation of the patients. General signs include shock, vomiting and headache. Examine bite for signs 124 such as local necrosis, bleeding or tender local lymph node enlargement. Specific signs depend on the venom and its effects. These include: Common Paediatric Emergencies — Shock — Local swelling that may gradually extend up the bitten limb — Bleeding: external bleeding from gums, wounds or sores; internal bleeding especially intracranial is seen with Viper bites — Signs of neurotoxicity: respiratory difficulty or paralysis, ptosis, bulbar palsy (difficulty swallowing and talking), limb weakness are observed with Cobra and Krait bites — check for signs of muscle breakdown: muscle pains and myoglobinuria Check haemoglobin and coagulation profile. Treatment i) First aid  Reassurance of the victim is essential, as most of them would certainly be terrified. It may also prevent neurogenic shock in an occasional patient due to extreme fear.  Splint the limb to reduce movement and absorption of venom. If the bite was likely to have come from a snake with a neurotoxic venom, apply a firm bandage to affected limb from fingers or toes to proximal of site of bite.  Clean the wound.  Transport to hospital which has antivenom as soon as possible. If snake has already been killed, take this with child to hospital.  Avoid cutting the wound or applying tourniquet. ii) Hospital care All patients with suspected snakebite, who are brought to the emergency, should be admitted. Rapid clinical assessment and immediate institution of appropriate treatment is the key to survival. If the snake can be diagnosed confidently as non-venomous, the patient can be discharged after observation and receiving a booster dose of tetanus toxoid. In case of suspected venomous snakebite, an IV line should be immediately secured. Treatment of shock/respiratory arrest  Treat shock, if present.  Paralysis of respiratory muscles can last for days and requires intubation and mechanical ventilation until respiratory function returns. Attention to careful securing of endotracheal tube is important. An alternative is to perform an elective tracheostomy. Antivenom Antivenom is indicated in cases if there are systemic signs ( Neurotoxic signs or clinical bleeding or coagulopathy or lab signs of myoglobinuria or acute kidney injury) or severe local signs (swelling of more than half of the limb or severe necrosis). . 125 ChildhoodMorbidity  Prepare epinephrine and chlorpheniramine and be ready if allergic reaction occurs (see below).  In India the antivenom available is a polyvalent preparation effective against the four common species found in India. The freeze dried powder is reconstituted with 10 ml saline. Follow the directions given on the antivenom preparation. The dose for children is the same as for adults.  Give intravenously infusion at rate of 20 ml/kg/hour initially and slowed later. Monitor closely for anaphylaxis or other serious adverse reactions.  If itching/urticarial rash, restlessness, fever, cough or difficult breathing develop, then stop antivenom and give epinephrine 0.01 ml/kg of 1/1000 IM . This should be followed by Injection chlorpheniramine 0.2 mg/ kg IV over a few minutes and injection hydrocortisone 2mg/kg IV . When the child is stable, re-start antivenom infusion slowly.  More antivenom should be given after 6 hours if there is recurrence of blood incoagulability, or after 1–2 hr if the patient is continuing to bleed briskly or has deteriorating neurotoxic or cardiovascular signs.  Blood transfusion should not be required if antivenom is given. Clotting function returns to normal only after clotting factors are produced by the liver. Response of abnormal neurological signs to antivenom is more variable and depends on type of venom.  If there is no response to antivenom infusion this should be repeated.  Anticholinesterases can reverse neurological signs in some species of snake. Other treatment Surgical opinion  Seek surgical opinion if there is severe swelling in a limb, it is pulseless or painful or there is local necrosis.  Surgical care will include: — Excision of dead tissue from wound — Incision of fascial membranes to relieve pressure in limb compartments, if necessary — Skin grafting, if extensive necrosis — Tracheostomy (or endotracheal intubation) if paralysis of muscles involved in swallowing occurs Supportive care  Give fluids orally or by NG tube according to daily requirements. Keep a close record of fluid intake and output.  Provide adequate pain relief  Elevate limb if swollen

126  Give antitetanus prophylaxis  Antibiotic treatment is not required unless there is tissue necrosis at Common Paediatric wound site Emergencies  Monitor very closely immediately after admission, then hourly for at least 24 hours as envenoming can develop rapidly. 33.5.2 Scorpion Sting Scorpion stings can be very painful for days. Systemic effects of venom are much more common in children than adults. Diagnosis of envenoming Signs of envenoming can develop within minutes and are due to autonomic nervous system activation. They include:  shock  high or low BP  fast and/or irregular pulse  nausea, vomiting, abdominal pain  breathing difficulty (due to heart failure) or respiratory failure  muscle twitches and spasms. Check for low BP or raised BP and treat if signs of heart failure. Treatment First aid  Transport to hospital as soon as possible. Hospital care Antivenom  If signs of severe envenoming give scorpion antivenom, if available (as above for snake antivenom infusion). Other treatment  Treat heart failure, if present.  Consider use of prazosin if there is pulmonary oedema. Supportive care  Give oral paracetamol or IM morphine according to severity. If very severe, infiltrate site with 1% lignocaine, without epinephrine. Check Your Progress 2 1) Name two important causes of anaphylaxis......

...... 127 ChildhoodMorbidity 2) Outline the treatment of anaphylactic shock...... 3) What steps will you take to prevent drug induced anaphylactic shock in your clinic? ......

33.6 LET US SUM UP In this unit you have learnt to identify, assess and decide appropriate management for some of the common pediatric emergencies, poisoning, and accidents. Poisoning: Immediate intervention to remove poisons and decrease its toxic effects can only be done if the diagnosis is suspected. Supportive measures to keep the airway patent and resuscitation of the sick child is very important. To prevent toxicity, the absorption of ingested poison is reduced by emesis, gastric lavage and administration of activated charcoal. Elimination is increased by forced diuresis and in some cases by dialysis. If the nature of poison is known, an antidote can be given. Accidents: Injuries represent another important cause of preventable pediatric morbidity and mortality. Common accidents in children are burns, falls, drowning, foreign body inhalation. Accidents can be prevented by making the environment safe for the child and anticipatory guidance of the parents. Anaphylaxis: It is an IgE mediated hypersensitivity reaction to an allergen to which the body has been exposed earlier. Many drugs, venoms, and food products are known to cause this serious reaction. Immediate administration of injection adrenaline given IM is life saving. IV fluids, oxygen, hydrocortisone and antihistaminic are other agents used for the treatment of anaphylaxis.

33.7 ANSWERS TO CHECK YOUR PROGRESS Check Your Progress 1 1) i) N-acetylcysteine ii) Desferrioxamine iii) atropine and pralidoxime. 2) Corrosive poisoning and kerosene oil poisoning. 3) i) Burns and scalds can be prevented by educating parents about dangers of cooking on floor ii) proper designing of products used by children e.g. toys 128 iii) making the environment safe by using dummy plug (to prevent Common Paediatric electrocution),railing on staircase (to prevent falls), keeping water Emergencies tanks and open drains covered (to prevent drowning). Check Your Progress 2 1) Injection penicllin, insect bite. 2) Make the patient lie down, give oxygen and injection adrenaline 0.01ml/ kg I/M . Admit the patient if event is out of hospital. If patient has hypotension, set up IV drip and give a bolus of Ringer lactate 20 ml/kg. Start dopamine if hypotension persists. Injection hydrocortisone 5-10 mg/ kg IV can be given. Educate patient about avoiding the offending agent. 3) Enquire about allergies and hypersenstivity to any drug from all patients. Always do a sensitivity test to injections which are known to cause hypersensitivity e.g. penicillin,vaccines, contrast media etc. Keep an emergency tray containing drugs (adrenaline, hydrocortisone, saline / ringer lactate). Patients should be observed for sometime after an injection or vaccination.

