An Evidence-Based Approach to the Evaluation and Treatment Of

June 2007 An Evidence-Based Approach To Volume 4, Number 6 The Evaluation And Treatment Of Author Brent R. King, MD, FAAP, FACEP, FAAEM Pharyngitis In Children Professor of Emergency Medicine and Pediatrics; Chairman, Department of Emergency Medicine, The University of Texas Medical School at Houston, TX You are somewhat puzzled as you enter the examination room. The chart in your hand has a chief complaint of “strep throat, not getting better,” which is, Peer Reviewers in your experience, unusual. Joseph Toscano, MD In the room, you find a mother and her adolescent daughter. The girl looks Emergency Physician, San Ramon, CA tired and pale, but not seriously ill. Her mother looks at you and, with near-des- peration in her voice, says, “I hope you can help us, Doctor. My daughter has Paula J. Whiteman, MD, FACEP been to our regular doctor twice and to another emergency room. She is on her Medical Director, Pediatric Emergency Medicine, Encino-Tarzana Regional Medical Center; Attending third different antibiotic but her throat is still sore and she sometimes has trou- Physician, Cedars-Sinai Medical Center, Los Ange- ble swallowing. This afternoon she really scared me because she said she was les, CA having trouble breathing!” When you examine the girl’s throat, you see very swollen tonsils coated with CME Objectives exudates. You are momentarily confused but then remember something from After reading this article, you should be able to: way back in residency. You look at the mother and say, “Ma’am, I think I know what’s wrong but I need to do a blood test to be sure.” 1. Identify life-threatening causes of pharyngitis in children. or most experienced clinicians, sore throat is a “run of the 2. Describe the differences between the recom- mended diagnostic evaluation of older adoles- Fmill” complaint and hardly a reason for serious concern. cents and younger children. However, sore throats can herald life-threatening illnesses. Addi- 3. Discuss the role of the clinical examination in tionally, the management of this “simple” condition is the subject the management of the child or adolescent with of considerable controversy. Most physicians understand that pharyngitis. pain relief and hydration are important considerations in all 4. Describe the role of various testing strategies in patients, but there is considerable disagreement regarding the cri- the evaluation of the child or adolescent with teria by which patients with group A beta hemolytic streptococcal pharyngitis. pharyngitis are identified, and there is some disagreement 5. Discuss the treatment of pharyngitis, including regarding the appropriate choice of antibiotic therapy for the use of analgesics. confirmed cases. In this issue of Pediatric Emergency Medicine Practice, an evidence-based approach to the management of Date of original release: June 1, 2007. Date of most recent review: April 5, 2007. pharyngitis in children is presented. After reading this article, See “Physician CME Information” on back page. you should be able to accurately identify most life-threatening causes of pharyngitis and discuss the various acceptable

Editorial Board Emergency Medicine, Chicago, Pritzker School of Assistant Professor of Gary R. Strange, MD, MA, Morristown Memorial Hospital. Medicine, Chicago, IL. Emergency Medicine and FACEP, Professor and Head, Jeffrey R. Avner, MD, FAAP, Pediatrics, Loma Linda Department of Emergency Professor of Clinical Ran D. Goldman, MD, Alson S. Inaba, MD, FAAP, Associate Professor, PALS-NF, Pediatric Medical Center and Children’s Medicine, University of Illinois, Pediatrics, Albert Einstein Hospital, Loma Linda, CA. Chicago, IL. College of Medicine; Director, Department of Pediatrics, Emergency Medicine Pediatric Emergency Service, University of Toronto; Division Attending Physician, Kapiolani Brent R. King, MD, FACEP, Adam Vella, MD, Assistant Children’s Hospital at of Pediatric Emergency Medical Center for Women & FAAP, FAAEM, Professor of Professor of Emergency Montefiore, Bronx, NY. Medicine and Clinical Children; Associate Professor Emergency Medicine and Medicine, Pediatric EM Pharmacology and of Pediatrics, University of Pediatrics; Chairman, Fellowship Director, Mount T. Kent Denmark, MD, FAAP, Toxicology, The Hospital for Hawaii John A. Burns School Department of Emergency Sinai School of Medicine, FACEP, Residency Director, Sick Children, Toronto. of Medicine, Honolulu, HI; Medicine, The University of New York Pediatric Emergency Pediatric Advanced Life Texas Houston Medical Medicine; Assistant Professor Martin I. Herman, MD, FAAP, Mike Witt, MD, MPH, Attending FACEP, Professor of Support National Faculty School, Houston, TX. Physician, Division of of Emergency Medicine and Representative, American Pediatrics, Loma Linda Pediatrics, Division Critical Robert Luten, MD, Professor, Emergency Medicine, Care and Emergency Heart Association, Hawaii & Pediatrics and Emergency Children’s Hospital Boston; University Medical Center and Pacific Island Region. Children’s Hospital, Loma Services, UT Health Sciences, Medicine, University of Instructor of Pediatrics, Linda, CA. School of Medicine; Assistant Andy Jagoda, MD, FACEP, Florida, Jacksonville, Harvard Medical School Director Emergency Services, Vice-Chair of Academic Jacksonville, FL. Michael J. Gerardi, MD, FAAP, Research Editor Lebonheur Children’s Medical Affairs, Department of Ghazala Q. Sharieff, MD, FAAP, FACEP, Clinical Assistant Center, Memphis TN. Emergency Medicine; Christopher Strother, MD, Professor, Medicine, FACEP, FAAEM, Associate Mark A. Hostetler, MD, MPH, Residency Program Director; Clinical Professor, Children’s Fellow, Pediatric Emergency University of Medicine and Director, International Studies Medicine, Mt. Sinai School of Dentistry of New Jersey; Assistant Professor, Hospital and Health Center/ Department of Pediatrics; Program, Mount Sinai School University of California, San Medicine, Chair, AAP Section Director, Pediatric Emergency of Medicine, New York, NY. on Residents Medicine, Children’s Medical Chief, Section of Emergency Diego; Director of Pediatric Center, Atlantic Health Medicine; Medical Director, Tommy Y. Kim, MD, FAAP, Emergency Medicine, System; Department of Pediatric Emergency Attending Physician, Pediatric California Emergency Department, The University of Emergency Department; Physicians.

Commercial Support: Pediatric Emergency Medicine Practice does not accept any commercial support. All faculty participating in this activity report no significant financial interest or other relationship with the manufacturer(s) of any commercial product(s) discussed in this educational presentation. management options. As with all forms of treat- self-limited. The test of treatment effectiveness is ment, the goals to be achieved include: identifica- the prevention of rheumatic fever and its attendant tion of serious illness, relief of symptoms, assurance complications. Of course, rheumatic fever is incred- of adequate hydration, and, when appropriate, ibly rare in the developed world. It would be administration of effective antibiotics. Attention to nearly impossible to conduct a study to demonstrate these issues will ensure that patients receive safe, that one treatment strategy was more effective than appropriate, and cost-effective care while serious another in the prevention of rheumatic fever. There- complications are prevented and inappropriate fore, even when using well-conducted studies, the antibiotic use is limited. emergency physician may find limited guidance. Critical Appraisal Of The Literature Guidelines The clinician seeking guidance on the management Despite these limitations, many organizations have of pharyngitis will find ample information in the published proposed guidelines for the management medical literature. However, all of this information of patients with pharyngitis. Some of these are should be viewed with a somewhat jaundiced eye. intended to apply to adults and are less relevant to First, it must be recognized that the vast majority of the management of pediatric patients, but because children with pharyngitis require only management they do include older adolescents, they are pre- of their symptoms. In fact, of all of the potential sented here. Given the flaws in the available litera- causes of pharyngitis in children, the emergency ture, it is not surprising that the guidelines disagree physician is primarily concerned with the diagnosis on some issues. In fact, the limitations in the med- and treatment of infections caused by group A beta ical literature require that some of the guideline rec- hemolytic streptococci (GABHS). Even if one nar- ommendations be based upon the opinions of rows his/her search to focus on GABHS, there are experts rather than randomized controlled trials. In severe limitations to the available literature. For many cases, the practitioner is presented with a example, the most frequently employed criterion range of acceptable options, offering yet more evi- standard for the diagnosis of GABHS is a throat cul- dence of the previously described difficulties with ture on sheep’s blood agar. However, a streptococ- the medical literature. Table 1 summarizes the most cal carrier with viral pharyngitis may still have a important practice guidelines. positive throat culture and the patient with a true While it is true that the practice guidelines dis- GABHS infection may have a negative throat cul- agree in some areas, they agree about many impor- ture if the culture was collected or incubated tant issues. First, all guidelines recognize that a improperly. Studies of treatment are also severely subset of patients have associated symptoms, sug- limited. After all, the real test of treatment effective- gesting a viral illness. Patients with conjunctivitis, ness is not the relief of symptoms. It is well under- cough, rhinorrhea, mucosal ulcers, or skin rash stood that even proven GABHS infections are (other than scarlatina) are very likely to have a viral

Table 1. Practice Guidelines Patients With Viral Patients With Symptoms Culture After Recommended Guideline Population Symptoms Of GABHS Negative RADT? Antibiotic Infectious Disease Adolescents and Do not test or RADT or culture Children - Yes Penicillin Society of America Children treat Treat only those with positive results Adults - No Erythromycin (if Penicillin allergic) Centers for Disease Adolescents Do not test or Use Centor Criteria No Penicillin Control (endorsed by (patients older treat Centor Score = 4 – Perform RADT or Erythromycin (if the American Acad- than 15 years of treat presumptively Penicillin allergic) emy of Family Physi- age) cians and the Ameri- Centor Score = 3 – Perform RADT or can College of treat presumptively Physicians – Centor Score = 2 – Perform RADT or American Society of Do not test or treat Internal Medicine) Centor Score = 1 or 0 – Do not test or treat. In all cases in which an RADT is performed, treat only those with positive results. American Academy Children Do not test or RADT or Culture – Treat only patients Yes Penicillin of Pediatrics treat with positive results Erythromycin (if Penicillin allergic) Institute for Clinical Adolescents and Do not test or RADT or Culture – Treat only patients Yes Penicillin Systems Children treat with positive results Erythromycin (if Improvement Penicillin allergic)

Pediatric Emergency Medicine Practice© 2 June 2007 • EBMedicine.net infection. When these symptoms are found in asso- (a modification of the Centor score), and throat cul- ciation with pharyngitis, all of the guidelines recom- ture. Both of the clinical guidelines and the modi- mend symptomatic treatment only. Also, the guide- fied Centor score detected all of the children with lines recognize that both the risks of acquiring positive throat cultures. Rapid streptococcal testing rheumatic fever and the potential complications of was only 85% sensitive. Furthermore, use of the the disease are much lower in older adolescents. clinical guidelines would have resulted in only three Therefore, a high-sensitivity rapid antigen detection unnecessary antibiotic prescriptions and 29 of 299 test (RADT) alone is adequate for the exclusion of children with negative throat cultures would have GABHS in these patients. In patients 15 years of age been treated had the modified Centor score been and older, confirmatory throat cultures are not nec- used.5 essary. However, all guidelines recognize that a negative RADT does not eliminate the possibility of Evidence-Based Reviews GABHS in younger children. In this population, The most comprehensive evidence-based review to confirmatory cultures are recommended. All of the date is found in the Cochrane database.6 The guidelines state that a positive RADT confirms the authors of this systematic review focused solely on diagnosis of GABHS and allows for treatment with- the costs and benefits of treatment; diagnostic strate- out further testing. Finally, all of the guidelines gies were not considered. The authors reviewed 27 agree that, while many antibiotics will effectively studies, including 2835 cases of sore throat. They eradicate GABHS, penicillin remains the drug of concluded that antibiotics conferred a modest bene- choice, and erythromycin is recommended for peni- fit in terms of prevention of suppurative complica- cillin-allergic individuals. However, several of the tions and earlier relief of symptoms but “protecting guidelines acknowledge that once or twice daily sore throat sufferers against suppurative and non- amoxicillin may represent a more palatable and con- suppurative complications in modern Western soci- venient alternative. ety can only be achieved by treating many with The guidelines disagree as to whether clinical antibiotics, most of whom will derive no benefit.” criteria alone are sufficient to begin antibiotic test- A review intended to determine the optimal ing. The most widely accepted guideline for adults diagnostic strategy concluded that clinicians can use and older adolescents recommends presumptive standard clinical decision rules to risk-stratify testing of patients with a certain constellation of patients. Those at low risk require symptomatic symptoms.1 However, even when patients have all treatment only. For those patients with an interme- of the necessary symptoms, only about half may be diate or higher risk of GABHS infection, an RADT expected to have culture-proven GABHS.2 On the can reduce the number of unnecessary antibiotic other hand, attempts to create guidelines which prescriptions and those patients with a positive reduce over-treatment have not been successful result may be treated without further testing. The because the new guidelines failed to identify many latest technology RADTs, when used properly, have children with GABHS infections.3 This debate very high sensitivities. Physicians who have con- clearly demonstrates one of the key differences firmed that these tests have sensitivities similar to between emergency department practice and office- throat culture can consider using the RADT as their based practice. Most authorities agree that antibi- sole diagnostic tool. Others should confirm the otic treatment can be delayed for several days and RADT results with a throat culture in patients less still effectively prevent rheumatic fever. An office- than 15 years old.7 based practitioner with an adherent panel of patients can choose to use throat culture as his/her Epidemiology, Etiology, And Pathophysiology sole criteria for treatment because he/she can be The actual incidence of pharyngitis in unknown, reasonably assured that the patient will return for primarily because many affected children are not treatment if the culture is positive. The emergency seen by healthcare providers. It has been estimated physician usually lacks such assurance but is no less that only a small percentage of symptomatic liable for the patient’s outcome. The emergency patients actually seek treatment.8 However, pharyn- physician must, therefore, rely more heavily upon gitis is the second most common diagnosis given to strategies likely to result in an early diagnosis while children.9 This means that literally millions of chil- at the same time minimizing unnecessary treatment dren with pharyngitis are seen by emergency physi- and testing. cians each year. Two recent studies have compared published Although pharyngitis has many potential causes, guidelines to one another using throat culture as the including local trauma and irritation, the most criterion standard. The first tested the World Health common causes are infectious agents and the subse- Organization guidelines and found them to be quent immune response. In children, viruses are the highly specific but insensitive.4 The second com- typical etiologic agents.10 Roughly 15 to 30% of pared the guidelines from the Infectious Disease cases of pharyngitis in children are caused by Society of America and those from the American GABHS. However, the incidence of GABHS varies College of Physicians-American Society of Internal across geographic regions and populations. For Medicine/American Academy of Family Physi- example, it is more common among Native Ameri- cians/US Centers for Disease Control and Preven- cans and Inuits.11-13 GABHS is most common tion to rapid testing alone, a clinical prediction rule among school-aged children and the incidence

