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Page No. Page No. Editorial Special Article : Juvenile Idiopathic Arthritis a) SERVQUAL: A Service Quality Model — Dr. Santa Subhra Chatterjee 5 to Measure Performance of Eye Hospitals for VISION 2020 Original Article: — Dr. Bhaskar Mukherjee, a) Juvenile Idiopathic Arthritis - A Dr. Malini Majumdar 35 Clinic Based Study — Dr. S. Guha, Case Report: Dr. S. R. Pal, a) Epidermolysis Bullosa Pruriginosa: Dr. Indranil Das 8 Successfully Treated with Topical b) An Observational Study on Evaluation And Tacrolimus Management of Type 1 Diabetic Patients — Dr. Heena Parmar, Attending a Diabetes Clinic in West Bengal Dr. Leelavathy Thiyagarajan, — Dr. Debasish Maji, Dr. Jayanta Kr Das, Dr. Ram Udayan Roy 13 Dr. Asok Gangopadhyay 40 c) Short Stature: The Only b) Your Suspision May Save A Life Morphological Stigmata for — Dr. Pradeep Chakraborty, IsochromosomeXq Dr. Sujata Mazumder, — Dr. Shanoli Ghosh, Dr. Dilip Kumar Bera 44 Dr. Pritha Pal, c) A Case of Diuretic Induced Dr. Atreyee Dutta, Hyponatremia Dr. Sanchita Roy, — Dr. Ankit Roy, Dr. Ajanta Halder 18 Dr. Soumen Bhat, Review Article : Dr. Debdatta Kar, a) Primary Immuno-Deficiency Disorder Dr. P. Mukherjee, — Dr. Tapabrata Chatterjee, Dr. Dinabandhu Naga, Dr. Ajanta Haldar, Dr. S. Roychowdhury, Dr. Suparna Guha 23 Dr. P. Banerjee, b) Modified Septoplasty Dr. Jayanta Chakraborty 49 — Dr. B. K. Roychaudhuri, Pictorial CME : Dr. Amitabha Roychoudhury, Dr. S. Ghosh 27 a) Hirsutism c) Prescriptions for the Mind...... — Dr. Debdatta Kar, Neither Mindlessness Nor Brainlessness, Dr. Jayanta Chakraborty 51 Brain-Mindfulness Paradigm — Dr. Uday Chaudhuri, Dr. Ishan Chaudhuri 31 JOURNAL OF THE VIVEKANANDA INSTITUTE OF MEDICAL SCIENCES Instructions to Authors

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Printed by : Print Excel 4 Editorial Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is the most manifesting with villous hypertrophy of common rheumatic disease in children. synovium and hyperplasia of the synovial lining Many children with JIA have active disease that layer. Pannus formation may result and articular can persist into adulthood and may result in short cartilage and bone gets eroded. or long term morbidity. Oligoarthritis JIA JIA is an arthritis of unknown aetiology that In this type, girls are more commonly affected begins before the sixteenth birthday and persists and usually occurs under the age of 6 years. It for atleast 6 weeks other conditions being involves mainly knees, ankles and joints will excluded. The incidence of JIA is 2 to 20 per be swollen but pain may not be severe. 100,000 and the prevalence 16 to 150 per A limp may be the only sign of the disease. 100,000.[1] The minimal incidence of the disease ANA positivity can occur in this type with the was 9.2 per 100,000 children at risk in a report risk of developing asymptomatic chronic anterior [2] [3] from Michigan ; in Finland, 18.2 per 100,000 ; uveitis (inflammation of iris and ciliary body).[9] and in Sweden 11 per 100,000.[4] The prevalence Polyarthritis JIA in Michigan was 65 per 100,000 and 86 per 100,000 in Swedish study. In India constituted Rheumatoid factor positive type usually affects 41% among patients reported from a single girls in late childhood. Because of the tertiary referral centre.[5] JIA can be oligoarticular development of severe arthritis with bony erosion (60%), systemic onset (10%), polyarticular (30%) and extra articular manifestation including and enthesitis related.[6] While oligoarticularrheumatoid nodules, it is called adult type of being 40% of newly diagnosed among Caucasian JIA. The manifestations will be symmetrical population, polyarticular is predominant in polyarthritis involving larger and smaller joints African, East Indian and Indian population. In a including metacarpophalangeal, interphalangeal, study of 495 JIA cases from Chennai, South India temporomandibular joints and cervical spine. systemic onset was 105 (21.2%) oligo arthritis Rheumatoid factor negative type occurs 75 (15.2%), polyarthritis 175 (35.3%), enthesitis throughout childhood and the disease severity related arthritis 131 (26.46%), psoriatic arthritis will be less. ANA positivity can be associated (1.6%) and undifferentiated arthritis 1 (0.2%).[7] with chronic anterior uveitis.[10] JIA is an autoimmune disease involving innate Enthesitis related arthritis immune system, T cells, immune complexes, This type is characterised by enthesitis at the cytokines etc. with complex genetic traits. Both site of insertion of tendoachilles, plantar fascia the IL2RA / CD 25 gene and VTCN1 gene have and also in tarsal area. Asymmetrical arthritis been implicated as JIA susceptibility loci.[8] predominantly affecting the lower limbs will JIA has same histological characteristics as RA occur. Hip joint involvement is not uncommon

5 and erosion at the site of enthesitis can be found. development of secondary sexual characteristics. Eye involvement as symptomatic recurrent acute Osteopenia resulting in increased risk of fracture anterior uveitis is a frequent extra articular in adulthood is a major determinant of functional manifestation. Boys above the age of 6 years are outcome. One of the most determinant affected and are often HLA B27 positive. Many complication is chronic nongranulomatous children in this type may develop acroiliac and uveitis specially in girls who are ANA sero- spinal joint involvement. positive with oligoarthritis developing at a young Ultimately some develop one of the age.[12] spondyloarthropathies like Juvenile onset Sacroiliac arthritis is not characterized by the ankylosing spondylitis and undifferentiated degree of reactive sclerosis as in juvenile spondyloarthropathy. ankylosing spondylitis. Systemic onset JIA (SoJIA) JIA has a list of differentials as rheumatic fever, This type of onset is also known as Still’s disease, SLE, spondyloarthropathy, infectious arthritis, who made earliest formal description of Juvenile serum sickness, inflammatory enteropathy and Arthritis in 1897. SOJIA constitute 10-20% of hematologic diseases.[13] all JIA but highest morbidity occurs in this type. Investigations There is equal sex incidence and can occur at Laboratory tests should not be solely relied upon any age during childhood. The characteristic of to make the diagnosis of JIA. Children with JIA fever will be one or two spikes a day in the usually have normochromic normocytic anemia, evening or early morning lasting for few hours, polymorphonuclear leucocytosis, thrombocytosis comes back to normal and subside on its own, and elevation of erythrocyte sedimentation rate whether treatment is given or not. and C-reactive protein. RF will be positive in During the peak of the fever evan less number of patients with JIA (polyarticular escingmaculopapular rash occurs predominantly RF positive). Anti-Cyclic citrulinated peptide in the covered portion of the body. The other (Anti.CCP) is positive mostlyin patients with manifestations are lymphadenopathy, hepato- RF positivity. ANA can be positive mostly in splenomegaly, pericarditis and rarely oligoarticular type and less frequently in myocarditis.[11] The clinical course is variable. polyarticular type. HLA-B27 can be positive in Systemic features like fever may precede arthritis Enthesitis Related Arthritis (ERA). False positive by weeks or months. In 50% of cases the extra Anti Streptolysin-O, can occur due to articular features subside during initial years of inflammation and polyclonal B cell activation– the disease. The polyarticular course of the disease anamnestic reaction. involving larger and smaller joints will be X-rays show soft tissue swelling, subchondral progressive in nature. Many patients who have osteoporosis, periosteal elevation and rarely persistent active disease, develop cervical spine bony erosion. Cervical spine x-ray is useful in involvement that will lead on to ankylosis. diagnosing fusion and atlanto axial subluxation. Linear growth is usually retarded during active Ultrasound with high power Doppler and disease. There is often delayed puberty and Magnetic resonance imaging are useful in the

6 early detection of synovitis and erosions. and TNF alpha blockers. In the treatment arm amentarium there are Indian studies on JIA are limited and we need NSAIDs, IA steroid, hydroxychloroquine, to strengthen our Indian database on JIA pattern methotrexate, sulphasalazine, oral or IV steroids, that is characteristic and representative of Indian leflunomide, cyclosporine A, IV immunoglobulin pediatric population.

References : 1. Martini A. Systemic juvenile idiopathic arthritis. SJ, Handa R, Mahajan AEds, Indian Rheumatology Autoimmun Rev 2012; 12:56–9. Association, 2009:268-280. 2. Sullivan DB, Cassidy JT, Petty RE : Pathogenic 8. Risch N. Linkage strategies for genetically complex implications of age of onset in juvenile rheumatoid traits. I. Multilocus models. Am J Hum Genet 1990; arthritis. Arthritis Rheum 18:251, 1975. 46: 222-28. 3. Kunnamo I, Kallio p, Pelkonen P : Incidence of arthritis 9. Wallace CA, Levinson JE, : Juvenile rheumatoid in urban Finnish children : A prospective study. Arthritis arthritis : Outcome and treatment for the 1990s. Rheum 29 : 1232 – 1238, 1986. Rheum Dis Clin North Am 17 : 891 – 905, 1991. 4. Gare BA : Juvenile Chronic Arthritis : A Population 10. Hagglund KJ, Schopp LM, Alberts KR, et al : based study on Epidemiology, Natural History and Predicting pain among children with juvenile Outcome. Goteborg, Sweden, University of Goteborg, rheumatoid arthritis. Arthritis care Res 8:36 – 42, 1994. 1995. 5. Sawhney S, Magatha-es CS. Pediatric Rheumatology- 11. Goldenberg J, Ferraz MB, Pessoa AP, et al: A global perspective. Best Practice and Research Symptomatic cardiac involvement in juvenile Clinical Rheumatology 2006; Vol.20, No. 2 : 201 – rheumatoid arthritis. Int J Cardiol 34 : 57 – 62 , 1992. 321. 12. Edelston C, Lee V, Bentley CR, et al : An evaluation 6. Petty RE, Southwood TR, Manners P, Baum J, Glass of baseline risk factors predicting severity in juvenile DN, Goldenberg J, et al. International League of rheumatoid arthritis associated uveitis and other chronic Associations for Rheumatology classification of juvenile anterior uveitis in early childhood. Br J Ophthalmol idiopathic arthritis: second revision, Edmonton, 2001. 86 : 51 – 56, 2002. J Rheumatol 2004; 31:390–2. 13. Cassidy JT : Miscellaneous conditions associated with 7. Rajendran CP. Manual of Rheumatology 3rd Edn, Rao arthritis in children. Pediatr Clin North Am 33 : 1033 URK, Pispati P, Mahendranath KM, Misra R, Gupta – 1052, 1986.

Dr. Santa Subhra Chatterjee, Asst. Prof., Dept. of Medicine, RKMSP, VIMS

7 Original Article Juvenile Idiopathic Arthritis - A Clinic Based Study

Dr. S. Guha1, Dr. S. R. Pal2, Dr. Indranil Das3

Introduction : following 3 signs-

Arthritis is an inflammation of the joint cavity[1]. 1. Swelling of joint. It may be directly or indirectly caused by 2. Restricted mobility of a joint with warmth, infectious agent, it may be idiopathic or may be tenderness or pain. associated with other diseases.[2] Early diagnosis and treatment is necessary to prevent chronic These should atleast last for a period of 6 weeks. life threatning and debilitating conditions[3,5]. Exclusion Criteria : Key words : JIA Patients whose complaints are due to an obvious Aims and Objectives : local cause like trauma or who are suffering Data on Juvenile Idiopathic Arthritis (JIA) is from non rheumatological disorders (malignancy, hemophilia, sickle cell anemia) and patients of lacking from Eastern India[4]. This study is an attempt to describe early disease, patient rheumatic fever are excluded from this study. characteristics, microbiological features and Post Streptococcal Reactive Arthritis (PSRA) immunological factors in children with different and post viral reactive arthritis may be classified subgroups of childhood arthritis using a clinic as undifferentiated arthritis as per ILAR based approach. classification. These patients fit the inclusion Study Design : criteria of having arthritis of >6 weeks. This is a cross sectional observational study. Methodology : Pediatric patients attending the rheumatology After careful history taking patients were clinic of Vivekananda Institute of Medical subjected to meticulous musculoskeletal Sciences were enrolled from March 2013 to ophthalmological and systemic examination. clarification September 2014 and classified as DAS 28[15] and JAFAS[16] were noted. per ILAR (International League Against Rheumatism)[1]. Besides routine investigations all patients were Study Population : tested for rheumatoid factor (RF), ASO titre by latex agglutination anti nuclear antibody(ANA) Children less than 16 years of age with possible using indirect immunoflurosence, and HLA- or evident arthritis determined on the basis of B27 assay were also done. Among imaging one or more of the following criterion, described studies, Echocardiography, ultrasonography as inclusion criteria. power Doppler and magnetic radio imaging Inclusion Criteria : (MRI) were performed. Slit lamp examination Children <16 yrs. of age with at least one of the of the eyes were performed in all subjects.