129 ChildhoodMorbidity UNIT 34 COMMON PEDIATRIC SURGICAL PROBLEMS Structure 34.0 Objectives 34.1 Introduction 34.2 Problems in Antenatal Period 34.3 New Born Period 34.3. Nervous System 34.3.2 G.I. System 34.3.3 Abdominal wall Defects 34.4 Infants and Toddlers 34.4.1 Head and Neck 34.4.2 G.I. System 34.4.3 Reproductive System

34.5 Paediatric Tumours

34.6 Let Us Sum Up

34.7 Answers to Check Your Progress

34.8 Further Readings

34.0 OBJECTIVES

After going through this unit, you will be able to:

 list congenital anomalies in different period of gestation and child hood

 discuss identification and management of congenital anomalies; and

 advise prevention of congenital anomalies where possible.

34.1 INTRODUCTION

Pediatric surgery forms an integral part in managing childhood diseases. There are a variety of conditions, especially congenital malformations, which may require services of a pediatric surgeon. There is a great lack of awareness about such diseases among the general population. This may due to inadequate exposure of medical and paramedical students, during their medical or nursing training programme. Special training is required for personnel to take care of these conditions. A few of the common pediatric surgical problems are discussed here. With advancements in antenatal imaging, the parents usually need consultation regarding the future course of malformations detected antenatally. 130 Common Paediatric 34.2 PROBLEMS IN ANTENATAL PERIOD Surgical Problems A significant number (60 %) of structural congenital anomalies can be detected by an ultrasound (US) scan for fetal anomalies between 14- 20 weeks gestation. The commonest involve the brain (hydrocephalus), the spinal cord (myelomeningocele), and the urinary tract (hydronephrosis and posterior urethral valves). Most of these can be treated after birth. The delivery of fetuses with complex anomalies such as esophageal atresia, congenital diaphragmatic hernia (CDH), bowel atresias, abdominal wall defects such as an omphalocele or gastroschisis, and major urinary tract anomalies should be planned at a center with tertiary- level care facilities for pediatric surgery. Fetal surgical intervention (, EXIT procedures) is indicated for selected anomalies. This is performed on the fetus while still in the mother’s to halt or lessen the harmful effects of the anomaly and improve the outcome during the post-natal period. It has been found beneficial in myelomeningocele, hydrocephalus, posterior urethral valves (PUV), large cystic hygromas, lung malformations, and sacrococcygeal teratoma. Check Your Progress 1 If the fetus is detected to have congenital malformation on antenatal US scan, where should the delivery be planned? 1. Primary Health Centre ...... 2. District hospital ...... 3. Nursing home ...... 4. Tertiary care public /private sector hospital with pediatric surgical services...... 131 ChildhoodMorbidity 34.3 NEW BORN PERIOD

General measures applicable to the management of all neonates during the perioperative period are to maintain:

1. Temperature (36.7 -37.3 degree Celsius; thermometer inserted in axilla for three minutes and read 10 seconds following removal)

2. Blood glucose (Hypoglycemia - if < 40 mg/dl)

3. Calcium (Hypocalcemia - Serum Calcium – Total <7 mg/dl or ionized - < 3.5 mg/dl)

4. Electrolytes)

5. Acid Base balance

6. Dealing with the space constraints due to small size, especially in preterms.

7. Daily hygiene and skin care.

The common congenital malformations and their management are described in the following section according to the system affected. 34.3.1 Nervous System

i) Neural Tube Defects (NTD)

These are the most common of all human birth defects, the incidence being 1 per 1000 live births. Maternal folic acid supplementation during the 1st trimester of pregnancy reduces the risk of occurrence by 50 to 70 %. The common NTD include myelomeningocoele and meningocoele.

a) Myelomeningocele (MMC): The commonest NTD is MMC which presents as a midline swelling in the back. This occurs due to arrest in the closure of the neural tube that forms the brain and spinal cord. The swelling contains cerebrospinal fluid (CSF), neural tissue and lipomatous tissue which has herniated through a dorsal defect in the vertebrae. The commonest site is the lumbosacral region. It needs immediate surgical attention if it has ruptured or is open (leaking). Otherwise, with gentle care to avoid trauma, it can be operated upon soon after birth, in the newborn period. It is usually associated with neurological deficit in the lower limbs, urinary bladder and bowel. There may be associated defects in the spinal cord (tethering, split cord or syrinx) and in the vertebrae (kyphoscoliosis). Approximately 80- 90 % of these cases have associated hydrocephalus. b) Meningocoele: In these cases, the herniation of meninges through a dorsal defect in the vertebrae is similar to that in MMC but the sac does not contain neural tissue and there are no associated neurologic deficits or hydrocephalus. Meningocoeles are most common in the lumbar, cervical, or thoracic region. Repair is usually straightforward with a good outcome. 132 Common Paediatric Surgical Problems

ii) Hydrocephalus The incidence is 0.9 to 1.8 per 1000 live births. The dilatation of the ventricles in the brain results in an abnormal enlargement of head. Hydrocephalus occurs due to faulty circulation of cerebrospinal fluid (CSF) – anatomical obstruction, under-absorption (damage to meninges following meningitis), and rarely overproduction (tumor of choroid plexus). It may be an isolated disease or associated with approximately 80- 90 % of MMC (either synchronous or metachronous - after MMC repair). The patient may present in the neonatal period or infancy with a progressively enlarging head size, bulging anterior fontanelle, “crackpot or Macewen’s sign (tympanitic resonant note on percussion of skull of such patients where sutures have separated due to raised ICP; only historical importance), bossing of frontal bones, ‘sunset’sign of eyes (6th nerve palsy), prominent scalp veins, translucent scalp (transillumination), generalized increase in tone of body and poor head holding. Medical management is by drugs to reduce CSF production. Acetazolamide (Diamox) is commonly used. Anatomical obstruction at level of cerebral aqueduct is corrected surgically by creating a bypass pathway. The commonest surgical procedures are placement of a ventriculoperitoneal shunt and endoscopic third ventriculostomy.