EBMedicine.net • June 2007 3 Pediatric Emergency Medicine Practice© among younger children is a matter of debate.14,15 children. However, older adolescents may still Although some cases of pharyngitis are ascribed to acquire this disease. Older patients can present in Mycoplasma and Chlamydia, their role remains the same fashion as their younger counterparts, but unclear. the presentation is usually more subtle. In many While most cases of pharyngitis are minor and cases, the patient has only intense pharyngitis and short-lived, sore throat is rarely the presenting com- hoarseness. Other symptoms may include odyno- plaint for one of a handful of potentially deadly phagia and mild respiratory distress. Drooling and infections. In the recent past, all practitioners who stridor occur in more severe cases. Older patients cared for children were alert for the signs of acute may not be febrile and may have been symptomatic epiglottitis. This disease entity has several possible for days rather than hours. The emergency physi- causes, but, until the early 1990’s, the most common cian should be especially wary of the adolescent was Haemophilus influenza type B. This invasive, who complains of intense throat pain but has little encapsulated gram negative coccobacillus is spread evidence of inflammation of the tonsils and hypo- via respiratory droplets; in addition to epiglottitis, it pharynx. Dyspnea at the time of admission has been causes meningitis, severe facial cellulitis, and sev- reported to be an important sign of potential airway eral other serious illnesses.16 However, after nearly obstruction. twenty years of immunization against Haemophilus influenza type B, infections caused by this organism, Ludwig’s Angina including epiglottitis, have all but disappeared This infection of the submandibular and sublingual among children and adolescents. Other organisms spaces was originally described by Wilhelm Freder- can still cause epiglottitis but do so far more rarely, ick von Ludwig in 1836. Although often thought of and many younger clinicians have never seen a as an adult infection, Ludwig’s angina infections in 28,29 patient with this once relatively common children are well-described. Dental disease is condition.17-24 the usual predisposing factor, but it has also been In the United States and most of the developed associated with recent dental treatment, local world, immunization has also virtually eliminated trauma, immunocompromise, and tongue piercing. Corynebacterium diphtheriae. However, there have It can also occur in patients lacking any of the 30,31 been recent outbreaks of diphtheria in many parts of known predisposing factors. the world, including the former Soviet Union.25,26 In addition to fever, patients with Ludwig’s This disease is caused by a gram-positive bacillus angina present with a variety of complaints related and, like Haemophilus influenza type B, is spread to the mouth and throat. Mouth, neck, and tooth from person to person through respiratory droplets pain can occur. Patients may have dysphonia and 29,30 or contact with infected secretions. odynophagia, trismus, or drooling. Both of the aforementioned infections can occur Peritonsillar Abscess in unimmunized children. Furthermore, there is some evidence that certain immunizations, including Peritonsillar abscesses occur primarily in older chil- those against Haemophilus influenza type B, are less dren and adolescents, although they can occur in effective in children who are HIV positive. Therefore, any patient with large tonsils. The infection forms these infections should be considered when evaluat- in the area between the palatine tonsil and the ton- ing immunocompromised children and those who sillar capsule. This infection may be thought of as are unimmunized or under-immunized, such as the most severe form of tonsillitis, as the most sig- immigrants from countries lacking effective immu- nificant suppurative complication of GABHS nization programs.27 pharyngitis, and, with approximately 45,000 cases per year, the most common serious head and neck Additionally, sore throat may be the presenting 32 complaint or a part of the clinical picture of patients infection. Though peritonsillar abscesses may with Ludwig’s angina, peritonsillar abscess, retro- complicate GABHS pharyngitis, they are often pharyngeal abscess, infectious mononucleosis, gas- polymicrobial infections including aerobes (e.g., troesophageal reflux, throat or neck trauma, and GABHS) and anaerobes (e.g., Fusobacterium). oral or pharyngeal tumors. Several of the more Peritonsillar abscess is often a complication of important of these entities are briefly discussed in pharyngitis. As such, the patient’s initial symptom this article. is sore throat which may be accompanied by fever. However, over a period of 24-72 hours, the pain Differential Diagnosis worsens and localizes to one side. The patient may have fever and complain of dysphagia, odynopha- Epiglottitis gia, or ear pain. In severe cases, the patient may Classically, epiglottitis is a disease of toddlers and have drooling or dysphonia. Limited mouth open- preschool-aged children. In this population, the ing (trismus) is common and may also affect presentation is dramatic. The child first develops a speech.37 fever, but within a few hours, has symptoms of res- piratory distress. In addition to a high fever and Infectious Mononucleosis toxic appearance, many patients present with drool- Infectious mononucleosis is caused by the Epstein- ing and dysphonia.19,20 As previously described, Barr virus (EBV), a member of the herpes virus immunization against Haemophilus influenzae type B family. In poorly developed countries, most of the has all but eliminated epiglottitis among young population is infected with EBV in early childhood

Pediatric Emergency Medicine Practice© 4 June 2007 • EBMedicine.net and these infections are often asymptomatic. How- limited. Treatment may have little influence on the ever, in developed nations, infections often occur course of bacterial pharyngitis and will have none during adolescence. Because EBV is easily spread whatsoever on the course of viral pharyngitis.40 in bodily fluids, including saliva, infectious mono- However, GABHS infections are associated with so nucleosis is sometimes called “the kissing disease.” called “non-suppurative” complications, primarily The classic constellation of symptoms (fever, sore rheumatic fever and post-streptococcal glomerulo- throat, lymphadenopathy, general malaise, and nephritis. Also, GABHS is associated with “suppu- sometimes, splenomegally)35,36 along with the rative” complications (e.g., peritonsillar abscess). patient’s age often makes the practitioner suspect The incidence of these diseases and the degree to that the patient has infectious mononucleosis rather which they can be prevented by antibiotic therapy than a more routine pharyngitis. Tonsillopharyngi- has sparked significant controversy. At issue are tis, which can be (but often is not) exudative, is one questions about the need for and methods of diag- of the most prominent features of the disease and nosis and the need for treatment. In this debate, occurs in 74-83% of patients. In practice, it may be diagnosis and treatment are inextricably linked. difficult for the emergency physician to distinguish Decisions about one influence the other. For exam- infectious mononucleosis from other causes of ple, many clinicians pursue a “treat all” strategy. pharyngitis. However, the usual course of the ill- They prescribe antibiotics to all or most patients ness may provide an important clue. Unlike with pharyngitis. For these physicians, bacterio- patients with a routine viral pharyngitis, those with logic testing is little more than a useless exercise in mononucleosis first experience a day or two of epidemiology. On the other hand, the clinician who malaise. This is followed by the onset of fever. The aims to limit the use of antibiotics will usually want sore throat typically begins on the third, fourth, or to have a diagnosis before treating. This problem is fifth day of illness, worsens for a few days, and then further complicated by the fact that the incidence of gradually improves. The patient may present seek- GABHS varies widely across the population. It is ing a second opinion because, after taking much more common among school aged children antibiotics, their “strep throat” is not getting better. than either infants or adolescents, and there are Some patients with infectious mononucleosis local and regional variations as well.10,13,41 Addi- develop severe lymphadenopathy and tonsillar tionally, some people are asymptomatic carriers of hypertrophy. In some cases, this leads to upper air- GABHS. Like the disease, the carriage rate varies way obstruction.38 with age and location. Whenever a throat culture is obtained from a carrier, it is likely to grow GABHS, Retropharyngeal Abscess yet these patients are highly unlikely to have an The retropharyngeal space, which lies anterior to actual GABHS infection.13,41 the prevertebral layer of deep cervical fascia and GABHS is the most important cause of infectious posterior to the pharyngeal mucosa is, in reality, a pharyngitis, but a variety of other bacterial and viral group of three potential spaces separated by fascial agents have been described. These include: planes. These spaces extend from the upper phar- 1. After GABHS, Group C and Group G ynx to the mediastinum. In young children, these streptococci are the most common bacterial spaces contain lymph nodes which gradually invo- causes of exudative pharyngitis. Group C is lute with age. Suppuration of these nodes allows most common in adolescents and young adults. infection to spread throughout the retropharyngeal The pharyngitis caused by this organism is less spaces. Involution of the nodes occurs relatively severe than that caused by GABHS. Group G early in life so retropharyngeal abscesses primarily streptococci have been implicated in “mini-epi- occur in children less than four years old.33 When demics” and in association with food borne out- an older child or adolescent develops a retropharyn- breaks (e.g., ingestion of cold, hard boiled geal abscess, it is often because the posterior pha- eggs).42,43 ryngeal wall has been penetrated by a foreign object 2. Arcanobacterium haemolyticum is an interesting (e.g., toothpick, fishbone).34 organism that can, depending upon when it is Fever and throat pain are the typical symptoms stained, be either gram-positive or gram-nega- of retropharyngeal abscess, though throat pain is tive. The typical patient is an adolescent or not a universal symptom. However, as compared to young adult so, not surprisingly, A. haemolyticum many of the other causes of sore throat, clinical outbreaks have occurred in the military barracks. symptoms of retropharyngeal abscess progress more Most patients have exudative pharyngitis and slowly. The patient may have already been seen by tender anterior cervical lymph nodes. However, a physician and placed on oral antibiotics. In addi- unlike GABHS, many patients develop pruritus tion to fever, many patients have decreased oral and have a non-productive cough. One to two- intake. Patients may also complain of neck pain or thirds of patients with A. haemolyticum infections stiffness; this combination may lead the clinician to develop a scarlatiniform but non-peeling rash. consider meningitis.33,39 The rash generally appears on extensor surfaces one to four days after the onset of pharyngitis, Infectious Pharyngitis and then spreads to the trunk.42-45 Patients who lack signs of serious illness nonethe- 3. Anaerobes - The three anaerobic organisms most less present a diagnostic and therapeutic challenge. frequently associated with pharyngitis are Almost all cases of acute pharyngitis are self-

EBMedicine.net • June 2007 5 Pediatric Emergency Medicine Practice© Fusobacterium, Peptostreptococcus, and Baceroides. Adenovirus: Adenovirus often presents as an intense Anaerobes are associated with two entities. The exudative pharyngitis. In about half of the cases, first and most important of these is peritonsillar the patient also has follicular conjunctivitis which abscess. The second and more potentially seri- can be unilateral or, less commonly, bilateral. In ous type of anaerobic infections tend to occur in patients with so-called “pharyngoconjunctival malnourished or immunosuppressed patients fever,” no further diagnostic evaluation is required. and in those who have undergone local irradia- Although a few patients with adenovirus become tion of the neck. Affected individuals present quite ill, in the vast majority of cases, the patient has with severe throat pain and foul breath odor. On about one week of uncomplicated pharyngitis fol- examination, they are found to have purulent lowed by resolution of symptoms.42,43 42 membranous exudates. Herpes Simplex: While parents of young children 4. Neisseria – Neisseria gonorrhea is spread to the with primary herpes simplex infections may con- pharynx by orogenital contact. Females are two clude that their child has a sore throat, in reality this to three times more likely to be infected than viral infection primarily involves the mouth. In males. Homosexual males have the highest most cases, the diagnosis is made by the symptoms infection rates. Unfortunately, most infections of fever and decreased oral intake coupled with the are asymptomatic, but some patients complain presence of multiple shallow ulcers distributed over of mild pharyngitis and have cervical lymph- the entire oral cavity. Herpes simplex gingivostom- adenopathy. The clinician should remember to atitis and pharyngitis is self-limited in immunocom- consider gonococcal pharyngitis in the presence petent individuals. However, the patient may expe- of other sexually transmitted diseases. It goes rience such significant pain that he or she is unable without saying that any gonococcal infection in a to consume enough liquid. Attention to pain child should lead to a diagnosis of sexual 42,43,46 control and hydration is, therefore, mandatory. In a abuse. few cases, severely affected patients may require 5. Diphtheria - Thanks to widespread immuniza- intravenous rehydration in addition to antiviral Corynbacterium diphtheriae tion, infection by is therapy.42,43,47 exceptionally unusual in most of the developed world. However, in recent years there have been Coxsackievirus: Coxsackievirus also presents with outbreaks in parts of the former Soviet Union. stomatitis or pharyngitis associated with ulcerative The characteristic gray or gray-brown pseudo- lesions. However, the lesions of coxsackievirus are membrane is the clinical finding that distin- fewer in number, located in the posterior pharynx, guishes diphtheria from other causes of pharyn- and are often larger than those found in herpes sim- gitis. Although the pseudomembrane can cause plex infections. Young children with coxsackievirus airway compromise, the morbidity and mortality may also present with the hand-foot-mouth syn- associated with diphtheria is primarily related to drome. In addition to oral lesions, these children the cardiac and nerve toxins produced by the may also have ulcerative lesions on their hands, bacteria. The presence of the pseudomembrane feet, buttocks, or genitals.42,43 and the associated clinical findings are generally Influenza Virus: Pharyngitis is often a part of the sufficient to warrant the initiation of treatment clinical picture of influenza A and influenza B infec- with diphtheria antitoxin and penicillin or eryth- tions. As is the case for many types of viral pharyn- romycin. However, a culture of the pseudo- gitis, the constellation of associated symptoms helps membrane should be performed on tellurite 26,42,43 the clinician to distinguish influenza from GABHS. selective media or Loeffler’s media. The pharyngitis associated with influenza is non- 6. Atypical organisms – The role of Chlamydia pneu- exudative and the patient does not have cervical moniae and Mycoplasma pneumoniae in pharyngi- adenopathy. Furthermore, most patients with tis is unclear. Chlamydial pharyngitis may occur influenza experience other symptoms, such as prior to or during an episode of pneumonia. cough, myalgias, and headache. Rapid tests for The presence of cough suggests that the pharyn- influenza can help to identify patients with gitis is not caused by GABHS. Mycoplasmal influenza infections thus distinguishing them from pharyngitis might be associated with other children with other forms of pharyngitis.42,48 constitutional symptoms, like headache and abdominal pain, or gastrointestinal symptoms, Human Immunodeficiency Virus: Primary infection in addition to cough. Both of these organisms by human immunodeficiency virus type 1 (HIV-1), are treated with macrolide antibiotics or, in older is often accompanied by sore throat but is also usu- children, with tetracycline. ally associated with arthralgias and myalgias. Adenopathy is common but pharyngeal exudates Viral Pharyngitis are rarely, if ever, seen. Rash sometimes occurs. Cytomegalovirus: Cytomegalovirus (CMV) presents When faced with these symptoms, the physician in a fashion much like EBV but with much milder should take a careful history in order to identify symptoms. This virus should be considered in the those patients with risk factors for HIV infection. patient with a clinical picture resembling mononu- As is the case for gonococcal pharyngitis, identifica- cleosis who has a negative test for EBV. CMV can tion of a child with HIV infection warrants a child be cultured and there are specific antibody tests for abuse report unless the child is known to have the virus, but these are generally not indicated.42 contracted the infection congenitally.