1, 2Dept. of Rheumatology RKMSP, VIMS 3Dept. of Community Medicine ICAER West Bengal

8 Results : One child with polyarticular JIA had overlap Of the 26 patients diagnosed as JIA using ILAR with juvenile dermatomyositis had exhibited classification 3 presented with oligoarticular gottron papule and heliotrope rash. Muscle arthritis, 5 were systemic in onset, 9 of enzymes (creatinine phosphokinase, CPK, polyarticular variety, 7 were enthesitis related aldolase) were elevated and there was evidence arthritis (ERA), 1 PSRA, 1 post viral reactive of muscle inflammation in MRI (T2). USPD arthritis. There was a male preponderance (8 of showed enthesitis in 2 cases of ERA. MRI done 9) in polyarticular variety and in ERA. Systemic over one year follow up picked up bilateral onset variety and oligoarticular arthritis had a sacroilitis in 2 cases of ERA. female predominance. Majority of the JIA in our Echo cardiography revealed grade 2 mitral study had a later age of onset (>10years) except regurgitation(MR) and grade 1 mitral valve the systemic onset variety which showed an prolapse in one case of oligoarticular variety, earlier presentation (earliest being 3 months). and grade 2 MR was seen in PRSA. None of The PSRA and post viral arthritis were oligo the patients had any cardiovascular symptoms. articular in onset and mean age of presentation Discussion : were similar. JIA is the most common cause of arthritis in 50% of the cases were below 3rd percentile of children and represents upto 65% of arthritic height for age (WHO criteria). This was disease in children [6]. Various epidemiological distributed through out all the subtypes studies of JIA report divergent results owing to commonest with systemic onset variety. The total heterogenecity of the disease, differnces in joint scores varied according to age of onset and standerdised diagnostic criteria, patient retrieval type of disease. They were highest in systemic and study designs [7-10]. Although JIA is a rare onset variety (SOJIA) and in poly articular disease, its true frequency is not known in our subtypes. country. In the west its incidence is reported to All the SOJIA patients had fever ranging from be 6-8/100,000 population per year [10]. moderate to high grade, mostly of the classical 1. JIA has been divided into various subgroups, quotidian variety. Evanescent maculopapular and this categorization helps in diagnosis, follow rash was universally present. 3 of the 5 SOJIA up and subsequent care of these children. Like patients had generalized lymphadenopathy and other indian studies [9, 10] polyarticular variety hepatosplenomegaly. was the commonest in our study though Singh and colleuges reported oligoarticular variety to Pan uveitis was present in one case of be more commoner from the northern part of oligoarticular JIA. One patient with ERA had the country [11]. This was closely followed by anterior uveitis. RF was positive in one case ERA. Unlike North America and Europe where of polyarticular JIA. oligoarticular represents 50-75% cases of JIA, ANA was positive in low titre (1:80) in one case this variety was the least common in our study, of oligoarticular JIA with panuveitis. HLA-B27 an observation similarly reported by Aggarw et was positive in 4 out of 7 cases of ERA, the al [11]. youngest being 7 years of age. 2. The mean age of onset in the west is usually

9 1-3 years[10] and rare below 6 months. It appears cases. Studies from the west[18] report that 6- that in India JIA has a later age of onset. An 19% of JIA cases are ERA. Barring one, all indian study by Kabra et al[9] showed that the were males and >10 years of age. Only one had mean age of onset aws earliest in SOJIA a family history of spondyloarthropathy. Of the (5.2YRS), followed by oligoarticular (6.8yrs) 7 cases of ERA, 6 presented with peripheral and polyarticular (7.2 yrs) subtypes. The overall arthritis, 2 had history of axial involvement. onset of disease in our study tended to peak in Enthesitis was present in 2 cases as demonstrated later age groups. The mean age of onset was by USPD. 2 patients had bilateral sacroilitis in lowest in SOJIA, with the earliest case report MRI over 1 year follow up. HLA-B27+vity being 3 months. was present in 4 cases. This observation is at 3. Regarding sex, males predominated over par with a study on ERA in indian children by females in all subtypes like other indian studies Agarwal. M et al[19] which showed a higher [9, 10]. However females predominatedproportion in of HLA-B27+VITY, early onset oligoarticular variety and SOJIA, unlike most axial involvement, and paucity of family history, indian observations. The male preponderance of unlike their western counterparts. JIA in this part of the subcontinent may be due Heart disease is a rare complication of JIA. None to the special characteristic of the disease seen of the patients had any history of breathlessness in India; another explanation may be that boys or palpitations. Grade 2 MR was seen in the in our country are cared more by family members sole child with PRSA. This finding was not and hence brought early for treatment. diagnostic of rheumatic carditis. In absence of 4. Unlike studies from western countries [13] we any control group this finding cannot be taken had a very low incidence of uveitis, a similar as significant. finding reported from most parts of the country Types of JIA and its distribution : [10, 4]. Uveitis could be only detected in 2 case 4% inspite of thorough slit lamp examination of eyes 4% 11% of all patients. One was an oligoarticular ANA+ 27% 19% case and the other was an HLA-B27 + ERA variety. Probably occurrence of uveitis is closely related to ANA+vity() which is again reported 35% to be very low in indian children. 5. RF+vity was seen in only 1 child with polyarticular variety. RF +vity is seen only in Oligoarticular variety 15-20% of JIA cases[6]. None of our children had Systemic onset rheumatoid nodules. 6. Of all the 26 cases of JIA 7 were ERA. This Polyarticular finding was at par with other indian studies[19]. Enthesitis related arthritis This is in contrast to a similar clinic based study PSRA from Eastern India by ghosh et al[4] where only 2 cases of ERA were reported out of 50 JIA Post viral reactive arthritis

10 Table 1: Characteristics of JIA according to different relevant clinico-pathological factors:

Number Hepato- Male Mean Rash Lymphade- Uveitis RA ANA HLA JIA of cases female age of spleno- nopathy factor (%) ratio onset megaly B-27 Polyarticular 9(35) 8:1 9.5 yrs - - - - 1 - - SOJIA 5(19) 1:4 9.5 yrs 5 3 3 - - - - Oligoarticular 3(11) 1:3 9.5 yrs - - - 1 - 1 - ERA 7(27) 6:1 9.5 yrs - - - 1 - - 4 PSRA 1(4) All F 9.5 yrs ------PVRA 1(4) All M 9.5 yrs ------

Table 2: Clinico-Immunological Profile of JIA in Other Studies

Clinico- Present Parkodi Singh et al Casidy et al. (1) Seth et al. (2) immunological study et al. (4) M:F ratio 1.8:1 1:2 1.3:1 1.6:1 Pauciarticular (%) 11 42.2 50 30 49 Polyarticular (%) 35 37.8 40 46 41 Systemic (%) 19 14.8 10 24 10 Rheumatoid nodules (%) - 5.4 10 0.8 3 Uveritis (%) 7.7 1.3 5 1.1 3 ANF* (%) 3.8 0 45 6.5 - Rheumatoid factor* (%) 3.8 0 10 15 9.7

Conclusion : short study period. Like other Indian studies JIA is the commonest cause of chronic arthritis polyarticular was the commonest with a male in children. Data from Eastern India is lacking. predominent followad closely by ERA. In future Ours was a pilot study attempting to study the more data need to be collected over prolonged incidence reporting at a tertiary care hospital. period, to show the pattern of JIA from Eastern The limitation was the small sample size and India.

Reference : 1. Brewer EJ. Standard methodology for segment I, II 3. Special Writing Group of the Committee on Rheumatic and III, prdiatric rheumatology collobarative study Fever, endocarditis and Kawasaki Disease of The group studies. J Rheumatol. 1982:9 (1): 109-113. council on Cardiovascular Disease in the Young of the Ammerican Heart Association. Guidelines F for 2. Kunnamo J, Kallio P et al. Clinical signs and laboratory the diagnosis of Rheumatic Fever. Jones Criteria, 1992 tests in the differential diagnosis of arthritis in children. update JAMA.1993; 269(4) :476. Am. J Dis. Child. 1987; 141 (1) :34-40.

11 4. Sircar D, Ghosh B et al. Indian Pediatrics. 2006; 43:429- 13. Anderson GB, Fasth A. Incidence and prevalence of 433. JRA. Annals of Rhematol 1987; 46:277-81. 5. Martal W, Cassidy JT. Roentgenologic manifestation 14. Pakodi R, Subramanium R. Pattern of rheumatic dis. of juvenile rheumatoid arthritis. Am J Roentgenol in South India. Clinical profile of JRA. J of API.38: Radium Ther Nuci Med. 1962;88:400-423. 771-773. 6. Cassidy JT, Petty RE. Text Book of Paed. Rheumatol. 15. Prevoo ML, Kupper HH et al. Modified disease activity Third edition. 1995; 133-223. scores that include 28 joint counts. Development and 7. Gare BA, Fasth A. Epidemiology of juvenile chronic validation in a propespective longitudinal study of arthritis in southwestern Sweden : A 5 year retrospective patients with rheumatoid arthritis. Arthritis Rheum population study. Pediatrics 1992; 90:950-958. 1995; 38:44-48. 8. Aggarwal A, Misra R. Juvenile chronic arthritis in 16. Ozher H, Alehan D, Ozme S. Mitral and aortic india: is it different from that seen in Western countries? insufficiency in polyarticular juvenile rheumatoid Rheumatol Int 1994;14:53-56. arthritis. Peditr. Cardiol. 1994; 15:151-153. 10. Singh S, Kumar L et al. Clinico-immunological profile 17. Scaller JG. Rheumatic diseases of childhood. Nelson of juvenile rheumatoid arthritis at Chandigarh. Indian text book of Pediatrics vol 15th. Ped. 1999; 36:449-454. 18. Ozen S, Demirkaya E et ai. Distribution of JIA in the 9. Seth, V, Kabra SK Clinico-immunological profile in in the Eastern Mediterranean : Results from the Turkish juvenile rheumatoid arthritis – an Indian experience. registry. Clinical and experimental rheumatology; Ind. J. Ped, 1996; 63:293-300. 29:111-115. 11. Aggarwal A, Misra R. JRA in India : rarity of ANA 19. Agarwal M, Jariwala M. 110 patients with ERA, : A and uveitis. IJP. 1996; 63:301-304. demographic and clinical study from a tertiary level 12. Chandrasekharan AN. JRA Madras experience: 1996; ped rheum. centre in India. Annals of rheum; 2012; 63:501-511. 71:264.

12 Original Article An Observational Study on Evaluation And Management of Type 1 Diabetic Patients Attending a Diabetes Clinic in West Bengal

Dr. Debasish Maji1, Dr. Ram Udayan Roy2 Summary : people per year[1]. The global incidence is 1 per Incidence of type 1 diabetes is very low in India, 100000[2]. But presently the incidence of Type although a large section of Indian population is 1 diabetes (T1DM) is also increasing like type suffering from type 2 Diabetes. Perhaps due to 2 diabetes, even though not in the same that reason, researchers are interested only on proportion, but still with a trend of 3-5% type 2 diabetes and therefore epidemiologic as increase/year. India has three new cases of well as other information for type 1 diabetes in T1DM/100,000 children of 0-14 years[3]. Because Eastern India is not easily available. The present of this small incidence, maximum research work is an observational study on type 1 diabetics efforts were taken on the diagnostic, therapeutic based on their multiple clinic visits. Some data and management status of type 2 diabetics were generated which showed that most of the ignoring the importance of type 1 patients. patients were diagnosed with classical symptoms, Sufficient data on the glycemic status, patient their follow up and compliance were related to compliance and relation with the development their socio economic status and majority of them of diabetic complications, marital and fertility (around 51%) were suffering from micro- profile along with the morbidity and mortality angiopathy. It was also observed that End Stage status are lacking particularly in Eastern India. Renal Disease was responsible for highest no. In this situation, parents and relatives of type 1 of deaths among them. Above all, it was diabetic children became panicky and considered interesting to note that a good no. of patients ill luck as their children had been diagnosed as (both males and females) got married, had diabetic. They thought that they have lost children and were enjoying a cheerful life. everything in their lives as would have not been Keywords : permitted to eat many things, do anything or in Type 1 Diabetes, IDDM Epidemiology one word; their lives would be a RESTRICTED Introduction : one. Type 1 diabetes is considered largely as a disorder Aims and Objectives : in children and adolescents. It is an immune In this scenario, an observational study on type associated selective destruction of insulin 1 diabetes mellitus has been aimed to get a true producing pancreatic Beta cells and as a result, picture of different parameters related to the exogenous insulin is the only treatment for the glycemic status, control pattern, social patients throughout their lives. Although, India involvement (marriage) and morbidity and is becoming the diabetic capital of the world mortality profile of type 1 diabetic patients of very soon and the maximum of the diabetic Eastern India, particularly West Bengal because population is of type 2 whereas the incidence of almost all the patients attending diabetes clinic type 1 diabetes is too low, only 0.1 of 100000 of this centre and chosen as participants of the

1MD.DM., Prof., Dept. of Medicine, RKMSP, VIMS; 2PH.D., Assoc. Prof., RKMSP, VIMS

13 study, have came from different parts of West disease, operation and infections were noted. Bengal. The vital signs like pulse, blood pressure, height Study Design : and weight were also recorded and whole Longitudinal Observational Study. systemic examinations were done. The relevant Study Population : past investigation reports were recorded. They Type 1 diabetic patient of either sex or different were advised to follow the lifestyle modification age groups attending the diabetic clinic for last and necessary insulin regimen as per standard 10 years. protocol followed by the clinic. In the next visit, they were carefully followed up both clinically Sample Size : and by investigation reports. Their compliance As it is an observational and epidemiological and follow up were carefully monitored. Data study for type 1 diabetic, all such patients who obtained from minimum six follow up visits or have attended the diabetes clinic in different six years’ follow up were taken into account for times have been included in the study with no analysis. The mean values of the numerical pre determined sample size. In this way, we variables like Fasting and Post Prandial Plasma recruited 82 participants (subjects) for our study. Glucose, HbA1C levels etc. obtained from each Inclusion Criterion : patient were calculated. A grand total of those Type 1 diabetic patient of either sex or age group. values for 82 patients were considered further Exclusion Criteria : to generate a mean value. The data expressed No specific exclusion criteria for type 1 diabetic as mean ± S.D. The other categorical variables patients. like type of insulin used, social involvement Materials and Methods : (marriage), fertility, compliance and follow up, All type 1 diabetic patients attending the clinic morbidity and mortality etc. were expressed in were included in the study. In the first visit, a percentage. As this was an observational (non detailed clinical history was recorded including interventional, non comparative) study, no null the age of onset/duration and symptoms at onset hypothesis was there and therefore no statistical of the disease with diet and drug received so far. analysis was performed. The results obtained Any relevant family history and past history of were compared with some other studies only. Results Table-1

Age (M) Male Female Height (cm) Weight (kg) 16.26yrs±6.16 45(54.88%) 37(45.12%) 156.12 ±11.22 49.6±6.33 FPG (mg/dl) PPPG (mg/dl) HbA1c (%) Age/diag Symptoms at Onset 171.39±13.12 248.65±20.32 9.63±1.02 13.34 yrs±2.02. Classic 89% DKA 11%

Patients reported in the clinic at the age of 10- polyuria, Polydipsia loss of weight etc (89%) 26 years with a mean value of 16.26 years. Most whereas some of them with acute state (Diabetic of them diagnosed with classic symptoms like KetoAcidosis-11%). They were diagnosed at 14 11-15 years of age with a mean value of 23.34 compliance group. More patients found their place years. A male preponderance was found among in the moderate group. Their socio economic status the patients. Desirable control could not be was also evaluated using Kuppuswami scale and achieved as evidenced from mean HbA1C level. a direct relationship was found between the socio Table -2 economic status and the follow up/compliance Good Moderate Poor grading. Follow up 23% 46% 31% Table-3 Compliance 23% 47% 30% Management of Type 1 Diabetes Socio-economic 21% 60% 19% Insulin Regimen Followed Status Premixed (30/70) Bid 68% Figure -1 Basal-Bolus 25% Others 07% Type -1 Diabetes Compliance & Socio-eco Status Maximum patients were treated with pre mixed 100% (30/70) insulin twice daily. 25% was on Basal- 90% 80% Bolus insulin therapy and only 7% were on other 70% types like Rapid Acting etc. 60% 50% 40% Poor Table-4 30% Moderate 20% Good TYPE – 1 DIABETES 10% Marital status & Fertility Profile 0% TYPE – 1 DIABETES

Follow up Compliance S/E Status Reached Got Married Having Children Monthly, 3 monthly and more than three monthly Marital Age follow up were considered as good, moderate and Male– 57.77% Male – 57.69% Male – 73.33% poor respectively. Maximum patients fall in the Female – 62.16% Female – 43.48% Female – 50% moderate category. During monitoring, patients who were found to be restricted on life style The marital status and fertility profile of the modification and insulin regimen and at least one type 1 diabetic patients are showed here. It has phone call to the clinic for consultation were been found that 57.77% of males and 62.16% categorized as good complied patients. Relaxations of females have reached marital age and out of in lifestyle and/or insulin regimen for two to three them, 57.69% male and 43.48% females got times in a month were considered as moderately married. 73.33% males and 50% females have complied and beyond that was grouped in poor children.