133 ChildhoodMorbidity PREVENTION: The incidence of occurrence of these neural tube defects can be reduced by more than half by Folic Acid supplementation as follows: all females planning pregnancy or no previous affected child – 0.5 mg / day; if previous affected child – 5 mg/day. Check Your Progress 2 Supplementation of which vitamin can prevent the occurrence of neural tube defects? 1. Vitamin B-12 ...... 2. Vitamin B-6 ...... 3. Folic Acid...... 4. Vitamin D ...... 34.3.2 G.I. System i) Esophageal atresia (EA) with/ without tracheo-esophageal fistula (TEF) Incidence: 1 in 3000 to 4500 births; M:F = 3:2. Etiology: Developmental malformation during separation of the esophagus and trachea. Classification:

Clinical Features: Antenatal – Polyhydramnios and absent stomach bubble. Postnatal –drooling of saliva, respiratory distress (choking, coughing and cyanosis) Diagnosis: Clinical - failure to pass infant feeding tube (IFT) [naso- gastric or oro-gastric] beyond 9 – 12 cms from the angle of the mouth (preterm – 7 Fr., term –10 or 12Fr). Radiological: X-Ray Neck + Chest + Abdomen: Tip of the IFT in the upper thorax and bowel gas in the abdomen (Distal TEF) or gasless abdomen (Pure EA). Associated Anomalies: VACTERL association (three or more of these anomalies) of defects – vertebral (25%), anorectal (16%), cardiac (60%), tracheoesophageal, renal (22%) and limb-radial ray hypoplasia (skeletal 6%). These need to be looked for during examination. It is present in one-third of patients. 134 Surgical management: Common Paediatric Surgical Problems Fistula present-Emergency right thoracotomy, disconnection of TEF and anastomosis between upper and lower esophagus over an IFT 5/ 6 Fr. as a transanastomotic stent and for feeding. No fistula(Pure EA) – Surgery in stages, First Stage –Emergency cervical esophagostomy and feeding gastrostomy, Second Stage – Esophageal lengthening or substitution. In the preoperative period, head- up nursing to prevent gastric acid aspiration through the TE Fistula is essential. Frequent or continuous low- pressure suctioning of the upper esophageal pouch using Replogle suction tube is necessary along with observation for respiratory distress which may require oxygen support or mechanical ventilation. Similarly, in the postoperative period, head- up nursing, frequent and gentle oral suctioning, minimal handling of nasogastric IFT, and avoidance of hyperextension of neck to prevent disruption of anastomosis are important modalities. Outcome (Survival rate): Spitz criteria –>1500 gms and no major cardiac anomaly-97%; <1500 gems or major cardiac anomaly- 59%; <1500 gms and major cardiac anomaly- 22%. Early post-operative complications include an anastomotic leak, anastomotic stricture, or a recurrent TEF. Late complications include gastroesophageal reflux (GER), tracheomalacia, and esophageal dysmotility. ii) Congenital diaphragmatic hernia (CDH) / Eventration of the diaphragm Incidence: 1 in 2000 to 5000 births. Left : Right = 80 : 20 Etiology: Arrest in the development of lung and separation of the thorax from the abdomen. CDH - Posterolateral defect in the diaphragm (Bochdalek’s hernia), Eventration – segmental or diffuse thinning of the diaphragm on the affected side.

135 ChildhoodMorbidity Clinical features: Antenatal – US showing polyhydramnios, fluid-filled loops and abdominal solid organs at the same cross-sectional level as the heart, a small stomach. Postnatal – Neonatal (80 - 90%) - respiratory distress at birth or later, scaphoid abdomen, asymmetric distended chest, shift of mediastinum and heart sounds to the contralateral side, persistent pulmonary hypertension (PPHN), Infancy and later – Chronic or recurrent respiratory illness and gastric volvulus (acute abdominal pain with severe retching and inability to pass NG tube) Associated anomalies: skeletal defects 32%, cardiac anomalies 24%, tracheobronchial anomalies 18%, NTD, syndromic associations. Diagnosis (including associated anomalies): X-Ray Chest (with a naso- or oro-gastric tube to locate stomach), Echocardiography and US of the chest, abdomen, and cranium. Management: Resuscitation including ventilation as per severity of respiratory distress (conventional, HFOV or ECMO), pharmacological treatment of PPHN, prognostication based on various indices like the oxygenation index, and surgery when a reasonable gas exchange can be achieved with resuscitation. Surgical management: Timing – mild respiratory distress requiring low ventilatory settings and/or stabilization of PPHN. Access – open, thoracoscopic or laparoscopic Steps: Reduction of contents from hemi- thorax into peritoneal cavity and repair of diaphragmatic defect (closure in CDH and plication in eventration). Outcome: CDH with no or mild respiratory distress – 80 to 93% survival, associated PPHN – around 34% survival. iii) Bowel atresia / stenosis Atresia represents complete luminal obstruction while stenosis is the term used for incomplete luminal obstruction. Incidence: Duodenal – 1 in 5,000 – 10,000 live births; Jejuno-ileal – 1 in 330- 1,500 live births; Colonic – rare,1 in 20,000 live births. Approximately half the babies are preterm in small bowel atresia as associated polyhydramnios may induce premature labour. Clinical features: Antenatal –1.Polyhydramnios (30 to 65%), especially in proximal bowel atresia, and absent in colonic atresia, 2.Double- bubble in duodenal atresia, 3.Dilated hyperperistaltic loops in jejunoileal and colonic atresia . Postnatal – Bilious vomiting (more than 30 ml of bilious naso-gastric tube aspirate/ day), upper abdominal distension (in duodenal and jejunal atresia), generalized abdominal distension (in ileal and colonic atrsia), visible peristalsis, non-passage of meconium, and jaundice.

136 Common Paediatric Surgical Problems

Classification (Types): I. Membrane II. Fibrous cord III. V-shaped defect – Further modification for jejunoileal atresia III A. Simple defect, III B. Apple- peel or Christmas tree deformity IV. Multiple atresias Associated anomalies: These are mostly seen with duodenal atresia (>50%). These include Down’s syndrome (30% cases of duodenal atresia), annular pancreas, congenital heart disease (CHD), malrotation (US showing altered relation of SMA & SMV in volvulus & whirlpool sign),EA with/ without TEF, genitourinary malformations, anorectal malformations (ARM), vertebral and musculoskeletal anomalies, and Hirschsprung’s disease (in colonic atresia) Radiographic findings: The babygram may show- 1. Paucity of bowel gas: double bubble – duodenal atresia, very few air- fluid levels– jejunal atresia. 2. Multiple air fluid levels: ileal or colonic atresia. 3. Calcification: this suggests associated meconium peritonitis with vascular injury to bowel and antenatal intestinal perforation. 4. Associated anomalies. Upper G.I. contrast study and US abdomen differentiate duodenal atresia from volvulus in midgut malrotation. Contrast enema- in jejunoileal or colonic atresia to look for – 1.microcolon, 2.site of obstruction, 3.cecum which may indicate associated anomaly of intestinal rotation. 137 ChildhoodMorbidity Treatment: Preoperative management 1. Correction of dehydration & dyselectrolytemia including hypoglycemia and hypocalcemia. 2. NG or OG tube- gastric decompression with a wide bore (8/ 10 Fr.) IFT. 3. Replacement of gastrointestinal losses with Ringer’s lactate. 4. Placement of peripherally inserted central (PIC) line anticipating delay in establishment of enteral nutrition postoperatively (due to ineffective peristalsis of dilated proximal bowel). 5. Intravenous antibiotics. Operative procedure – Exploratory laparotomy, confirmation of diagnosis, rule out associated anomalies (midgut malrotation and atresia in distal bowel) and establishing intestinal continuity as per the site of atresia: Duodenal – duodenoduodenostomy; Jejunoileal and colonic - resection anastomosis or enterostomy with staged reconstruction based on intraoperative assessment. Postoperative management- This includes naso-gastric (NG) aspiration; intravenous (I.V.) fluids; i.v.. antibiotics; parenteral nutrition (if delay in achievement of full enteral feeds especially in proximal bowel atresia or due to Short Bowel Syndrome [SBS] secondary to limited length of remaining bowel); and tailored enteral feeds in cases of lactose intolerance or SBS. Complications: Early - Anastomotic leak, delayed achievement of enteral nutrition, SBS; Late – Blind loop syndrome. Outcome: Isolated mid-ileal atresia and colonic atresia has better survival rates (>80%) iv)Anorectal Malformations (ARM) or Imperforate anus Present with absence of anal opening at normal site; however, a normal- looking anus may not be patent higher up (rectal atresia). A feeding tube should pass beyond 2 cms from anal verge to rule out ARM.

