Emergency Department Management of Rash and Fever in the Pediatric Patient

January 2020 Emergency Department Volume 17, Number 1 Authors

Management of Rash and Rhonda L. Philopena, MD Assistant Professor of Emergency Medicine and Pediatric Emergency Medicine, SUNY Upstate Medical University, Syracuse, NY Fever in the Pediatric Patient Erin M. Hanley, MD Assistant Professor of Pediatrics and Emergency Medicine, SUNY Abstract Upstate Medical University, Syracuse, NY Kayla Dueland-Kuhn, MD SUNY Upstate Medical University, Syracuse, NY Rash and fever are some of the most common chief complaints Peer Reviewers presenting to the emergency department. The evaluation of Jeffrey R. Avner, MD, FAAP rashes in the febrile pediatric patient includes a broad differen- Chairman, Department of Pediatrics, Professor of Clinical Pediatrics, tial diagnosis and use of the history and physical examination Maimonides Children’s Hospital of Brooklyn, Brooklyn, NY Nicole Gerber, MD to identify red flags, such as hemodynamic instability, erythro- Assistant Professor of Clinical Pediatrics, Department of Emergency derma, desquamation, petechiae/purpura, mucous membrane Medicine, Division of Pediatric Emergency Medicine, New York- involvement, and severe pain, that should increase suspicion Presbyterian/Weill Cornell Medical Center, New York, NY for worrisome disease. This issue reviews characteristics of Prior to beginning this activity, see “CME Information” common rashes as well as rarer, potentially life-threatening on the back page. rashes, to guide management and treatment and improve pa- This issue is eligible for 4 Infectious Disease CME credits tient outcomes. and 0.5 Pharmacology CME credits.

Editors-in-Chief Ari Cohen, MD, FAAP Alson S. Inaba, MD, FAAP Garth Meckler, MD, MSHS David M. Walker, MD, FACEP, FAAP Chief of Pediatric Emergency Pediatric Emergency Medicine Associate Professor of Pediatrics, Chief, Pediatric Emergency Ilene Claudius, MD Medicine, Massachusetts General Specialist, Kapiolani Medical Center University of British Columbia; Medicine, Department of Pediatrics, Associate Professor; Director, Hospital; Instructor in Pediatrics, for Women & Children; Associate Division Head, Pediatric Emergency Joseph M. Sanzari Children's Process & Quality Improvement Harvard Medical School, Boston, MA Professor of Pediatrics, University Medicine, BC Children's Hospital, Hospital, Hackensack University Program, Harbor-UCLA Medical of Hawaii John A. Burns School of Vancouver, BC, Canada Medical Center, Hackensack, NJ Jay D. Fisher, MD, FAAP, FACEP Center, Torrance, CA Medicine, Honolulu, HI Clinical Professor of Emergency Joshua Nagler, MD, MHPEd Vincent J. Wang, MD, MHA Tim Horeczko, MD, MSCR, FACEP, Medicine and Pediatrics, University Madeline Matar Joseph, MD, FACEP, Assistant Professor of Pediatrics Professor of Pediatrics and FAAP of Nevada, Las Vegas School of FAAP and Emergency Medicine, Harvard Emergency Medicine; Division Associate Professor of Clinical Medicine, Las Vegas, NV Professor of Emergency Medicine Medical School; Associate Division Chief, Pediatric Emergency Emergency Medicine, David Geffen and Pediatrics, Assistant Chair, Chief and Fellowship Director, Division Medicine, UT Southwestern Marianne Gausche-Hill, MD, FACEP, School of Medicine, UCLA; Core Pediatric Emergency Medicine of Emergency Medicine, Boston Medical Center; Director of Faculty and Senior Physician, Los FAAP, FAEMS Medical Director, Los Angeles Quality Improvement, Pediatric Children’s Hospital, Boston, MA Emergency Services, Children's Angeles County-Harbor-UCLA Emergency Medicine Division, Health, Dallas, TX County EMS Agency; Professor of James Naprawa, MD Medical Center, Torrance, CA University of Florida College of Clinical Emergency Medicine and Attending Physician, Emergency International Editor Editorial Board Pediatrics, David Geffen School Medicine-Jacksonville, Department USCF Benioff Jacksonville, FL Lara Zibners, MD, FAAP, FACEP, Jeffrey R. Avner, MD, FAAP of Medicine at UCLA; Clinical Children's Hospital, Oakland, CA Faculty, Harbor-UCLA Medical MMed Chairman, Department of Stephanie Kennebeck, MD Joshua Rocker, MD Center, Department of Emergency Associate Professor, University of Honorary Consultant, Paediatric Pediatrics, Professor of Clinical Associate Chief and Medical Emergency Medicine, St. Mary's Pediatrics, Maimonides Children's Medicine, Los Angeles, CA Cincinnati Department of Pediatrics, Director, Assistant Professor of Cincinnati, OH Hospital Imperial College Trust, Hospital of Brooklyn, Brooklyn, NY Michael J. Gerardi, MD, FAAP, Pediatrics and Emergency Medicine, London, UK; Nonclinical Instructor Steven Bin, MD FACEP, President Anupam Kharbanda, MD, MSc Cohen Children's Medical Center of of Emergency Medicine, Icahn Associate Clinical Professor, UCSF Associate Professor of Emergency Chief, Critical Care Services, New York, New Hyde Park, NY School of Medicine at Mount Sinai, Medicine, Icahn School of Medicine Children's Hospital Minnesota, School of Medicine; Medical Director, Steven Rogers, MD New York, NY Pediatric Emergency Medicine, UCSF at Mount Sinai; Director, Pediatric Minneapolis, MN Associate Professor, University of Emergency Medicine, Goryeb Benioff Children's Hospital, San Tommy Y. Kim, MD, FAAP, FACEP Connecticut School of Medicine, Pharmacology Editor Children's Hospital, Morristown Francisco, CA Associate Professor of Pediatric Attending Emergency Medicine Aimee Mishler, PharmD, BCPS Medical Center, Morristown, NJ Richard M. Cantor, MD, FAAP, FACEP Emergency Medicine, University of Physician, Connecticut Children's Emergency Medicine Pharmacist, Professor of Emergency Medicine Sandip Godambe, MD, PhD California Riverside School of Medicine, Medical Center, Hartford, CT Program Director – PGY2 Chief Quality and Patient Safety Officer, Riverside Community Hospital, Emergency Medicine Pharmacy and Pediatrics; Section Chief, Christopher Strother, MD Pediatric Emergency Medicine; Professor of Pediatrics, Attending Department of Emergency Medicine, Associate Professor, Emergency Residency, Valleywise Health Medical Director, Upstate Poison Physician of Emergency Medicine, Riverside, CA Medicine, Pediatrics, and Medical Medical Center, Phoenix, AZ Children's Hospital of The King's Control Center, Golisano Children's Melissa Langhan, MD, MHS Education; Director, Pediatric APP Liaison Hospital, Syracuse, NY Daughters Health System, Norfolk, VA Associate Professor of Pediatrics and Emergency Medicine; Director, Ran D. Goldman, MD Emergency Medicine; Fellowship Simulation; Icahn School of Medicine Brittany M. Newberry, PhD, MSN, Steven Choi, MD, FAAP MPH, APRN, ENP-BC, FNP-BC Chief Quality Officer and Associate Professor, Department of Pediatrics, Director, Director of Education, at Mount Sinai, New York, NY University of British Columbia; Pediatric Emergency Medicine, Yale Faculty, Emory University School Dean for Clinical Quality, Yale Adam E. Vella, MD, FAAP Research Director, Pediatric University School of Medicine, New of Nursing, Emergency Nurse Medicine/Yale School of Medicine; Director of Quality Assurance, Practitioner Program, Atlanta, GA; Vice President, Chief Quality Officer, Emergency Medicine, BC Children's Haven, CT Pediatric Emergency Medicine, Hospital, Vancouver, BC, Canada Nurse Practitioner, Fannin Regional Yale New Haven Health System, Robert Luten, MD New York-Presbyterian, Hospital Emergency Department, New Haven, CT Joseph Habboushe, MD, MBA Professor, Pediatrics and Weill Cornell, New York, NY Blue Ridge, GA Assistant Professor of Emergency Emergency Medicine, University of Medicine, NYU/Langone and Florida, Jacksonville, FL Bellevue Medical Centers, New York, NY; CEO, MD Aware LLC Case Presentations diagnosis is broad, most management decisions will be directed by key components of the history You arrive to a busy afternoon shift in the ED. Your first and physical examination, and any red flags. These patient is a 1-year-old boy with rhinorrhea, congestion, findings should prompt consideration of diseases cough, and 3 days of fever up to 39.4°C (103°F), mea- that would be severely detrimental to the child’s sured rectally. His parents state that he has been playful health if missed. at home and continues to eat and drink normally. They Some rashes, such as varicella, measles, and have been giving him acetaminophen and ibuprofen rubella, may represent a public health concern. sporadically, but today he developed a generalized rash, Diseases such as these have become slightly more and they became concerned. His vital signs are as follows: prevalent in the United States, due to caregiver temperature, 38.7°C (101.7°F); heart rate, 135 beats/min; concerns regarding vaccinations. Rates of meningo- and blood pressure, 85/55 mm Hg. On examination, the coccal disease have decreased; however, this disease 2 rash is macular, erythematous, and blanching, but his does have high rates of morbidity and mortality. eyes and mouth appear normal. This issue of Pediatric Emergency Medicine Prac- In the next room, there is a 3-year-old boy with a tice reviews various disease states, from benign to similar history who had mild rhinorrhea and a low-grade life-threatening, that can present as a fever with rash fever of 38.1°C (100.5°F) at home. His parents are con- in a child. Workup, treatment, and disposition rec- cerned that he has been complaining of pain in his legs, ommendations are provided based on key features on which they have noticed dark spots. He has continued of the history and physical examination. to drink well, though he has been eating slightly less. His vitals signs are as follows: temperature, 37.5°C (99.5°F); Critical Appraisal of the Literature heart rate, 120 beats/min; and blood pressure, 90/60 mm Hg. You observe some nonblanching spots on his lower A literature search was performed using PubMed. extremities and buttocks, as well as mild edema and ten- Search terms included fever, rash, viral exanthema, derness of his knees and ankle, but the boy is still able to measles, scarlet fever, rubella, varicella, roseola, parvovirus, bear weight with a mild limp. lyme disease, erythema migrans, Rocky Mountain spotted Before you finish examining the boy, a nurse asks you fever, acute rheumatic fever, erythema marginatum, Kawa- to see another patient who she says does not look well. The saki disease, Henoch-Schönlein purpura, HSP and steroids, patients is a 9-year-old girl with a history of ulcerative erythroderma, staphylococcal scalded skin syndrome, me- colitis who was sent from her pediatrician's office. She has ningococcal disease, Neisseria meningitidis, purpura and had 4 days of sore throat and low-grade fever at home, and fever, and toxic shock syndrome. her parents assumed she had a cold. She tested positive Multiple reviews and case reports were found, for strep throat at her appointment today. Her vital signs but, overall, evidence-based literature and original are as follows: temperature, 38.5°C (101.3°F); heart rate, research was scarce. Information from the World 126 beats/min; and blood pressure, 85/60 mm Hg. On Health Organization (WHO) and the CDC was also examination, her skin appears diffusely erythematous as if incorporated, as well as information from textbooks she has a severe sunburn. in infectious disease, emergency medicine, and pedi- These 3 patients all presented with dermatologic find- atrics specialties. ings and fever. How do you determine which patients are truly ill, and which are not? Are there any red flags for Etiology and Pathology recognizing rashes that could be life-threatening? Are there any key components to the history that are concerning? Do The combination of rash and fever can be a chief all of the patients need laboratory workup, or can you safely complaint that many clinicians find challenging to offer supportive care? Should any of these children be on manage, as there are a multitude of etiologies that isolation, either for their safety or for the safety of others? can present with these symptoms; some are common diagnoses and others are “can’t miss” diagnoses. Introduction (See Table 1, page 3.) The can't miss diagnoses, when not identified and treated in a timely manner, According to a 2015 United States Centers for can cause significant morbidity and mortality. Disease Control and Prevention (CDC) report, the Most well-recognized childhood exanthems are single most common chief complaint for children caused by viral etiologies. Many viruses can present aged < 15 years was fever, and the fifth most com- with nonspecific exanthema; most commonly, a mac- mon was skin rash.1 When paired, fever and rash ulopapular/morbilliform pattern is seen.3 Table 2, may create a diagnostic dilemma for the emer- page 4 describes some of the typical exanthema seen gency clinician. Although many relatively benign in pediatric patients. When attempting to determine conditions present with these symptoms, some the etiology, it is best to identify the characteristics life-threatening disease states will also present as of the rash first and then develop an appropriate dif- a rash in a febrile patient. Since the differential ferential diagnosis.