15 Table-5 deals on the status of the type 1 patients while Type 1 Diabetes living with diabetes. In our study, we found the Morbidity/Mortality age of onset at 11-15 years which closely 10 Years’ Follow up resembles the findings of other western workers[5-7]. We have found a male Mediun Age 26 years preponderance (54.88%) over female (45.12%). Mediun duration 11 years One observation suggested the equally affection CKD 15% rate in both the sexes[8], while another systematic Neuropathy 13% review showed that T1D incidence was larger Retinopathy 15% in males than in females in 44 of the 54 (81%) studies reporting incidence by sex in people >15 CAD 8% years of age. The overall mean male-to-female Cause of Death 16% (of Cohort) ratio in the review was 1.47[9]. 89% of the patients CAD 7% presented with classical symptoms and 11% Acute complication 7% with complications like DKA (Diabetic ESRD 30 KetoAcidosis) at diagnosis in the present study which was supported by other workers[10]. We Accidental 7% have found mean HbA1C level 9.63±1.02 Infection 15% whereas in SEARCH study, they reported a Others 15% mean HbA1C level 8.2% in youth with type 1 The morbidity and Mortality table showed that Diabetics with 17% having HbA1C = 9.5%[11]. over 50% of the patients were suffering from We have observed the patient follow up and microangiopathy of which, Chronic Kidney compliance level and also analyzed the socio Disease (CKD) and Retinopathy together economic status of the patients[12] and found that occupied the highest position (30%). 16% of the most patients were within the moderate group patient died and again, the cause of death was as compliance level and follow up status were End Stage Renal Disease in maximum cases considered. When compared with socio (30%) which showed that even a patient was not economic status, it was found that the patients a known case of kidney disorder, he might be belong to the good socio economic status had died of renal disease. good compliance and follow up visits. Same Discussion : was true in moderate group but percentage of As discussed before, the detailed data about the patients in poor complied and follow up group type 1 diabetic population in Eastern India are was greater than that in the poor socio economic not enough till now. Some observations on the class. Perhaps some patients though belonged incidence and prevalence percentage of type 1 to the good or moderate socio economic category, diabetic patients were studied earlier in Cuttack did not show interest in good compliance and by Samal et. Al. from 1983-88 with 54 patients follow up. The socio economically backward and then in Kolkata by Mazumder et.al. from patients might find some difficulties in regular 2004-2006 with 41 patients.[4] The present study consultation, purchase of insulin or glucometer

16 for regular monitoring of blood glucose etc. and Conclusion : therefore their compliance level or follow up The observations from the present study come visits decreased. into the following conclusion: 68% of our patients were controlled with pre Incidence of Type 1 diabetes is rare in India. mixed insulin and here we can also quote other There is no specially planned care for this small study where pre mix insulin was advised in the population of type 1 diabeties particularly in treatment guideline for type 1 diabetics although Eastern India and as a result, majority do not get proper healthcare. Poorer people, especially Basal Bolus therapy was also recommended[13]. the people living in remote areas have poor A morbidity/mortality profile of the type 1 patients diabetic control, poor compliance and therefore, was prepared and compared with the observations poor outcome including early development of of Johenson from Denmark, published in 2013. complications and even death. Type 1 diabetic Their median age (44 years vs. 26 years), duration patients need extensive training for proper (18 years vs. 11 years) and complications like lifestyle modification, insulin injection technique, CKD, Neuropathy, Retinopathy and CAD) were use of glucometer and monitoring of their health more than those we found but the incidence of status from very beginning since detection of death was almost same (14% vs. 16%). Highest the disease. The family members, class teacher cause of death was CKD in our study (30%) in the school employers in the employment area whereas it was CAD in the comparator study also need proper education so that the patients (31%) the percentage being almost same. remain healthier. References : 1. Maahs DM, West NA, Lawrence JM, Mayer-Devis EJ. childhood type 1 diabetes incidence--what can we Epidemiology of type 1 diabetes. Endocrinol Metab learn from epidemiology? Pediatr Diabetes. 2007; 8 Clin North Am 2010; 39: 481-97. (Suppl 6):6–14.[PubMed] 2. Whiting DR, Guariguta I, Well C, Shaw J. JDF Diabetes 9. Paula A Diaz-Valencia, Pierre Bougnères and Alain- Atlas: Global estimates of the prevalence of diabetes Jacques Valleron. Global Epidemiology of Type 1 for 2011 and 2030. Diabetes Res Clin Pract 2011; Diabetes in young adults and adults: a systemic review. 94:311-21. BMC Public Health. 2015; 15:255. 3. Das Ashok Kumar. Type 1 diabetes in India: Overall 10. Levy-Marchal C, Patterson CC, Green A. Geographical insights. Indian Journal of Endocrinology and variation of presentation at diagnosis of type I diabetes Metabolism 2015;19(7):31-33. in children: the EURODIAB study. European and 4. Ananda Kumar Anutha, Kalpana Thai, Mohan Dibetes. Diabetol. 2001; 44 (Suppl 3):B75–B80. Viswanathan. Childhood and Adolescent onset type 1 [PubMed] Diabetes in India. MGN Journal of Medical Sciences, 11. Petitti DB, Klingensmith GJ, Bell RA, et al. Glycemic Oct-Dec 2013; 1(1) 46-53. control in youth with diabetes: the SEARCH for 5. Dabelea D, Bell RA, D’Agostino RB, Jr, et al. Incidence diabetes in Youth Study. J Pediatr. 2009; 155:668–672. of diabetes in youth in the United States. JAMA. 2007; [PMC free article] [PubMed] 297:2716–2724.[PubMed] 12. P Dudeja, P Bahuguna, A Singh, N Bhatnagar. 6. Incidence and trends of childhood Type 1 diabetes Refining a socio-economic status scale for use in worldwide 1990–1999. Diabet Med. 2006; community-based health research in India. JPGM 23:857–866.[PubMed] 2015; 61(2) : 77-83. 7. Variation and trends in incidence of childhood diabetes 13. Silverstein J, Klingensmith G, Copeland K, et al. Care in Europe. EURODIAB ACE Study Group. Lancet. of children and adolescents with type 1 diabetes: a 2000; 355:873–876. [PubMed] statement of the American Diabetes Association. Diab 8. Soltesz G, Patterson CC, Dahlquist G. Worldwide care. 2005;28:186–212. [PubMed]

17 Original Article Short Stature: The Only Morphological Stigmata for IsochromosomeXq Ms. Shanoli Ghosh1, Ms. Pritha Pal2, Ms. Atreyee Dutta3, Dr. Sanchita Roy4, Dr. Ajanta Halder5 Abstract : Isochromosome of long arm of X Many genotype phenotype analyses have proved chromosome i(Xq), which occurs due to abnormal that short stature has a strong genetic component. transverse cleavage of the centromere during cell Either autosomal or sex chromosomal division, found in some cases of Turner abnormality or both the abnormalities can Syndrome. The aim of this study is to estimate contribute its effect in growth. Turner syndrome the prevalence of isochromosome X in patients (TS) is considered to be the important genetic with short stature with or without primary (PA) abnormalities leading to short stature in females and secondary amenorrhea (SA) in our affecting 1 in every 2000 girls. (Donaldson et population. An observational study was conducted al., 2006) TS is characterized cytogenetically at Vivekananda Institute of Medical Sciences either by X chromosome monosomy (45, X), (VIMS), Kolkata, India between 2013 to the presence of an abnormal X chromosome December 2014. Female patients aged between (Isochromosome/ring chromosome/deletion in 12-25yrs who were referred to Cytogenetic short arm), or mosaicism of a 45, X cell line outdoor, VIMS for chromosomal analysis with with another cell line, which might be 46,XX, history of short stature and with or without 46,XY or have an abnormal sex chromosome Primary Amenorrhea were included in this study. rearrangement like isochromosome or ring Lymphocyte culture followed by Karyotyping chromosome etc. (Jacobs et al., 1997) was done for all the patients. We have Isochromosome is defined as the structurally documented 4 such cases of IsochromosomeXq abnormal chromosome consisting of either two among 50 female patients presented mainly with short or long arms, because of the abnormal short stature, with or without Primary amenorrhea. transverse middivision of the centromere (centric Our study emphasizes the importance of fission), resulting in unbalanced chromosomal chromosomal analysis of short stature patients constitution, and monosomy for the missing and with or without PA or SA to eliminate diagnostic trisomy for the duplicated arms (Young 2005). dilemma for the children. The formation may also be because of the more Keywords : complex U-type exchange resulting in acentric Isochromosome, Karyotyping, short stature or dicentric products. The process of isochromosome may occur in pre meiotic Introduction : gamete, during meiotic cell divisions or in Short stature is defined as a standing height more postzygotic cell divisions of a normal or than 2 standard deviations (SDs) below the mean trisomicconceptus (Gardner and Sutherland (or below the 2.5 percentile) for sex according 2004). Manifestations of classical TS usually to standard growth chart (Cohen et al. 2007). include short stature,webbed neck, broad chest 1,2,3Research Scholar, M.Sc., Dept. of Genetics RKMSP, VIMS; 4Asst. Prof., MBBS, DCH, MD, Dept. of Anatomy, IPGMER, Kolkata; 5Assoc. Prof., PhD., Dept. of Genetics, RKMSP, VIMS

18 with widely spaced nipples, cubitus valgus, (Rosewell Park Memorial Institute) culture congenital lymphedema, lack of spontaneous medium. Peripheral blood lymphocytes induced pubertal development resulting from ovarian sex with 2% phytohaemagglutinin (PHA) were hormone insufficiency, amenorrhea, low-posterior incubated at 37.5°C for 72 h. One and a half hairline. but the X isochromosome patients hours prior to harvest, the cultures were arrested present with short stature with absence or minor with colchicine and treated with 0.75 M KCl Turner stigmata thus creating really a challenge (potassium chloride) for 30 min and fixed in to the clinicians. fixative (3:1 ratio of methanol : glacial acetic This study is done to find out the prevalence of acid). After air drying, conventional GTG isochromosome X in female patients with short banding was performed to identify the stature in population of West-Bengal. chromosomes. After banding, 50 metaphases were scanned under low power for each case Materials and Methods: on OLYMPUS BX51 microscope and then 10 This study was carried out at Department of metaphases were analyzed by automated Genetics, Vivekananda Institute of Medical karyotyping system (CYTOVISION software). Sciences (VIMS), Kolkata,West Bengal and is In cases of mosaics 30 metaphases were approved by the ethical committee of VIMS. analyzed. Informed consent was obtained from the patients Result: after the procedure was fully explained to them. The female patients having short stature with or Fifty females ranging from 10 to 35 years having without amenorrhea between the age group of short stature with primary or secondary 12-25 years were selected who were referred to amenorrhea were considered for chromosome the cytogenetic outdoor for chromosomal analysis examination. Karyotype analysis was carried from different hospitals of West-Bengal. A total out by standard methods in all patients. Among of 50 patients were included in the study. The 50 patients, 21 patients were diagnosed as having physical examination included the accurate chromosomal abnormalities and 29 patients were measurement of the height and weight and with normal karyotype, having some other causes thorough inspection and palpation of the external rather than chromosomal defect. The patients genitalia, the primary and secondary sexual under study were categorized into five groups characters and a search for the other congenital on the basis of karyotype obtained; 11 patients anomalies. Tanner-Whitehouse growth charts were with classical Turner syndrome, 3 patients were used for monitoring the growth and were having mosaic TS, 29 patients were with assessment of heights among the patients. After normal 46, XX chromosomal complement and taking brief clinical and family history peripheral 4 were with isochromosome X (variant TS). blood karyotyping was done. The blood sample Patients with isochromosome X have no other was collected from the patients in a completely gross morphological phenotypic stigmata of TS sterile heparinized vacutainer tube and mixed except short stature and their short histories are well. The cultures were set up with RPMI 1640 given in Table.