Incidence: 1 in 5000 live births; M:F=3:2 Clinical features: Antenatal – low sensitivity and specificity, Neonatal – Males: Absent anal opening with an anal dimple at the site of normal anus (High/ Intermediate ARM)

138 Or Thin membrane with meconium bulging through at the site of anus or a Common Paediatric meconium (covered anus) or a meconium filled tract along the midline Surgical Problems perineal raphe (Low ARM) + -Abdominal distension – rapidly progressive in absent fistula, variable in cases with fistula depending on its site and caliber. In males, the commonest ‘high’/ ‘intermediate’ anomalies are rectourethral fistula (bulbar or prostatic urethra) and rectovesical fistula and these boys may present with meconium in urine. Females: Most common is a narrow opening in the vestibule (Vestibular fistula) or anteriorly in the perineum (Perineal fistula). In both sexes, rectal atresia (1- 2 %), and ARM without fistula can occur (usually associated with Down’s syndrome) Classification: Wingsread (1984) – High, intermediate, and low i.e. above, through and below the levator ani muscle (pelvic diaphragm) respectively, based on the relation with terminal end of rectum. Another, later, (Peña 2005) is based on the anatomical defect and its correlation with the clinical management. Some girls (5- 20 %) with ARM have a condition known as ‘persistent cloaca’ in which the urethra, and rectum open into a chamber with a single perineal opening to the exterior. This condition is often associated with complex malformations of the genitourinary tract and severe sacral abnormalities. *Special Variants (common in Indian subcontinent); both are high type of malformation. 1. Congenital pouch colon (CPC)- common in northern India. 2. Rectal atresia- common in southern India. Associated anomalies: These must be ruled out at initial examination, as they can also be life-threatening. The most common group is the VACTERL association of defects. Lumbosacral anomalies are common (30- 40 %), including a hemisacrum. The most common intraspinal anomaly is tethered cord. EA with or without TEF can occur in around 10%, and duodenal atresia in 1-2%. GU anomalies occur in 33- 50 % cases and vesicouretric reflux is the most common followed by renal agenesis and dysplasia, undescended testis and hypospadias. Associated gynecologic (approx.30%) anomalies are also common in girls. Investigations: 1. Invertogram / Prone cross table lateral film to assess if ‘high’ or ‘low’ ARM: This is a special view done in newborn patient after 18 – 24 hrs of birth to allow bowel gas to reach the terminal rectum. 2. Babygram (AP & Lateral): Sacral ratio is calculated to assess sacral agenesis based on the bony pelvis to prognosticate about continence (Normal sacral ratio- AP = 0.74 and lateral = 0.77; if < 0.3 high chances of postoperative fecal incontinence). 139 ChildhoodMorbidity

3. Echocardiography – major cardiac anomaly especially cyanotic heart disease carries very poor prognosis. 4. USG KUB – severe anomaly can affect clinical course and may need to be tackled accordingly. 5. Pressure augmented distal cologram: Usually done before planning definitive surgery in male patients on colostomy, to delineate anatomy better and choose appropriate surgical procedure. Treatment:

LOW ARM HIGH ARM High Sigmoid Colostomy Low anomaly in males – Perineal Anoplasty. High Anomaly in Males – 1. Correction in 3 stages, first stage being high divided sigmoid colostomy during newborn period, the 2nd stage repair by posterior sagittal anorectoplasty (PSARP) at 6 weeks to 3 months of age, followed by colostomy closure. 2. Primary repair in selected cases during neonatal period without major associated anomaly, as they may be saved from morbidity of colostomy and multiple surgeries. * Majority of the female patients i.e. those without a persistent cloaca have an external fistula (vestibular fistula/ perineal fistula or anterior ectopic anus) and evacuate stools without much difficulty. There is a trend nowadays to observe such patients for first 3 months and then do the corrective surgery in a single stage to avoid any morbidity due to colostomy.

140 Common Paediatric Surgical Problems

In girls with ‘persistent cloaca’, separation of the urinary tract, vagina, and rectum from the cloaca to create separate openings in the perineum is required by the procedure of PSARVUP (posterior sagittal ano-recto-vagino- urethroplasty. Post-operative care: High divided colostomy: Gentle cover with oil soaked cloth (to prevent desiccation) and skin soothening (emollient) agents for surrounding skin to prevent excoriation. Following definitive surgery, daily anal dilatation is started 3 weeks after surgery with appropriate sized Hegar’s dilators and continued for 3 months to 1 year. Outcome: Mortality: – high in cases with associated severe malformations of other systems especially cardiac. Morbidity: -Fecal continence is the most important parameter of all: rectourethral fistula in males and majority of female ARM except cloaca: reasonable fecal continence can be achieved. Worst prognosis is with rectovesical in males and cloaca in females and they need an active bowel management programme for achieving socially acceptable continence. v) Hirschsprung’s Disease (HD) This disease, first described by Harald Hirschsprung, is characterized by absence of ganglion cells in the myenteric and submucosal plexuses of the distal intestine leading to functional obstruction till the level of aganglionosis.

141 ChildhoodMorbidity Incidence: 1: 5,000 live births. In about 75- 80 % cases, aganglionosis extends to the recto-sigmoid region while in the remaining, the proximal and even the entire colon and part of the small intestine may be affected.

Etiology: Failure of migration of neural crest cells from the neural crest to the distal intestine. Normally, these cells mature to form ganglion cells. HD is a heterogenous condition with multiple genetic causes and etiologic mechanisms, and is associated with a number of syndromes including Down’s syndrome.

Clinical features: 50- 90 % cases with HD present in the neonatal period with failure to pass meconium in the 1st 24 hours after birth in 90 %. Other features include abdominal distension, bilious vomiting, and feed intolerance suggestive of distal bowel obstruction. Older children present with chronic constipation, abdominal distension that may be marked, and dependence on enemas without significant encopresis. Approximately 10 % children may present with severe life- threatening Hirscsprung’s disease associated enterocolitis (HAEC).

Diagnosis:

1. Radiologic evaluation: Plain X-rays may show dilated loops suggestive of distal bowel obstruction. The characteristic findings on a water- soluble contrast enema are the collapsed bowel distally with a cone- shaped ‘transition zone’ leading to the dilated proximal bowel.

2. Anorectal manometry: The normal recto- anal inhibitory reflex (RAIR), defined as reflex relaxation of the internal anal sphincter in response to rectal distension is absent in HD.