The differential diagnosis is very broad for the Prehospital care should begin with evaluation and febrile pediatric patient with rash and is narrowed management of the patient’s airway, breathing, and down by the history and physical examination circulation; obtaining initial vital signs; and stabi- findings to differentiate potentially dangerous or lizing an unstable patient. If prehospital personnel life-threatening diseases from those that will need have acetaminophen or ibuprofen, either would be minimal testing and treatment. (See Table 3, page 5.) appropriate to administer to the febrile child, after Endemic diseases, including mosquito-borne and checking with the caregivers for allergies and any tick-borne illnesses will not be discussed in this issue. previous medications given. If the patient appears For more information on management of tick-borne severely dehydrated or is hypotensive, intravenous illness, see the September 2018 issue of Pediatric Emer- (IV) access should be obtained to start IV fluids. Care gency Medicine Practice, “Tick-Borne Illnesses: Identi- should be taken to assess blood pressure in relation fication and Management in the Emergency Depart- to the patient’s age. If the patient is not alert and ori- ment,” available at: www.ebmedicine.net/ticks. If the ented, or if they have not been eating, point-of-care history is consistent with these etiologies, they should glucose is indicated. be kept in the differential. If there is any concern for a communicable dis- While beyond the scope of this article, drug ease that would require isolation, emergency medi- reactions are both common (eg, serum sickness-like cal services should utilize personal protection equip- reaction) as well as dangerous (eg, Stevens-Johnson ment and alert hospital personnel so that the proper syndrome/toxic epidermal necrolysis and drug precautions can be taken on arrival to the emergency reaction with eosinophilia and systemic symptoms department (ED). One of the main barriers to proper [DRESS]) and are important considerations in the isolation precautions is timely initiation. differential of a febrile rash. Emergency Department Evaluation

History Multiple etiologies of fever with rash are possible, and key components in the history can guide the Table 1. Common, Non–Life-Threatening clinician in determining the need for additional Diagnoses and “Can’t Miss,” Life- testing and the next steps in evaluation. The history Threatening Diagnoses should begin with determining the timeline (eg, Which came first, the rash or the fever? Has the fever Type of Disease Diagnoses resolved?) and characteristics of the rash as well as Common, non– • Viral exanthema other symptoms of the illness. Additionally, consider life-threatening • Roseola the time of the year, the region in which the patient • Parvovirus lives, and any recent travel history, as this will guide • Coxsackievirus (hand, foot, and mouth disease) consideration of any endemic diseases. • Varicella Vaccination status in pediatric patients should • Measles prompt the clinician to consider moving some diseases • Epstein-Barr virus/cytomegalovirus higher or lower on the differential diagnosis. Vaccine- • Eczema herpeticum preventable diseases, such as measles, varicella, and • Scarlet fever rubella, all have classic exanthems. If a patient has • Lyme disease recently moved to the United States, the child may not • Erythema multiforme only be unvaccinated but may also have been ex- • Henoch-Schönlein purpura posed to diseases that are considered to be eradicated • Cellulitis/erysipelas in the United States. Questions related to immune Life-threatening, • Staphylococcal scalded skin syndrome compromise are important to include, as immuno- “can’t miss” • Meningococcal disease (Neisseria compromised patients have different susceptibility to meningitidis) pathogens that do not affect the general population. • Toxic shock syndrome Additional considerations include recent medication • Stevens-Johnson syndrome/toxic epidermal necrolysis use that may indicate drug-related conditions, recently • Kawasaki disease received vaccines, and sick contacts in the home. • Drug reaction with eosinophilia and systemic symptoms (DRESS) Physical Examination • Acute rheumatic fever The physical examination should begin with a review • Rocky Mountain spotted fever of the patient’s vital signs to determine whether the www.ebmedicine.net child requires immediate intervention. In general, a

January 2020 • www.ebmedicine.net 3 Copyright © 2020 EB Medicine. All rights reserved. happy, playful child indicates a more benign etiology Additional Body Systems Examination in comparison to an irritable or ill-appearing child Examination of the head, eyes, ears, nose, and who might have a more serious illness. Key compo- throat can provide many important clues regarding nents of the physical examination include a thorough the etiology of the rash and fever. Other physical investigation of the skin as well as searching for as- examination findings, such as lymphadenopathy, sociated signs in other body systems. abdominal pain, arthritis, and cardiac murmurs, may also aid in determining the diagnosis. A cardiac Skin Examination examination should be performed to assess for rubs The child should be completely undressed, and a (suggestive of pericardial irritation or effusion) or good light source should be used during the ex- for any new murmurs. The abdominal examina- amination. Correctly describing the qualities of the tion should be used to assess for splenomegaly or rash not only helps with documentation and when diffuse abdominal tenderness. If diagnoses such as discussing the case with other clinicians but also fa- rheumatic fever, Lyme disease, or meningitis are cilitates formulation of the differential. When exam- being considered, a neurologic examination should ining the skin, look for the major distribution of the be performed to identify any focal deficits, chorea, or rash, with particular attention to involvement of the other abnormalities. Table 5, page 5 provides some palms and soles. Note whether the rash is primarily of the nondermatological examination findings that on the extremities or only in a localized area, whether may correlate with certain etiologies. the mucous membranes are involved (including the mouth, conjunctiva, and genitals), and whether the Diagnostic Studies rash blanches or not. Another important clue is the presence or absence of the Nikolsky sign (the exten- One of the more difficult aspects of diagnosing a sion of peeling or blistering skin caused by separa- pediatric patient who presents with a fever and rash tion of the layers of skin when firm, sliding pressure is that no single test provides a diagnosis. To avoid is applied to the skin). Tables 3 and 4, page 5 include unnecessary testing, diagnosis should rely on visual identifying skin examination characteristics and rash examination together with the history and other morphologies that can guide the differential. physical examination findings. Diagnostic testing specific to individual etiologies is discussed in the "Management of Specific Etiologies of Rash and Fever" section, beginning on page 5. Table 6, page 6 provides a summary of diagnostic testing that can be obtained based on suspicion for specific diseases.