19 Table : Profile of patients having Isochromosome of long arm of X chromosome

Sl.no Age Physical features Hormonal profile USG findings Karyotype (yrs) 1 16 height - 129 cm LH-20.98mIU/mL; ovaries not 45,X[15]/ weight- 28 kg FSH -111.68mIU/mL; visualised, 46,X,i(Xq)[15] high arched palate, estradiol- uterus clinodactyly 15.12pg/mL hypoplastic Breast development : TSH- 3.92uIU/Ml (48x23x14mm) Tanner stage -2, GH-normal sparse pubic hair normal intelligence average school performance. Primary Amenorrhea 2 10 height -117.5 cm TSH-24 mIU/ml (á) hypoplastic 46,X,i(X)(q10) weight- 21 kg uterus with poor school normal sized performance ovaries behavioural disorder (temper tantrum) 3 32 Height-132 cm FSH-47.93mIU/mL Infantile Uterus 46,X,i(Xq)[16]/ weight -36 kg LH-42.20 mIU/Ml (47.5x 20.8×21. 45,X[10]/ H/O secondary FT4-1.7ng/dl, 6mm) small 46XX[4] amenorrhea TSH-2.06 mIU/ml sized ovary Breast well developed, no axillary hair but scanty pubic hair. 4 14 Height-115cm TSH-2.16 mIU/ml uterus with 45,X[15]/ Weight-22kg FT4-1.6ng/dl, bilateral 46,X,i(Xq)[15]. Short neck, GH- 12 ng/mL, ovaries academic IGF- 160 ng/mL present. performance good

20 [Normal hormone levels: FSH- 3.50–12.50 of one of the long arm of X chromosome (i(Xq)) mIU/mL, LH-2.40–12.60 mIU/Ml, oestradiol- causes skeletal abnormality like short stature. 24.50–195.00 pg/ml, Free thyroxine (FT4)- 0.7- Some reports (Sönmezet al., 1997; Garcíaet al., 1.9 ng/dl,TSH-0.27–4.20 µIU/ml, Insulin like 1991; Zinmanet al., 1984) have indicated that growth factor(IGF-1)- 182 to 780 ng/ml for ages patients with the 46,X, i(Xq) karyotype have 16 to 24 & 114 to 492 ng/ml for ages 25 to 39, characteristics similar to those observed in Random growth hormone-Women: < 10 ng/ml classical TS but in a milder form. Sybert and Children: 0-20 ng/ml] McCauley (2004) have reported the 46,X,i(Xq) Discussion : karyotype in 7% of patients with TS. In our study we have found pure IsochromosomeXq There are numerous variant karyotypes seen in in 1 patients and in 3 cases it was mosaic TS other than the classic monosomy X. IsochromosomeXq. Patient 1 with mosaicism Isochromosome X that is 46, X, i(Xq) syndrome showed few phenotypical features of TS like one of those variant. There are a lot of cytogenetic clinodactyly and high arched palate, but others and clinical differences than classical Turner isochromosome-Xq didn’t show any syndrome. This isochromosome X consists of morphological stigmata of TS except short the two long arms of the X chromosome but no short distal arm. Lyon (1961) hypothesized that stature. Most of the patient with TS shows normal early in the development of a normal female intelligence though 70% patients have learning embryo, random inactivation of one of the two disabilities affecting nonverbal perceptual motor X-chromosomes in each cell occurs which allows and visuo-spatial skills (Ross et al., 2000). The the female to have the same amount of X- patients with i(X) are at a higher risk of mental chromosome material as the average male has. retardation, learning difficulties, autistic spectrum There are certain genes that escape this X disorders, and structural brain abnormalities due inactivation like homeobox gene (SHOX), XIST to loss of X-inactive specific transcript (XIST) gene etc. (Santana et al., 1977) These are located region. (Skuseet al., 2006) We observed no predominantly in the small regions of homology mental retardation in either of these patients but and pairing that persist on the sex chromosomes patient no.2 showed very poor school called the pseudoautosomal regions (PAR) present performances and temper tantrum disorders for on the short distal arm. (Raoet al., 1997) In this which she needed psychological counseling by way, the normal female has functioning genes professionals. In our study we did not find any from one complete X-chromosome plus congenital malformations found in classical TS. functioning genes from the still active short distal Hypothyroidism is common in 15-30% of arm of the mostly inactivated X-chromosome. patients with TS. There are reported cases of The short stature phenotype is a result of more incidence of autoimmune thyroiditis in haploinsufficiency of SHOX (short stature isochromosome X (Garcíaet al., 1991; homeobox-containing gene located at Xp22.33) Chiovatoet al., 1996; Medeiros et al., 2000). In which encodes a transcription factor implicated our study patient 2 presented with in skeletal development. Thus, Patients with hypothyroidism. She had a history of alopecia- monosomy X or deletion in Xp or isochromosome totalis, an autoimmune disorder, thus she was

21 advised to have thyroid scan to rule out found only growth retardation as constant feature autoimmune thyroiditis but didn’t turn up with with primary amenorrhoea in 1case. We found the report. Normal gonadal development needs that the i(Xq) form of TS was generally milder the zinc finger protein, X-linked (ZFX) gene in than classic TS. A female with short stature, but the X chromosome short arm. Although oocyte without typical clinical findings of TS, should development requires only a single X be evaluated for this chromosomal form, because chromosome, oocyte maintenance requires two 45, X karyotype can be diagnosed at birth due X chromosomes. In absence of a second X to typical dysmorphic features or cardiac chromosome, therefore, oocytes in fetuses and abnormalities, but in isochromosome-X neonates with TS degenerate and their ovaries diagnosis may be delayed until childhood, atrophied into streaks of fibrous tissue. Women adolescence or unfortunately until adulthood with an X monosomy, a X long arm while evaluation for short stature,pubertal delay, isochromosome and short arm deletions primary amenorrhea and infertility. Early commonly present with gonadal dysgenesis due diagnosis is an important aspect of ideal to haploinsufficiency of this gene. (Ogata et al., treatment for these variant type of TS patients 2001). Alteration in some regions of the X because growth hormone supplementation in chromosome longarm results in ovarian failure. proper time can help in achieving normal height Presence of an IsochromosomeXq even in mosaic at per age followed by sex hormone form with other cell lines, do not present supplementation for overcoming ovarian spontaneous menarche. In our study we have dysfunction.

References: to DXYS15: localisation of a growth gene(s) in the 1. Cohen P, Rogol A, Deal C, Saenger P, Reiter E, pseudoautosomal region. I Med Genet 1992;29:455-9. Chernausek S, et al on behalf the 2007 ISS Consensus 5. Morgan T. Turner syndrome: Diagnosis and Workshop participants. Consensus guidelines for the management. Am Fam Physician., 2007;76:405–410. diagnosis and treatment of children with idiopathic short stature: a summary statement of the growth hormone 6. Santana JAM, Gardner LI, Neu RL. The research society in association with the Lawson Wilkins isochromosome-X syndrome [46,Xi(Xq)]: Report of Pediatric Endocrine Society and the European Society three cases with review of the phenotype. Clin Pediatr for Pediatric Endocrinology. J ClinEndocrinol Metab., (Phila). 1977; 16:1021–1026. 2008; 93:4210-7. 7. Rao E, Weiss B, Fukami M, Rump A, Niesler B, Mertz 2. Donaldson MD, Gault EJ, Tan KW, Dunger DB. A et al. Pseudoautosomal deletions encompassing a Optimising management in Turner syndrome: from novel. infancy to adult transfer Arch Dis Child. 2006 Jun; 91(6): 8. homeobox gene cause growth failure in idiopathic short 513-20. Jacobs P, Dalton P, James R, et al. Turner stature and Turner syndrome. Nat Genet., 1997 syndrome: A cytogenetic and molecular study. Ann Hum May;16(1):54-63. Genet., 1997; 61:471–483. 9. García CB, Robles CP, González VA, et al. 3. Ogata T, Petit C, Rappold G, Matsuo N, Matsumoto T, Hypothyroidism and isochromosome X in Turner’s Goodfellow P. Chromosomal localisation of a syndrome [in Spanish]. An EspPediatr., 1991; pseudoautosomal growth gene(s). _7 Med Genet 34:161–162. 1992;29:624-8. 10.Skuse D, Elgar K, Morris E,Turner C. Ring-X 4. Ogata T, Good fellow P, Petit C, Aya M, Matsuo N. Chromosomes: Their cognitive and behavioural Short stature in a girl with a terminal Xp deletion distal phenotype. Ann Hum Genet., 2006; 64: 295-305.

22 Review Article Primary Immuno-Deficiency Disorder

Dr. Tapabrata Chatterjee1, Dr. Ajanta Haldar2, Dr. Suparna Guha3

Introduction : organisms responsible are gram+ve encapsulated Primary immunodeficiency disorder is rare when bacteria, micoplasma and echovirus. considered individually. However taken together T-cell deficiency presents early with systemic as a group, they represent a significant health GIT and respiratory infections. The organisms problem with a frequency compatible to disorders responsible are viruses, pyogenic bacteria, fungi, such as cystic fibrosis and childhood leukemia.[1] protozoa and mycobacterium. Clinical indicators of primary immunodeficiency The defect in the phagocytic system represents states, includes infections with opportunistic with skin infection, lymphadenitis, abscesses, organisms, unusual infections or severe infections gastro-intestinal manifestations, osteo-myelitis with organisms of low pathogenicity, infections and septic arthritis. The common organisms are failing to respond to appropriate therapy, staphylococcus, gram –ve bacteria and fungi. persistence of infection beyond what is expected, Though the presentation may be early, family history of immunodeficiency and recognition as an immunodeficiency disorder dysmorphic feature suggestive of syndromes may be late. associated with immunodeficiency.[2] Compliment deficiency presents systemic Key Words : bacterial infection, commonly as recurrent Antibody Deficiency, Phagocytic defects, infection by common and uncommon strains of Immune dysregulation, Primary immunod- Neisseria meningitis.[2,3,4] eficiency disorders, Severe combined Common Immunodeficiency Disorder : immunodeficiency (SCID). l Severe Combined Immunodeficiency : Classification and Manifestation : The presentation of SCID can be early with Immunodeficiency disorders can be broadly significant bacterial infections, pneumocystis classified into: carnii pneumonia and disseminated BC A) B-cell and immunoglobulin deficiency Geosis. The children with this disorder fail B) T- Cell Deficiency to thrive, have persistent diarrhoea, respiratory infection and thrush. The C) Deficiency in phagocytosis disorders are characterised by defects in both D) Compliment deficiency T & B lymphocytes. Early treatment of B- cell deficiency generally presents around 6 infections with antibiotics and early months of age with respiratory, GIT infection, institution of immunoglobulin therapy skin, sepsis and meningitis. The common improves the prognosis. Bone marrow

1Prof. of Paediatrics, RKMSP, VIMS; 2Assoc. Prof. of Clinical Genetics, RKMSP, VIMS; 3Assoc. Prof. of Paediatrics, RKMSP, VIMS

23 transplantation is the only curative sinopulmonary infection and treatment.[5] malabsorption.[2] l Panhypogamma Globulinemia : l Chronic Granulalomatous Disease : Chronic granulomatous disease is the most It presents as a X-linked recessive disorder common inherited disorder of phagocyte and male infants presents in the first two function presenting as a x-linked or years of life. Extracellular bacteria are the autosomal recessive state. In chronic usual pathogens but severe enteroviral granulomatous disease, there is failure of infections are also common. Arthritis affecting production of superoxide radical important large joints is the common manifestation for killing phagocytosed bacteria. Children apart from overwhelming sepsis. Tonsillar present with lymphadenopathy, tissue and lymph nodes are conspicuously hepatosplenomegaly, pneumonia, including unremarkable and all types of abcesses in unusual site, osteomyelitis and immunoglobulin are either absent or present dermatitis. Intestinal granuloma formation well below the age appropriate normal range. may mimic inflammatory bowel disease. Treatment includes administration of gamma The prognosis is guarded and even bone globulins periodically and aggressive marrow transplant, have limited success.[2] treatment with antibiotics for infections.[6] l Hyper IgM Syndrome : Selective IgG Subclass Deficiency : l Hyper IgM syndrome is X-linked disorder Though IgG subclass deficiency is of no due to defect in the CD40 ligand gene. CD40 clinical relevance in vast majority, children ligand found on T cells interacts with CD40 with low or absent IgG2 subclass can be on Bcells, promoting their growth and symptomatic. There can be coexistent IgA differentiation as well as for isotope subclass deficiency in some of these switching. Failure of this important signal children.[6] leads to increased number of B-Cells l Selective IgA Deficiency : producing normal or increased quantities of IgM but no IgG, IgA or IgE.[7, 8] IgA are as common as 1 in 400 in Caucasian population and most often are not identified l Compliment and Associated Disease : as the infections are often trivial. However, Most children with compliment deficiency patients with IgA deficiency may have has increased susceptibility infection and recurrent sino-pulmonary infections and can there is a higher incidence of autoimmune present autoimmune diseases.[2, 4] disorder, perhaps because of failure to adequately clear circulating immune Common Variable Immunodeficiency : l complexes. Defciencies of individual The genetic defects underlying this group of components can be detected by immune- disorders are largely unknown. It presents assays using specific antiserum. However, with manifestation of predominantly B-cell screening can be done by CH50 assay for defect and minimum T-cell defect. The onset the classical pathway and AP50 for the of clinical manifesatins, are late with alternate pathway.[9]

24 l Wiskott Aldrich Syndrome : functions, there is increased susceptibility Both B & T cell lines are affected in this X- to viral and candida infections. There is also linked disorder. Lymphopenia elevated IgE increased incidence of auto-immune disorder, and IgA and low IgM leads to frequent which presents at an older age. Bone marrow infections with capsulated and non capsulated transplant and Thymus transplant can be bacteria and viruse. Autoimmune disease, often curative.[2] eczema and increased incidence of Conclusion : malignancy especially Epstein Barr, Early suspicion of primary immunodeficiency associated malignancies like lymphoma and disorders lead to earlier diagnosis, accurate brain tumour is common.[2] determination of diseases outcome s, appropriate l Di George Syndrome : genetic and family counselling, better insight Di George syndrome consists of conotruncal of management strategies and potential cures cardiac defects, immunodeficiency secondary for some. Future research is directed towards to thymic aplasia and hypocalcaemia, delineation of gene identification of new commonly known as Catch 22 syndrome. As unrecognised immunodeficiency disorders and there is impairment in T cell number and development of new strategies like gene therapy.

25 Reference : 1. Al-Herz W, Bousfiha A, Casanova JL, Chapel H, series: an approach to the patient with recurrent Conley ME, Cunningham-Rundles C, et al. Primary infections in childhood. Clin Exp Immunol. immunodeficiency diseases: an update on the 2008;152:389-96. classification from international Union of 6. Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Immunological Societies Expert Committee for Primary Scholl PR, Geha R, et al. The X-linked hyper- Immunodeficiency. Frontiers in Immunology. IgMsyndrome: clinical and immunologic features of 2011;2:54. 79 patients. Medicine (Baltimore). 2003;82:373-84. 2. Piquet D, Tosi C, Luthi JM, Andresen I, Juge O. 7. Berrington JE, Flood TJ, Abinum M, Galloway A, Redimune ((R)) NF Liquid, a ready to use, high Cant AJ. Unsuspected Pneumocystis carinii concentration intravenous immunoglobulin therapy pneumonia at presentation of severe primary preparation, is safe and typically well tolerated in the immunodeficiency. Arch Dis Child. 2000;82:144-7. routine clinical management of a broad range of conditions. Clin Exp Immunol. 2008;152:45-9. 8. Bouma G, Ancliff PJ. Thrasher AJ, Burns SO. Recent advances in the understanding of genetic defects of 3. Notarangelo LD, Forino C, Mazzolari E. Stem cell neutrophil number and function. Br J Haematol. transplantation in primary immunodeficiencies. Curr 2010;151:312-26. Opin Allergy Clin Immunol. 2006;6:443-8. 9. Wood P, Stanworth S, Burton J, Jones A, Peckham 4. Subbarayan A, Colarusso G, Hughes SM, Gennery DG, Green T, et al. UK Primary Immunodeficiency AR, Slatter M, Cant AJ, et al. Clinical features that Network. Recognition, clinical diagnosis and identify children with primary immunodeficiency management of patienys with primary antibody diseases. Pediatrics. 2011;127:810-6. deficiencies: a systematic review. Clin Exp Immunol. 5. Slatter MA, Gennery AR. Clinical immunology review 2007; 149:410-23.