3. Rectal biopsy: Absence of ganglion cells in the submucosal and myenteric plexuses with presence of hypertrophied nerve trunks is the gold standard and rectal biopsy should be taken at least 1.5 cm above the dentate line. Immunochemical identification of calcitonin (Calretnin staining) is useful as this is almost always absent in patients with HD.

Management: Preoperative resuscitation includes intravenous fluids, antibiotics effective against enteral organisms, and rectal stimulation or enemas for emergency decompression.

Surgical management: the goal is to remove aganglionic bowel and bring the normally innervated proximal intestine to the anus while preserving sphincter function. The most commonly performed procedures are the Swenson, Duhamel, and the Soave procedure, of which the Duhamel retrorectal pull- through is currently the most popular. A preliminary colostomy is often performed, sited in normal proximal colon and is a must in very sick children and those with HAEC. In recent years, single- stage pull- through aided by frozen section biopsy, to assess the extent of proximal resection, has become increasingly popular. In patients with long segment HD (LSHD), in order to increase the available absorptive surface of the bowel, use of a left- or right- colon patch and J- pouch construction along with the pull- through have been described. 142 Results: The long-term results of the 3 main pull- through procedures are Common Paediatric good. Long-term problems described include ongoing obstructive symptoms, Surgical Problems soiling, and enterocolitis. These need individualized assessment and management.

34.3.3 Abdominal Wall Defects i) Omphalocoele and Gastroschisis

These come under the category of abdominal wall defects. Omphalocele is described as a defect in the umbilicus with the contents covered with amniotic membrane, variable in size from small to large. It has a strong association with other congenital anomalies especially cardiac anomalies, and syndromes, the most common being Beckwith-Weidemann syndrome.

ii) Gastroschisis is a defect on the right side of umbilicus with no membrane covering, although there may be thick peel over the viscera as a result of irritation from exposure. These babies require prompt attention to temperature regulation and fluid resuscitation during the preoperative period. Treatment is tailored to the size of the defect. Small defects can be closed primarily. Large defects require staged reconstruction by placing the contents in a prosthetic bag (SILO) held vertically for reduction with help of gravity which reduces edema and creates space in the peritoneal cavity. The primary aim is to achieve skin closure; fascial defects are repaired later on the lines of an incisional hernia repair. 143 ChildhoodMorbidity Check Your Progress 3 1. Which type of Esophageal Atresia is most common? ...... 2. Congenital Diaphragmatic Hernia is common on which side? ...... 3. Down’s syndrome is strongly associated with which type of small bowel atresia? ......

4. Name the most popular surgical procedure for Hirschsprung’s Disease?

...... 5. What are the components of VACTERL association in patients with Esophageal Atresia and Anorectal Malformations? ......

34.4 INFANTS AND TODDLERS 34.4.1 Head and Neck i) Dermoid cysts– Slow growing benign cysts resulting from sequestration of ectodermal cells at the junction of sutures or at other sites of embryonic fusion most commonly in the midline of the body. They contain dirty white pultaceous toothpaste- like material composed of sebum, sweat and desquamated epithelial cells. The most common sites are in the head and are: 1. Vertex of scalp over the anterior fontanelle. 2. External angular dermoid. Either of the two may have an intracranial extension. Hence, a CT scan of head is necessary to rule this out. 144 Dermoid cysts usually present as a painless, slowly growing swelling or, rarely, Common Paediatric as an acutely inflamed swelling due to infection which may be recurrent if not Surgical Problems diagnosed correctly during the first episode. The treatment is excision; neurosurgical assistance may be required in cases with intracranial extension. An important postoperative complication is recurrence; the incidence of recurrence is however very low if there has been no infective episode. ii) Branchial cysts and sinuses- Six branchial arches contribute to the development of the jaw and neck. As the embryo develops, the 2nd branchial arch overgrows to fuse with the 6th arch, and the resulting potential space (cervical sinus of His) drains the 2nd, 3rd, and 4th branchial clefts. Complete fusion without obliteration of this space results in a branchial cyst and incomplete fusion with a persistent external opening forms the embryologic explanation for branchial sinus.

Branchial Sinus Tracts Branchial Cyst More than 90% of branchial cleft anomalies arise from the 2nd branchial cleft. Branchial sinus typically presents as very small pit with intermittent mucoid discharge while a branchial cyst presents as a soft tissue mass below the upper third of sternocleidomastoid. Both can also present as an inflammatory swelling secondary to infection. Treatment for both conditions is excision, taking care to prevent damage to important structures – carotid artery and its bifurcation, glossopharyngeal and hypoglossal nerves. Recurrence can happen when the excision is not complete, mostly in cases with past history of secondary infection. iii) Thyroglossal cyst and sinus- This is an anomaly related to the development of the thyroid gland. A diverticulum appears in the developing tongue at the junction of its anterior two-thirds and posterior one-third in the midline. This descends into the lower neck anterior to the hyoid bone, where it develops into the thyroid gland. The tract formed during the descent is called the thyroglossal duct. Most of its superior portion disappears with only terminal end persisting as the pyramidal lobe of the thyroid gland. If this persists, it may present as a swelling in the neck i.e. a thyroglossal cyst. This cyst may communicate exteriorly following spontaneous rupture or incision & 145 ChildhoodMorbidity drainage (I&D) following pyogenic infection. Recurrent discharge will occur through this communication forming a thyroglossal fistula. So, the clinical presentation can be of an asymptomatic cyst or recurrent inflammation and discharge through the thyroglossal fistula. The treatment is surgical excision of the tract (Sistrunk’s operation) along with a central part of the hyoid bone and a core of tissue between the hyoid bone and the tongue which usually contain multiple remnant branching tracts. These may be the cause for recurrence if not excised. Post-operative recurrences can occur especially in patients with previous incisional drainage for suppurative inflammation.

34.4.2 G.I. System i) Inguinal hernia and hydrocele Incidence: 0.8 to 4.4%, which is a high incidence. Etiology: During testicular descent, an invagination of peritoneum called the processus vaginalis (PV) follows the testis into the scrotum through the deep inguinal ring. Once the descent is complete, the segment of PV between the deep inguinal ring and the scrotum disappears. If remains patent as a PV sac, it acts as a path for the abdominal contents to herniate. In females, the canal of Nuck corresponds to the PV. The type of content depends on the caliber of patent PV; if narrow, only peritoneal fluid gradually enters causing a hydrocele. However, if the PV is wide in caliber, bowel or other abdominal organs like omentum, ovary, appendix etc. can herniated, resulting in an inguinal hernia. Clinical Presentation: Inguinal hernia – It appears as a bulge in the groin while straining i.e. crying, coughing, sneezing, blowing, defecation or any other manoeuvre which increases abdominal pressure. This bulge disappears either spontaneously or with gentle manipulation to push it back. Typical clinical signs are thickening of cord structures, ‘silk glove’ sign, cough/cry impulse, reduction with gentle manipulation and absence of transillumination. 146 Inguinal Hydrocele- As the caliber of communication is small, it appears Common Paediatric slowly over a period of time especially during erect posture like prolonged Surgical Problems standing or playing. It typically disappears slowly in lying down position. Typical signs are positive ‘silk glove’ sign, no cry/cough impulse, very slow (may be incomplete) or no reduction with manipulation, brilliant transillumination. Another peculiar variant is the swelling higher up and separate from testis i.e. encysted hydrocele of the cord in males and hydrocele of canal of Nuck in females.