Pediatric Emergency Medicine Practice© 6 June 2007 • EBMedicine.net Other Causes Of Pharyngitis circumstances should a patient with signs of upper A variety of non-infectious processes can also cause airway obstruction be forced to recline. Should the pharyngitis. In general, all of these processes result patient undergo complete airway obstruction dur- in pharyngeal irritation. Examples include smoke ing transportation, he or she should be managed inhalation, thermal or chemical burns, swallowed with bag-mask ventilation, tracheal intubation, or a objects (either foreign substances or foods), and surgical airway. Many so-called “rescue” airway vocal strain such as might occur at a sporting event. devices, like the Laryngeal Mask Airway® and the Allergens may result in mild pharyngeal irritation Combitube®, may be ineffective in the management either directly or as an effect of posterior nasal dis- of patients with upper airway obstruction. Like- charge. In most cases, the diagnosis can be made, or wise, the use of transtracheal jet ventilation in cases at least suspected, based upon the history alone. In of complete airway obstruction is, at best, controver- more subtle cases, the emergency physician need sial. When faced with a patient with signs suggest- only exclude serious causes of pharyngitis and ing upper airway obstruction, prehospital personnel GABHS in order to refer the patient for further should consider transport to a facility capable of evaluation.42 providing surgical airway management. Finally, although not a cause of pharyngitis, Second, many patients with severe pharyngitis Kawasaki disease has some features in common have been unable to drink enough fluids and have with a few disorders that do cause pharyngitis. become dehydrated. In such cases, the administra- Kawasaki syndrome is a disease of unknown etiol- tion of intravenous fluids may make the patient feel ogy characterized by at least five days of fever better. However, in urban environments with greater than 39.4°C and four of the following five relatively short transport times, intravenous hydra- features: tion is mandatory only for those patients who are 1. Non-exudative, scleral conjuncitivits, often significantly dehydrated. with limbal sparing. Emergency Department Evaluation 2. Erythema of the lips (which are sometimes cracked or fissured) and oropharynx, and a so called Initial Assessment “strawberry tongue.” While most children with pharyngitis are not signif- 3. Cervical lymphadenopathy which usually icantly ill and do not require immediate attention, manifests as a single large lymph node. the emergency physician should begin by consider- 4. A polymorphus exanthema which may resem- ing serious and life-threatening causes of sore ble scarletina. throat. Signs of potentially severe disease include: 5. Swelling of the hands and feet with erythema dysphonia/aphonia, trismus, drooling, stridor, toxic noted on the palms and soles. appearance, and air-hunger. In some cases, the The clinical picture of Kawaski syndrome may physician will need to treat the patient’s respiratory occasionally be confused with scarlet fever or aden- symptoms before determining their etiology. Before oviral infection. However, as stated above, the for- treating the patient like “just another sore throat,” mer disorder does not cause pharyngitis. Addition- systematically answer the following questions: ally, Kawasaki syndrome occurs primarily in young 1)Does the patient exhibit signs of existing or children whereas scarlet fever is more common in impending airway compromise? 2) Is the patient school aged children. Furthermore, adenoviral severely dehydrated? 3) Could the patient have infections and scarlet fever generally do not cause epiglottitis, retropharyngeal abscess, Ludwig’s sustained high fever. angina, peritonsillar abscess, or infectious mononu- When Kawaski syndrome is strongly suspected, cleosis with severe tonsillar and lymphoid hypertro- treatment with gamma globulin and aspirin should phy? Only after these questions have been consid- be initiated and the child should be admitted to the ered and answered negatively can the physician be hospital for further evaluation. Children who are reassured that he or she is not dealing with a seri- not treated with gamma globulin may acquire coro- ously ill patient. nary artery aneurysms. History Prehospital Care Although few causes of pharyngitis can be identi- The role of prehospital providers in the manage- fied by the history alone, the history can offer the ment of children with pharyngitis is limited. For physician clues to the etiology and guide the diag- the non-toxic patient, ambulance transport is not nostic evaluation. Assuming that the patient is not required. Emergency medical service personnel in obvious distress, the emergency physician’s first should focus on two key issues. task is to elicit historical clues suggesting a more First, they should be alert for signs of respiratory serious course of illness. These include the inability compromise resulting from upper airway obstruc- to speak, a muffled voice, severe pain with phona- tion. When these signs are identified, the patient tion, and complaints of decreased oral intake result- should receive high flow oxygen in route to an ing from significant pain. An abrupt onset of symp- emergency center. Additionally, he or she should be toms or rapid progression of the illness are also transported in the position that affords him or her worrisome. However, equally concerning are symp- the greatest comfort. Many patients are more com- toms that gradually worsen and do not remit. fortable when seated or semi-erect. Under no Under such circumstances, consider entities like

EBMedicine.net • June 2007 7 Pediatric Emergency Medicine Practice© retropharyngeal abscess.33,34,42,43 In more routine Physical Examination cases, the history is important in helping to limit the In most cases, the physical examination begins differential diagnosis. In the simplest cases, the when you enter the examination room. By that patient or the parents can relate a clear history of time, you may have already seen the patient’s vital inhalational injury, direct trauma, chemical expo- signs and nursing assessment and may have formed sure, vocal strain, or other causative event. Expo- an opinion as to the likely etiology of the patient’s sure to others with similar symptoms suggests an symptoms and the likelihood of serious or life- infectious etiology. As in more severe cases, the tim- threatening disease. Tachycardia, tachypnea, and ing of the symptoms is an important consideration. hypotension are clearly worrisome and should The patient with viral or bacterial pharyngitis is prompt an immediate and thorough evaluation. likely to have had onset of symptoms early in the The presence of fever strongly supports an course of his or her illness, whereas the patient with infectious etiology. infectious mononucleosis may have had a few days Identification and management of existing or of lethargy followed by the onset of throat impending airway obstruction takes precedence pain.35,36,42,43,49 Likewise, associated signs and over other aspects of care; be alert for signs of this symptoms are important. For example, GABHS condition. Severely affected patients will prefer to infections are not commonly associated with coryza, lean forward with their necks extended. When they cough, conjunctivitis, or viral exanthem. The pres- attempt to recline, their symptoms worsen. They ence of several of these symptoms can effectively are often unable to swallow their secretions so exclude GABHS from the differential diag- drooling is a common sign. Likewise, such individ- nosis.13,42,43,50-55 Conversely, a scarlatiniform rash in uals may have muffled speech (or, in the case of association with pharyngitis in a school aged child babies, muffled cry) or may be unable to phonate at and in the absence of other viral symptoms makes all.17 GABHS the most likely cause of the patient’s Be alert for signs of dehydration since some symptoms.54,55 patients experience significant odynophagia and are The patient’s age, the season, and the geographic unable to maintain adequate fluid intake. In addi- location are also important parts of the history. tion to tachycardia, the patient may have sunken GABHS is far more common in school age children eyes, dry or “tacky” mucous membranes, decreased and in the fall and winter months, while infectious elasticity of the skin, and depressed mental status. mononucleosis is more common in adolescents.13, In more routine cases, the examination begins 42,43,49,51 The incidence of rheumatic fever and strep- with the initial introductions. The quality of the tococcal carriage vary with geographic location.55,56 patient’s speech or cry is an important clue to possi- Finally, the physician should note any history of ble pathology. A muffled voice or cry may suggest a recent oral or pharyngeal trauma, dental work, or more serious condition. Patients with peritonsillar cosmetic oral piercing.28-30 abscess or cellulitis may have a so called “hot The patient’s past history is equally important. potato” voice. This is caused by inflammation of A history of rheumatic fever or congenital heart dis- the pharynx and trismus; the patient tends to speak ease should be noted. It is especially important to with as little jaw movement as possible. Next, pro- determine whether the patient might have valvular vided that the child is old enough to cooperate, ask heart disease. Immunization status should be the patient to open his/her mouth and protrude noted, as should a history of immunodeficiency. his/her tongue. Trismus indicates severe inflamma- Patients who have previously had acute mononucle- tion and is often associated with peritonsillar osis are unlikely to have it again. If the patient abscess and peritonsillar cellulitis.34,37 Inside the reports a medication allergy, it is important to know oral cavity, look for dental disease and ascertain the type of reaction that occurred. Many patients whether the tongue appears to be elevated. Both mistakenly believe that they are allergic to certain are clues to Ludwig’s angina. This diagnosis is sup- medications because they experienced an untoward ported by a firm, almost “woody” feeling when the but non-allergic reaction to a previous dose of med- sublingual and submental tissues are palpated.28-30 ication (e.g., vomiting after erythromycin). Prior The oral and buccal mucosa should be examined for surgical history is likewise important. A patient the presence of lesions. Multiple ulcerations in the who has had a tonsillectomy cannot have tonsillitis. anterior mouth suggest primary herpes simplex Finally, the patient should be asked about his or her infection, while a few larger lesions on the soft attempts to treat the symptoms. Home remedies, palate are more indicative of coxsackie virus infec- herbal treatments, and traditional medicines all con- tion.42,43 tribute to the clinical picture. Given the ready avail- In the posterior pharynx, attention should be ability of antibiotics, many patients present after directed to the tonsils (if present) and the uvula. having treated themselves with leftover antibiotics Relatively large but uniformed tonsils are normal in or antibiotics prescribed to a friend or relative. young children. However, unilateral enlargement Although the patient may be embarrassed to admit and peritonsillar cellulitis are findings classically that he or she has taken medication, this history is associated with peritonsillar abscess and tonsillitis. potentially important and should be obtained, if Additionally, an enlarged tonsil may displace the possible. uvula laterally. In cooperative older children and adolescents, a fluctuant mass may be seen or

Pediatric Emergency Medicine Practice© 8 June 2007 • EBMedicine.net palpated in the palatal tissue surrounding the ton- some have hepatomegaly, as well. If treated with sil.28-30 Inflamed tonsils with exudates are typical of amoxicillin, patients with infectious mononucleosis many types of infectious pharyngitis. However, may develop a morbilliform rash. Such a rash in a diphtheria causes a gray membrane that is adherent patient with the appropriate history should be con- to the tonsils and posterior pharynx. Attempted sidered de facto evidence of EBV infection.35,36,49 removal of the membrane reveals a hemorrhagic Finally, patients with coxsackie virus A16 may base.43 In some cases of infectious mononucleosis, develop hand, foot, and mouth syndrome. These the tonsils become so enlarged that the patient children present with ulcers on the hands, feet, geni- develops symptoms of upper airway obstruction.49 tals, or buttocks in addition to oral and pharyngeal Likewise, several infections and non-infectious lesions.42,43 inflammatory conditions can cause significant edema of the uvula. In some cases, the uvula may Clinical Decision Rules become so enlarged as to create a potential obstruc- tive process.42 Clinical decision rules, which are sometimes also The palatal examination can also be helpful in called clinical scoring systems, are designed to identifying the cause of the patient’s symptoms. reduce the subjectivity of clinical decision making Palatal petechiae, in particular, are more often asso- by forcing the clinician to identify certain features of ciated with bacterial pharyngitis. Likewise, as men- the patient’s condition known to either increase or tioned previously, masses or bulging of the pharynx decrease his/her likelihood of having culture can suggest peritonsillar abscess. Bulging may proven GABHS. These rules, which have met with occasionally be seen at or near the midline of the varying success, have generally been designed to posterior pharynx in patients with retropharyngeal serve one of two purposes. In some cases, the abscesses.28-30,33,42,43 investigators focused primarily upon cost-effective- Examination of the neck is also important. ness, paying less attention to clinical utility. In Limitation in neck mobility, particularly the inability others, the opposite has been true. or unwillingness to extend the neck to look up Cost Effectiveness Rules (Bolte’s sign), has been shown to be a reliable sign 33 One of the primary reasons for the development of of retropharyngeal abscess. A recent report clinical decision rules was to provide cost-effective demonstrated the subtle nature of the presenting treatment while avoiding unnecessary exposure to symptoms of retropharyngeal abscesses in young antibiotics and avoiding complications of either the children. The clinician who considers the diagnosis disease or its treatment. Many of these rules were only in those children with signs of upper airway designed primarily for the management of adult obstruction will not identify many patients. patients. Rules intended for the management of Attempting to distract the child into looking up can adults should only be applied to older adolescents. help in the identification of less obvious cases. The Among the earliest rules were those developed child with a retropharyngeal abscess will look up by Tompkins. The Tompkins rules were based on only with his or her eyes whereas unaffected chil- 33 the costs of various testing and treatment strategies. dren will look up by extending their necks. Exam- They take into account the cost associated with ination of the neck also includes palpation of lymph rheumatic fever and its complications, the cost of nodes. Enlarged, tender anterior cervical nodes are treatment itself, and the cost of caring for individu- a part of the Centor criteria and their presence is an 52 als who have an allergic reaction to penicillin. important clue to the diagnosis of GABHS. On the However, rules do not account for certain other other hand, posterior cervical lymph nodes are more 35-37 important costs. For example, they do not account often associated with infectious mononucleosis. for the costs associated with alternative day care The remainder of the physical examination is arrangements, missed work time, and other “social also of some value. Patients with other symptoms costs.” The rules assume that either oral or intra- suggestive of viral illness are unlikely to have a 13,42,43,50-55 muscular penicillin will be used for treatment and, GABHS infection. These include conjunc- therefore, do not include the costs of other agents. tivitis, rhinorrhea, viral exanthem, serous otitis These rules were also created in an era before the media, and wheezing. Unilateral or, less commonly, development of rapid antigen tests for GABHS so bilateral follicular conjunctivitis associated with the costs of these tests are not considered. The exudative pharyngitis is a hallmark of adenovirus 42 Tompkins rules recommend that all patients who infection. In a school age child with pharyngitis, have at least a 20% chance of having a GABHS the presence of a scarlatiniform rash is, on the other infection be treated presumptively without obtain- hand, almost diagnostic of GABHS infection and ing a culture. Conversely, those who have less than many clinicians advocate treating such patients 54,55 a 5% chance should neither be tested nor treated. without testing. However, A. haemolyticum pro- Those patients who have a 5 to 19% chance of hav- duces a very similar rash. Patients with A. haemo- ing a GABHS infection should be cultured.57 lyticum infections, however, are generally older and Neuner et al undertook a cost-effectiveness more often have associated cough. Additionally, analysis using these five strategies: 1) Observation their rash is highly pruritic and, unlike the rash of 42,44 without testing or treatment, 2) Empirical treatment scarlet fever, does not peel. Patients with infec- of all patients with penicillin, 3) Throat culture, tious mononucleosis often have splenomegaly and 4) Optical immune assay (OIA) RADT followed by