26 Review Article Modified Septoplasty

Dr. B. K. Roychaudhuri1, Dr. Amitabha Roychoudhury2, Dr. S. Ghosh3

Summary : Anatomically the nasal valve area gives rise to Deviated nasal septum is one of the commonest maximal nasal obstruction in DNS. clinical conditions encountered in the day to day Nasal Valve : otolaryngological practice. Surgical correction The upper lateral cartilage is overlapped by the of this condition has undergone numerous cephalic edge of the alar cartilage, to which it modifications over the centuries, owning to is attached by dense connective tissue. This various drawbacks of the classical submucous creates a ridge across the roof of the nasal resection of septum, which was initially described vestibule which forms the inner nasal valve (Fig in the nineteenth century. The pitfalls of various 1). This is the narrowest part of the nasal cavity. procedures are discussed at length. We put Clinically this obstruction to nasal airflow can forward a few modifications of the surgical be confirmed by the Cottle’s test. Septal deviation technique, considering the merits and demerits in the region of nasal valve area causes the of the radical submucous resection of septum as greatest obstruction. well as conservative septoplasty surgery. We further propose a new nomenclature “Modified Nasal Valve Region Septoplasty” to incorporate the modifications. Lateral Nasal Key words: Wall

Septoplasty, Septal incisions, Columellar Inferior retraction, Septal perforation, Supratip deformity. Turbinate Introduction : Deviated nasal septum (DNS) is a clinical entity which can give rise to a number of complications Septum and can jeoparadise the quality of one’s life if not treated judiciously. A patient with a DNS can Internal Nasal Valve suffer from nasal obstruction, mouth breathing, (Cross-section view) recurrent and persistent epistaxis requiring Fig 1: Nasal Valve Area hospital admission, chronic sinus problems, headache, recurrent sore throats, middle ear Review of Literature : effusions and even voice problems. Significant Over the centuries numerous surgeries have septal deviations require surgical correction to been proposed for the correction of DNS. Sub prevent these serious complications. mucosal resection, more commonly known as

1Prof. & Senior Consultant; 2Prof .& HOD; 3Associate Prof. Dept. of ENT and Head-neck Surgery, RKMSP, VIMS

27 the SMR operation, is the time tested and the technique of Metzenbaum. He advocated established surgical procedure for treating a reinsertion of the cartilage as a free graft. This patient with DNS. SMR was probably first done operation developed the concept of cartilage by Ingall in 1881[1]. But Killian and Freer did excision followed by cartilage replacement. the refinement and popularized the actual Galloway (1946)[5] removed the entire nasal procedure of Ingall (1882). It was Killian (1904)[2] cartilage and replaced the anterior septum with who described the technique where a dorsal and a single free autograft fashioned from the excised caudal strut of septal cartilage is retained and cartilage. It was always successful. most of the cartilaginous and bony septum is The whole process of septal removal followed removed. Freer (1902)[3] opined that the septal by septal replacement has some inherent cartilage did not contribute to the support of the drawbacks and consequently the alternative nasal pyramid and could be completely removed solution of mobilisation and repositioning of if required by the extent of the pathology. SMR septal cartilage has been revived and further operation had quite a few complications on record developed. like saddling of the nose (supratip deformity), collumellar retraction, septal perforation, epistaxis This concept received a new nomenclature etc. “Septoplasty” and has been popularized by Cottle and his associates. Rubin (1983)[6] advocated Killians admitted that “saddling” of the dorsum the morselization of the deviated septal cartilage did sometimes occur in the supratip region, but by crushing with a morselizer after the mucosal concluded that this was always due to rough flaps have been elevated on both sides. It is surgery, which damaged or partly removed the claimed that the new flattened shape of the upper lateral cartilages. The supratip saddling cartilage is retained on a permanent basis. and columellar retraction are the complications Incisons : which were documented too frequently in Killian’s technique. Immediate saddling is rare The different incisions advocated for the septal but it usually occurs as a result of scar contraction surgeries are as follows: in the septum. Some surgeons have attempted to Hajek / Freer’s Incision (Fig. 2) : Fashioned solve the problem of scar contraction by replacing at the extreme anterior margin of the septal all or part of the excised cartilage. Other authors cartilage if the deviation extends into the have avoided producing a large defect in the vestibule of the nose. It may result in columellar cartilaginous septum by mobilizing and retraction, if not properly taken. repositioning the septum in the central position, To prevent columellar retraction the Freer’s so that the bulk of the cartilage is retained and incision is to be made as high as possible because is still attached to it mucoperichondrium as part a low incision through the membranous septum of a compound flap: Metzenbaum’s “Swinging may be followed by a retraction of the columella. door” technique (1929)[4]. Recurrence of It is therefore necessary to displace the columella deflection was common in this technique. downwards and to the opposite side by means Peer in 1937, completely excised with a deviated of traction exerted with dissecting forceps or a caudal segment to overcome the problem with Cottle’s columellar clamp. The lower border of

28 the septal cartilage will then be plainly visible and the incision made down to the perichondrium, which is incised and the subperichondrial flap elevation then commenced. This is known as the “Maxilla-premaxilla” approach of Cottle. Killian’s Incision (Fig. 3): Fashioned at the junction of the vestibular membrane with the mucous membrane of the septum. According to Ballenger, Killian’s incision is preferable for septal surgery and it should be made upon the left side of the septum. In reality it has been seen that in Septoplasty cases if the patient has a caudal deviation or a deviation at the anterior part and the valve area is encroached Fig 3: Killian’s Incision by the deviated cartilage, Killians incision is not satisfactory. As this incision is fashioned over Advocated Modifications : the mucocutaneous junction a residual deviation is maintained at the anterior septal end which 1. The incision should be taken 1 to 2 mm abuts over the nasal valve area and the nasal posterior to caudal end of quadrilateral obstruction is maintained. cartilage, as classical Freer’s/Cottle’s incision may give rise to columellar retraction. Therefore the preferred incision in Cottle’s septoplasty is as advocated by Freer. This incision 2. After elevation of the mucoperichondrial is made at the lower border of the septal cartilage. flaps on both sides like SMR operation, the A unilateral (hemitransfixation) incision is deviated quadrilateral cartilage and the adequate for a septoplasty and for a right handed perpendicular plate of ethmoid are cut close surgeon this is usually made on the left side. to their attachment with upper lateral cartilage and crest of the nasal bones respectively by the Ballenger's scissors or any such types of scissors. Thereafter, the deviated cartilage and bone of the septum are removed. This would prevent supratip deformity. 3. To prevent flap damage which results in septal perforation, the anterior and inferior tunnel should be created routinely, as advocated by Cottle. These recommendations if followed meticulously in septoplasty, the complications like columellar Fig 2: Freer’s / Cottle’s Incision retraction, supratip deformity and septal

29 perforation which commonly give rise to facial Hence we strongly suggest that a new deformity, can be avoided. nomenclature “Modified Septoplasty” should be acknowledged.

References: 1. Scott Brown’s Otolaryngology 5th ed. (1987) septal cartilage. Archives of Otolaryngology, Vol 4, Rhinology (Chapter 10) by David Brain, 9, 282. page 158 - 169, Butterworth & Co. (Publishers) Ltd, London. 5. Galloway, T. (1946) Cited by Bolotow, N., Fomon, S., Pullen, M. and Syracuse, V. R. 2. Killian, G. (1904) Die submucose Plastic repair to the deflected nasal septum. Fensterresektion der Nasen-scheidewand. Archives of Otolaryngology, 44, 141. Archivs fur Laryngologie und Rhinologie, 16, 362. 6. Cottle, M. H., Fischer, G. G., Gaynor, I. E. and Loring, R. M. (1958) The maxilla- 3. Freer, O. (1902) The correction of deflections premaxilla, approach to extensive nasal of the nasal septum with a minimum of septum surgery. Archives of Otolaryngology, traumation. Journal of the American Medical 68, 301. Association, 38, 636. 7. Rubin, F. F. (1983) Controlled tip sculpturing 4. Metzenbaum, M. (1929) Replacement of the with morselizer. Archives of Otolaryngology, lower end of the dislocated cartilage versus 109, 160-163. submucous resection of the dislocated end of

Acknowledgement: We are grateful to the Secretary, Swami Satyadevananda Maharaj, Vivekananda Institute of Medical Sciences for allowing us to publish the article. We are thankful to Dr. Abhishek Gupta, DNB PGT, for helping us in preparing the article. We are also thankful to all the doctors in the department for their assistance.

30 Review Article Prescriptions for the Mind...... Neither Mindlessness Nor Brainlessness, Brain-Mindfulness Paradigm Dr. Uday Chaudhuri1, Dr. Ishan Chaudhuri2 1950 onwards academic Psychiatry was Almost simultaneously, the European dominated by psychodynamic theories, Commission announced that the Human Brain psychotherapy and psychosocial interventions. Project would be awarded 1.19 billion euros During that period Psychiatry suffered from the (about $ 1.6 billion) to create a computer lack of knowledge about the brain. The Harvard simulation of the human brain. Using the power Psychiatrist Leon Eisenberg rightly named it — of the biggest super computers on the planet, Brainlessness in Psychiatry. the human Brain Project will create a copy of 1990 onwards the period was announced as the the human brain made of transistors and steel. Decade of Brain. We saw phenomenal advances Key Wards : Brain-Mindfulness, Psychotherapy in brain imaging, electrophysiological and Three Approaches to the Brain : multimodal studies of neurosciences. Empowered Brain is so complex, there are at least three by that knowledge there was a revolution in distinct ways in which it can be taken apart, psychopharmacology. Today psychiatrists are neuron by neuron. The first is to simulate the busy prescribing drugs only. The pendulum has brain electrically with super computers, which swung from one direction to the other. Leon is the approach being taken by the Europeans. Eisenberg pointed out that Psychiatry was The second is to map out neural pathways of suffering from mindlessness. In January 2013, living brains, as in BRAIN (either anatomically, two bombshells were dropped that could alter neuron by neuron or by function and activity). the medical and scientific landscape forever. And third, one can decipher the genes that control First, in his State of the Union address, president the development of the brain, which is an Barack Obama stunned the scientific community approach pioneered by Paul Allen of Microsoft. by announcing that federal research funds, There is a caveat in the concept. Instead of perhaps to the tune of $3 billon might be allocated modelling the entire brain, Scientists try to to the Brain Research through Advancing duplicate just the connections between the cortex Innovative neuro technologies (or Brain) and thalamus where much of brain activity is Initiative. Like the Human Genome Project, concentrated. This means that the sensory Which opened the floodgates of Genetic research, connections to the outside world are missing in Brain will pry open the secrets of the brain at this simulation. Today, using the full power of the neural level by mapping its electrical the Blue Gene Computer Scientists have pathways. Once the brain is mapped, a host of simulated 4.5 percent of the human brain’s intractable diseases like Alzheimer’s, neurons and synapses. Schizophrenia, bipolar disorder, Autism might In the decade of brain, many prefers to talk be understood. about brain disorder in place of mental disorders. 1Prof., Unit of Psychiatry, RKMSP, VIMS 2PG, Resident, Dept. of Psychiatry, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra 31 There is not a single mental of neurological Several factors contribute to this shift of focus: diseases in which anybody knows what is 1) The discovery of neurobiological malfunctioning in this circuit which pathway, correlates. which synapse, which neuron, which receptor. 2) A shift towards the medical model as the Brain can be thought of as hard disc of the dominant paradigm away from bio- computer simulation. The software comes from psychosocial model. the environmental and outside connections with 3) The efficacy assessment of psychotropic the world at large- culture & social factors are drugs by RCT and rise of quasi-scientific important in software and make it holistic one. evidence based psychiatry. In this conundrum of paradigm shift the burning 4) Equating genes with mental diseases and question is the role of psychiatrists. Psychiatry over expectation from the Human Genome has now become very much biologically focused. Project. Psychotherapy and psychosocial orientation are 5) The considerable influence and financial equally important in patient care to promote power of the psychopharmacological functional recovery in the continuum of industry. Patienthood to Personhood. Biological There has been a visible decline in provision of reductionism has created a blind spot in the psychotherapy in postgraduate training program mindscape of psychiatrists by three false and in clinical practice. The place of assumptions : psychotherapy in psychiatry is endangered. In 1) Genes = Disease. the present scenario should psychiatrists continue 2) Patients present with single disorder that to focus on this reductionistic “bio-bio-bio” responds to single evidence based model or broaden its medical model for treatment. integration of brain and mind — Brain- 3) The best treatment is pills. Mindfulness Paradigm? Hundreds of studies suggest that behavioural, Psychiatry is more than applied neuroscience. psychodynamic and other forms of psychotherapy It is Humanistic Medicine. Integration of are effective treatments. The combination of Psychopharmacological therapy (bottomup medications and psychotherapy is often better approach) and psychotherapy (topdown than either used alone. Brain changes associated approach) will make psychiatry unique and very with psychotherapy, as seen by imaging special in the medical arena . techniques, allow therapy responders to be False assumptions in psychiatry : We need to differentiated from non responders. correct our biologically reductionistic stance as Psychotherapy is as much a medical treatment well as three critical false assumptions connected as pharmacotherapy as scientists have pointed with patient care. out. Inspite of this, psychotherapy and False Assumpsion # 1 : GENE = DISEASE : psychosocial interventions have taken a backseat Mental Disorders are clearly heritable. It was in the present scenario. Psychiatrists today focus hoped that sequencing of human genome would on single diagnosis as per ICD or DSM and the reveal the genetic underpinnings of mental only modality of treatment is pharmacotherapy. disorders. In schizophrenia, over a hundred