Table 2. Common Exanthem Characteristics Seen in Pediatric Patients

Characteristic Measles Scarlet Fever Fifth Disease Roseola

Causative agent Measles virus Group A Streptococcus Human parvovirus B19 Human herpesvirus 6

Transmission method Respiratory droplets Respiratory droplets Respiratory droplets Saliva

Incubation period 8-12 days 2-5 days 4-21 days 10-15 days

First-stage symptoms • Mild fever • Fever • Malaise • Mild sore throat • Cough • Sore throat • Fever • Rhinorrhea • Coryza • Red “slapped” cheeks • Conjunctivitis • Conjunctivitis • High fever • Koplik spots

First-stage duration 2-4 days 1-2 days 4-14 days 3-5 days

Second-stage Maculopapular rash Fine, erythematous Pruritic, lacy rash sparing After fever, tiny erythematous symptoms beginning on head and papular eruption palms and soles papules on trunk spreading to spreading to the trunk and neck/extremities extremities

Second-stage duration 7-10 days 3-4 days Up to 3 weeks 1-3 days

Treatment Supportive Penicillin or Supportive Supportive cephalosporin

Vaccine Ye s No No No

Copyright © 2020 EB Medicine. All rights reserved. 4 Reprints: www.ebmedicine.net/pempissues Management of Specific Etiologies Maculopapular Rashes of Rash and Fever Measles According to a survey from the CDC, rates of measles 2 Management should be based on the etiology of cases increased from 63 in 2010 to 667 in 2014. Most the rash. The majority of cases will be benign viral recent reports from the CDC have noted that, as of exanthema, and often, the only treatment necessary October 1, 2019, > 1000 cases of measles have been is supportive care. Giving acetaminophen 15 mg/ reported, the most since 1992. The virus is extremely kg every 4 hours or ibuprofen 10 mg/kg every 6 contagious and is spread by both respiratory droplets hours (in children aged > 6 months) will help with and aerosolized particles that remain in the air for up fever and discomfort. Etiology-specific treatment is to 2 hours. This leads to a high rate of transmission in discussed in the following sections. those who are not immune and are exposed to the virus. Once exposed, there is an incubation period of approximately 10 to 14 days prior to the development of fever. Up to 9 out of 10 susceptible persons with close contact to a measles patient will develop measles.4 For this reason, the CDC recommends that anyone with suspected measles should be placed on airborne precautions immediately, including staying in a negative pressure room, and healthcare staff should use an Table 3. Differential Diagnosis Based on N-95 respirator (or equivalent airborne precautions). Rash Morphology Morphology Additional Disease/Condition Table 4. Rash Morphologies Characteristics Morphology Description Maculopapular Central, blanching • Measles Macule Flat, nonpalpable lesion, change in color of skin, • Roseola • Parvovirus < 1 cm • Viral exanthem Papule Raised, palpable lesion, < 1 cm Central, • Acute rheumatic fever Vesicle Fluid-filled, clear, palpable blister, < 1 cm nonblanching Bullae Large fluid-filled blister, > 1 cm Peripheral, • Erythema multiforme Pustule Fluid-filled blister containing purulent fluid, < 1 cm targetoid Wheal Erythematous elevated area of edema Peripheral, • Meningococcemia Petechiae Nonblanching, small, area of underlying nontargetoid hemorrhage

Vesicular/ Diffuse • Varicella Purpura Nonblanching, palpable, area of underlying bullous hemorrhage, larger than petechiae Localized • Coxsackievirus • Eczema herpeticum www.ebmedicine.net

Erythematous Positive Nikolsky • Staphylococcal signb scalded skin syndrome Table 5. Nondermatological Physical • Stevens-Johnson Examination Findings by Disease/Condition syndrome • Toxic epidermal Disease/Condition Physical Examination Findings necrolysis Herpangina due to Vesicles in the posterior coxsackievirus oropharynx Negative Nikolsky • Toxic shock syndrome signb • Kawasaki disease Measles Koplik spots • Scarlet fever Toxic epidermal necrolysis Mucosal ulcerations • Lyme disease Kawasaki disease Conjunctival injection, mucous Petechial/ Palpable • Rocky Mountain membrane changes spotted fevera purpuric Kawasaki disease, Anterior lymphadenopathy • Henoch-Schönlein undiagnosed streptococcal purpura pharyngitis • Meningococcemia Epstein-Barr virus Posterior adenopathy, • Disseminated Nonpalpable splenomegaly intravascular Henoch-Schönlein purpura Diffuse abdominal tenderness coagulation (bowel inflammation) aCan also have a less-specific maculopapular rash. Erythema multiforme, Joint pain, swelling bNikolsky sign: the extension of blistering by lateral pressure. acute rheumatic fever www.ebmedicine.net www.ebmedicine.net

January 2020 • www.ebmedicine.net 5 Copyright © 2020 EB Medicine. All rights reserved. Once a person is infected, the virus moves from The rash begins to fade around the fifth day after the respiratory tract to the lymphatic system and development, in the same cephalocaudad pattern.6 the bloodstream. The disease begins with a viral At this point, fever tends to be quite high, typically prodrome characterized by mild to moderate fever, ranging from 39°C to 40.5°C (102.2°F-104.9°F).7 The cough, coryza, and conjunctivitis.5 During this time, patient is contagious from 4 to 5 days prior to and children may also develop Koplik spots that ap- after appearance of the rash, and strict isolation pre- pear as small white, grey, or bluish spots with an cautions should be put into place. erythematous base that develop along the buccal Measles can have multiple complications, rang- mucosa opposite the molar teeth. Koplik spots are ing from relatively benign to quite severe, including pathognomonic for measles, and if noted by a clini- death. According to the WHO, in 2015, there were cian, the diagnosis of measles can be made even 134,200 deaths worldwide from measles.6 Death is before the rash appears. Approximately 3 to 4 days most often the result of measles-associated pneu- after symptoms begin, a morbilliform rash appears, monia. It is estimated that 30% to 40% of patients starting on the head, behind the ears and then ex- infected with measles will suffer at least 1 complica- tending to the torso and extremities. (See Figure 1.) tion, including hearing loss or blindness, or death. As the rash progresses, confluent areas may appear. Those who suffer from malnourishment and vitamin A deficiency specifically have the highest rate of complications.8 Table 6. Recommended Diagnostic Studies Treatment of measles is mainly supportive care, Based on Suspected Etiology as well as treatment of any secondary infections. As vitamin A deficiency has been linked to worsened Suspected Etiology or Recommended Testing outcomes, patients with an acute case of measles Signs/Symptoms (especially immunocompromised patients) should • Petechiae • Prothrombin time be treated with vitamin A.6 For more information • Purpura • Partial thromboplastin time on management of measles, see the December 2016 • Unexplained bleeding • International normalized ratio issue of Pediatric Emergency Medicine Practice, “Vac- • Henoch-Schönlein purpura • Urinalysis cine-Preventable Diseases in Pediatric Patients: A • Kawasaki disease Review of Measles, Mumps, Rubella, and Varicella,” • Fever of unknown origin available at: www.ebmedicine.net/vaccine. (evaluate for source of infection) • Scarlet fever • Rapid strep test • Toxic shock syndrome • Throat culture Figure 1. Morbilliform Rash of Measles • Acute rheumatic fever • Antistreptolysin titers • Acute rheumatic fever • Electrocardiogram • Kawasaki disease • Lyme disease • Persistent tachycardia (evaluate for myocarditis) • Acute rheumatic fever • Echocardiogram • Kawasaki disease • Lyme disease • Myocarditis • Measles • Disease-specific testing • Rubella • Varicella • Rocky Mountain spotted fever • Lyme disease • Lyme disease with signs of • Cerebrospinal fluid studies meningitis Content provider: Heinz F. Eichenwald, MD. Available at: • Concern for Neisseria https://phil.cdc.gov/Details.aspx?pid=3168 meningitidis To view full-color versions of the images in this issue, scan the QR • Concern for viral meningitis code below with an enabled device or go to: • Henoch-Schönlein purpura • Abdominal ultrasound www.ebmedicine.net/fever-rash-figures with abdominal pain (evaluate for intussusception) • Kawasaki disease • Erythrocyte sedimentation • Acute rheumatic fever rate • C-reactive protein

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Copyright © 2020 EB Medicine. All rights reserved. 6 Reprints: www.ebmedicine.net/pempissues Erythema Infectiosum (Fifth Disease) Roseola Erythema infectiosum (also known as Fifth disease) Roseola is caused by Human herpesvirus 6 and is is caused by Human parvovirus B19. The classic transmitted via saliva. Up to 90% of children are exanthema is best characterized by the “slapped infected by the age of 2 years; however, only 20% of cheek” appearance of the rash; the perioral region patients develop the nonspecific rash, so many will and nasal folds are spared. However, a whole-body, remain undiagnosed.9 itchy, lacy rash can also develop, potentially lasting After an approximate 10-day incubation period, for weeks.9 (See Figure 2.) Prior to appearance of roseola typically presents with upper respiratory the rash, the patient will exhibit symptoms typical symptoms accompanied by high fever and cervical of an upper respiratory illness. By the time the rash lymphadenopathy. The hallmark of the illness is that appears and the diagnosis is suspected, the patient the rash does not appear until approximately 12 to 24 will no longer be contagious. The virus is spread hours after the fever resolves, and it is characterized by via respiratory droplets. Patients with suspected small, erythematous, blanching papules, often starting Fifth disease should be placed in proper isolation, on the trunk and spreading outward.11 (See Figure 3.) primarily because infection in a pregnant woman A known complication of the disease is an increased may cause severe hydrops fetalis or intrauterine prevalence of febrile seizure, occurring in up to 15% of fetal death, although in the vast majority of cases, those infected.12 Treatment is symptomatic. the pregnancy is uncomplicated. Older individuals may develop arthralgias, and rarely may develop an Acute Rheumatic Fever itchy, irritating extremity rash referred to as papular- Acute rheumatic fever (ARF) is an inflammatory dis- purpuric gloves and socks syndrome.10 Treatment order caused by an autoimmune response following for Fifth disease is symptomatic. group A streptococcal infection,13 typically occurring within 2 to 4 weeks after the initial infection. His-

Figure 2. Rash of Erythema Infectiosum Figure 3. Viral Exanthema of Roseola (Fifth Disease)

Note the appearance of the “slapped cheeks” and the full-body rash. Republished with permission of McGraw-Hill Education, from Atlas Republished with permission of McGraw-Hill Education, from Atlas of Emergency Medicine, Kevin J. Knoop, et al, 4th edition, © 2016; of Emergency Medicine, Kevin J. Knoop, et al, 4th edition, © 2016; permission conveyed through Copyright Clearance Center, Inc. permission conveyed through Copyright Clearance Center, Inc.