EBMedicine.net • June 2007 9 Pediatric Emergency Medicine Practice© culture to confirm negative results, and 5) OIA valued at two points. Therefore, the maximum pos- RADT alone. They determined that observation sible score was five points. A patient with a score of alone, culture alone, RADT with culture, and RADT zero had only a 12% chance of having a positive alone were very similar in both effectiveness and throat culture (approximately the GABHS carriage cost. However, provided that the incidence of true rate in the community studied), while a patient with GABHS infection was approximately 10% or greater; four or more points had a 79% chance of having a throat culture was the most effective and least positive throat culture. Unfortunately, a score of expensive strategy.58 four or five points was only possible in the presence Tsvat et al performed a similar analysis. They of a scarlatiniform rash, a relatively rare finding. compared the cost-effectiveness of seven strategies Those patients with a score of one to three had, in which included neither testing nor treating any aggregate, only a 36% chance of having a positive patient, treating all patients presumptively without culture.54,55 testing, and various combinations of treating and Perhaps the best known scoring system is the testing. They concluded that, in a population of one published by Centor and co-investigators in what they termed “adherent” patients, the most 1981. They used logistical regression models to cre- cost-effective strategy was throat culture followed ate a four item score. The four items are: 1) Tonsil- by treatment of only patients with positive cul- lar exudates, 2) Swollen, tender, anterior cervical tures.12 Unfortunately, this study is more applicable lymph nodes, 3) Lack of cough, and 4) Fever or a to office-based practitioners who have a reliable history of fever. In a group of patients over 15 years patient base. Likewise, the rules developed by of age, they found that those who met all four crite- Neuner and colleagues are somewhat more applica- ria had a 56% probability of having a positive throat ble to office-based physicians, but they suggest that culture while those who met none of the criteria had OIA RADTs are nearly as effective as cultures. The only a 2.5% probability of having a positive rules developed by Tompkins would, unfortunately, culture.52 With slight variations in the results, these result in gross overtreatment. In an era in which rules have been prospectively validated in three rheumatic fever is a relatively unusual disease, such adult populations and are considered to be among overtreatment is hard to justify. Finally, rather than the most reliable clinical decision rules.52,59,60 Addi- slavishly apply these criteria, emergency physicians tionally, the Centor rules have been endorsed by should understand that there is a real or potential several respected specialty societies and by the Cen- cost, whether immediate or delayed, associated with ters for Disease Control (CDC).1 In fact, the CDC any treatment strategy. endorses a treatment strategy that includes sympto- matic management only for patients with a Centor Clinical Rules score of zero. The CDC guidelines allow presump- One of the first scoring systems was developed in tive treatment of patients with a Centor score of 1977 by Breese. He called his system a “simple four, though the patient may be tested with a RADT scorecard” for the diagnosis of GABHS. In reality, at the physician’s discretion. In patients with scores this scorecard was not so simple. It was a nine item, of two or three, clinician discretion with regard to weighted scoring system with a maximum possible testing and treatment is also permitted. score of 36 points. Unfortunately, the validation Unfortunately, the Centor scoring system has study contained serious methodological flaws. only been validated in adult populations. However, Additionally, the scoring system recommended the McIsaac and colleagues have tested a modified ver- routine use of a white blood cell count. These prob- sion of this score in children. The McIsaac modifica- lems make this system impractical for emergency tion adds two age-based criteria to the original Cen- department use.50 tor score. If the patient is less than 15 years old, an In 1998, Wald and colleagues published a study additional point is added; if the patient is older than using a simplified version of the Breese scorecard. 45 years of age, a point is subtracted. Patients with They eliminated the white blood cell count and a modified Centor score of zero or -1 are very reduced the scorecard from nine to six items. These unlikely to have a positive throat culture, while items included: 1) Age, 2) Season, 3) Temperature of those with a score of four or greater have at least a at least 38.3°C, 4) Adenopathy, 5) Pharyngeal ery- 51% chance of having a positive throat culture.5,60 thema, edema, or exudates, and 6) No symptoms of One of the primary problems with clinical scor- viral upper respiratory tract infection. The ing systems is the lack of standardized definitions. maximum possible score was six. In their validation For example, one clinician might describe a few group, they found that a score of five or six white patches on the tonsils as an “exudate” while predicted a positive culture in 59% and 75% of chil- another might require the tonsils to be coated before dren, respectively. On the other hand, a significant applying the same definition. In order to address number of children with scores of two or three had this problem, Jensen and colleagues attempted to im- positive throat cultures.51 prove inter-observer reliability by exposing clinicians A four item model was developed and tested by to visual aids which included pictures of the various Attia and his co-investigators. The items in their stages of critical findings. Unfortunately, their inter- model included tonsillar swelling, cervical vention did not result in improved inter-observer lymphadenopathy, and absence of coryza. These reliability. Perhaps future attempts to standardize three items were valued at one point each. The clinical findings will meet with more success.61 fourth item, presence of a scarlatiniform rash, was

Pediatric Emergency Medicine Practice© 10 June 2007 • EBMedicine.net Diagnostic Testing certain non-pathogenic strains of Neisseria are known to colonize the pharynx (especially in young Laboratory Tests children) and because of the potential consequences Throat Culture: When diagnostic and testing strate- of the diagnosis of gonococcal pharyngitis in a gies for GABHS are discussed, their sensitivity and child, a second set of confirmatory cultures are rec- specificity are virtually always compared to that of ommended prior to a conclusive diagnosis. DNA throat culture. In fact, the very name of the organ- probe tests for Neisseria gonorrhea are not currently ism comes from the appearance of the colonies recommended for the diagnosis of gonococcal when they are cultured on blood agar plates. How- pharyngitis.25,46 ever, throat cultures are an imperfect “gold stand- Rapid Antigen Detection Tests: Rapid antigen detec- ard.” First, the results are heavily dependent upon tion tests (RADT’s) became available in the 1980s the technique employed to obtain the sample. The and have rapidly evolved. RADT testing is done in physician or nurse who attempts to obtain a culture a fashion similar to throat culture. A swab is passed from a crying and uncooperative child by shoving a over the tonsils and posterior pharynx. In a person swab somewhere into the child’s mouth is wasting with GABHS in their throat, this swab should col- money and time. The swab should instead be lect organisms which are the source of the bacterial passed along the surface of the tonsils and soft antigens for the test. This material is treated and palate. In patients who have undergone tonsillec- then exposed to antibody against GABHS. A tomy, the throat swab should be passed along the 62 marker is used to detect the antigen-antibody com- tonsillar fossae. The use of a second swab im- plex. The earliest RADT systems were based upon proves the chance of obtaining a positive culture. latex agglutination (LA) technology. Because this Patients with relatively few organisms in their 42 test involves several steps and requires subjective throats may not have positive cultures. The interpretation by a technician, there are many method of culture is also important. However, since opportunities for the technique to fail. Therefore, most emergency departments rely upon the hospital LA based tests have relatively low sensitivities. laboratory to properly process samples, this issue is (Mean 80%, range 62-97%).63-65 not important to the emergency physician. Emer- The next RADT tests to be developed were based gency department personnel are, however, responsi- upon enzyme-linked immunoabsorbent assay ble for ensuring that the specimen is collected prop- (ELISA). ELISA technology still involves several erly. Although the throat culture is generally steps; however, the use of a color indicator means regarded as the reference standard by which diag- that the result is less reliant upon subjective inter- nostic methods are compared, the issues described pretation by laboratory personnel. Even with these above result in culture being only 90 to 99% sensi- advantages, however, many ELISA tests have a per- tive for the detection of GABHS infection. It is, of formance profile very similar to that of latex aggluti- course, almost 100% specific for the identification of nation. (Mean sensitivity 79%, range 61-96%).63-65 bacteria in the pharynx. However, a positive culture The newest widely used tests employ optical does not necessarily imply infection. GABHS carri- immunoassay (OIA) technology. OIA tests rely ers may have positive cultures despite having a upon the changes in the reflection of light to indi- viral pharyngitis. The distinction between the car- cate that the antibody has bound to the antigen rier state and actual infection requires antibody test- 13,42,43 sample. Test results are generally available in less ing (see next page). than one hour, allowing a treatment decision to be For the emergency physician, the primary prob- made while the patient is still in the emergency lem with throat culture is the time delay between department. Many studies comparing OIA detec- obtaining the sample and the availability of results. tion tests to culture on blood agar plates have been This delay is problematic for several reasons. The conducted. Virtually all agree that OIA detection emergency department must establish a method for tests are very specific for GABHS. A positive test contacting those patients with positive cultures and result means that the patient can be assumed to arranging for them to be treated. Records must be have streptococcal pharyngitis and should be kept so that attempts to contact are verifiable. Such treated accordingly. Unfortunately, the reported systems are time and labor intensive. The patient sensitivity of OIA RADT’s has varied. Studies of may be forced to miss one or more days of school or OIA tests have reported sensitivities as low as 77% work while waiting for their test results and may be and as high as 95-99%.63-67 This is an important further inconvenienced by a second medical visit. issue. If these tests truly are 95-99% sensitive, then Finally, one of the benefits, albeit a relatively minor their ability to detect true GABHS infection while one, of treatment is that the patient’s symptoms simultaneously identifying patients who have might improve somewhat sooner. A delay in treat- another type of pharyngitis is on par with throat ment while waiting for culture results is likely to 42 culture. This implies that confirmation of a negative obviate this benefit. OIA RADT by throat culture is unnecessary. In cases of suspected gonococcal pharyngitis, Indeed, two recent articles have suggested this strat- routine throat cultures on sheep’s red blood cell egy. Webb and colleagues published a retrospective agar are unlikely to be positive. Neisseria review of 30,036 cases of pharyngitis over a four gonorrhea is a somewhat fastidious organism and is 43,46 year period. During the first two years, virtually all best cultured on Thayer-Martin agar. Because patients had a throat culture performed during the