32 relevant genetic loci have been identified, is a function not only of genes but also of indicating a very complex and polygenic Environment squared (a function of both the inheritance. Genome Wide Association Studies early and recent environments). Recently there (GWAS) in large samples of depression did not has been an effort to include environmental reveal meaningful SNPs that illuminate the factors in the search for biomarkers. genetic basis. No biomarkers for any mental According to Holmes : disorders have been found to date and some have Phe = GE2 likened the search to that of the Holy Grail. l Phenotype is a function of genes and Tully et al report that the presence of maternal l of the environment squared (i.e both depressive disorder during child rearing increase the early and recent environments). the risk of depression in both adopted and nonadopted adolescents. Other studies provide False Assumption #2 : Patients present with support to the theory that early adversity is an single disorders that respond to specific important “Enviromarker” associated with the evidence based treatment. risk of mental disorders. Hence it is logical to Practice guidelines and RCTs generally assume deduce that psychotherapy and psychosocial that most patients have single disorders that treatment will have a great impact in patient care. respond to evidence based medicine, which are The biomedical approach focuses on a tested in carefully selected, non- comorbid “vulnerability model” of disease rather than a samples. How far this assumption fits real world “plasticity model”. This is a genuine blind spot patients is anybody’s guess. in psychiatry. Results from authentic STAR*D sample suggests A plasticity model, with its concept of almost 78% had comorbid conditions that RESILIENCE lays great importance on past and exclude them from RCTs. The response and present beneficial environment and relationships, remission of depressive symptoms are 39% and highlighting the value of psychosocial 25% respectively. Other evidence from the intervention. Environmental factors interact with Collaborative Longitudinal Personality Disorder genes to shape individuals by turning genes on Study (CLPS) suggests personality disorders and off. It is more Gene-by-Environment (G×E) specially BPDs robustly predicted persistence than genes alone. Epigenetic model is the recent of MDD. The mainstay of treatment of way of expression of bio-psycho-social model. personality disorders is psychotherapy. Hence British psychotherapy researcher, Holmes opines there is substantial evidence that most patients that “Phenotype does not come just from genes present with multiple disorders and comorbidity. but rather, Phe = GE2”. Here Holmes mirrors The future of psychotherapy and integration of Einstein’s transformative E = mc2 equation that psychosocial intervention in patient care will taught us energy and matter are different depend on the psychiatrists ability to make a manifestations of the same entity and even a mid course correction of the false assumption small amount of matter can produce a huge about patients and the treatment they need. amount of energy. In this transformation Phe = FALSE ASSUMPTION # 3 : The best GE2 equation, Holmes suggests that phenotype treatments are pills.

33 Current psychotropic medications are essay “Psychotherapy and single synapse” undoubtedly effective and powerful agents with emphasised that psychotherapy works at the their limitations as well. Antidepressant efficacy same level in neural circuits and synapses as studies are confounded by high placebo response drugs. Psychotherapy changes gene expression. rates. Effect sizes of psychotherapy are greater Learning changes neural connections. This point than the effect sizes of medications. There is of view integrates brain and mind in the frontiers evidence that patients with chronic and complex of neuroscience. This echoes the opinion of comorbid depression, specially those with history Leon Eisenberg “Neither mindlessness nor of early adversity respond well to CBT and other brainlessness, brain-mindfulness “is the forms of psychotherapy. Similarly cluster B paradigm of patient care for today and tomorrow. personality disorders respond well with DBT The mission of psychiatry : We look forward and CBT more than medications. to a psychiatry that is neither brainless nor Nemeroff et al conclude “Our findings suggest mindless but focuses on brain-mindfulness. This that psychotherapy may be an essential element will help in patient care. The most important in the treatment of patients with chronic forms responsibility is to care for the large number of of major depression and with a history of people with mental illness who are victims of childhood trauma”. Jerome Frank says stigma, myth and misconceptions. Research will “Psychotherapy is not a technical procedure but continue to influence the future of psychiatry. a healing relationship — in which patients arrive As science develops, and as the mind and the demoralized and hopeless but improve by brain are better understood, new methods of regaining morale and hope. Therapist is an expert treatment will emerge. The commitment of companion who understands patients distress psychiatry should be to science and science tells and help him out of morass. Empathy and feel us both biological and psychological good factor in therapeutic alliance is the lynch interventions are each in their own way, pin of functional recovery. Eric Kendel in his prescriptions that can heal the mind.

Reference : 1. Anderson N.C.(2001): Brave new : Conqusing mental 6. Eisenberg, L(2000). Is Psychiatry more mindful & illness in the era of genome. New York; Oxford brains than it was a decade age? British Journal of University Press. Psychiatry (1-5). 2. Applebaeen P. (2004). Forenward. In J. Raddig(Ed), 7. Fisher, S & Greenberg R. (1996) Freud scientifically The Philosopy of psychiatry (pp. VII-IX) New York; reappraised: testing the theories and therapy, New Oxford University Press. York; Wily & Sons. 3. Bliss, M(2002). William Osler; A life in medicine. 8. Holnnes, O.W. (1972). Theworks of oliver Wendell Torento, ON: University Torento Press. Holines. St. Clair Shores, MI: Scholary Press. Pp 4. Devan, MJ., Steenbarger, B.N. & Greenberg R.P 306-309. [Eds]; 2004, The art and science of brief 9. Insel. T, & Quirion, R,(2005). Psychiatry as a psychotherapies; A reaction’s guide, Washington, clinical neuroscience discipline. JAMS: The Journal DC; American Psychiatric publishing. of American Medical Association, 294, 2221-2224. 5. Eisenberg, L.(1986), Miudlessness and brainfulness 10. Lambert, M (2003), Bergin and garfield’s Handbook in psychiatry, British Journal of Psychiatry, 148, of Psych..... and behave is change. New York: Wiely. 497-508.

34 Special Article SERVQUAL: A Service Quality Model to Measure Performance of Eye Hospitals for VISION 2020

Dr. Bhaskar Mukherjee1, Dr. Malini Majumdar2 Introduction : 90% of blindness in South East Asian region is Marketing of healthcare services focuses on avoidable i.e preventable & curable. The identifying marketing opportunities, Zeroing on prevalence of cataract in India increases with the target market, strategising marketing efforts each decade of life. From a low of 3.1% in the and implementing and controlling them. In this age bracket of 40-49 years, it progressively respect,we propose that a model study can be increases to 75.2% in the age bracket of 70-80 done to analyze services marketing measures years. It is said that every individual will adopted by Kolkata eye hospitals in cases of ultimately develop a cataract provided he lives cataract surgery and whether they are at par a long life.[6] with the objectives of VISION 2020, formulated Measure of prevalence for cataract as a disease by WHO. causing blindness indicates that approximately The healthcare market in India, with a 7 million people suffer from cataract-induced population of 121 million growing at an average blindness whereas these cases are added by rate of 1.96% per annum, has the potential to 6.15 million every year, which can be become a huge market.[1] The National Health termed as incidence.[7] Accounts Report 2004-05 predicted that the cost Key Word : associated with health infrastructure would grow SERVQUAL - Performance of Eye Hospitals - at an average of 5.8% per annum between 2009 Vision 2020 and 2013, covering all the states of India, Cataract : while the total expenditure in 2013 stood at USD Cataract is a condition in which the clear lens 14.2 billion.[2] However, in 2012, the sum ofof the eye loses its transparency to become public and private health expenditure stood at progressively opaque. 4% of GDP, which indicates of having only USD The Procedure - Cataract surgery procedures 157 as per capita expenditure on health.[3] are of three types. The National Health Accounts Report covers 1. Extra capsular cataract extraction-ECCE. 32 states, and West Bengal figures as one of 2. Small incision cataract surgery-SICS or the six states forecasted to account for Manual Phaco approximately 50% of this expenditure.[4] 3. Phacoemulsification Among all the non communicable diseases 4. Femto second laser cataract surgery leading to decrease of manpower of a nation & DALY (Disability adjusted life year), blindness However, despite increase in the number of due to cataract is one of the most important cataract operations, the cataract surgery rate diseases.[5] remains low as there is a rapid increase in the 1Consultant Ophthalmologist, Medical Superintendent, Dr. Nihar Munshi Eye Foundation, Kolkata; 2Assoc. Prof., Army Institute of Management

35 number of new cataract cases as a result of the pace, the backlog of operable cases will continue growing population, particularly the geriatric to increase. The backlog of cataract cases is population. more prevalent in the rural areas, especially The cataract surgical rate in India is about 3400 among females, schedule castes & labourers. per million of population. The principal cause In India, considering its population, even 1% of blindness in India today is cataract, responsible blindness cases (vision 6/60 or less than 6/60) for about 62.6% of all cases.[8] amounts to 1 crore 21 lakhs patients. In India, as per the statistics published by the Approximately 62% of this (7.2 million) are National Programme for control of blindness cataract-induced blindness. Incidence rate, as (report as on 30-9-2013), national target of defined before, is 0.4 to 0.5%. Thus the cataract operation is 7000000. Number of Cataract opportunity for fresh cataract surgery cases each operations achieved till date (National) is year stands at 61.5 lakhs (6.15 million).[11] 1716582. In the year 2011-2012, number of Therefore to eradicate avoidable blindness, cataract operations done (National) was World Health Organization (WHO) had 6349205.[9] formulated an action plan named Vision 2020 Similarly in West Bengal target for cataract in February 1999. operation in West Bengal (2013-14) was 529820 Objectives of Vision 2020 – Who Guidelines[12] and the number achieved as on 30/9/2013 was 1. To increase awareness, among the 69367. Target for cataract operation in West population, regarding the causes of Bengal in 2011-2012 was 456000 and achieved 2. Avoidable blindness and the solutions to the was 345352.[10] problem; These figures show that there exists a backlog 3. To advocate for and find the necessary in cataract surgery. More emphasis has to be resources to implement the WHO Global given on cataract surgery at optimum cost in Plan 2014-19; and high volumes. 4. To facilitate the planning, development Phacoemulsification is considered as the “gold and implementation of National standard” for cataract surgery. However, it is 5. Vision 2020/ Eye Health programmes in all neither practical nor feasible to adopt this for the countries, who are signatories to Vision entire population suffering from cataract. 2020. SICS, on the other hand, is as a low cost, but National Programmes have three main elements; equally effective technique and thus is a viable 6. To control the disease in a cost effective alternative for a country like India, where manner. developments are unequal across categories of population. 7. Development of available human resource. As the life expectancy of the population increases, 8. Development of infrastructure and more & more patients with cataracts will be technology. identified. If surgical performance does not keep Achieving the mission of Vision 2020 needs not

36 only the development of affordable technology with ensuring the quality of the delivered service. and infrastructure, but also a successful Service quality, however, is defined as implementation of the programme through ‘customers’ perception of how does a service properly managed healthcare support maintaining meet or exceed their expectations”. Several a considerable level of quality. The stakeholders practitioners define service quality as “the need to be aware of as well as perceive the quality difference between customer’s expectations for of the service providers in this regard. the service encounter and the perception of Service Marketing by Eye Hospitals : service received”.[15] Customers judge quality as “low” if performance (perception) does not “Services are economic activities offerered by meet their expectation and judge quality as one party to another which is often time-based. ‘‘high’’ when performance exceeds expectation. In exchange for money, time and effort, for which customers expect value from access to Servqual : goods, labour, professional skills, facilities, Service quality is often measured using models, networks, systems; but they do not normally take and the most acknowledged and applied model ownership of any of the physical elements is the SERVQUAL (service quality) model involved”. Therefore, Health care Marketing by developed by Parasuraman et al (1985), which various Eye Hospitals is services marketing.[13] measures the quality against five dimensions. Service Marketing is defined by the American These five dimensions are : tangibles (Physical Marketing Association as “a process of planning appearance of the facilities, equipments, people & executing the conception, pricing, promotion and other materials associated with the service & distribution of services to create exchanges delivery), reliability (delivering the service as that satisfy individual & organizational goals. promised, with accuracy), responsiveness Service marketing has increased in importance (responding to customers’ queries promptly over the last decade with the advent of and willingness to solve customers’ problems competition”.[14] sincerely), assurance (knowledge, skill and Health care organization has to decide how to ability of the employees to solve the problems divide the total health care marketing budget encountered during service delivery and gaining among the various tools in the marketing mix trust and confidence from the customers), and (the 7 P’s) empathy (individual attention to the customers 1. Product so that everyone feels special). However, among 2. Price all these dimensions, reliability is considered to be most important in relation to the quality 3. Place or distribution aspect as other dimension will be taken into 4. Promotion (or communication) consideration if and only if a service is reliable.[16] 5. Process Research Gap : 6. Physical environment Although there are various single speciality 7. People. (Ophthalmology) and multispecialty hospitals Marketing of any service is always associated in Kolkata performing cataract surgery on regular

37 basis, yet have no previous study has been primary data will be collected through structured conducted on ascertaining the SERVICE interview techniques and non-disguised QUALITY perception of patients and doctors in questionnaire to Medical Superintendent / CEO relation to cataract surgery performed by Kolkata / HOD of Ophthalmology of various Kolkata hospitals. It is also important to find out what based hospitals conducting cataract surgery measures the hospitals are taking to bridge the regularly. Patients undergoing cataract surgery gap between perceived and delivered service. at these hospitals will be interviewed to know Therefore the research gap exists. the level of customer perception in relation to Objective of Study Model : service quality. 1. To study services marketing strategy related Data Collection Tools : The tools for collecting to cataract surgery by various Kolkata based data shall be structured, undisguised hospitals, in order to verify whether there questionnaire. However, sometimes researcher exist relationship between the 3P’s namely may use depth interviews to unravel the attitudes, process, physical evidence and people. as and when required. 2. To assess how the important factors influence Scales- In our study we can use ordinal scales. services quality of these hospitals. Sample size - The sample size shall be variable 3. To analyze the target markets of these and evolving. The target respondents will include hospitals. MS/CEO/HOD of Ophthalmology, of Kolkata eye hospitals, and patients undergoing cataract 4. To analyze and interpret whether their surgery there. services marketing techniques is in tune with the increasing social requirements like Hypothesis - These will be framed to understand cataract surgery backlog and recent how far the service quality dimensions are developments in the medical sciences. important for perception of service quality. Each hypothesis will be tested by using Chi-square 5. To analyze if Kolkata hospitals conducting test and final inferences can be framed. cataract surgery can deliver the expected service quality, in sync with the objectives Formulation of Hypothesis: of Vision 2020. H0- there is a significant difference between Research Methodology Model : services delivered by hospitals and WHO Vision 2020 guidelines. Research Design : Research design could be descriptive in nature, highlighting on identifying H1- there is no significant difference between the factors influencing the service quality for the services delivered by eye hospitals of Kolkata hospitals and studying their performances in and WHO Vision 2020 guidelines. delivering quality service. H2- the service quality dimensions are perceived Source of Data :The data shall be primary and to be important to fulfil patients’ (customers) secondary data. The secondary data shall be satisfaction. institutional and commercial data available Data Analysis Tools - Data analysis shall be publicly and for commercial use from available carried out using the tools including both of publications and other official sources. The descriptive & inferential statistics.