January 2020 • www.ebmedicine.net 7 Copyright © 2020 EB Medicine. All rights reserved. torically, ARF has a higher incidence in developing countries as well as in certain geographical areas, An MDCalc online tool for the Jones such as among indigenous populations in Australia Criteria is available at: www.mdcalc. and New Zealand.14 com/jones-criteria-acute-rheumatic- Clinical manifestations of ARF include carditis, fever-diagnosis. arthritis, chorea, and skin manifestations such as subcutaneous nodules and erythema marginatum.13 Primary prophylaxis (ie, treatment of group A Subcutaneous nodules are firm, painless growths streptococcal pharyngitis) reduces the risk of devel- found on the extensor surfaces of the knees, elbows, oping ARF. Penicillin is the first-line treatment and and wrists; they can also occur on the occiput and may be given orally for a complete 10-day course. along the thoracic and lumbar spinous processes. However, intramuscular penicillin G benzathine (pa- Erythema marginatum is a pink rash with pale cen- tients weighing ≤ 27 kg, 600,000 units as a one-time ters and rounded or serpiginous margins. Confirma- dose; patients weighing > 27 kg, 1.2 million units tion of the diagnosis is made using the Jones criteria, as a one-time dose) can obviate the need for daily which were last revised in 2015 by the American compliance.16 Secondary prophylaxis, intramuscular Heart Association.15 (See Table 7.) penicillin G benzathine every 3 to 4 weeks to prevent If there is high suspicion for ARF, the patient additional streptococcal infections, has been shown should be admitted to the hospital for further diag- to reduce rheumatic valvular lesions over time.16 nostic workup and management. Diagnostic studies Due to the nature of this injection, this course of care in patients with concern for ARF include a complete should be discussed with the caregivers. Aspirin blood cell (CBC) count with differential; inflamma- remains first-line treatment for carditis, although tory markers, including erythrocyte sedimentation naproxen may be as effective with fewer side effects. rate (ESR), C-reactive protein (CRP); antistreptolysin Corticosteroids in addition to IV immunoglobulin G O (ASO) titers; and electrocardiogram and echocar- (IVIG) may also be considered in patients with mod- diogram. erate to severe carditis.17 Treatment goals include elimination of the group A streptococcal infection, supportive treatment, and treatment to prevent long-term sequelae, such as chronic rheumatic heart Table 7. Modified Jones Criteria for disease. Overall, the incidence of ARF is declining; Diagnosing Acute Rheumatic Fever14,15 however, the morbidity rate for rheumatic heart disease or its complications is still approximately Diagnosis* 305,000 cases per year.18 Initial diagnosis requires: For more information on management of acute 2 major criteria or rheumatic fever, see the August 2016 issue of Pediatric 1 major + 2 minor criteria Emergency Medicine Practice, “Acute Rheumatic Fever: Recurrent diagnosis requires: An Evidence-Based Approach to Diagnosis and Initial 1 major + 2 minor criteria Management,” available at: www.ebmedicine.net/ARF. or 3 minor criteria Vesicular Rashes Criteria for Diagnosis Varicella Major criteria: Varicella-zoster virus is a herpesvirus responsible for • Carditis chickenpox and shingles. Chickenpox is a vesicular • Chorea rash that appears in different stages and is likened • Polyarthritis in low-risk populations; monoarthritis or to a “dew drop on a rose petal.”7 (See Figure 4, polyarthralgia in moderate-risk and high-risk populations page 9.) The disease is highly contagious; however, • Erythema marginatum rates of infection have dropped since a vaccine was • Subcutaneous nodules licensed in the United States in 2006. Otherwise- Minor criteria: healthy, unvaccinated children with varicella will • Fever > 38.5°C (101.3°F) often present with a chief complaint of a pruritic • Polyarthralgia in low-risk populations; monoarthralgia in rash and may have a mild fever. Generally, there are moderate-risk and high-risk populations minimal complications; infants and those who are • Prolonged PR interval; patient cannot have carditis as a major immunocompromised are at risk for more severe criterion 19 • ESR > 60 mm/h in low-risk populations, ESR > 30 mm/h in disease. moderate-risk and high-risk populations, or CRP > 3 mg/dL Patients who have been vaccinated may develop “breakthrough varicella,” characterized by < 50 skin *Patient must have evidence of preceding group A streptococcal lesions (mainly maculopapular lesions with few infection for diagnosis. or no vesicles) and a milder course of illness.20 Abbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate. This form of varicella may be missed by clinicians

Copyright © 2020 EB Medicine. All rights reserved. 8 Reprints: www.ebmedicine.net/pempissues due to the less-defined rash and mild symptoms; Diseases in Pediatric Patients: A Review of Mea- it is important to perform confirmatory testing, as sles, Mumps, Rubella, and Varicella,” available at: diagnosis by examination alone may prove difficult. www.ebmedicine.net/vaccine. Children who have had only 1 vaccine dose instead of the CDC-recommended 2-dose regimen may Hand, Foot, and Mouth Disease have more classic symptoms. Although vaccinated Hand, foot, and mouth disease is most commonly persons are less contagious than unvaccinated per- caused by coxsackievirus A16, although it may be sons, all patients are contagious, and they will need caused by a range of other subtypes, as well as en- contact isolation until all lesions have crusted over. terovirus 71. Hand, foot, and mouth disease is most Clinicians should also use airborne precautions. prevalent in the summer months. After a brief pro- The most common complications in children dromal stage, patients generally present with mod- who are otherwise healthy are skin and soft-tissue erate to high fever, sore throat, and refusal to eat and infections from persistent scratching. More serious drink. The characteristic rash appears as blister-like invasive infections, such as pneumonia and central lesions on the hands and feet, including the palms nervous system infection, are rare but significant, and soles, and may be tender to palpation. Patients especially in immunocompromised children.20 may develop oral lesions that can be visualized, or Treatment is mainly supportive; however, in im- the lesions may be isolated to the posterior orophar- munocompromised children, neonates, or patients ynx (herpangina). Not all patients will present with with concern for severe systemic disease, IV acyclovir lesions in all 3 areas, and some may have a more should be administered at 30 mg/kg daily divided indistinct, widespread rash than others. The most every 8 hours for 5 days.19 Any superimposed soft- common complication tends to be dehydration due tissue infections should be monitored and treated to the refusal of oral intake. Rarely, central nervous with antibiotics, if needed. system or cardiac complications (eg, myocarditis) For more information on management of may develop.21,22 varicella, see the December 2016 issue of Pediatric In cases in which the child has painful oral le- Emergency Medicine Practice, “Vaccine-Preventable sions, pain management is especially important to ensure that the patient can tolerate oral intake in order to avoid dehydration. A “magic mouthwash” Figure 4. Vesicular, Multistage Rash of solution can be tried, consisting of liquid diphen- Varicella hydramine and a liquid antacid mixed in a 1:1 ratio, ideally as a swish-and-spit, to combat oral pain. Care should be taken to calculate the maximum doses (based on the weight of the child) of each medication to avoid overdose in the event that the medications are inadvertently swallowed. Ibuprofen can also be considered for pain relief, if tolerated. If the patient is still unable to maintain adequate fluid intake with these medications and attempts to give cold or frozen liquids, the patient should be admitted for further treatment and rehydration.

Erythematous Rashes Kawasaki Disease Kawasaki disease is an acute, multisystem vasculitis of unclear etiology and is the leading cause of pediatric acquired heart disease in the United States.23 Car- diac complications are secondary to coronary artery aneurysm, which occurs in 20% to 25% of untreated patients.24 Eighty percent of children diagnosed with Kawasaki disease are aged < 5 years; Kawasaki disease is rare in infants aged < 3 months and in children aged > 8 years.25 Diagnosis is based on clinical criteria, and laboratory results can aid in diagnosis. Irritability and fever, often unresponsive to antipyretics, are Republished with permission of McGraw-Hill Education, from hallmarks of the disease. Kawasaki disease is typi- Tintinalli's Emergency Medicine: A Comprehensive Study Guide, cally identified by fever lasting ≥ 5 days and at least Judith E. Tintinalli, 9th edition, © 2020; permission conveyed through 4 of the 5 following clinical features: (1) conjunctival Copyright Clearance Center, Inc.