EBMedicine.net • June 2007 11 Pediatric Emergency Medicine Practice© second two years; 77% of patients were tested with directed against an antigenic hemolysin produced an OIA RADT alone. The authors found no increase by the GABHS organism, is most familiar to clini- in suppurative complications during the second two cians. It has been used for many years to track the years and no cases of rheumatic fever were identi- recovery of patients with rheumatic fever and fied.68 Ehrlich et al performed a cost-effectiveness PSGN. In recent years, ASO titers and other anti- analysis of several strategies intended to prevent body tests have been incorporated into commercial rheumatic fever. They determined that RADT alone kits, making them easier to obtain. (at a cost of $727,000 per case of rheumatic fever However, as a clinical tool, antibody tests have prevented) to be the most cost effective strategy. many drawbacks. The most important problem is Throat culture alone would prevent 11 more cases that one titer says little about the status of the than RADT alone, at a cost of $13.7 million for each patient’s condition. There is no reference standard case prevented, while adding a confirmatory culture for a “normal” ASO titer. Many factors affect the to all negative RADTs would prevent 21 additional immune response to GABHS infection, including cases at a cost of $8 million per case.69 the age of the patient, the underlying incidence of On the other hand, if the true sensitivity of the disease in the population, the site of the infection OIA RADT is closer to 77%, then up to 20% of infec- (pharyngitis produces a more vigorous antibody tions that would have been detected by throat cul- response than skin infection), the season of the year, ture would be missed. Newer tests using molecular and whether or not antibiotics were given and the biology methods are available. These tests offer the timing of such treatment. Antibody testing, there- promise of even higher sensitivities. However, there fore, is only useful in tracking the course of illness are problems with the newer RADTs. First, their in an individual patient. The initial titer is only use- current turn-around-times are measured in hours ful in the presence of later “convalescent” titers. rather than minutes. From the perspective of the This limitation makes antibody testing nearly use- emergency physician, this makes them no better less to the emergency physician.72 than culture.63,65,67,70 Additionally, as sensitivity Heterophile Antibody Testing for Mononucleosis increases, so does the risk of identifying patients (Monospot): EBV infection can be identified with with only a few organisms in their throats. Such certainty by a variety of antigen tests; however, individuals are thought to be carriers rather than most of these are expensive and labor-intensive. patients with true GABHS infection. Undoubtedly, The most commonly used surrogate for specific tests these technologies will continue to develop. is the heterophile antibody response. This test is RADT tests have many of the same potential inexpensive and readily available, but imperfect. failings as cultures. Like cultures, they rely on a For example, the test is not specific for EBV infec- properly collected specimen and, like cultures, the tion. Furthermore, since the antibody response technique used to perform the test can influence the takes some time to occur, the test may not be posi- results. Some have noted that many of the cases in tive early in the course of illness. Only 60-70% of which the RADT is negative but the culture is posi- patients have a positive heterophile antibody test tive occur when the culture has a very low bacterial during the first week of illness. By the third week, colony count. This has led some to postulate that 80-90% of patients will have a positive test. In 15- these are patients with very few organisms in their 20% of adolescent and young adult patients with a throats, perhaps GABHS carriers with non-strepto- true infection, the test remains negative. In young coccal pharyngitis. For all of their failings, RADT’s children, even fewer have a positive heterophile perform as well or better than most clinical decision antibody response.49 rules but are, of course, more costly. There is, however, another potential problem The Complete Blood Count: In the evaluation of the with RADT’s. A recent study demonstrated that patient with pharyngitis, the role of the complete these tests are subject to so called “spectrum bias.” blood count (CBC) is limited. Patients with either That is, the sensitivity of the test varies with the like- bacterial pharyngitis or an abscess are likely to have lihood of disease in the subject. In this study, the an elevated white blood cell count. However, in RADT was 61% sensitive in subjects with zero or one most cases, the CBC is of no assistance in making of the Centor criteria, 76% sensitive in those with the diagnosis. Patients with infectious mononucleo- two Centor criteria, 90% sensitive in those with three sis do often have atypical lymphocytes noted on Centor criteria, and 97% sensitive in those with four peripheral smear and this finding may help a clini- Centor criteria. These findings imply that, among cian to confirm their suspicions, particularly when other things, in patients with a high clinical probabil- evaluating the patient early in the course of illness, ity of infection (e.g., three or four Centor criteria) when the heterophile antibody response is most who have a negative RADT, confirmatory cultures likely to be negative.49 may be unnecessary. These results may also explain the wide variation in the sensitivities of RADT’s.71 Radiologic Tests Soft-Tissue Lateral Neck Films: The soft-tissue lat- Anti-Streptolysin O (ASO) Testing: The human host eral neck film is used primarily in the evaluation of produces antibodies to certain components of the patients with symptoms of upper airway obstruc- GABHS cell wall (somatic or cellular antigens) and tion. A properly performed soft-tissue lateral neck to substances produced by the organism (extracellu- film can help the physician to diagnose epiglottitis, lar antigens). The test for ASO, the antibody

Pediatric Emergency Medicine Practice© 12 June 2007 • EBMedicine.net Clinical Pathway: Evaluation And Management Of Pharyngitis In Children

Assess airway and respiratory status. (Class Indeterminate)

Signs of airway compromise or respiratory distress? See pathway for serious Yes symptoms on page 15. No

Assess hydration. (Class Indeterminate)

Rehydrate with IV fluids or treat pain Is patient dehydrated? Yes and orally rehydrate. (Class I) No

Perform a history and physical examination. (Class Inderminate) No

Evidence of viral illness? Treat symptoms. (Cough, coryza, conjunctivitis, Yes Do not test or treat for GABHS. viral exanthem, etc.) (Class II)

No Manage accordingly. History and examination suggests an Class Indeterminate alternative diagnosis? Yes ( ) No

Does patient have: Consider presumptive Scarlatiniform rash OR all five of the following? treatment for GABHS. Class II 1. Age 5 to 15 years old Yes ( ) 2. Fall or winter season 3. Temperature of at least 38.3°C RADT testing is an acceptable 4. Tender and enlarged anterior cervical lymph nodes alternative. (Class III) 5. Exudative pharyngitis No Perform RADT. (Class II) Need for rapid diagnosis? Does patient have unreliable follow-up care? Yes Treat positives. Is patient likely to be non-compliant? Culture negatives AND document follow-up arrangements for culture results. Class III No ( )

Perform culture. Arrange follow-up for positive results. (Class II)

RADT testing followed by treatment of positives and culture of negatives is an acceptable alternative. (Class II)

The evidence for recommendations is graded using the following scale. For complete definitions, see back page. Class I: Definitely recommended. Definitive, excellent evidence provides support. Class II: Acceptable and useful. Good evidence provides support. Class III: May be acceptable, possibly useful. Fair-to-good evidence provides support. Indeterminate: Continuing area of research. This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon a patient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care. Copyright © 2007 EB Practice, LLC. 1-800-249-5770. No part of this publication may be reproduced in any format without written consent of EB Practice, LLC.

EBMedicine.net • June 2007 13 Pediatric Emergency Medicine Practice© Clinical Pathway: Evaluation And Management Of Pharyngitis In Adolescents

Assess airway and respiratory status. (Class Indeterminate)

See guideline for serious Signs of airway compromise or respiratory distress? Yes symptoms on page 15. No

Assess hydration. (Class Indeterminate)

Rehydrate with IV fluids or treat pain Is patient dehydrated? Yes and orally rehydrate. (Class I) No

Perform a history and physical examination. (Class Indeterminate)

Evidence of viral illness? Treat symptoms. (Cough, coryza, conjunctivitis, Yes Do not test or treat for GABHS. viral exanthem etc.) (Class II) No

History and examination suggests an Yes Manage accordingly. alternative diagnosis? (Class Indeterminate) No

Does patient have: Consider presumptive Scarlatiniform rash OR all four of the Centor criteria? treatment for GABHS. 1. Absence of cough (Class II) 2. Fever or history of fever Yes RADT testing is an 3. Tender and enlarged anterior cervical lymph nodes acceptable alternative. 4. Exudative pharyngitis (Class III) No Perform RADT. Treat positives. Do not Does patient have three of the Centor criteria? Yes culture. (Class III) Presumptive treatment is an acceptable Class III No alternative. ( )

Does patient have two of the Centor criteria? Yes Perform RADT. Treat positives. Do not culture. (Class III) No

Patient has only one or zero Centor criteria. Do not test or treat with antibiotics. Treat symptoms. (Class II)

The evidence for recommendations is graded using the following scale. For complete definitions, see back page. Class I: Definitely recommended. Definitive, excellent evidence provides support. Class II: Acceptable and useful. Good evidence provides support. Class III: May be acceptable, possibly useful. Fair-to-good evidence provides support. Indeterminate: Continuing area of research. This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon a patient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care. Copyright © 2007 EB Practice, LLC. 1-800-249-5770. No part of this publication may be reproduced in any format without written consent of EB Practice, LLC.

Pediatric Emergency Medicine Practice© 14 June 2007 • EBMedicine.net Clinical Pathway: Management Of Severe Causes Of Pharyngitis (Serious Symptoms)

Does patient have evidence of impending upper Airway management takes precedence airway obstruction or partial upper airway over diagnosis and treatment. obstruction (e.g., drooling, stridor, aphonia, Yes dysphonia, “tripod” position, etc.)? If management is to occur in the ED: 1. Prepare a “double set up” 2. Consider alternatives to paralytic agents 3. Have alternative airway adjuncts No immediately available (Class III) Perform a history and physical examination. (Class Indeterminate)

No

Evidence of Ludwig’s angina? Yes Surgical consultation. (Submental edema, elevation of the tongue, firm, (Class Indeterminate) “woody” sublingual area, history of dental disease, intraoral trauma, or tongue piercing)

No Visualize epiglottis using dental mirror or nasopharyngoscope (older adolescents Evidence of epiglottitis? only) OR obtain lateral neck film. (Class III) (Dyspnea at rest, intense throat pain out of Yes proportion to examination findings, dysphonia) If patient is a young child, consider immediate evaluation in the operating room. (Class III) No

Evidence of retropharyngeal abscess? Obtain CT scan. (Class III) (Neck stiffness, dysphonia, more gradual onset of symptoms; in adults: history of bone or Yes If diagnosis is confirmed, obtain surgical other sharp object ingestion) consultation. (Class Indeterminate)

No Consider needle aspiration followed by antibiotic treatment directed against typical flora and Evidence of peritonsillar abscess? anaerobes. (Class III) OR (Trismus, unilateral tonsilar enlargement, Yes tonsillar deviation of the uvula) Obtain surgical consultation. (Class Indeterminate) No

Evidence of mononucleosis with severe tonsilar hypertrophy? Admit. (History of symptoms consistent with mononucleosis Yes Begin treatment with steroids. AND Class III enlarged tonsils with signs of early airway obstruction) ( )

No

Consider alternative diagnosis; reconsider above diagnoses

The evidence for recommendations is graded using the following scale. For complete definitions, see back page. Class I: Definitely recommended. Definitive, excellent evidence provides support. Class II: Acceptable and useful. Good evidence provides support. Class III: May be acceptable, possibly useful. Fair-to-good evidence provides support. Indeterminate: Continuing area of research. This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon a patient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care. Copyright © 2007 EB Practice, LLC. 1-800-249-5770. No part of this publication may be reproduced in any format without written consent of EB Practice, LLC.

EBMedicine.net • June 2007 15 Pediatric Emergency Medicine Practice© retropharyngeal abscess, pharyngeal, esophageal, or finding in croup is narrowing of the tracheal air col- tracheal foreign bodies, and, when combined with umn in the subglottic region (so-called “steeple an AP soft-tissue neck film, croup. For patients with sign”), and on the lateral film a “foggy” or “ground epiglottitis, the classic finding is enlargement of the glass” appearance is commonly noted in the epiglottis (so-called “thumb sign”). It is important subglottic area.79 to understand that inflammation of the epiglottis is Computed Tomography: Computed tomography is not an isolated occurrence. Other tissues near the the modality of choice in the evaluation of epiglottis are also inflamed and their appearance on suspected deep tissue abscesses and can also be x-ray will be altered. The entire area around the used to identify peritonsillar abscesses in young, epiglottis appears edematous. Furthermore, the lat- uncooperative children.80 When the clinician eral neck film may be less helpful in the diagnosis of strongly suspects that the patient has, for example, a epiglottitis in adolescents than in pediatric patients retropharyngeal abscess, many experts argue that with the disease.17,24 When the symptoms are plain x-rays are superfluous and should be omitted strongly suggestive of epiglottitis, direct examina- in favor of a CT scan.33,39,73,74 CT scanning is also tion of the epiglottis is preferred for adoles- useful in the evaluation of patients with Ludwig’s cents.17,23,24 For patients with retropharyngeal angina.28-30 For all of its advantages, however, CT abscess, the classical finding on soft-tissue lateral scan does have some drawbacks. The patient must neck film is widening of the retropharyngeal soft- lie supine, if only for a few minutes, and this may tissues. This begs the question “how wide is too be difficult or impossible when he or she has symp- wide?” There is no single answer to this question. toms of airway obstruction. Likewise, young chil- Over the years, various rules of thumb have been dren, unless sedated, may move during the study. suggested. The most common of these states that Movement can be reduced or eliminated with the prevertebral space anterior to the second cervi- sedation but this has attendant risks. Finally, CT cal vertebrae should be no larger than the width of scan exposes the patient to significantly more radia- the vertebral body itself, provided that the patient is tion than plain radiography.81 a young child.73 More precisely stated, the retro- pharyngeal tissues should be 7 mm or less, meas- Ultrasound: ured from the most anterior portion of C2. The As ultrasound technology improves, many clinicians retrotracheal space should be measured from the are finding unique uses for this technology. Ultra- anterior aspect of C5 or C6 and should be less than sound can aid in the diagnosis of abscesses of all 14 mm wide.39,73 No evidence has demonstrated types. Several reports describe the use of intraoral this rule to be superior to the clinician simply look- ultrasound to diagnose peritonsillar abscesses.82-84 ing at the film and using his or her judgment. In order to provide the most useful information, the Treatment patient must be properly positioned. The retropha- “One of first duties of the physician is to educate the ryngeal space will appear falsely enlarged unless masses not to take medicine.” Sir William Osler 1849- the patient’s neck is well extended and the film is 1919. taken in full inspiration.39 When the patient is a young child (the typical victims of retropharyngeal Airway Management abscess are young children), a useful radiograph Although a complete discussion of emergency air- may be difficult to achieve. Furthermore, the CT way management is beyond the scope of this article, scan has been demonstrated to be more sensitive airway management is the first priority for the than plain radiographs and, therefore, it should be patient with respiratory distress. When faced with considered the modality of choice when retropha- such a patient, be prepared to intervene if necessary. ryngeal abscess is strongly suspected.33,39,73,74 The patient with complete airway obstruction obvi- Most radiopaque foreign bodies are readily ously requires immediate airway management. It is detectable on plain radiograph, however, only a rel- appropriate to attempt bag-mask ventilation (often, ative handful of foreign bodies are radiopaque. In a two-person technique is required) or orotracheal practice, plain films are most useful in the identifi- intubation as the initial management techniques. cation of metallic foreign bodies (e.g., coins). This However, should these fail, it is best to proceed to modality is not as useful for less dense objects.75-77 an alternate technique, usually an invasive While the appearance of these objects on plain x-ray procedure.85 is often touted as a means by which to distinguish For patients with impending airway obstruction, tracheal and esophageal foreign bodies; in practice, administration of 100% oxygen is the first priority. objects located within the trachea cause more seri- Definitive management of the airway might occur in ous respiratory symptoms. Furthermore, many the emergency department, the intensive care unit, objects that will readily pass into the esophagus are or the operating room, depending upon local proto- too large to enter the trachea of a young child.78 cols and the availability of personnel and equip- Although laryngotracheobronchitis, commonly ment. If the underlying cause of the patient’s symp- called “croup,” is largely a clinical diagnosis, when toms is surgical or possibly surgical, the appropriate the diagnosis is in doubt or when other diagnoses surgeon should be notified as soon as possible. are being considered, AP and lateral soft tissue neck films may be useful. On the AP view, the classic Peritonsillar Abscess In the past, most patients with peritonsillar abscess