Possible complications if not treated: In inguinal hernia: Incarceration – irreducibility with no signs of obstruction, Obstruction – lumen of herniating bowel compressed resulting in colicky pain and vomiting, Strangulation– ischemia of herniating contents, may be associated with frank signs of inflammation. Testicular loss: The resulting edema may cause ischemia by compressing on the testicular vessels. Therefore, it should be treated as early as possible and becomes an emergency if above mentioned complications occur. As regards hydroceles, they may disappear during the 1st year of life and there is no risk of incarceration or strangulation. Hence, it is prudent to wait till 1 year of age, beyond which it should be treated as fluid may interfere with the temperature regulation of testis and thereby development of sperms. Treatment: For both hernia & hydrocele, herniotomy is the treatment of choice in which the patent PV is closed at the internal inguinal ring through an inguinal incision. It is a day care procedure. Post-operatively, there may be residual swelling secondary to inflammation due to surgical handling of tissues. This reduces gradually over 6 weeks to 3 months. ii) Intussusception This condition results from invagination of a part (intussusceptum) of intestine along with its mesentery into another (intussuscipiens) as described by Swenson. Intussusception is the second most common cause of acute abdomen in infants and toddlers and it is important for concerned healthcare personnel to be aware of this condition. 147 ChildhoodMorbidity Incidence: It occurs in 1 in 2000 infants and children; M: F ratio being 2:1 to 3:2. The commonest age group affected is the weaning period i.e. 6 months to two years. Types: It can be classified based on the part of bowel involved – ileo-colic is the most common (85%); ileoileocolic (10%); appendicocolic; caecocolic or colocolic (2.5%); and jejunoileal or ileoileal (2.5%). It is usually a fixed and progressive phenomenon but can occasionally be transient. Recurrence, although known, is uncommon.

Etiology: It usually occurs due to a lead point which obstructs the lumen of bowel partially and is pushed, along with its mesentery,into the distal lumen with peristalsis. This lead point has been classified into idiopathic and pathologic. The most common etiology is idiopathic, which is due to hypertrophied Peyer’s patches (80%) in the terminal ileum causing partial obstruction of the lumen. This explains the most common age- group affected i.e. 6 months to 2 years. This is the period of weaning when the baby is exposed to different kind of food items besides breast milk, thus stimulating the lymphoid units in the Peyer’s patches. A pathologic lead point is more common beyond 5 years age group (60%). Meckel’s diverticuclum is the most common, followed by polyps, duplication cysts, appendicitis, and benign or malignant tumors. 148 Pathologic anatomy: The lumen of the invaginated bowel is obstructed causing Common Paediatric abdominal colic and reverse peristalsis results in vomiting. Intussusceptum Surgical Problems develops venous congestion resulting in edema and transudation of blood into the lumen of distal bowel. Mixing of this blood with mucus of bowel lumen give the typical appearance of ‘red currant jelly’ stools. Clinical features: A classic triad has been described –1. incessant, inconsolable intermittent crying (abdominal colic secondary to luminal obstruction), 2. several episodes of vomiting and 3. ‘red currant jelly’ stools. On examination, the patient will be usually a chubby baby with a vacant stare if quiet or very irritable due to colic; there will be an abdominal lump palpable around the umbilicus (sausage shaped) and the right iliac fossa will feel empty. Occasionally, intussusceptum can be seen prolapsing out of the rectum when it can be mistaken for a rectal prolapse. Diagnosis: US abdomen can diagnose 100% cases. “Claw sign” on plain X- ray abdomen with air as contrast or on a water- soluble contrast enema is very suggestive. Treatment: 1. Air- enema (pneumatic) reduction: This procedure can also be used for diagnosis if US is unavailable. Under fluoroscopic guidance, the colon is inflated with air which acts as a contrast medium. After demonstrating the “claw sign”, it is followed by gradually increasing the pressure maximum up to 120 mmHg. This sign gradually moves in retrograde manner till the Ileocecal junction. Complete reduction is seen as sudden delineation of small bowel loops by the air under pressure and the patient also relaxes. 2. US- guided saline enema reduction: The intussusception is followed with ultrasound probe instead of fluoroscopy and the contrast is saline under pressure by gravity. The advantage is no radiation exposure. 3. Surgery: Laparotomy/ laparoscopy and manual reduction or resection- anastomosis if irreducible. iii) Umbilical hernia An umbilical hernia in children is surrounded by the dense fascia of the umbilical ring through which a peritoneal sac attached to the overlying skin protrudes. As the ring continues to close and the surrounding fascia gets stronger, spontaneous resolution of the defect occurs in most children. Almost all umbilical hernias close by 3 years age. Hernias with a ring diameter < 1 cm tend to close sooner. These hernias are more common in children with Trisomy 13, 18, or 21 as well as other inherited conditions. In a few cases, incarceration of bowel or omentum or perforation may occur. Due to the high incidence of spontaneous resolution, repair should be postponed till later in childhood. Large defects (> 1.5 cm diameter) that persist beyond the age of 5 years should be repaired. Repair is performed via a curved transverse supra- or infra- umbilical incision that will be hidden by the umbilical skin crease. iv)Umbilical discharge This is a common condition and often needs evaluation to rule out significant underlying causes. An important cause is umbilical granuloma, which is a 149 ChildhoodMorbidity 1mm to 1cm mass of granulation, often pedunculated. It usually resolves with topical silver nitrate stick application which promotes epithelialization by gently cauterizing the granulation tissue. If there is no response, electrocautery of the granuloma or its excision may be performed. Omphalitis in the newborn was earlier a serious disease due to faulty cord hygiene. Bacterial infection by Staphylococcus aureus or Streptococcus pyogenes can lead to sepsis, necrotizing fasciitis and have serious consequences. Other causes of umbilical discharge include contact dermatitis, and the presence of vitello- intestinal or urachal remnants. 34.4.3 Reproductive System i) Phimosis In phimosis, the opening of the foreskin of the penis (preputial orifice) is too narrow for easy retraction over the glans. It may be a pin- point hole. This results in ballooning of the prepuce while voiding urine. This is considered physiological for 3 to 5 years of life if there are no other associated symptoms. During this period, the prepuce gradually separates from glans due to desquamation. Forceful retraction is not recommended as tearing will lead to secondary phimosis due to scarring. Treatment may be needed if retraction of foreskin is not possible by 4 years of age or if the child develops episodes of posthitis or balanoposthitis earlier. A course of topical steroid ointment application for 1 to 2 months may help in complete retraction of prepuce, otherwise circumcision is recommeded. ii) Hypospadias This is a congenital anomaly in which there is an abnormal location of the urinary meatus on the underside of penis at a variable distance from its normal location at the tip of the penis. The other features are – hooded prepuce, ventral chordee (abnormal ventral curvature of penis). It may also be associated with other structural anomalies of external genitalia like penoscrotal transposition and undescended testis. Besides genetic factors, environmental factors labelled as “endocrine disruptors” in the form of insecticides, pharmaceuticals and plant estrogens may cause impairment in the development of external genitalia. The treatment involves surgical reconstruction (urethroplasty) either in single stage or two stage as per the severity of hypospadias and discretion/ expertise of the surgeon.