Pediatric patient presents to the ED with fever and rash

Assess the patient to determine whether isolation precautions are needed (eg, measles, Fifth disease, varicella) • Manage ABCs • Order laboratory tests, as indicated, including blood culture YES Patient unstable or septic? • Administer empiric antibiotics

NO UNSTABLE STABLE

• Administer antipyretics if needed Continue stabilizing measures • Obtain historya and order additional testing, as • Perform physical examinationb, including needed, until the patient can evaluation for red flags (erythroderma, be admitted to the PICU desquamation, petechiae/purpura, pain out of proportion to symptoms)

Petechial/ Erythematous Vesicular/ Maculopapular rash purpuric rash rash bullous rash

Obtain PT, Obtain ASO, rapid Continued on page 11 PTT, INR strep, throat culture

Nikolsky sign present? Palpable NO DIC rash? YES NO

YES

• Staphylococcal • Toxic shock syndrome scalded skin • Rocky Mountain spotted • Kawasaki disease syndrome fever • Scarlet fever • Stevens-Johnson • Henoch-Schönlein purpura • Lyme disease syndrome • Meningococcemia • Toxic epidermal necrolysis

Obtain additional diagnostic testing, if needed, and determine disposition based on suspected etiology and other signs/symptoms (See Table 6, page 6 and the “Management of Specific Etiologies of Rash and Fever” section, beginning on page 5.)

www.ebmedicine.net aImportant historical questions include asking about timing of the rash, medications, concurrent symptoms, vaccination status, recent travel history, and any immunodeficiency. bThe physical examination should focus on the characteristics of the rash as well as concerning findings such as erythroderma, nonblanching lesions, desquamation, and severe pain.

Abbreviations: ABC, airway, breathing, and circulation; ASO, antistreptolysin O; DIC, disseminated intravascular coagulation; ED, emergency department; INR, international normalized ratio; PICU, pediatric intensive care unit; PT, prothrombin time; PTT, partial thromboplastin time.

Copyright © 2020 EB Medicine. All rights reserved. 10 Reprints: www.ebmedicine.net/pempissues Clinical Pathway for Emergency Department Management of Rash and Fever in the Pediatric Patient (Continued)

Vesicular/ Maculopapular rash bullous rash

Rash distribution? Rash distribution?

• Coxsackievirus Central Peripheral Diffuse Localized • Eczema herpeticum

YES Blanching? Targetoid? Varicella

NO YES NO

• Measles • Roseola Acute Erythema • Parvovirus Meningococcemia • Viral exanthem rheumatic fever multiforme

www.ebmedicine.net

January 2020 • www.ebmedicine.net 11 Copyright © 2020 EB Medicine. All rights reserved. injection, (2) mucous membrane changes (bright skinfolds, such as the axilla, antecubital fossa, and red, cracked lips, strawberry tongue), (3) changes in buttock creases, called Pastia lines. Desquamation of peripheral extremities such as edema and peeling of the skin generally occurs several weeks following the skin (usually a later finding), (4) polymorphous acute infection.27 rash, and (5) cervical lymphadenopathy. The rash is Cases of acute streptococcal pharyngitis with typically a widespread targetoid, morbilliform, or concern for scarlet fever can be diagnosed by clinical macular exanthema. Although these are the classic examination, but throat culture remains the gold findings, there are variations to this definition, and standard for testing. Rapid antigen testing is of great it is important to maintain a high level of suspicion benefit, as it is highly specific, and the results are -im for Kawasaki disease. Ancillary testing can aid in mediately available. Negative rapid antigen testing diagnosis of patients with an incomplete presenta- should be confirmed with a throat culture.29 tion. Laboratory findings may include white blood Treatment can shorten the duration and severity cell (WBC) count > 15,000 cells/mL, anemia, plate- of scarlet fever, as well as limit severe complications. lets > 450,000 platelets/mL, elevated CRP and ESR, S pyogenes can spread from direct extension of the elevated alanine transaminase and gamma-glutamyl pharyngeal infection to adjacent structures. There is transferase, albumin ≤ 3 g/dL, and pyuria. also the risk of hematogenous spread and lymphatic spread, leading to suppurative complications such An MDCalc online tool for the Ka- as peritonsillar abscess, retropharyngeal abscess, wasaki Disease Diagnostic Criteria sinusitis, otitis media, cervical lymphadenitis, is available at: www.mdcalc.com/ bacteremia, endocarditis, pneumonia, and menin- kawasaki-disease-diagnostic-criteria. gitis. Nonsuppurative complications such as ARF and poststreptococcal glomerulonephritis may also occur. Treatment of acute infection may help pre- According to the American Heart Association, vent the development of ARF; however, treatment children should be treated with IVIG and high-dose has not been shown to provide the same benefit for aspirin as soon as possible after diagnosis of Kawa- glomerulonephritis.30 Of note, ARF can occur even saki disease. The goal of treatment is to decrease the in patients who are properly treated.31 incidence of coronary artery aneurysm. IVIG 2 g/kg should be administered over 12 hours. The dosing of aspirin is variable by institution; aspirin should be stopped after the child is afebrile for approximately 2 days.26 Figure 5. Rash of Scarlet Fever For more information on management of Kawa- saki disease, see the January 2015 issue of Pediatric Emergency Medicine Practice, “Evidence-Based Manage- ment of Kawasaki Disease in the Emergency Depart- ment,” available at: www.ebmedicine.net/Kawasaki.

Scarlet Fever Scarlet fever is a toxin-mediated childhood exanthem resulting from Streptococcus pyogenes (group A A Streptococcus) infection, most commonly seen in patients aged 5 to 15 years. The diagnosis is made in approximately 10% of children presenting with streptococcal tonsillopharyngitis.27 Scarlet fever is caused by certain strains of group A beta hemolytic Streptococcus that release a streptococcal pyogenic exotoxin; the rash is a delayed hypersensitivity to this exotoxin.28 The classic scarlatiniform rash appears as a “sandpaper” rash that is blanching and maculopapular and spares the palms and soles.27 (See Figure 5.) The rash typically develops 1 to 2 days after the initial symptoms associated with pharyngitis. Patients may have palatal petechiae, circumoral pallor, and enlarged papillae on the tongue, with underlying erythema giving a “strawberry-like” appearance to the Republished with permission of McGraw-Hill Education, from Atlas tongue. The rash may be erythematous, nonblanch- of Emergency Medicine, Kevin J. Knoop, et al, 4th edition, © 2016; ing, and erupt in a linear fashion, concentrated in the permission conveyed through Copyright Clearance Center, Inc.

Copyright © 2020 EB Medicine. All rights reserved. 12 Reprints: www.ebmedicine.net/pempissues Toxic Shock Syndrome should be removed promptly. A comprehensive skin Toxic shock syndrome (TSS) is a potentially fatal dis- examination should be performed, as even subtle ease. The most common etiologies are Staphylococcus wounds can be the originating source of infection.32 aureus or S pyogenes. Both bacteria produce super- In TSS, penicillinase-resistant penicillins and first- antigens that activate T cells directly and bypass generation cephalosporins have proven to be effec- certain antigen-mediated immune responses. This in turn causes uncontrolled T-cell activation leading to 32 Table 8. Differentiating Staphylococcal and massive cytokine release. Streptococcal Toxic Shock Syndrome35,36 TSS is easily recognizable by physical examination. The hallmarks of presentation are fever, hypo- Staphylococcal TSS tension, and rash, and the patient can also present Clinical Criteria with multiorgan failure. Desquamation of the hands • Fever > 38.9°C (102°F) and feet may also occur.33 In staphylococcal-me- • Diffuse rash with macular erythroderma diated TSS, viral-like symptoms, including chills, • Desquamation 1-2 weeks after rash onset • Hypotension with SBP ≤ 5th percentile by age (for children aged weakness, malaise, headache, sore throat, vomiting, < 16 years), SBP ≤ 90 mm Hg (for adolescents aged > 16 years) diarrhea, abdominal pain, and lightheadedness, can • Multiorgan involvement (≥ 3 systems) be the first clinical signs. Streptococcal-mediated l Gastrointestinal: vomiting/diarrhea TSS most commonly arises from an invasive skin l Muscular: myalgias or CK ≥ 2 times upper limit of normal or soft-tissue infection, including necrotizing fas- l Renal: BUN or Cr ≥ 2 times upper limit of normal; sterile pyuria ciitis, cellulitis, or myositis. Flu-like symptoms l Hepatic: bilirubin, AST, or ALT ≥ 2 times upper limit of normal (eg, fever, sore throat, and lymphadenopathy) and l Hematologic: platelets ≤ 100,000 platelets/mL gastrointestinal symptoms may be present early in l Neurologic: AMS in the absence of fever or hypotension the disease process.34 For both staphylococcal- and Laboratory Criteria streptococcal-mediated TSS, patients develop diffuse Must be negative: erythema, watery diarrhea, decreased urine output, • Blood and/or CSF cultures; blood culture may be positive for and extremity edema. Erythroderma is a diffuse, red, Staphylococcus aureus and macular rash that resembles a sunburn. Skin • Serologies for Rocky Mountain spotted fever, leptospirosis, and and mucous membranes can be involved, including measles the conjunctiva, vaginal mucosa, and oral mucosa. Classification Patients may have neurological findings such as Probable: combination of 4 clinical criteria and laboratory criteria met headache, confusion, somnolence, and agitation, Confirmed: combination of 5 clinical criteria and laboratory criteria and in severe cases, symptoms of cerebral edema. met, including desquamation Cardiopulmonary symptoms include pulmonary Streptococcal TSS edema with decreased heart contractility and pleural effusion. Decreased vascular resistance leads to in- Clinical Criteria • Hypotension with SBP ≤ 5th percentile by age (for children aged creased leakage from the intravascular compartment < 16 years), SBP ≤ 90 mm Hg (for adolescents aged > 16 years) causing hypotension, one of the defining criteria for • Multiorgan involvement (≥ 2 systems) 32 TSS. l Gastrointestinal: vomiting/diarrhea Medical evaluation for TSS includes screening l Muscular: myalgias or CK ≥ 2 times upper limit of normal for signs of multiorgan failure. Patients can have l Renal: BUN or Cr ≥ 2 times upper limit of normal; sterile pyuria leukocytosis with increasing neutrophil counts, l Hepatic: bilirubin, AST, or ALT ≥ 2 times upper limit of normal anemia, thrombocytopenia, and elevation in co- l Hematologic: platelets ≤ 100,000 platelets/mL, DIC agulation factors. Elevated blood urea nitrogen and l Pulmonary: acute respiratory distress syndrome creatinine levels indicate renal injury, with elevation l Skin: soft-tissue necrosis, generalized erythematous macular of creatine kinase in the setting of rhabdomyolysis. rash Patients may develop hyponatremia, hypocalcemia, Laboratory Criteria hypophosphatemia, and hypoalbuminemia. Hepatic • Group A Streptococcus isolation from culture involvement is evident by elevated transaminases. Classification Though blood cultures are important, they are posi- • Probable: all clinical criteria met; isolation of group A tive in < 5% of patients with staphylococcal TSS, and Streptococcus from nonsterile site; absence of other etiology for illness in approximately 60% of patients with streptococcal 32,34 • Confirmed: all clinical criteria met; isolation of group A TSS. Definitive criteria for staphylococcal TSS Streptococcus from sterile site (blood, CSF, pleural/pericardial and streptococcal TSS are presented in Table 8. fluid) Recognizing TSS early is paramount, as patients will require aggressive fluid resuscitation to Abbreviations: ALT, alanine aminotransferase; AMS, altered mental increase intravascular volume. The examination status; AST, aspartate aminotransferase; BUN, blood urea nitrogen; should include a search for a nidus of infection, such CK, creatine kinase; Cr, creatinine; CSF, cerebrospinal fluid; DIC, as a foreign body (eg, a tampon), which, if found, disseminated intravascular coagulation; SBP, systolic blood pressure; TSS, toxic shock syndrome.