Pediatric Emergency Medicine Practice© 16 June 2007 • EBMedicine.net were admitted to the hospital for incision and First and easiest to use are non-prescription anal- drainage followed by antibiotic treatment. Recent gesic medications. These include acetaminophen, evidence, however, suggests that needle aspiration aspirin, ibuprofen, naproxen, and other medications. may be just as effective, but it may also be associ- Each of these has advantages and disadvantages. In ated with a higher rate of recurrence. Experienced appropriate doses, all are relatively effective pain emergency physicians may undertake this proce- medications and most are available in inexpensive dure but should be aware that care must be taken to generic preparations. In one metanalysis, NSAIDs, avoid complications. The most serious of these is acetaminophen, aspirin, and Benzydamine oral inadvertent puncture of the carotid artery.86,87 Oto- rinse were all more effective than placebo in reduc- laryngologists and, in some cases, emergency physi- ing the pain associated with sore throat.91 In cians may also attempt incision and drainage under another study of children with pharyngitis, aceta- local anesthesia in cooperative patients. In addition minophen and ibuprofen were compared to placebo. to aspiration, most patients should be placed on While both ibuprofen and acetaminophen provided antibiotics. Currently, clindamycin and second or more relief than placebo, only the difference third generation cephalosporins are the recom- between ibuprofen and placebo reached statistical mended agents.32 With proper aspiration and significance.92 If the patient has significant pain that antibiotic treatment and with the assurance of has not been relieved by one of these agents, the appropriate follow-up, many patients with periton- physician can certainly consider treatment with an sillar abscesses can be managed as outpatients. oral narcotic. Of the three commonly prescribed However, there is still some controversy as to the oral narcotics (codeine, oxycodone, and hydroco- most appropriate therapy for these patients.32,80,86,87 done), the latter two are slightly more effective and are associated with fewer unpleasant side effects.93 Infectious Mononucleosis With Impending A variety of topical agents are also available. Airway Obstruction Topical sprays containing benzocaine and phenol Although most cases of infectious mononucleosis are available over the counter and in prescription are little more than an annoyance, a few patients preparations. These preparations provide will develop significant lymphoid hypertrophy and temporary relief from pain and might allow the a subset (0.1 - 1%) will develop signs of airway patient to ingest enough liquids to maintain obstruction. In these patients, treatment with corti- adequate hydration or to swallow analgesics with- costeroids is generally recommended to reduce the out undue discomfort. On the other hand, they tonsillar hypertrophy and, therefore, to reduce the affect the taste buds and are rapidly washed away obstructive symptoms.88 Unless the patient has dif- by saliva and consumed liquids. These medications ficulty swallowing, prednisone (1 mg/kg/day – are very safe if used in the recommended doses. maximum dose, 60 mg) is generally effective. A Children might, however, find them unpalatable. recent study of single dose dexamethasone (0.3 Additionally, there is only limited evidence to sup- mg/kg – maximum dose 15 mg) demonstrated that port their use. In addition to these medications, dexamethasone was also effective but the pain relief European investigators have evaluated the effective- was relatively short-lived. These results imply that ness of other topicals. German investigators com- a single dose is not sufficient and subsequent doses pared the effectiveness of lozenges made from the of corticosteroids might be required.89 In those mucolytic agent ambroxol hydrochloride to placebo patients who cannot swallow, intravenous methyl- lozenges and found that the ambroxol hydrochlo- prednisolone (2 mg/kg/day – maximum dose 125 ride provided superior pain reduction.94,95 Unfortu- mg) is an acceptable alternative. nately, this medication is not available in the United Infectious Pharyngitis Treatment of infectious States. Likewise, British and Australian investiga- pharyngitis consists of therapy to reduce the tors have demonstrated that lozenges containing patient’s discomfort and antibiotic treatment of the 8.75 mg of flurbiprofen are superior to placebo in infectious agent. While all patients should receive reducing the pain associated with sore throat. Cur- rently, flurbiprofen is only available in the United the former, relatively few patients require the latter. 96 However, there is often little in the way of medical States as an ocular preparation. evidence to support many of these therapies. For Finally, no discussion of symptomatic treatment example, an antihistamine, with or without a decon- would be complete without consideration of the role gestant, could, in theory, eliminate the posterior of corticosteroids. Although many practitioners nasal drainage that causes pharyngeal irritation routinely prescribe or administer corticosteroids to associated with viral upper respiratory tract infec- patients with pharyngitis, there are no large trials to tion, but most studies of these agents find them to support this practice. However, the results of a be of little or no benefit.90 Likewise, acetaminophen number of smaller studies suggest that cortico- steroid treatment provides relief of pain several or nonsteroidal anti-inflammatory agents can reduce 97-100 fever and help with body aches. However, what hours sooner than might otherwise be expected. most patients desire is relief from the sore throat. Early studies centered upon the use of intramuscu- lar steroids but the results of more recent trials Such treatments come in a variety of forms. Some 98,99,101 are over-the-counter medications that are available indicate that oral agents are equally effective. at virtually any pharmacy or supermarket, while In adult-sized patients, such as older adolescents, others require a prescription. administer a single 10 mg dose of dexamethasone,

EBMedicine.net • June 2007 17 Pediatric Emergency Medicine Practice© either taken orally or injected intramuscularly, or a significance of these failures in terms of placing the single 60 mg dose of oral prednisone. Younger chil- patient at risk for rheumatic fever is debatable, no dren should receive a single dose of oral dexa- discussion of treatment can ignore these issues.102 methasone (0.6 mg/kg - maximum dose 10 mg). GABHS is not the only bacterial inhabitant of the Although some studies have suggested that the human respiratory tract. Haemophilus influenzae, greatest benefits occur in patients who have culture- Moraxella catarrhalis, and other bacteria are also proven bacterial pharyngitis, at least one recent often present. Many of these organisms produce study refutes this claim. In this study, the 37 beta lactamase which makes them resistant to peni- patients with non-GABHS pharyngitis who received cillin. Studies comparing patients with significant dexamethasone had a considerably shorter duration numbers of beta lactamase producing bacteria in of symptoms than the 27 patients with non-GABHS their throats with those who do not harbor such pharyngitis who were given placebo.101 Based upon organisms have concluded that penicillin is less the limited studies conducted thus far, cortico- likely to eradicate GABHS in the former group. It steroids appear to be safe. None of the authors has been theorized that the beta lactamase produced report any significant untoward events associated by the other bacteria actually decreases the concen- with the use of these agents. tration of penicillin in the pharynx, diminishing its effectiveness.105,106 Others have found that alpha Antibiotic Treatment Of GABHS hemolytic streptococci play an important role as There is little question that, despite years of use, well. It has been proposed that the alpha hemolytic penicillin, at least in vitro, remains effective against bacteria compete with other organisms for nutrients. GABHS. A study comparing GABHS cultures main- Patients with lower colony counts of alpha tained since the pre-antibiotic era to modern cul- hemolytic organisms coupled with higher counts of tures demonstrated that there has been essentially beta lactamase producers seem to fail treatment no change in penicillin’s efficacy.102 That being said, with penicillin more often.106 These findings have some authors have noted both bacteriologic and led some to assert that agents more effective against clinical failures in patients treated with penicillin. beta lactamase producing organisms either replace Depending upon the measure used, roughly 20-30% penicillin altogether or be used to treat those in of patients might be expected to “fail” treatment whom penicillin seems to have failed.102,105,107 Crit- with penicillin or relapse.103,104 While the ics of this approach argue that, in areas with a low

Cost Effective Strategies In Patients With Pharyngitis

1. Do not test or prescribe antibiotics to patients in some cases, but for most patients, a simple with obvious viral syndromes. prescription is less expensive and equally Patients with cough, coryza, conjunctivitis, and effective. other symptoms of a viral illness are very unlike- 5. Do not prescribe broad-spectrum, new, or ad- ly to have concomitant GABHS infections. Treat- vanced antibiotics to treat pharyngitis in ment of such patients should be directed toward patients who are not allergic to penicillin. making them feel better. Penicillin and amoxicillin are effective in the Risk management caveat: this rule applies to treatment of GABHS infections. There is no evi- otherwise healthy, immunocompetent patients who do dence of GABHS resistance to these agents and not live in areas where rheumatic fever is endemic. there is little reason to use more expensive More liberal treatment of high-risk patients is antibiotics to treat pharyngitis in patients who warranted. are not allergic to penicillin. For penicillin aller- 2. Do not perform throat cultures for GABHS in gic patients, the problem is somewhat more patients over 15 years old. complex. The cheapest agent available is eryth- Older adolescents are at a lower risk for romycin. However, there is a relatively high rheumatic fever and at a lower risk for severe incidence of GABHS resistance to erythromycin complications should they have rheumatic fever. and other macrolides. Furthermore, many ado- Therefore, most authorities recommend that lescents are simply unable to cope with the gas- these patients be managed with a combination of trointestinal side effects of erythromycin. In clinical guidelines and rapid antigen detection such patients, alternative agents are warranted. tests. Children tolerate erythromycin somewhat better Risk management caveat: see #1 above. and, unless the child is known to have had prob- 3. If you are going to treat based upon clinical lems with erythromycin in the past, it is proba- criteria, do not test. bly worth trying. Sending a culture or performing an RADT in a Risk management caveat: in communities with patient who has already received a prescription both an increased incidence of erythromycin resist- for antibiotics is a waste of time and money. ance and GABHS and an increased risk of rheumatic 4. Limit the use of injections. fever, an alternative agent should be chosen for chil- Injections ensure treatment and are appropriate dren with GABHS pharyngitis.

Pediatric Emergency Medicine Practice© 18 June 2007 • EBMedicine.net incidence of rheumatic fever (most of the U.S.), the Table 2. Recommended Antibiotics For benefits of microbiologic cure are questionable and GABHS Infections In may not be worth the risk of increasing bacterial Adolescents/Adults resistance and the cost of these agents.103,108 Given the difficulties associated with the performance of a Standard Treatment – Patient not allergic to penicillin definitive study to answer this question, most clini- Penicillin V – 250 mg PO every 6-8 hours for 10 days cians will be forced to rely upon the recommenda- Penicillin G Benzathine - 1.2 Million units IM X 1 tions of experts and specialty societies along with their own interpretation of the medical literature. Alternative Treatments – Patient not allergic to penicillin Penicillin V – 500 mg PO twice per day for 10 days For patients who are allergic to penicillin and Amoxicillin – 750 mg PO once per day for 10 days* other beta-lactam antibiotics, the alternative agent chosen most often is a macrolide. Unfortunately, Standard Treatment – Patient allergic to penicillin unlike the case of penicillin, macrolide resistance Erythromycin ethylsuccinate – 400 mg PO four times per day for among GABHS organisms is relatively common and 10 days some have cautioned that macrolides be used to treat pharyngitis only when absolutely necessary.109 Alternative Treatments – Patient allergic to penicillin Azithromycin – 500 PO on day one followed by 250 my PO on Treatment of pharyngitis, even documented days two-five. Each dose is taken only once per GABHS pharyngitis, is not without risk. Patients day. can experience allergic reactions and unpleasant Cefoxadril – 1000 mg PO once per day for 10 days† side effects from antibiotic treatment. Additionally, Cephalexin – 500 mg PO twice per day for 10 days† some authors have noted a higher relapse and recurrence rate among patients treated early in the * Research supports this regimen, however it is based upon a course of their illness as compared to those who are few relatively small studies. (Class II) treated later. These investigators have suggested † Cephalosporins should not be used in patients with immediate that later treatment might allow the patient to type penicillin allergy. mount a more vigorous immune response which may later serve to protect him or her from the 110 Table 3. Recommended Antibiotics For relapse. However, other studies refute these find- ings and some authors have noted that patients GABHS Infections In Children treated earlier experience relief of symptoms several Standard Treatment – Patient not allergic to penicillin hours sooner than those in whom treatment is 111,112 Penicillin V – Patients < 27 kg – 125 mg PO four times per day delayed. Others have noted that treatment of for 10 days pharyngitis has a “medicalizing” effect. That is, Patients > 27 kg – 250 mg PO every 6-8 hours patients who seek care for pharyngitis and are for 10 days treated tend to seek care for similar symptoms in Penicillin G Benzathine - < 27 kg - 600,000 units IM X 1 the future and are more likely to believe that antibi- >27 kg – 1.2 Million units IM X 1 otics are beneficial or necessary.113,114 Alternative Treatments – Patient not allergic to penicillin Although many antibiotics can effectively Penicillin V – Patients < 27 kg – 250 mg PO twice per day for 10 days Table 4. Other agents effective against Patients > 27 kg – 500 mg PO twice per day GABHS for 10 days Amoxicillin – Patients < 27 kg – 40 mg/kg/day PO divided Cefuroxime – Adolescents – 250 PO twice a day for 10 days three times per day for 10 days Children – 20 mg/kg/day PO in two divided doses Patients > 27 kg – 750 mg PO once per day for 10 days for 10 days*

Standard Treatment – Patient allergic to penicillin Clindamycin – Adolescents – 300-450 mg PO four times a day for 10 days Erythromycin ethylsuccinate – 40 mg/kg/day in two to four Children – 20-30 mg/kg/day in four divided doses divided doses (Maximum dose 400 mg) per day for 10 days for 10 days

Alternative Treatments – Patient allergic to penicillin Amoxicillin/Clavulanate – Adolescents – 250-500 mg PO three Azithromycin – 10 mg/kg (Maximum dose 500 mg) on day one times per day for 10 days followed by 5 mg/kg (Maximum dose 250 mg) on Children – 40 mg/kg/day in three days two through five. Each dose is taken only divided doses for 10 days once per day. Cefoxadril – 30 mg/kg/day in two divided doses (Maximum Alternative – Adolescents – 875 mg twice a day dose 1000 mg) for 10 days.† Children – 25-45 mg/kg/day in two divided doses Cephalexin – 25 to 50 mg/kg day in two to four doses (Maximum dose 500 mg) for 10 days.† Table 5. Agents Not Effective Against

* Research supports this regimen; however, it is based upon a GABHS few relatively small studies. (Class II) † Cephalosporins should not be used in patients with immediate • Tetracyclines • Trimethoprim type penicillin allergy. • Fluoroquinolones • Chloramphenicol • Sulfonamides

EBMedicine.net • June 2007 19 Pediatric Emergency Medicine Practice© Ten Pitfalls To Avoid