38 Conclusion : serve as a guide for adopting measures This model study could identify the dimensions appropriate in bridging the gap/s. The study of service quality that are relevant both for the could also qualitatively focus on what measures medical professionals and patients in perceiving the hospitals are taking in fulfilling the objectives the quality of service delivered by the hospitals. set by WHO towards achievement of Vision The inferences could help the hospitals in 2020 and how the service quality dimensions finding out where the gap/s lie between perceived are gaining significance in achieving so. This and delivered service quality and will definitely could be the implication of our proposed study.

References :

1. Srinivasan SA, Managing a Modern Hospital, Response 12. Books, New Delhi, 2009;73. accessed on 12.12.2015 2. accessed People, Technology, Strategy, Pearson Education, on 21.11.2015 Noida, 2011;15. 3. accessed on 21.11.2015. Management-A South Asian Perspective, Pearson 4. National Health Accounts publication,2004-05 Education, Noida, 2009;06. 5. Park K, Park’s Text Book Of Preventive and Social 15. Munusamy J, Chelliah S, Mun H, Service Quality Medicine, M/S Banarsidas Bhanot, Jabalpur,2009;375 Delivery and its Impact On Customer Satisfaction in the Banking Sector in Malaysia, International Journal 6. Murthy GVS. Primary Eye Care and Epidemiology of of Innovation, Management and Technology, 2010; Common Eye Diseases. 1(4), 398-404. National Society for the prevention of blindness India. 16. Parasuraman A, Zeithaml VA, Berry, LL, A conceptual Quarterly Publication.2013;38(2):4-10. model of service quality and its implications for future 7,8,9,10,11. accessed on research, Journal of Marketing,1985;49(3),41-50. 20.10.2015

39 Case Report Epidermolysis Bullosa Pruriginosa: Successfully Treated with Topical Tacrolimus

Dr. Heena Parmar1, Dr. Leelavathy Thiyagarajan2, Dr. Jayanta Kr Das3, Dr. Asok Gangopadhyay4

Abstract : codon of COL 7A (G2028R and G2028A).[3] Dystrophic epidermolysis bullosa is a rare and This form of inherited epidermolysis bullosa clinically heterogeneous mechanobullous may not clinically develop until adult life, leading disorder. One unusual clinical variant is to confusion regarding it's inherited nature.[4] epidermolysis bullosa pruriginosa (EBP), in Case Report : which the combination of pruritus and skin A 21-year-old male patient presented to our fragility can lead to hypertrophic, lichenified outpatient department with complaint of blisters nodules and plaques. Here we report a case of all over body since the age of five years. The epidermolysis bullosa pruriginosa in a 21-year- blisters first appeared on the scalp, progressed old male patient who presented with albopapuloid to involve back, chest, arms, thighs and legs, and prurigo-like lesions over body including and healed with pruritic papules or scars. Prior scalp, causing alopecia, since five years of age to his visit to us, he had been treated for the skin and was successfully treated with topical disease with various modalities, including topical tacrolimus for both body and scalp lesions. and systemic steroids, with no long-lasting Keywords : benefit. No family members of the patient had any similar skin disease. Cutaneous examination Epidermolysis Bullosa, Preriginosa; Alopecia; demonstrated whitish papules (the so-called Tacrolimus albopapuloid lesions), as well as prurigo-like Introduction : lesions over back [Figure 1] and chest [Figure Epidermolysis bullosa pruriginosa (EBP) presents 2]. There were pruriginous papules in linear either at birth with mild acral blistering and distribution over both the shins. There were erosions, or during infancy or childhood. It is irregular patches of alopecia mostly on the characterized by extremely pruritic, lichenified temporal region of the scalp above both the ears, or nodular lesions predominantly over legs, milia with crusting, scaling, and prurigious papules formation and albopapuloid lesions on the trunk. scattered over the hairless areas. Mucosae, nails, Most cases are sporadic[1]; however, bothpalms and soles were free from any lesion and autosomal recessive and dominant inheritances teeth were normal. Systemic examination was are recognized.[2] The study of the molecularunremarkable. Complete blood count, routine basis of dominant dystrophic EB (classical) and blood biochemistry and urine examination were EB pruriginosa shows that both diseases are within normal limits. Immunoglobulin E level caused by a missense glycine substitution was elevated (880 IU/ml). Histology of a lesion mutation by different amino acids in the same on the back showed sub-epidermal separation 1, 2 MBBS, DVD, Medical Officer, Deptt. of Dermatology, RKMSP, VIMS 3MD (Dermatology & Venereology), Prof., Deptt. of Dermatology, RKMSP, VIMS 4MD (Dermatology & Venereology), Prof. & Head, Deptt. of Dermatology, RKMSP, VIMS

40 Fig. 1. Prurigo like lesion over back. Fig. 4. Post treatment after 6 weeks demonstrated reduction in lichenified plaques over back.

Fig. 5. Post treatment after 6 weeks demonstrated Fig. 2. Albopapuloid and prurigo like lesion over reduction in lichenified plaques and scarring over chest. chest.

Fig. 3. Histopathology of body lesion. (H&E, X10). Sub-epidermal separation with variable mixed Fig. 6. Post treatment of scalp lesion after 6 weeks inflammatory cell infiltrate in the upper dermis. showed reduction in scaling.

41 with mixed inflammatory cell infiltrate in upper Ultrastructurally, there is blister formation below dermis [Figure 3]. Histology from scalp lesion the level of the lamina densa, and quantitative showed sub-epidermal separation. Direct or qualitative changes in anchoring fibrils at the immunefluorescence (DIF) of the lesional and dermoepidermal junction. Reduction in perilesional skin was negative for IgA, IgG, IgM anchoring fibril numbers is found in lesional, and C3 in both the areas. We diagnosed it as a perilesional and non-lesional skin of patients case of epidermolysis bullosa pruriginosa on the with EB pruriginosa.[7] However, we could not basis of long history, albopapuloid lesions, perform electron microscopy (EM) or antigen pruritus, histopathological finding of dermo- mapping (as alternative to EM to determine the epidermal separation and negative DIF. The level of blister formation) in our case as we do patient was advised topical tacrolimus ointment not have facility for the same. (0.1%) and lotion (0.03%), to be applied twice Treatment is aimed at controlling pruritus and daily, for body and scalp lesions respectively. halting the progression of cutaneous lesions. When the patient came for follow-up after 6 weeks, he had significant relief from itching, Potent topical steroids and intralesional and reduction of both body and scalp lesions triamcinolone have been reported to reduce the [Figure 4], [Figure 5], [Figure 6]. pruritus in some cases, but don’t produce sustained improvement. Other helpful Discussion : interventions include topical tacrolimus[8], EBP is a type of dystrophic epidermolysis bullosa systemic cyclosporine[9], cryotherapy[10]. (EB) described by McGrath in 1994.[5] In the Tacrolimus is a macrolide immunosuppressant one original series of eight cases reported by produced by the soil fungus streptomyces McGrath, three had family history of similar skin tsukubaensis. We believe that topical tacrolimus disease, with two showing an autosomal dominant has potential benefits over topical corticosteroids and the other an autosomal recessive pattern of when treating epidermolysis bullosa pruriginosa. inheritance. In our case there was no family history of similar complaints, indicating the There are currently no reports of systemic likelihood of its being a sporadic case. However, adverse effects after topical tacrolimus our case is remarkable as involvement of the application. scalp is rare in EBP. To the best of our knowledge, this is the first The exact cause of pruritus in this condition is reported case of epidermolysis bullosa unknown. Possibly, the exposure of type VII pruriginosa from India successfully treated with collagen triggers the activation of the kinin topical tacrolimus. With its steroid sparing effect cascade. Bradykinin, possibly interacting with and lack of documented systemic adverse other mediators, might be responsible for the reactions, we consider topical tacrolimus to be severe pruritus.[6] of significant benefit in treating EB pruriginosa.

42 References :

1. Wojnarowska F, Eady RA, Burge SM. Bullous 6. Anton-Lamprecht 1, Schnyder UV. Epidermolysis eruptions. In: Champion RH, Burton JL, Burn DA, bullosa dystrophica dominans. Eiri Defekt der Breathnach SM, editors. Rook/ Wilkinson/ Ebling anchoring fibrils? Textbook of Dermatology. 6th Ed. Oxford: Blackwell Dermatologica 1973;147:289-98. Science; 1998. p. 1817-97. 2. Mellerio JE, Ashton GH, Mohammedi R, Lyon CC, 7. McGrath JA, Ishida-Yamamoto A, O’Grady A, Leigh Kirby B, Harman KE, et al. Allelic heterogeneity of IM, Eady RA. Structural variations in anchoring dominant and recessive COL7A1 mutations fibrils in dystrophic epidermolysis bullosa: correlation underlying epidermolysis bullosa pruriginosa. J Invest with type VII collagen expression. J Invest Dermatol Dermatol 1999;112:984-7. 1993;100:366-72. 3. Murata T, Masunaga T, Shimizu H, Takizawa Y, 8. Banky JP, Sheridan AT, Storer EL, Marshman G. Ishiko A, Hatta N, et al. Glycine substitution mutations Successful treatment of epidermolysis bullosa with by different amino acids in the same codon of COL topical tacrolimus. Arch Dermatol 2004 7A lead to heterogeneous clinical phenotypes of Jul;140(7):794-6. dominant dystrophic epidermolysis bullosa. Arch 9. Yamasaki H, Tada J, Yoshioka T, Arata J. Dermatol Res 2000; 292:477-81. epidermolysis bullosa pruriginosa (McGrath) 4. Ee HL, Liu L, Goh CL, McGrath JA. Clinical and successfully controlled by oral cyclosporine. Br J molecular dilemmas in the diagnosis of familial Dermatol 1997; 137: 308-10. epidermolysis bullosa pruriginosa. J Am Acad Dermatol 2007; 56:S77-81. 10. Das JK, Sengupta S, Gangopadhyay AK. Epidermolysis bullosa pruriginosa: report of three 5. McGrath JA, Schofield OM, Eady RA. Epidermolysis cases. Indian J Dermatol Venereol Leprol bullosa pruriginosa: dystrophic epidermolysis bullosa 2005;71:109-11. with distinctive clinicopathological features. Br J Dermatol 1994;130:617-25.

43 Case Report Your Suspision May Save A Life

Dr. Pradeep Chakraborty1, Dr. Sujata Mazumder2, Dr. Dilip Kumar Bera3

Abstract : symptoms, altered sensorium or seizures. Secondary HLH or MAS is a severe, potentially He has no significant past medical history life threatening complication of several rheumatic or addictions. disorders or infections. It is charactrized by On admission he was conscious, alert but proliferation of macrophages, which demonstrate restless. He has obesity with a BMI of 33.46. phagocytosis of hematopoetic cells, in bone He has pallor, blanching macular rash over marrow, liver, spleen etc. It is a broader spectrum trunks, face and extremities and few palpable disorder, infection associated called sec HLH anterior cervical lymph nodes. Vitals were and chronic rheumatic disorder called MAS. The stable. He had soft, non tender, smooth disease is characterized by high fever, cytopenias, hepatomegaly 3 cm below right coastal hepatosplenomegaly, CNS dysfunction, margin at mid clavicular line and just coagulopathy. Laboratory features are falling palpable splenomegaly. He has no ESR, raised Triglyceride, ferritin and presence neurodeficit or meningeal signs. Other of macrophage hemophagocytosis in bone system examinations were unremarkable. marrow. Main stay of treatment with supportive Keywords : Secondary Hemophagocytic care, corticosteroids, cyclosporine. Newer Lymphohistiocytosis. advances in treatment are anti thymocyte globulin, Chronic Rheumatic Disorder, Macrophage IVIg, anti TNF agent etanercept, anti IL 1 receptor Activation Syndrome. antagonist anakinra. Though reported mortality Initial investigations: is 15- 60%, early recognition and prompt therapy may give better outcome. Complete Blood Counts A 15 year old boy with no known co u Haemoglobin of 8.6gm/dl morbidities was admitted with the history of u Total WBC counts of 3600 with 65% high grade intermittent fever rising up to 103 neutrophils degrees F, with 3-4 peaks per day, for the last u Platelet count of 1,15,000 8 days. Fever was associated with generalised u LFT showed elevated ALT (356 U/L) AND body ache, headache and anorexia. After 4 AST (412 U/L) days of onset of fever, he developed loose st u ESR was 55 mm 1 hr stools, occurring 3-4 times a day but without any blood streaking, not associated with any u CRP was raised- 24 mg/dl cramps. There was no associated joint pains, u MPDA was negative and no malarial parasite cough, sore throat, shortness of breath, urinary seen on peripheral smear.

1MD, Prof., Dept. of Medicine, RKMSP, VIMS; 2MD, Assoc. Prof., Dept. of Medicine, RKMSP, VIMS; 3MD PGT, Dept. of Medicine, RKMSP, VIMS

44 u Blood Culture was also sent he also developed 3 episodes of fresh lower Initially we proceeded with the clinical diagnosis GI bleeding. With such a devastating turn of Enteric Fever and started treatment with IV of events, we had to rethink our diagnosis. antibiotics and fluid replenishment. Further Investigations Shows: u However, on Day 2 since admission, he u WBC count was further decreased to 2900. developed tachypnoea (respiratory rate of u Platelet count dropped to 50,000/cumm. 40/min), tachycardia (pulse rate 120/min) and rapidly began to desaturate. With the suspicion u Peripheral smear showed microcytic of ARDS, he was shifted to the Intensive Care hypochromic anaemia, anisopoikilocytosis, Unit of our hospital. left shift with toxic granules, no malarial parasite. u Arterial Blood Gas analyses showed: u ESR was 32 mm Hg (decreasing). u PaO2 56 mm Hg u INR became 2.3 from 1.1. u PaCO2 29 mm Hg u Serum ANA, Rheumatoid Factor, Viral u pH 7.62 markers, Dengue IgM, IgG negative u HCO3 23 mEq/L u Reticulocyte count was 1.2%. u Chest X-ray was suggestive of Acute u USG revealed enlarged liver and mild Respiratory Distress Syndrome. splenomegaly but was otherwise normal. u Thus, he was put on Mechanical Ventilation. u Routine urine and stool examinations were normal. u Echocardiography showed no valvular vegetation. u CSF studies showed 4 lymphocytes with normal biochemical parameters and ADA 4.1 mg/dl. u Blood Culture was positive for Salmonella typhi. In this clinical context with diagnosis of sepsis with multiorgan dysfunction or Intestinal Perforation due to Typhoid Ulceration or Splenic Rupture due to Enteric fever orTyphoid fever with haemolytic uraemic syndrome we think about secondary HLH or MAS. u But Even after two days on mechanical ventilation, and stepping up IV antibiotics, Investigations Shows: he showed poor response. GCS was dropping Serum Ferritin was seen to be highly raised and he showed a worsening sensorium. Now (>6000mg/dl).