January 2020 • www.ebmedicine.net 13 Copyright © 2020 EB Medicine. All rights reserved. tive. Clindamycin has inhibitory actions on protein SSSS is most commonly seen in children and synthesis, which includes inhibition of superantigen neonates. The diaper area of newborns is a very production and decreases in toxin production.33 common surface for skin rashes associated with Therefore, IV clindamycin 40 mg/kg/day divided SSSS. Other symptoms of SSSS include intense every 8 hours should be administered first to inhibit pain around the infection site, weakness, fatigue, exotoxin release, in addition to a cephalosporin, and dehydration.39 In some instances, a prodromal with consideration for methicillin-resistant S aureus localized skin infection precedes the illness that may (MRSA) coverage with vancomycin or linezolid. IVIG originate in the throat, mouth, nose, umbilicus, or has shown some benefit in treating TSS by inhibit- gastrointestinal tract. SSSS has a low mortality rate ing T-cell activation, thus blocking and inactivating of 1% to 5%, but has complications including cel- superantigens leading to decreased cytokine release.34 lulitis, sepsis, pneumonia, and scarring.37,39 Patients with SSSS should be hospitalized, and IV antistaph- Staphylococcal Scalded Skin Syndrome ylococcal antibiotics should be administered once S aureus can produce suppurated infections or sepsis blood cultures are obtained. with different types of manifestations, such as skin lesions (impetigo, pyoderma, cellulitis, abscess) and Petechial/Purpuric Rashes pneumonia. The bacteria have multiple virulence Meningococcal Disease factors and secrete several exotoxins. In staphylococ- Neisseria meningitidis is an aerobic, gram-negative cal scalded skin syndrome (SSSS), exfoliative toxins diplococcus present in the nasopharynx of approxi- are produced and act at a remote site, causing a red mately 4% to 24% of the population. It is transmitted rash and separation of the epidermis beneath the through respiratory secretions and saliva. Most cases granular cell layer (ie, intraepidermal splitting).37 occur in preschool-aged children, especially in- The separation of the epidermis causes a painful, fants, with other peaks in adolescents and in people sunburn-like rash and development of bullae (large, aged > 65 years.40 Purpura, caused by bleeding fragile, fluid-filled blisters). The blisters burst and into the skin or mucosa from small vessels, may be slough in a sheet-like manner, leaving the remaining the presenting symptom of serious and potentially layer without the epidermis and exposing a moist life-threatening meningococcal disease, such as and reddish area on the topical surface.37-39 (See meningococcal sepsis. (See Figure 7, page 15.) The Figure 6.) cardinal sign of purpura is that is does not blanche with pressure. Small petechiae can also be present. When a patient presents with fever and purpura or Figure 6. Sloughing Skin of Staphylococcal petechiae, the diagnosis of meningococcal disease Scalded Skin Syndrome must be considered, and intervention should occur immediately.40 The development of invasive meningococcal disease will typically cause life-threatening meningitis or sepsis. Meningococcemia is a rapidly invasive disease, and mortality in patients in whom the disease is recognized early and who are treated appropriately is still 5% to 10% within 24 to 48 hours after developing symptoms. Long-term sequelae, including severe skin necrosis, loss of limb, neurologic damage, and hearing loss, will occur in 10% to 20% of survivors.41,42 Some patients have a genetic predisposing factor that increases their risk for invasive meningococcal disease. In addition, preceding viral infection, crowd- ing, smoke exposure, and working in a healthcare environment can increase the risk of this disease.42 Given the devastating and life-threatening effects of meningococcal disease, guidelines have been proposed to recognize and identify this disease early upon presentation. The Petechiae in Children (PiC) study developed in the United Kingdom and Ireland evaluated point-of-care testing for meningococcal disease and procalcitonin levels. Loop-mediated iso- thermal AMPlification (LAMP) testing is a rapid mo- Republished with permission of McGraw-Hill Education, from Atlas lecular amplification test that identifies serogroups of Emergency Medicine, Kevin J. Knoop, et al, 4th edition, © 2016; of meningococcal infection; the results take approxi- permission conveyed through Copyright Clearance Center, Inc.

Copyright © 2020 EB Medicine. All rights reserved. 14 Reprints: www.ebmedicine.net/pempissues mately 30 minutes to obtain. Procalcitonin levels leads to the formation of IgA immune complexes increase in the presence of infection and are not only that deposit in the skin, joints, gastrointestinal tract, more sensitive but also more specific for diagnosing and kidneys. This necrosis of small blood vessels early meningococcal disease when compared to CRP results in a nonthrombocytopenic purpura. Rash is levels and WBC counts. Bedside LAMP testing and the initial presenting feature in approximately 75% analysis of procalcitonin levels may aid in identify- of cases. HSP may affect all age groups but is most ing patients with invasive meningococcal disease in common in children aged 2 to 6 years,46 with peak a more timely manner.43 incidence in the fall and winter months.47 Patients who present with purpura (nonblanch- The classic presentation is an otherwise well child ing rash), fever, meningeal signs, and hypotension with purpura, arthralgias, and colicky abdominal pain should undergo immediate diagnostic workup 1 to 3 weeks after upper respiratory infection symp- including blood cultures, with empiric antibiotics toms. Patients with HSP are not always febrile, but started as soon as possible. In meningococcal dis- may present with low-grade fever; higher tempera- ease, a third-generation cephalosporin (eg, ceftriax- tures are unlikely. The characteristic rash of HSP is a one 50 mg/kg IV twice daily, max 2 g/dose) is an symmetric, dark red or purple, nonblanching, palpable appropriate antibiotic choice until culture results are exanthem. During the first 24 hours, the rash may have available. Bacterial cultures should be obtained, but a maculopapular or urticarial appearance that evolves this should not delay treatment. into typical purpura. The rash may also appear as deep bruises, or bullous or hemorrhagic lesions. Typically, Henoch-Schönlein Purpura the lesions are not painful and are not pruritic. The Henoch-Schönlein purpura (HSP) is the most com- rash tends to predominate in pressure areas, such as mon pediatric vasculitis,44 and cutaneous manifesta- the buttocks, and in the extensor surfaces of the lower tions occur in 100% of cases.45 HSP is caused by an extremities. Of note, HSP may also present with tender, abnormal immune response in which immunoglobu- localized, subcutaneous edema affecting the forehead, lin A (IgA)-mediated systemic small-vessel vasculitis periorbital region, or hands and feet.44

Figure 7. Meningococcemia Lesions

A. Scattered petechiae in the early stages of meningococcemia. B. Early disseminated intravascular coagulation, presented as petechial and purpuric lesions. C. Purpura fulminans and cutaneous infarction in disseminated intravascular coagulation. Republished with permission of McGraw-Hill Education, from Fitzpatrick's Dermatology in General Medicine, Lowell A. Goldsmith and Thomas B. Fitzpatrick, 8th edition, © 2012; permission conveyed through Copyright Clearance Center, Inc.