1. “Sure the kid was in distress, but with epiglottitis treatment has no impact on the disease, but patients out of the picture, I figured it would be OK to just with “mono” who take amoxicillin can get a diffuse, sedate him and take a look in the ER.” morbiliform rash. The rash is harmless and doesn’t Pediatric epiglottitis is but one form of upper airway represent medication allergy but patients may find the obstruction and Haemophilus influenza type B is not the rash upsetting. The rash can be avoided by treating only cause of epiglottitis. Chemical and thermal patients who might have mononucleosis (e.g., adoles- injury and, uncommonly, other types of infection can cents with several days of malaise prior to the onset of result in edema of the epiglottis and the surrounding pharyngitis) with penicillin instead of amoxicillin or tissues. Management of the child with impending air- by testing them with an RADT before treating. way obstruction is best conducted in the most con- Patients who are presumptively treated with amoxi- trolled environment possible. Definitive management cillin should be warned about this complication. in the emergency department should be considered as 5. “I sent the new tech in to do the rapid strep test. It a last resort. When forced to manage a patient with was negative, but now the throat culture is positive airway obstruction in the emergency department, the and I have to call the child back.” physician should be prepared with several alternative There are many reasons why an RADT might be nega- airway devices available and, in most cases, should tive even though the patient has GABHS pharyngitis. prepare for a surgical airway with a “double set-up.” However, the most common reason is undoubtedly It should be noted that there are several studies which poor collection technique. The swab should be passed have demonstrated that it is safe to visualize the over both tonsils and the posterior pharynx. In epiglottis outside of the operating room in adult patients whose tonsils have been removed, the tonsil- patients. However, no such studies in children exist. lar fossae are an adequate substitute. Failure to per- Evaluation in the operating room represents an estab- form the test correctly can cause false-negative results. lished standard of care that is published in hundreds All members of the staff responsible for performing of respected sources. Given that epiglottitis is now an these tests should be thoroughly trained in the proper extremely rare disease, it would be virtually impossi- collection method. ble to design a study to refute this standard. An attempt at visualization in the emergency department 6. “I was worried about a retropharyngeal abscess. The places the physician on extremely thin ice from a med- lateral neck film seemed to confirm my suspicions, ical legal standpoint. so I ordered a CT scan. For the patient’s sake, I’m happy that the scan was normal but I just don’t 2. “Hey, it was just a sore throat, what do you mean she understand how this could have happened.” came back the next day severely dehydrated?” The soft-tissue lateral neck film remains an excellent Pharyngitis can be exceptionally painful, making it and inexpensive screening test for retropharyngeal difficult for patients to consume enough liquids. abscess, although some authors advocate direct CT Ensure that the patient is adequately hydrated at the scanning of high-risk cases. Enlargement of the pre- time of his or her initial evaluation, and then be cer- vertebral soft tissues suggests the presence of this dis- tain to suggest or prescribe medications and other ease. However, the truly enlarged pre-vertebral space strategies to reduce the patient’s pain so that he or she must be distinguished from one that only appears to can maintain adequate fluid intake. be enlarged. In most cases, false enlargement of the 3. “My strategy is a quick exam and a prescription; pre-vertebral space is caused by flexion of the patient’s what’s wrong with that?” neck. It is easy to say that the patient must always be While many physicians employ a strategy of presump- positioned with his/her neck fully extended for the tive treatment for all cases of pharyngitis, this ap- lateral neck film but, retropharyngeal abscess is most proach is flawed on several levels. First, many patients common in young children and it can be very difficult and parents would prefer to understand their disease for the radiology technician to properly position these and why the physician is recommending one course of often uncooperative patients. Additionally, young chil- treatment rather than another, instead of just getting a dren often cry during x-rays and, should the film be prescription. Second, unnecessary antibiotic treatment taken while a vigorously crying child is in expiration, increases the cost of health care, increases the incidence the prevertebral soft tissues may appear enlarged. of resistant bacteria, places the patient at risk for Despite these difficulties, do not accept the film unless medication allergy and other untoward reactions, and proper technique was used. In very young children, creates an expectation of antibiotics for future illnesses. CT scanning is no small matter and sedation might be required to obtain a good study. Given the risks of 4. “That teenager had all four Centor criteria, so I sedation, it is vital that, if a screening test is used, it is treated her with amoxicillin. Her mom was really of good quality. mad about the rash.” 7. “I gave the child the right antibiotic but the family Patients who have infectious mononucleosis can close- complained about me anyway. They said I didn’t ly resemble those with GABHS pharyngitis. Penicillin care enough about their child’s pain.”

Pediatric Emergency Medicine Practice© 20 June 2007 • EBMedicine.net eradicate GABHS, Tables 2 and 3 list the most com- restricted to the drugs on a prescription plan formu- monly recommended agents and their doses for lary. The first question to be answered is, “shot or adolescents and children. Table 4 lists alternative pills?” An intramuscular injection is very uncom- agents and their doses, and Table 5 lists agents that fortable but provides one time, single-dose treat- are ineffective against GABHS. Other than issues of ment. Parents are spared the need to administer allergies and other untoward side effects, the choice further doses of medication to an uncooperative of treatment method and agent is largely a matter of child and busy adolescents do not have to remem- physician and patient preference. However, the rel- ber to take antibiotics. No notes are needed allow- ative cost of the agents used should also be consid- ing medication to be given at school or day care and ered and, in many cases, the physician will be the indigent family, who cannot even get back to the

Ten Pitfalls To Avoid (continued)

At most, only about one-third of children with emergency department can be accomplished by expe- pharyngitis will benefit from antibiotics, but most will rienced emergency physicians. Although, even in this have some degree of discomfort as a result of their relatively cooperative patient population, use local or illness. One of the emergency physician’s primary topical anesthetic liberally and take care to avoid duties is to assess and treat the patient’s pain. Some injury to underlying vascular structures. This is most patients will benefit from simple over-the-counter commonly accomplished by using tape or a plastic gargles, analgesics, and topical agents, while others needle guard to prevent the needle or scalpel from might require narcotic pain medications in order to penetrating too deeply. In younger children, however, receive maximum benefit. There is a growing body of even under the best of circumstances, cooperation is evidence suggesting that steroids might also be effec- more difficult to achieve. These children are often best tive. Pain relief has always been one of the physician’s managed in an operating room setting. primary duties, but recently it has come under 10. “The rapid strep test was positive and I sent the fam- scrutiny by regulatory agencies. As such, ensure that ily out with a prescription for penicillin. One of my all patients with painful conditions receive adequate partners told me that they were back a few nights analgesia. later and the kid was still sick.” 8. “Hey, I work in a busy ED. I don’t have time to do a There are many potential reasons for treatment failure social history on every little sore throat.” or relapse. Probably the most common reason is non- In most cases, pharyngitis is a benign, self-limiting compliance with prescribed therapy. Although the illness. However, in certain circumstances, more lib- term “noncompliance” has a pejorative connotation, eral treatment is indicated. It is particularly important there are sometimes valid explanations for lack of to know which patients are at greater risk for serious cooperation with the prescribed regimen. Very poor forms of pharyngitis and for complications. For exam- families may be unable to afford the prescription and ple, recent immigrants from certain countries (e.g., the may be too proud to admit that fact. Additionally, former Soviet Union) might be more likely to have many parents struggle with their children to get them diphtheria. Likewise, rheumatic fever, though rare, to take medicine. In some cases, they give up in frus- occurs with greater frequency in certain parts of the tration. Although there is some evidence to the con- United States and in some other countries. In the trary, many authorities still recommend a full 10 days United States, rheumatic fever outbreaks have of treatment in order to avoid relapse. Some authors occurred in Pennsylvania, Utah, West Virginia, and have suggested that the presence of other beta-lacta- Texas, among others. Worldwide, rheumatic fever mase producing bacteria in the patient’s throat might remains a problem in much of the Third World. prevent beta-lactam antibiotics, like penicillin, from Patients who are at greater risk for these illnesses are eradicating a sufficient number of GABHS organisms. candidates for a thorough evaluation. It is very Patients who fail therapy or relapse shortly after treat- important to recognize that virtually all clinical deci- ment might benefit from treatment with antibiotics sion rules and treatment pathways designed for effective against beta-lactamase producing organisms. pharyngitis are intended for use under normal circum- Although penicillin remains the drug of choice for stances. These rules should not be used during out- treatment of GABHS pharyngitis, patients who are breaks and should not be applied to individuals at allergic to penicillin are generally treated with erythro- greater risk for serious disease. mycin. Erythromycin resistance is relatively common 9. “The ENT convinced me to try draining a peritonsil- among GABHS organisms. Erythromycin treated lar abscess in a five year old in the ED. I tried topi- patients who fail therapy should be treated with cal anesthetic but he still wouldn’t cooperate. Even another antibiotic. sedation didn’t work.” Finally, as stated previously, infectious mononu- cleosis can closely resemble GABHS pharyngitis. In Fortunately, peritonsillar abscesses occur primarily in the adolescent who has failed presumptive treatment adolescents and young adults. In this patient popula- for GABHS, mononucleosis should be considered. tion, needle aspiration or incision and drainage in the

EBMedicine.net • June 2007 21 Pediatric Emergency Medicine Practice© shelter without assistance from the hospital, is and will prevent rheumatic fever. Finally, a small spared the cost of an antibiotic prescription. The minority of children will have a more serious physician is assured that the medication has been illness. A careful history and physical examination, given and need not worry about lack of patient coupled with judiciously selected ancillary tests, compliance. On the other hand, injections are asso- will identify most of these patients. The emergency ciated with more severe allergic reactions, are physician must, as always, be vigilant to detect the painful, and, when the cost of the medication and few with serious illness among the many with rou- the nursing time to administer it are considered tine pharyngitis. together, are expensive. Oral medications have to be taken for many days. Many authorities still rec- Case Conclusion ommend a 10-day course of most oral agents. How- An hour later, the “monospot” test is back and it’s positive. ever, a recent meta-analysis demonstrated that a You spend the next few minutes explaining mononucleosis to five-day course of a cephalosporin achieved the mother and her daughter. You advise the daughter to avoid superior bacterial cure rates. Similar results were soccer practice until her physician determines that it is safe for not found with macrolides.115,116 Another recent her to play. You also tell them that antibiotics are not neces- study evaluated treatment with five days of sary. Although you are not able to offer them a cure, they seem happy to have received a diagnosis and to have been reassured clarithromycin, five days of amoxicillin/clavulanate, that things will likely improve. The mother even gives you a or 10 days of penicillin. The authors found that the hug on her way out of the door. There is, however, little time to three treatments were similar in terms of clinical enjoy the feeling of a job well done. The charts are piling up efficacy but that amoxicillin/clavulanate and peni- again and it is time to go back to work. cillin achieved superior bacterial cure rates, prima- rily because clarithromycin failed to eradicate References macrolide resistant strains of Streptococcus Evidence-based medicine requires a critical appraisal of pyogenes.117 In recent years, several studies have the literature based upon study methodology and number demonstrated that either once or twice daily amoxi- of subjects. Not all references are equally robust. The find- cillin is an effective alternative to penicillin therapy. ings of a large, prospective, randomized, and blinded trial One recent study comparing once per day should carry more weight than a case report. amoxicillin and twice per day amoxicillin found no To help the reader judge the strength of each reference, difference between the two regimens.118-121 Compli- pertinent information about the study, such as the type of ance with medication increases as the number of study and the number of patients in the study, will be doses per day decreases, so regimens allowing included in bold type following the reference, where fewer doses of medication are attractive. Further- available. In addition, the most informative references, as more, once or twice daily dosing eliminates the determined by the author, will be noted with an asterisk need for a child to take a dose of medication at (*) next to the number of the reference. school or day care. However, caution is warranted. Athree day course of the long-acting macrolide *1. Cooper RJ, Hoffman, JR, Bartlett JG, Besser RE, Gonzales R, Hickner JM, Sande MA. Principles of appropriate antibi- azithromycin was found to be inferior to standard otic use for acute pharyngitis in adults: Background. Ann 122 penicillin therapy. Emerg Med 2001;37:711-19. (Practice Guideline) In addition to problems with compliance, oral 2. Centor RM, Witherspoon JA, Dalton HP, Brody CE, Link K. medications are associated with some unwanted The diagnosis of strep throat in adults in the emergency side effects. Gastrointestinal symptoms, like vomit- room. Med Decis Making 1981;1:239-46. (Controlled clinical ing and diarrhea, are not uncommon. Furthermore, trial 286 patients) many liquid medication preparations are rather 3. Steinhoff MC, El Khalek MKA,Khallaf N, Hamza HS, El unpalatable. It is difficult to force a struggling tod- Ayadi A, Orabi A, Fouad H, Kamel M. Effectiveness of clinical guidelines on the presumptive treatment of strep- dler to take a medication that he or she does not tococcal pharyngitis in Egyptian children. Lancet 1997;350: want. All of these factors should be considered with 918-21. (Controlled clinical trial, 451 children) the patient and his or her parents before a final deci- 4. Rimoin AW, Hamza HS, Vice A, Kumar R, Walker CF, Chi- sion regarding treatment is made. tale RA, da Cunha LAL, Qazi S, Steinhoff MC. Evaluation of the WHO clinical decision rule for streptococcal pharyn- Summary gitis. Arch Dis Child 2005;90:1066-70. (Observational study, 1810 children) The vast majority of patients who come to the emer- 5. McIsaac WJ, Kellner JD, Aufricht P, Vanjaka A, Low DE. gency department for treatment of pharyngitis will Empirical validation of guidelines for the management of have a self-limited viral illness. These patients have pharyngitis in children and adults. JAMA 2004;291:1587-95. a right to expect pain relief and education but do (Controlled clinical trial 787 patients) not require antibiotics. A substantial number of 6. Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore patients, particularly school-aged children, will have throat. The Cochrane Data Base of Systematic Reviews 2006;4. an infection caused by GABHS. These children (Systematic review of the literature) should be evaluated and treated using a combina- 7. Merrill B, Kelsberg G, Jankowski TA, Danis P. What is the most effective diagnostic evaluation of streptococcal tion of clinical findings and testing. Diaz et al pharyngitis. J Fam Pract 2004;53: 734,737-738,740. (System- found that a standardized treatment protocol atic review of the literature) allowed more children in a pediatric emergency *8. Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore department to be treated appropriately.123 Antibi- throat. The Cochrane Database of Systematic Reviews 2000;2. otics may decrease the duration of their discomfort (Systematic review of the literature)