45 u LDH levels>600mg/dl. u He attended the Medicine OPD 2 weeks and u Serum Triglycerides>650mg/dl. 1 month after discharge, and continues to be afebrile with no new complaints. u Coagulation Profiles (PT, APTT) were significantly altered with Fibrinogen Secondary Haemophagocytic Lympho- <150mg/dl and detectable fibrin degradation histiocytosis and Macrophage Activation products. Syndrome : u With pancytopenia, hepatosplenomegaly and u Haemophagocytic Lymphohistiocytosis lymphadenopathy, with acute GI bleed, we (HLH) is a rare but potentially fatal disease went for a bone marrow biopsy. of normal but overactive histiocytes and u Macrophage Haemophagocytosis seen on lymphocytes, commonly appearing in Bone Marrow biopsy slides. infancy but also seen in older age groups. u Primary HLH is an inherited form, with heterogenous autosomal recessive inheritance. Secondary HLH occurs after strong immunologic activation, i.e., with systemic infection, immunodeficiency or underlying malignancy. u Macrophage activation syndrome (MAS) is a part of the broader spectrum of secondary HLH where it occurs as a life threatening complication of severe chronic rheumatological disorders of childhood. The diagnosis of HLH may be established by u With the diagnosis of HLH we started high dose IV Methylprednisolone therapy at 1. A molecular diagnosis consistent with HLH 30mg/kg for 3 days, followed by 2mg/kg IV (for example, pathologic mutations of PRF1, in 4 divided doses for the next 4 days. UNC13D or STX11 are identified) u Supportive management in the form of FFP OR transfusion given also. 2. Fulfilment of five out of the eight criteria u Antibiotics given and proper nutrition listed below: maintained. Fever > 38.5o C u Within 3 days of initiation of said therapy, Splenomegaly he showed dramatic response and could be Cytopenias (affecting at least two of three taken off of ventilator support. lineages in the peripheral blood): u His blood counts improved and he became Hemoglobin <9g/100ml (in infants <4 weeks: th afebrile by 7 day since admission. hemoglobin <10g/100ml) u He was discharged after a few days of close Platelets <100 103/ml observation in the general ward. Neutrophils <1 103/ml 46 Hypertriglyceridemia (fasting, 265mg/100ml) complication of several chronic rheumatic and/or hypofibrinogenemia (150mg/100ml) diseases of childhood caused by activation and Hemophagocytosis in BM, spleen or lymph uncontrolled proliferation of T lymphocytes and nodes well differentiated macrophages leading to widespread hemophagocytosis and cytokine Low or absent NK cell activity overproduction. It commonly occurs with Ferritin 500ng/ml Systemic Onset Juvenile Idiopathic Arthritis. It Soluble CD25 (that is, soluble IL-2 receptor) has been commonly described with SLE, >2400U/ml (or per local reference laboratory) Kawasaki disease or Adult Onset Still, s Disease. Secondary HLH is associated with infection and Primary Diagnostic Guideline for MAS as a sepsis. Complication of SOJIA : Pathogenesis of MAS or HLH is poorly Laboratory Criteria : understood. The cytotoxic activity of NK cells 1. Decreased platelet count <262 x 109 / L and T lymphocytes is mediated by release of 2. Increased AST cytolytic granules which contains performing, granulozymes and other serine proteases to the 3. Decreased WBC Count <4000/cmm target of cells. 4. Hypofibrinogenemia Mutations in several genetic loci related to Clinical Criteria : release of cytotoxic granules (i.e polymorphism 1. CNS Dysfunction (i.e irritability, or heterozygous mutation in PRF 1 or UNC 13 disorientation, lethargy, headache, seizure or D) causes decreased activity of cytotoxic coma ) granules. 2. Hemorraghe (i.e purpura, easy bruising or This impairment in cytotoxic functions causes mucosal bleeding) excessive expansion and activation of cytotoxic cells and macrophages. 3. Hepatomegaly (3 cm below rt coastal arch) This causes hyper secretion of proinflammatory Histopathological Criteria : cytokines i.e IFN gamma, alpha, IL 6,IL 10,M Evidence of macrophage hemophagocytosis in CSF. These in turn causes tissue necrosis and Bone Marrow aspiration organ failure. Diagnostic Rule : In a 2014 study by Pilonieta et al, it is stated, The diagnosis of MAS requires the presence of “Hemophagocytes, a subset of macrophages, 2 or more laboratory criteria or any 2 or more are characteristic of severe acute infection in clinical/ laboratory criteria. A bone marrow patients with, for instance, typhoid fever, aspiration for demonstration of hem phagocytes brucellosis, tuberculosis, and leishmaniasis. may be required in doubtful cases. Each of these diseases has the potential to become chronic. Hemophagocytes (blood-eating Pathogenesis: cells) engulf and degrade red and white blood It is a severe potentially life threatening cells for unknown reasons. The bacterial

47 pathogen Salmonella acquires the essential or anti TNF agent, Etanercept may be used nutrient iron from murine hemophagocytes. but these may trigger infection susceptibility. We report that Salmonella stimulates u Supportive treatment with transfusion of macrophages to engulf blood cells, indicating RBC, platelets or FFP, antibiotics, may be that cells of this bacterium actively promote the needed along with proper nutritional support. formation of a specialized cellular niche in which Prognosis : they can acquire nutrients, evade killing by the host immune system, and potentially transition u It is related to the severity of infection. to chronic infection. u Such patients require close monitoring as Management And Follow up: recurrence may occur. u Mortality may be 15-60% but statistics are u IV Methylprednisolone 30mg/kg for 3 consecutive days, followed by 2-3mg/kg/day improving with early intervention. in four divided doses or Dexamethasone IV u A high index of clinical suspicion is to be at 6mg/m2. maintained due to the swift progression of HLH and possible mortality and morbidity. u Cyclosporine A may be used in Familial or severe or Corticosteroid resistant HLH after In patients with high grade fever, pancytopenia, 24-48 hours of no response, at 2-7mg/kg/day hepatosplenomegaly and lymphadenopathy, IV. presenting with bleeding manifestations, HLH is to be kept as a differential diagnosis as it u High dose IVIG, cyclophosphamide, plasma exchange, etoposide have been tried with shows dramatic response when therapy is started conflicting results Antithymocyte Globulin early. Thus an early diagnosis could save lives.

Reference : l Harrison’s Textbook of Clinical Medicine, 19th edition. l Koul PA, Khan U, Shah S, et al. Adult hemophagocytic l API update 2015. lymphohistiocytosis: a 25-year experience at a tertiary l Huang DB, Du Pont HL. Problem pathogens: extra- care hospital. Webmed Central Infectious Diseases intestinal complications of Salmonella enterica serotype 2010; 1:WMC00674. Typhi infection. Lancet Infect Dis. 2005; 5:341–8.

48 Case Report A Case of Diuretic Induced Hyponatremia Dr. Ankit Roy1, Dr. Soumen Bhat2, Dr. Debdatta Kar3, Dr. P. Mukherjee4, Dr. Dinabandhu Naga5, Dr. S. Roychowdhury6, Dr. P. Banerjee7, Dr. Jayanta Chakraborty8

History : was unable to maximally dilute the urine in A 44-yr old man, Mr. PD, presented to us with response to hyponatremia. Serum TSH was 0.71 complaints of headache, dizziness and vomiting microU/ml Ft4- (no hypothyroidism) and for the past 1 week. He had no history of fever morning 8 am serum cortisol was 38.0 or any other signs or symptoms suggestive of a microgm/dl (no adrenocortical insufficiency). local infection. Neither were there any features By this time it came to our knowledge that the of a neurological deficit. He was also a recently patient had been on Chorthalidone as a part of diagnosed hypertensive, on a prescribed oral his antihypertensive medication. Thus the cause antihypertensive drug, the details of which he of hyponatremia was established to be induced was unable to remember at the time of admission. by a diuretic. Serum uric acid was also low. No other significant past history was present. Management : Key Word : Since the symptoms of the patient could be Hyponatremia - sodium imbalance described as mild, at best, it was decided that a slow and cautious approach would be taken to Work-up : correct his Serum Na+ level. He was administered On examination, patient was well-oriented with oral salt, i.v. 0.9% NaCl 500 ml 12 hourly and most clinical parameters within normal limits. his oral water intake was restricted to 500 ml/day. His tongue was moist. No edema was present. The steady improvement in serum Na+ level Blood pressure was 130/80 mm of Hg. could be seen as follows : Neurological examination did not reveal any neurodeficit. Posterior column signs were absent, l Day 0: 98 meq/l as were cerebellar signs. l Day 1: 102 meq/l

His blood was sent for routine investigations l Day 2: 110 meq/l which revealed a Serum Na+ level of 98 meq/l. l Day 3: 115 meq/l calculated serum osmolality was 216 mosm/l. As neither edema nor dehydration was present, l Day 4: 123 meq/l the case was classified as one of euvolemic l Day 5: 128 meq/l hypotonic hyponatremia. l Day 6: 136 meq/l Urine Osmolality was 185 mosm/l and urinary Following this, intravenous NaCl and oral salt spot Na+ was 35 meq/l, both of which werewere stopped and oral fluid intake was increased inappropriately high. This meant that the kidney to 1.5 l/day. Serum Na was maintained at 136

1,2,3MD (PGT); 4MD Asst. Prof.; 5MD (PGT); 6MD MRCP, Prof.; 7MD Prof.; 8MD Prof. and HOD, Dept. of Medicine, RKMSP, VIMS

49 meq/l when it was repeated 2 days later. Patient Conclusion : was discharged with advice to avoid diuretics. The management and outcome of this case Discussions : envisage that in cases of chronic (>48hours) Hyponatremia is a recognized complication of euvolemic hypotonic hyponatremia of severe treatment with thiazide diuretics.[1] degree (<125 meq/l) with only mild and no neurologic symptoms, drastic correction of Chlorthalidone and hydrochlorothiazide are Serum Na+ by intravenous 3% NaCl is not widely used as as antihypertensive agents. always required. Adequate improvement in However greater nocturnal blood pressure sodium levels was achieved in this case simply reduction and pleiotropic effects have drawn the by oral fluid restriction and extra salt intake favour of chlorthalidone by many authorities. A and infusion, with withdrawal of the causative recent study has shown increased risk of adverse agent. events with chlorthalidone, including hyponatremia.[2]

References : 1. The silent epidemic of Thiazide induced hyponatremia, 2. Risk of hyponatremia with diuretics: chlorthalidone Samuel J. Mann.vol 10, No 6, 477-484, June 2008, j versus hydrochlorothiazide. Jan C van Blijderveen et Clin. Hypertens. al, Am j Med.2014. Aug 127(8):763-71,

50 Pictorial CME Hirsutism Dr. Debdatta Kar1, Dr. Jayanta Chakraborty2

Glucocorticoid resistance Specific Conditions of Pregnancy : Luteoma of pregnancy Hyperreactio luteinalis Aromatase deficiency in foetus Others : Hyperprolactinaemia Medications (danazol, testosterone, anabolizing agents) Idiopathic Clinical Features : Age of onset- idiopathic hirsutism usually begins at puberty. Hirsutism that occurs in middle age should point towards probable adrenal or ovarian Hirsutism refers to excess growth of terminal tumour. hair in a woman in a male pattern. It is one of Positive family history points towards CAH, the most common endocrine disorders,and implies however, idiopathic hirsutism and PCOS can the presence of abnormal androgen action. also be familial. Causes of Androgen Excess in Women of Early development of adrenarche points towards Reproductive Age : CAH. While ovarian hyperandrogenism is Ovarian : associated with normal adrenarche and delayed Polycystic ovarian syndrome menarche. Physical Examination : Hyperthecosis Ferriman and gallwey scale may be used to Ovarian tumour (eg sertoli leydig cell tumour) quantitate androgen overactivity by judging hair Adrenal : growth in each of the 11 androgen sensitive Nonclassic adrenal hyperplasia areas. In women with moderate to severe hirsutism, additional signs of hyperandrogenism Cushing syndrome like temporal hair recession, oily skin etc may Adrenal tumour (hyperplasia, resistance) be present.

1MD PGT, Dept. of Medicine, RKMSP, VIMS 2Prof. & Head, Dept. of Medicine, RKMSP, VIMS

51 A thorough abdominal and pelvic examination 2. patient counselling and reassurance to look for tumors. 3. systemic therapies- Skin examination to look for acanthosis nigricans. l Oral contraceptives-ethinyl estradiol, Laboratory Investigations : drospirenone and levomefolate

l Initial testing- l Ethinyl estradiol and norethindrone

l Total testosterone l Ethinyl estrdiol and norgestimate

l Prolactin l Ethinyl estrdiol and drospirenone

l TSH Glucocorticoids – prednisone/dexamethasone Further testing based on clinical presentation Aldosterone antagonists-spironolactone

l 17 OH progesterone 5 alpha reductase inhibitors- finasteride

l 17 OH progesterone 60 mins after Flutamide intravenous ACTH Insulin sensitizers-metformin and thiazoli- l Overnight dexamethasone suppression test dinediones

l 8 AM serum cortisol Cosmetic measures-plucking, waxing, hydrogen peroxide bleaching, shaving, chemical l DHEAS depilatories. l Imaging of ovary/adrenals Laser therapy has been shown to be beneficial, Treatment of Hirsutism : not only in reducing unwanted hair, but also to 1. lifestyle modification – in obese, PCOS improve depression and anxiety in women with women hirsutism.

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