January 2020 • www.ebmedicine.net 15 Copyright © 2020 EB Medicine. All rights reserved. The diagnosis of HSP is mainly clinical as there Neonates is no single laboratory test that is diagnostic of the The evaluation of the febrile neonate is very specific, disease. Laboratory work is necessary, however, to and is not discussed in detail in this article. Workup investigate for other potential dangerous causes of for febrile neonates should most likely include a sepsis purpura. General recommendations are to obtain a evaluation, and, when rash is present, neonatal herpes CBC, ESR, clotting profile, serum chemistry, albumin, simplex virus should be high on the differential. ASO titer and antideoxyribonuclease-B antibody Neonatal SSSS should also be considered if suspicion (anti-DNase B), urinalysis, and further evaluation for is high based on the physical examination. For more 48 sepsis as indicated. In most children, HSP is self- information on management of the febrile young limited and generally requires symptomatic treat- infant, see the July 2019 issue of Pediatric Emergency ment only. Because the onset of nephritis may follow Medicine Practice, “Evaluation and Management of the the onset of the skin lesions by several weeks, blood Febrile Young Infant in the Emergency Department,” pressure and urinalysis should be monitored month- available at: www.ebmedicine.net/FebrileInfant. 47 ly for up to 6 months in all patients with HSP. Patients With Predisposition to Hemolytic Special Populations Anemia For patients with a predisposition to hemolytic Pregnant Patients anemia, such as those with sickle cell disease, thalas- Some diseases that present with rash and fever have semia, and hereditary spherocytosis, a CBC count and a higher likelihood of crossing the placenta, and thus reticulocyte count should be obtained in the setting of represent a threat to the fetus. Table 9 provides the possible parvovirus infection. The decreased survival mnemonic TORCH to aid in recall of these diseases. of red blood cells and the reticulocytopenia that is Once diagnosed with one of these diseases, the pa- caused by Human parvovirus B19 increases the risk of tient should avoid contact with pregnant women. If a patient developing acute aplastic crisis.49 Fortunate- a pregnant woman comes into contact with a patient ly, this complication is usually transient. Although who has one of these diseases, the woman’s obste- rare, acute aplastic crisis can also develop in other- trician should be notified. Additionally, pregnant wise healthy individuals, so if there are signs, such as healthcare workers should always exercise caution severe pallor, laboratory tests should be obtained.49 when evaluating patients who have a rash. Some of these patients may have functional or ana- tomic asplenia as well, putting them at higher risk for Unvaccinated Patients diseases caused by encapsulated organisms. Rash and fever in an incompletely vaccinated or unvaccinated child should raise a concern for diseases Controversies and Cutting Edge that are seen less often in the United States, such as measles and varicella. These patients are also at a Blood Cultures higher risk for more serious bacterial complications Recent studies have worked toward developing and may require more extensive testing than other algorithms for determining when to obtain cultures patients. Travelers from other countries who have dif- in pediatric patients,50 suggesting that more strict ferent vaccine schedules or who have not received any criteria may aid in decreasing the number of blood vaccines may also present with diseases that are no cultures obtained, without increasing mortality. In longer common in the United States, such as rubella. some patients, such as febrile neutropenic patients or those who have signs of sepsis, blood cultures Immunocompromised Patients are indicated. However, in the non-ill patient with Immunocompromised patients are a high-risk a nonspecific rash, the decision to obtain blood cul- population in the setting of many diseases. They tures should be weighed heavily against the risks of often require more extensive testing than otherwise obtaining a false-positive result with its subsequent healthy individuals with the same symptoms, and implications in management. they are more susceptible to complications from illness. Early empiric broad-spectrum antibiotics or Corticosteroid Use in Patients With Henoch- antiviral therapy (if available) may be required. Schönlein Purpura and Other Rashes HSP is generally a self-limited disease that requires Table 9. TORCH Diseases supportive treatment only. However, corticosteroids are typically considered in patients with severe extrarenal symptoms and patients who present T: Toxoplasmosis O: Other (syphilis, varicella, Human parvovirus B19) with renal involvement. Corticosteroid use in HSP R: Rubella remains controversial; a literature review found vary- C: Cytomegalovirus ing results regarding improvement following corti- H: Herpes simplex virus costeroid use. Two studies found corticosteroid use

1. “This child had a sore throat with exudate and 6. “This patient had a pretty nasty rash. I thought a rash. I thought it must be scarlet fever and corticosteroids would help.” gave him antibiotics.” Often corticosteroids are not indicated and may, Prior to prescribing antibiotics, the characteris- in fact, worsen the underlying disease process. tics of the rash, associated symptoms, history, For many rashes, research does not support rou- and physical examination findings should be tine corticosteroid use, and corticosteroids can taken into account to develop the differential cause a bounce-back phenomena. diagnosis. Many viruses can cause skin rash and exudative pharyngitis that would not benefit 7. “This patient presented with symptoms of from antibiotics (eg, mononucleosis). joint pain, rash, and fever, but I didn't think it could be acute rheumatic fever because the 2. “The patient did not have strep throat recently, patient completed the full course of antibiotics so it can’t be acute rheumatic fever.” for treatment of a streptococcal infection.” Often, children have an episode of pharyngitis ARF can still occur even in patients who re- and do not have a rapid strep test performed ceived complete antibiotic treatment for strepto- to make the diagnosis of “strep throat.” coccal pharyngitis. If the presentation is sugges- Additionally, the symptoms of ARF appear tive of ARF, then appropriate testing should be after a 2- to 3-week latent period following the performed. Diagnostic studies in patients for streptococcal pharyngitis, so prior infection may whom there is concern for ARF include a CBC not be evident at the time of presentation. with differential; inflammatory markers, including ESR and CRP; ASO titers; and electrocardio- 3. “The patient has had 5 days of fever and now has gram and echocardiogram. a rash; this is probably just a viral exanthem.” In the setting of 5 days of fever, Kawasaki disease 8. “The patient had the varicella vaccination, so should be considered, especially in infants who he can’t have chicken pox.” may not have the classic presentation of fever ≥ 5 Vaccines can fail, and mild cases of break- days and at least 4 out of the 5 following clinical through varicella can occur as well. If the features: (1) conjunctival injection, (2) mucous symptoms and morphology are consistent with membrane changes (bright red, cracked lips, the diagnosis, varicella should be considered, strawberry tongue), (3) changes in peripheral especially in immunocompromised patients. extremities (usually a later finding), (4) polymorphous rash, and (5) cervical lymphadenopathy. 9. “This 4-week-old had obvious mild cellulitis in her left leg, so I discharged her home on oral 4. “This patient had a rash and fever for 5 days, antibiotics.” but no cervical lymphadenopathy or conjuncti- Even if the skin infection appears to be localized, val injection, so I ruled out Kawasaki disease.” the immature immune system of a neonate may Patients can have an incomplete presentation of increase susceptibility to spread of the infection Kawasaki disease that still necessitates the stan- to other parts of the body. Therefore, it is rea- dard workup and treatment. Furthermore, they sonable to perform an evaluation for sepsis and may not have conjunctival injection at the time of admit the neonate for empiric IV antibiotics. Ad- presentation to the ED, but may have it at some ditionally, with any skin rash in this age group, point during the illness; it is important to clarify neonatal HSV infection must be considered, as this with the caregivers. Additionally, changes in this is a diagnosis that cannot be missed. the peripheral extremities are a later finding. 10. “The patient had a rash on the palms of her 5. “The patient was upset and had a fever, so I hands and the soles of her feet, so I diagnosed figured that was why he was tachycardic.” her with hand, foot, and mouth disease.” Often, pediatric patients with fever are tachy- Although this would be the likely diagnosis, cli- cardic due to elevated body temperature, anxiety, nicians should keep the differential wide so that and crying. However, clinicians should ensure other more-serious diagnoses, such as Rocky that the patient's vital signs normalize prior to Mountain spotted fever, are not missed. discharge. If not, consider less common diagnoses such as meningococcemia or alternative diagnoses such as underlying sepsis, bacteremia, and myocarditis.

January 2020 • www.ebmedicine.net 17 Copyright © 2020 EB Medicine. All rights reserved. seemed to improve abdominal and joint pain as well rash may require admission for IV antibiotics, and as renal symptoms when compared to placebo.51,52 patients with rheumatologic disease may require Other studies, including a recent meta-analysis, did admission for IV corticosteroids or other standard not find any significant difference between corticoste- treatments. Extra caution should be taken for chil- roid administration and placebo in resolution of renal dren who are immunocompromised, as they may re- involvement.53-55 Additionally, the use of corticoste- quire admission for close observation and empiric IV roids was not found to prevent renal disease.51 antibiotics until blood culture results are available; The proposed use of corticosteroids in HSP is the decision to admit and/or treat with IV antibiot- generally at high doses and for at least 2 weeks. ics should be made in conjunction with the patient’s High-dose corticosteroids have their own associated primary care provider. Patients with signs of shock risks in children and should be used with caution. (septic or cardiogenic) that is not improved with IV For children with mild HSP, corticosteroid therapy fluids should be admitted to a pediatric intensive is not warranted. There may be some benefit in care unit for close monitoring and management. patients with severe gastrointestinal symptoms who Patients with SSSS or TEN with significant skin are unable to tolerate oral medication and require sloughing may be better served in a burn unit, as hospitalization. In this case, other etiologies, such as management may be complicated by ongoing fluid intussusception, should be ruled out before initiat- loss and/or superinfection. Patients with concern for ing corticosteroid therapy. In patients who present Kawasaki disease should be admitted for additional with severe renal involvement, aggressive therapy is testing, observation, and an echocardiogram. indicated and this generally includes corticosteroids. From a public health standpoint, some diseases For patients who present with mild renal involve- require special consideration upon discharge. Refer ment, the benefit of corticosteroids remains unclear, to the local Office of Public Health for a list of re- and corticosteroid use is left to clinician judgment. portable diseases. Some require immediate reporting The role of corticosteroids is controversial in via telephone, while others should follow up within other illnesses as well. The management of Kawasa- days. ki disease with IVIG and aspirin is well established; however, a Cochrane review suggests that the addi- Summary tion of corticosteroids may have increased benefit.56 Additional research is needed to define the role of Fever and rash is a very common combination of corticosteroids in these disease processes. chief complaints seen in the ED setting. Keys to dif- Very little evidence is available to support the ferentiating deadly from benign causes are in obtain- use of corticosteroids for treatment of a rash of ing a detailed history and performing a thorough unknown etiology. However, given the negative physical examination looking for red flags. Evalua- side-effect profile of systemic corticosteroids (eg, tion should always begin with a general impression immunosuppression, adrenal suppression) as well and assessment of vital signs to identify children as the lack of evidence of benefit of corticosteroids who need immediate intervention. Important his- when treating a rash of unknown etiology, it is rec- torical questions include asking about medications, ommended for clinicians to proceed with caution. concurrent symptoms, vaccination status, recent travel history, and any immunodeficiency. The phys- Disposition ical examination should focus on the characteristics of the rash as well as concerning findings such as If the child is well appearing after administration of erythroderma, nonblanching lesions, desquamation, antipyretics, has no concerning findings on history and severe pain. If there are any concerns for sepsis, and physical examination, and is able to tolerate shock, meningitis, or other severe bacterial infection, oral intake without difficulty, then the child can be empiric antibiotics should be started, with investiga- discharged and the caregivers instructed to fol- tion of underlying causes dependent on the stability low up with the primary care provider, generally of the patient. Treatment and disposition depend on within the following 2 to 3 days. Younger patients, etiology, but symptomatic care is often the mainstay especially those aged < 6 months, are more prone to of treatment. rapid decompensation, and, therefore, should be re- evaluated in 1 to 2 days. Most school-aged children can return to school after they have been afebrile for 24 hours without using antipyretics and symptoms have resolved. Reasons for admission may include the inabil- ity to tolerate oral intake in the case of painful oral lesions or abdominal pain in the setting of HSP. Patients with fever and a bacterial etiology of the