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Dexamethasone for the treatment of sore throat beta-hemolytic streptococcal pharyngitis: A meta analysis in children with suspected infectious mononucleosis: A supporting the concept of microbial copathogenicity. Pedi- randomized, double-blind, placebo-controlled, clinical atr Infect Dis J 1991;10:275-81. (Meta analysis; 19 studies) trial. Arch Pediatr Adolesc Med 2004;158:250-4. (Randomized 106. Brook I, Gober AE. Role of bacterial interference and beta- trial; 40 patients) lactamase producing bacteria in the failure of penicillin to 90. Smith MBH and Feldman W. Over-the-counter cold med- eradicate group A streptococcal pharyngotonsillitis. Arch ications: A critical review of clinical trials between 1950 Otolaryngol Head Neck Surg 1995;121:1405-9. (Controlled and 1991. JAMA 1993;269:2258-63. (Meta-analysis; 51 trial; 52 patients) articles) 107. Pichichero ME. Cephalosporins are superior to penicillin *91. Thomas M, Del Mar C, Glasziou P. How effective are treat- for treatment of streptococcal tonsillopharyngitis: Is the ments other than antibiotics for acute sore throat? Br J Gen difference worth it? Pediatr Infect Dis J 1993;12:268-74. Pract 2000;50-817-20. (Meta analysis; 22 studies) (Review Article) 92. Bertin L, Pons G, d’Athis P, Lasfargues G, Maudelonde M, 108. Gerber MA, Tanz RR. New approaches to the treatment of Duhamel JF, Olive G. Randomized, double-blind, multi- group A streptococcal pharyngitis. Curr Opin Pediatr center, controlled trial of ibuprofen versus acetaminophen 2001;13:51-8. (Review Article) (paracetamol), and placebo for treatment of symptoms of 109. Jacobs MR, Johnson CE. Macrolide resistance: An increas- tonsillitis and pharyngitis in children. J Pediatr ing concern for treatment failure in children. Pediatr Infect 1991;119:811-14. (Randomized trial; 231 patients) Dis J 2003;22:S131-8. 93. Tuturro MA, Paris PM, Yealy DM, Menegazzi JJ. 110. Pichichero ME, Disney FA, Talpey WB, Green JL, Francis Hydrocodone versus codeine in acute musculoskeletal AB, Roghmann Klaus J, Hoekelman RA. Adverse and ben- pain. Ann Emerg Med 1991;20:1100-3. (Randomized trial; 62 eficial effects of immediate treatment of group A beta- patients) hemolytic streptococcal pharyngitis with penicillin. Pediatr 94. Fischer J, Pschorn U, Vix, JM, Peil H, Aicher B, Muller A, Infect Dis J 1987;6:635-43. (Prospective, randomized trial; de May C. Efficacy and tolerability of ambroxol hydrochlo- 142 patients) ride lozenges in sore throat. Randomised, double-blind, 111. Randolph, M F. Gerber, M A. DeMeo, K K. Wright, L. placebo-controlled trials regarding the local anaesthetic Effect of antibiotic therapy on the clinical course of strepto- properties. Arzneimittel-Forschung 2002;52:256-63. (Two coccal pharyngitis. J Pediatr 1985;106:870-5. (Randomized, randomized trials; 714 patients) placebo-controlled trial; 260 children) 95. Schutz A, Gund HJ, Pschorn U, Aicher B, Peil H, Muller A, 112. Gerber MA, Randolph MF, DeMeo KK, Kaplan EL. Lack of de May C, Gillissen A. Local anaesthetic properties of impact of early antibiotic therapy for streptococcal pharyn- ambroxol hydrochloride lozenges in view of sore throat. gitis on recurrence rates. J. Pediatr 1990;117:853-8. (Prospec- Clinical proof of concept. Arzneimittel-Forschung tive, randomized trial; 113 patients) 2002;52:194-9. (Randomized trial, 218 patients) *113. Little P, Gould C, Williamson I, Warner G, Gantley M, Kin- 96. Benrimoj SI, Langford JH, Christian J, Charlesworth A, month AL. Reattendance and complications in a random- Steans A. Efficacy and tolerability of the anti-inflammatory ized trial of prescribing strategies for sore throat: The med- throat lozenge flurbiprofen 8.75 mg in the treatment of icalising effect of prescribing antibiotics. BMJ sore throat: A randomized, double-blind, placebo- 1997;315:350-2. (Randomized trial; 716 patients) controlled study. Clinical Drug Investigation 2001;21:183-93. (Randomized trial; 320 patients) 114. Little P, Williamson I, Warner G, Gould C, Gantley M, Kin- month AL. Open randomized trial of prescribing strategies *97. O’Brien JF, Meade JL, Falk JL. Dexamethasone as adjuvant in managing sore throat. BMJ 1997;314:722-7. (Randomized therapy for severe acute pharyngitis. Ann Emerg Med trial; 716 patients) 1993;22:212-15. (Randomized trial; 58 patients) 115. Dajani Adnan, Taubert K, Ferrieri P, Peter G, Shulman S. et *98. Wei JL, Kasperbauer JL, Weaver AL, Boggust AJ. Efficacy al. Treatment of acute streptococcal pharyngitis and pre- of single-dose dexamethasone as adjuvant therapy for vention of rheumatic fever: A statement for health profes- acute pharyngitis. Laryngoscope 2002;112:87-93. (Random- sionals. Pediatrics 1995;758-64. (Position statement) ized trial; 118 patients)

EBMedicine.net • June 2007 25 Pediatric Emergency Medicine Practice© 116. Casey JR, Pichichero ME. Metaanalysis of short course a. He is highly likely to have GABHS and can be antibiotic treatment for group A streptococcal treated presumptively tonsilopharyngitis. Pediatr Infect Di J 2005;24:909-17. b. An RADT is likely to be positive (Meta-analysis; 22 trials) c. An RADT is likely to be negative but a throat 117. Syrogiannopoulos GA, Bozdogan B, Grivea IN, Ednie LM, culture will make the diagnosis Kritikou DI, Katopodis GD, Beratis NG, Appelbaum PC and the Hellenic Antibiotic-Resistant Respiratory d. There are no tests which can make the diagnosis Pathogens Study Group. Pediatr Infect Dis J 2004;23:857-65. e. The heterophile antibody test might be negative (Randomized trial; 626 children) 118. Feder HM, Gerber MA, Randolph MF, Stelmach PS, 51. Regarding the patient described in question number Kaplan EL. Once-daily therapy for streptococcal pharyngi- 2, which of the following medications is most likely tis with amoxicillin. Pediatrics 1999;103:47-51. (Random- to be effective? ized trial; 152 patients) 119. Shvartzman P, Tabenkin H, Rosentzwaig A, Dolginov F. a. Penicillin Treatment of streptococcal pharyngitis with amoxycillin b. Amoxicillin once a day. BMJ 1993;306:1170-2. (Randomized trial; 157 c. Ceftriaxone patients) d. Tetracycline *120. Lan AJ, Colford JM. The impact of dosing frequency on the e. None of the above efficacy of 10-day penicillin or amoxicillin therapy for streptococcal Tonsillopharyngitis: A meta-analysis. Pedi- 52. The patient described in question number 2 returns a atrics 2000;105,19. (Meta-analysis; 6 studies) few days later with complaints that he cannot lie 121. Clegg HW, Ryan AG, Dallas SD, Kaplan EL, Johnson DR, supine without respiratory difficulty. Which of the Norton J, Roddey OF, Martin ES, Swetenburg RL, Koonce following treatments is most likely to be effective? EW, Felkner MM, Giftos PM. Treatment of streptococcal pharyngitis with once-daily compared with twice-daily amoxicillin: A noninferiority trial. Pediatr Infect Dis J a. Dexamethasone 10 mg 2006;25:761-7.(Randomised non-inferiority trial; 652 b. Amoxicillin 500 mg O BID for 10 days children) c. Penicillin 250 mg O QID for 10 days 122. Pacifico L, Scopetti F, Ranucci A, Patracchia M, Savignoni d. Humidified air and warm compresses only F, Chiesa C. Comparative efficacy and safety of 3-day e. None of the above azithromycin and 10-day penicillin V treatment of group A beta-hemolytic streptococcal pharyngitis in children. 53. A six-year-old presents to the emergency department Antimicrobial Agents and Chemotherapy 1996;40:1005-08. with a sore throat. He also has a temperature of (Randomized trial; 154 children) 38.4°C. He has no history of cough or coryza. On *123. Diaz MCG, Symons N, Ramundo ML, Christopher NC. examination, pharyngeal exudates and tender ante- Effect of a standardized pharyngitis treatment protocol on rior cervical lymph nodes are noted. Which of the use of antibiotics in a pediatric emergency department. Arch Pediatr Adolesc Med 2004;158:977-81. (Controlled trial; following statements is most correct? 443 children) a. He has a low probability of having GABHS b. Presumptive treatment, though controversial, is CME Questions an acceptable option c. RADT testing is not acceptable for this patient d. Most guidelines do not recommend culturing 49. A four-year-old girl is brought to the emergency this patient if his RADT is negative department for evaluation of a sore throat. Associ- e. None of the above is correct ated symptoms include low-grade fever, cough, rhin- orrhea, and bilateral conjunctivitis. Which of the 54. Regarding the patient described in question number following statements regarding management of this 5, which of the following statements is most correct? child is most correct? a. A positive RADT is not sufficient to begin treat- a. She should receive amoxicillin as presumptive ment. A culture must also be performed treatment b. A negative RADT in this patient implies a very b. A throat culture is mandatory low risk of having GABHS c. An RADT should be performed c. Given a choice of RADT test, a latex agglutina- d. Management of her symptoms without testing tion test is preferred over an optical immune or antibiotic treatment is acceptable assay test e. None of the above is correct d. A culture is never indicated in a patient like this e. None of the above is correct 50. A 14-year-old boy comes to the emergency depart- ment for evaluation of sore throat which began after 55. A three-year-old boy presents to the emergency a few days of general malaise. He is afebrile. On department with fever for several days. His parents physical examination, he has grossly swollen tonsils have noticed that he is not moving his head as much without exudates and also has enlarged posterior cer- as usual and are worried that he might have menin- vical lymph nodes. In total, he has had symptoms gitis. On physical examination, you note that the for five days. Which of the following statements child follows a light held above his head only with regarding this patient is most correct? his eyes. He will not look up. Which of the follow- ing tests should be done first?

Pediatric Emergency Medicine Practice© 26 June 2007 • EBMedicine.net a. An RADT a. The swab should be passed along the gum line b. A throat culture bilaterally c. A soft-tissue lateral neck film b. The new RADTs are so sensitive that the swab d. A lumbar puncture can be placed almost anywhere in the mouth e. None of the above c. The swab must touch the posterior portion of the tongue 56. A 17-year-old girl presents with complaints of fever d. Swabs are useless in patients without tonsils and sore throat. As you begin her evaluation, you e. The swab should pass along both tonsils and the note that she has a “hot potato” voice and significant posterior pharynx trismus. Which diagnosis is most likely? 61. Which of the following statements regarding infec- a. GABHS tious mononucleosis is most correct? b. Viral pharyngitis c. Infectious mononucleosis a. Patients with mononucleosis can closely resem- d. Peritonsillar abscess ble those with GABHS pharyngitis e. Retropharyngeal abscess b. The heterophile antibody test is usually positive on day one of illness 57. Regarding the patient described in question number c. Steroids are indicated for all patients 8, which of the following statements regarding man- d. Specific antigen tests should always be used agement is most correct? e. None of the above is correct

a. With proper attention to analgesia and 62. Regarding pain management in children with technique, the emergency physician may man- pharyngitis, which of the following statements is age her as an outpatient most correct? b. Hospital admission is mandatory as outpatient management is not appropriate a. Ibuprofen is no more effective than placebo c. Needle aspiration is not an acceptable manage- b. Narcotic agents are never indicated ment option c. Steroid treatment may result in a shorter dura- d. There is not currently an imaging modality tion of pain available to assist in the evaluation of this d. Gargles provide long-lasting relief patient e. None of the above is correct e. None of the above is correct 63. Regarding the role of steroids in pharyngitis, which 58. Which of the following statements regarding of the following statement is most correct? retropharyngeal abscess is most correct? a. Only intramuscular steroids are effective a. The disease is most prevalent in adolescents b. Several small studies suggest that steroid treat- b. Patients often present with their necks fully ment shortens the duration of discomfort extended and refuse to look down c. Steroids are only indicated in patients with c. When confirming the diagnosis, soft tissue lat- infectious mononucleosis and are ineffective in eral neck films are superior to computed tomog- other forms of pharyngitis raphy d. Steroid treatment reduces pain but the side d. Retropharyngeal abscess can occur as the result effects are worrisome of a toothpick or fishbone penetrating the e. None of the above is correct esophagus e. None of the above is correct 64. A 16-year-old presents to the ED with pharyngitis, absence of cough and coryza, but no fever or 59. A four-year-old HIV positive boy who is fully immu- adenopathy. You elect to perform an RADT. Which nized presents to the ED with sudden onset of fever, of the following statements is most correct? followed rapidly by dyphonia and drooling. Which of the following management approaches is most a. A negative RADT mandates a culture in this correct? patient b. A positive RADT allows treatment to begin a. Immediate intravenous line, hydration, and c. Most guidelines suggest that an RADT not be antibiotic treatment performed in patients like the one described b. Evaluation of his airway in the operating room above c. Lateral neck film in the x-ray department d. A positive RADT is meaningless because d. Immediate surgical airway RADT’s have poor specificity e. Throat culture and RADT testing e. None of the above is correct

60. You are training a group of residents in the proper collection technique for RADT and throat culture specimens. You are most likely to say:

EBMedicine.net • June 2007 27 Pediatric Emergency Medicine Practice© Physician CME Information

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