150 iii) Undescended testes Common Paediatric Surgical Problems Incidence: Infants – 4.3%, 1 year – 0.96%. Etiology: Testicular development starts in the abdomen near the kidneys. It has two phases – transabdominal and transinguinal. Arrest in this path results in incomplete descent. The PV sac also remains patent predisposing to the clinical manifestation of an associated inguinal hernia. Clinical features: Clinically, the affected side hemiscrotum is empty. The testis is palpable if it is present beyond the external ring (high scrotal or superficial inguinal pouch). If it is located higher up (inguinal canal or intraabdominal) it is not palpable. Occasionally, the testis may be absent (perinatal torsion or agenesis).

Problems if not treated: The normal descended testis functions at a temperature approximately 4 degree Celsius lower than in the abdomen. Hence, the physiology will not be normal in an undescended testis affecting its endocrine function and sperm development. There is always a possibility of inguinal hernia with its own risks. Torsion of such testis can occur as it is not fixed. Straps of clothes at the level of waist can cause trauma to the palpable variety of testis. Fertility is significantly impaired in bilateral cases. The risk of malignant transformation is 5-10 fold during the third decade of life (20 to 40 years). Above all, an inferiority complex resulting from a feeling of deficiency due to absent testis and an empty hemiscrotum causes significant psychological trauma. Management: The recommended age for surgery is 6 months. A palpable undescended testis is managed by an inguinal orchidopexy in which the testis is mobilized and after ligation of the hernial sac, brought to the scrotum. High or intra- abdominal testes will require laparoscopic mobilization and orchidopexy. Sometimes, for very high testes, laparoscopic ligation of the testicular vessels, preserving the collateral blood supply to the testis, to gain mobilization for bringing the testis to the scrotum in 1 or 2 stages may be necessary (Fowler- Stephen’s procedure). iv) Labial Adhesions/ Synechiae Labial adhesions or fusion of the labia minora is a common condition believed to occur as a result of chronic inflammation related to vulvo-vaginitis or chronic dampness. They may produce obstructive symptoms or present as postvoid drip incontinence and urinary tract infection. It may be misdiagnosed 151 ChildhoodMorbidity as a disorder of sexual differentiation. This can be quite distressing for the parents. Treatment is not warranted in the absence of symptoms as they resolve at puberty with the physiologic estrogen surge. If treatment is warranted, topical estrogen cream (0.01 %) or betamethasone cream (0.05 %) is usually effective. Persistent or well- developed adhesions may need lysis using an applicator tipped with local anesthetic cream. An antibiotic ointment applied locally for a few weeks is necessary to prevent re-adhesion. Check Your Progress 4 1. Which is the most common branchial cleft involved in branchial cyst / sinus anomalies? ...... 2. What complications can result if an inguinal hernia is not treated surgically? ...... 3. What is the recommended age for surgical treatment of Undescended Testis? ...... 4. Which type of intussusception is most common? ...... 5. What are the non-operative treatment options for intussusception? ......

34.5 PAEDIATRIC TUMOURS The most common pediatric malignancies in order of frequency are – leukemia, brain and spinal cord tumors, neuroblastoma, Wilms’ tumor, lymphoma, rhabdomyosarcoma, retinoblastoma and bone malignancies i.e. osteosarcoma and Ewing’s sarcoma. Apart from leukemia and lymphoma, the other tumors come under the category of solid tumors and comprise 152 approximately 30% of all pediatric malignancies. i) Neuroblastoma: It is the second most common pediatric solid tumor after Common Paediatric brain tumors and is the most common pediatric intrabdominal tumor. The Surgical Problems tumor arises from neural crest cells and therefore manifests in the adrenal medulla and sympathetic ganglion chain from the neck to the pelvis. This is the only pediatric tumor where outcome remains dismal despite advances in treatment. The anatomical sites involved in order of frequency are – adrenal (50%), paraspinal ganglia (25%), mediastinum (20%), pelvis (5%) and neck (5%). Median age of presentation is 18 months. Clinical features: Generalised: weight loss, failure to thrive, fever, anemia, abdominal pain. According to site: 1. Abdominal Mass (50 to 75%) which may be hard, nodular, and painful, 2. Paraspinal ganglia: paraplegia and neuralgia, 3. Mediastinum: respiratory distress and dysphagia, 4.Pelvis – bladder & bowel dysfunction, 5. Neck and upper mediastinum: Horner’s syndrome. Metastases: Lymphadenopathy, orbit (“panda eyes” or “racoon eyes”), bone cortex especially scalp, vertebral column, ribs, sternum, pelvis and metaphysis of long bones (bone pain and pathological fractures), bone marrow (anemia, pancytopenia & bleeding diathesis), liver (hepatomegaly) and skin (blue-berry muffin nodules) Metabolic by products: Hypertension in 25% of cases, flushing sweating, irritability, diarrhea (vasoactive intestinal polypeptide). Some patients may also have ‘dancing eye syndrome’ or opsomyoclonus (involuntary muscular contractions) and nystagmus (random eye movements) due to acute cerebellar ataxia. Its cause is unknown. Diagnostic Investigations: 1.Tumor markers in serum and urine (catecholamine by-products) –VMA i.e.vanillylmandelic acid (most common), adrenaline, noradrenaline, dopamine, metanephrine, homovanillic acid (HVA) and vanillylglycolic acid. 2. X-Ray of soft tissue mass (chest/abdomen): stippled calcification. 3. CECT of the involved region: findings typical to neuroblastoma – stippled calcification and encasement of vessels. 4. Bone marrow aspirate: ‘Rosettes’ of tumor cells and immunologic analysis. 5. Tumor biopsy (Trucut or open). 7. Radioisotope scans: Metaiodobenzylguanidine (MIBG) is a specific isotope. Staging: This is as per the International Neuroblastoma Staging System. Prognostic markers: 1. International Neuroblastoma Pathology Classification 2. Biologic & genetic alterations: N-myc is a specific oncogene associated with poor prognosis and on DNA flow cytometry, diploid tumors have worse prognosis than aneuploid tumors. Treatment: This involves a combination of chemotherapy, surgical excision, radiation and immunotherapy. Risk stratification forms the basis for selection of various treatment modalities. It helps in minimizing the adverse effects and optimizing the desired effect. Chemotherapy drugs used are – cisplatin, doxorubicin (Adriamycin), cyclophosphamide and etoposide (VP-16). 153 ChildhoodMorbidity Treatment strategy as per risk groups is: Low risk - surgery alone; intermediate risk - surgery and chemotherapy; and high risk – more intensive including radiation, and myeloablative chemotherapy with bone marrow rescue. Outcome: 5-year survival rates are as follows: Low risk >95%; Intermediate risk- 90-95%; and high risk- 40-50% in the best of centers. ii) Wilms’ Tumor Also known as nephroblastoma, it is next to neuroblastoma in prevalence of pediatric solid tumors. The median age of presentation is 38 months i.e. 3 years. Bilateral tumor accounts for 5- 10 % of all cases. The prognosis for this tumor is much better than neuroblastoma. Overall 2-year relapse free survival is >91%. The following syndromes have an increased risk for the occurrence of this tumor: Beckwith-Weidemann syndrome, hemihypertrophy, WAGR syndrome (Wilms’tumor, aniridia, genitourinary malformation, and mental retardation,) and Denys-Drash syndrome. Genetic mapping for alterations in loci in Wilms’ tumor has proven association with 11p13 (WT1), 11p15 (WT2) and 16q. Clinical presentation: An otherwise asymptomatic abdominal lump may be noticed by the mother while bathing or massaging the child. Examination may reveal other features of syndromic association. Patient also may also have hypertension secondary to renin production by tumor or compression on renal vasculature. Microscopic hematuria is seen in 1/3 of cases. Diagnosis: Initial US abdomen followed by CECT abdomen and exclusion of neuroblastoma which is a close differential diagnosis. A CECT chest to rule out lung metastasis. Histopathological diagnosis varies with the various management protocols. Treatment: The management protocol varies in different parts of the world: 1. SIOP (SocieteInternationaledÓncologiePediatrique): No histopathologic confirmation is needed. Upfront chemotherapy followed by radical nephrectomy. The philosophy is to allow minimal tumor spillage during during surgery, thus reducing the need for post-operative local radiation therapy. 2. NWTS (National Wims’tumor study) group: This is followed in the United States. Upfront surgery i.e. radical nephrectomy followed by adjunctive therapy (chemotherapy and radiotherapy) as per protocol. The philosophy is to confirm the diagnosis and accurate staging, thus, decreasing the chance of misdiagnosis (5%) as see with the SIOP protocol. Partial nephrectomy is an option in bilateral or solitary kidney Wilms’ tumor. Outcome: Overall 2-year relapse free survival is >90%. This is among the highest in pediatric cancers although data is emerging regarding long term morbidity in survivors due to chemotherapy & radiotherapy iii) Germ Cell Tumors (GCTs): These account for 1% of pediatric cancers under 15 years age. They occur in both gonadal and extragonadal sites. Extragonadal and testicular tumors predominantly affect children less than 3 years old whereas gonadal tumors predominate during and after puberty. 154 Etiology: GCTs arise from abnormally located nests of germs cells due to Common Paediatric perturbed migratory process along the hindgut to reach testis or ovary. Surgical Problems Site: sacrococcygeal region, mediastinum, retroperitoneum, pineal area of brain, testis and ovary. Histologic types: These are 7 in number - Dysgerminoma (or seminoma), yolk sac tumor (endodermal sinus tumor), embryonal carcinoma, polyembryoma, choriocarcinoma, teratoma, and mixed GCTs. iv) Sacrococcygeal teratoma is the most common extragonadal GCT of the fetus and newborn. Its incidence is 1:20,000 to 1:40,000 live births and has female predominance (2:1 to 4:1).It can be detected on antenatal US and a large tumor can cause intrauterine death of the fetus. 90% present as visible mass in the neonate; occasionally pelvic mass with no external component may present later (4 months to 4 years age) as constipation, anal stenosis, bladder outlet obstruction and a palpable presacral mass on rectal digital examination. This is why a rectal examination must be done during routine examination of any child with constipation. Alfa-feto protein (AFP) and beta human chorionic gonadotropin (beta HCG) are two specific tumor markers. They are elevated especially in malignant tumors and are monitored during post-treatment follow-up to detect recurrence. CECT helps in staging and differentiating from other pelvic masses. Treatment is by complete surgical excision including the coccyx with restoration of perineal and gluteal appearance. It should be done as early as possible. The chances of malignancy rise by 5 to 10 fold by 6 months of age. Chemotherapy is indicated in malignant tumors on histopathology. PEB (cisplatin, etoposide, and bleomycin) regimen is commonly used. A close follow-up is required to detect recurrence. v) Gonadal teratoma: Ovarian teratomas are the most common (50%) pediatric ovarian tumor and account for 25% of childhood teratomas. It occurs between 5- 16 years of age. Testicular teratoma is the most common neoplasm in childhood with bimodal age distribution (<2 years and teenage). Outcome: Overall survival in GCT approaches 90% even in presence of metastasis, as they are highly responsive to chemotherapy. Check Your Progress 5 1. Which are the precursor cells responsible for neuroblastoma? ...... 2. Nephroblastoma is synonym for which tumor? ...... 3. Which is the most common germ cell tumor during newborn period? 155 ChildhoodMorbidity ......

34.6 LET US SUM UP Considering the demographics of India, pediatric surgical conditions, including congenital malformations, form a large share of the disease load presenting at all levels of healthcare in the country. Awareness of common pediatric surgical conditions is necessary for all healthcare professionals. With increasing level of antenatal care, many malformations are detected by antenatal US and it is essential that these babies must be delivered at a center with pediatric surgery facilities. The preliminary management of babies with the commonly encountered severe congenital malformations like NTDs, esophageal atresia, congenital diaphragmatic hernia, ARM, Hirschsprung’s disease has been described so that optimal care may be administered before transport to the tertiary-care facility. The role of antenatal administration of folic acid to women in the reproductive age-group is emphasized. The presentation and management of other serious conditions in infancy and the toddler age group like intusussception are discussed. Very common but relatively benign conditions like umbilical anomalies, inguinal hernias, undescended testes do not need emergency treatment but should be referred to tertiary- care facilities for assessment and surgical management. Early diagnosis of relatively common pediatric solid tumors like neuroblastoma and Wilm’s tumor is important and this has been discussed in the relevant section.

34.7 ANSWER TO CHECK YOUR PROGRESS Check Your Progress 1 Option 4. Tertiary care public /private sector hospital with pediatric surgical services. Check Your Progress 2 Option 3. Folic acid. Check Your Progress 3 1. Esophageal atresia with distal Tracheoesophageal fistula. 2. Left side. 3. Duodenal atresia. 4. Duhamel retrorectal pull through. 5. Vertebral, Anorectal, Cardiac, Tracheoesophageal, Renal, Limb dysgenesis Check Your Progress 4

156 1. Second branchial cleft. Common Paediatric Surgical Problems 2. Incarceration, obstruction, strangulation, and testicular loss. 3. 6 months 4. Ileo-colic intusussception 5. Air-enema (pneumatic) or US guided saline-enema reduction.3. Check Your Progress 5 1. Neural crest cells. 2. Wilm’s tumor. 3. Sacrococcygeal teratoma.

34.8 FURTHER READINGS

1. Coran AG, Adzick NS, Krummel TM, Laberge J-M, Shamberger RC, Caldamone AA (eds). Pediatric Surgery,7th edition, Elsevier Saunders, Philadelphia PA, 2012. 2. Puri P, Hollwarth M (eds). Pediatric Surgery: Diagnosis and Management. Springer- Verlag, Berlin Heidelberg, 2009. 3. Taguchi T, Iwanaka T, Okamatsu T (eds). Operative General Surgery in Neonates and Infants. Springer, Japan, 2016. 4. Holschneider AM, Hutson JM (eds) Anorectal Malformations in Children. Year Book Medical Publishers, Chicago, 2006.

157