Copyright © 2020 EB Medicine. All rights reserved. 18 Reprints: www.ebmedicine.net/pempissues Time- and Cost-Effective Strategies ing fluids and food, you determined that he did not need an abdominal ultrasound. You discussed supportive care • Ensure that a thorough history and physical with his parents, who planned to follow up in 2 days with examination are completed to guide the choice their PCP for re-evaluation. You also discussed with them of diagnostic testing and treatment. The history the need to have his urine rechecked for protein at some should include the timeline and characteris- point as well, and noted that if he were to develop severe tics of the rash, other symptoms of the illness, abdominal pain, severe swelling of the extremities, or any immune compromise, recent medication use, changes in urination, then they should return to the ED. vaccination status, recently received vaccines, You obtained rapid IV access in the 9-year-old girl and and sick contacts in the home. Additionally, gave her 2 boluses of 20 mL/kg normal saline as well as consider the time of the year, the region in which antipyretics, with only mild improvement in her heart rate the patient lives, and any recent travel history. and blood pressure. You quickly obtained blood cultures The physical examination should begin with a and started her on the appropriate antibiotics for toxic review of the patient’s vital signs to determine shock syndrome, as you were concerned for this based on whether the child requires immediate interven- her positive rapid strep test and her immunocompromised tion. Key components of the physical examina- state from the medications she takes for ulcerative colitis. tion include a thorough investigation of the skin She was transferred quickly to the PICU, as she required as well as searching for associated signs in other close monitoring and possibly vasopressors to maintain an body systems. It is important to correctly de- adequate blood pressure. scribe the qualities of the rash. When examining the skin, look for the major distribution of the References rash, with particular attention to involvement of the palms and soles. Note if the rash is primarily Evidence-based medicine requires a critical ap- on the extremities or only in a localized area, if praisal of the literature based upon study methodol- the mucous membranes are involved (including ogy and number of subjects. Not all references are the mouth, conjunctiva, and genitals), and if the equally robust. The findings of a large, prospective, rash blanches or not. randomized, and blinded trial should carry more • Given the overall paucity of specific guidelines weight than a case report. regarding when to obtain diagnostic testing, To help the reader judge the strength of each many clinicians tend to overtest children, espe- reference, pertinent information about the study, such cially if the patient is not known to them. The as the type of study and the number of patients in the most effective strategies to reduce cost and time study is included in bold type following the references, to treatment include having a specific question where available. The most informative references cited or potential diagnosis prior to ordering testing in this paper, as determined by the authors, are noted in children, not drawing routine blood cultures, by an asterisk (*) next to the number of the reference. and not overtreating patients with empiric medications, such as corticosteroids. 1. Rui P, Kang K. National hospital ambulatory medical care survey: 2015 emergency department summary tables. Ac- cessed December 15, 2019. Available at: https://www.cdc. Case Conclusions gov/nchs/data/nhamcs/web_tables/2015_ed_web_tables. pdf. (CDC data) The 1-year-old boy received antipyretics and was smiling, 2. Adams D, Thomas K, Jajosky R, et al. Summary of notifi- playful, and eating a cookie. After reviewing the history able infectious diseases and conditions - United States, 2014. and physical examination findings, you decided that he MMWR Morb Mortal Wkly Rep. 2016;63(54):1-152. (CDC data) did not exhibit any red flags. He had been vaccinated 3. Aber C, Alvarez Connelly E, Schachner LA. Fever and rash in a child: when to worry? Pediatr Ann. 2007;36(1):30-38. appropriately for his age, had not traveled recently, had a (Review) blanching rash that spared the mucous membranes, and 4. United States Centers for Disease Control and Prevention. he otherwise looked very well. You explained this to his Measles. Accessed December 15, 2019. Available at: www. parents and discussed that this was most likely a benign cdc.gov/measles. (CDC data) viral exanthem related to his viral upper respiratory 5. Moss WJ. Measles. Lancet. 2017;390(10111):2490-2502. (Re- infection and that it should self-resolve. You recommended view) supportive care, as needed, until the rash resolved. 6.* Dyer JA. Childhood viral exanthems. Pediatr Ann. The 3-year-old boy in the next room was also look- 2007;36(1):21-29. (Review) ing well. You gave him ibuprofen for his joint pain, and 7. World Health Organization. Measles vaccines: WHO he was able to ambulate well. Given the purpuric lesions position paper, April 2017. Weekly Epidemiological Record. 2017;92(17):205-228. (Position paper, review) on the lower extremities and the joint pain, you suspected 8. Buchanan R, Bonthius DJ. Measles virus and associated HSP. His platelet, PT/INR, and creatinine levels were central nervous system sequelae. Semin Pediatr Neurol. within normal limits, and there was no proteinuria. As he 2012;19(3):107-114. (Review) was not complaining of abdominal pain and was tolerat- 9. O’Grady JS. Fifth and sixth diseases: more than a fever and a

January 2020 • www.ebmedicine.net 19 Copyright © 2020 EB Medicine. All rights reserved. rash. J Fam Pract. 2014;63(10):E1-E5. (Review) 26.* McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, 10. Smith PT, Landry ML, Carey H, et al. Papular-purpuric treatment, and long-term management of Kawasaki disease: gloves and socks syndrome associated with acute parvo- a scientific statement for health professionals from the virus B19 infection: case report and review. Clin Infect Dis. American Heart Association. Circulation. 2017;135(17):e927- 1998;27(1):164-168. (Case report, review) e999. (Practice guideline) 11. Watkins J. Red faces: making the diagnosis. Pract Nursing. 27.* Allmon A, Deane K, Martin KL. Common skin rashes in 2008;19(1):31-34. (Review) children. Am Fam Physician. 2015;92(3):211-216. (Review) 12. Mullins TB, Krishnamurthy K. Roseola infantum (exanthema 28. Brinker A. Scarlet fever. N Engl J Med. 2017;376(20):1972. subitum, sixth disease). StatPearls. StatPearls Publishing (Review) LLC; Treasure Island, FL: 2018. (Review) 29. Wessels MR. Pharyngitis and scarlet fever. In: Ferretti JJ, 13. Khan A, Sutcliffe N, Jawad AS. An old disease re-emerging: Stevens DL, Fischetti VA, eds. Streptococcus pyogenes: Basic acute rheumatic fever. Clin Med (Lond). 2018;18(5):400-402. Biology to Clinical Manifestations. Oklahoma City, OK: Univer- (Case report) sity of Oklahoma Health Sciences Center; 2016. (Textbook chapter) 14. Rhodes KL, Rasa MM, Yamamoto LG. Acute rheumatic fever: revised diagnostic criteria. Pediatr Emerg Care. 30. Parker MW, Shah SS. Infectious diseases. In: Shah BR, 2018;34(6):436-440. (Review) Mahajan P, Amodio J, et al, eds. Atlas of Pediatric Emergency Medicine. 3rd ed. New York, NY: McGraw-Hill Education. 15.* Gewitz MH, Baltimore RS, Tani LY, et al. Revision of the (Textbook chapter) Jones Criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography: a scientific state- 31. van Driel ML, De Sutter AI, Keber N, et al. Different an- ment from the American Heart Association. Circulation. tibiotic treatments for group A streptococcal pharyngitis. 2015;131(20):1806-1818. (Practice guideline) Cochrane Database Syst Rev. 2013;(4):CD004406. (Systematic review and meta-analysis; 19 trials, 5839 participants) 16. Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of rheumatic fever and diagnosis and treatment of acute 32.* Gottlieb M, Long B, Koyfman A. The evaluation and man- streptococcal pharyngitis: a scientific statement from the agement of toxic shock syndrome in the emergency depart- American Heart Association Rheumatic Fever, Endocarditis, ment: a review of the literature. J Emerg Med. 2018;54(6):807- and Kawasaki Disease Committee of the Council on Cardio- 814. (Review) vascular Disease in the Young, the Interdisciplinary Council 33. Peterson ML. A long road to a preventative for toxic shock on Functional Genomics and Translational Biology, and the syndrome. Lancet Infect Dis. 2016;16(9):985-986. (Commen- Interdisciplinary Council on Quality of Care and Outcomes tary) Research: endorsed by the American Academy of Pediatrics. 34. Lappin E, Ferguson AJ. Gram-positive toxic shock syn- Circulation. 2009;119(11):1541-1551. (Practice guideline) dromes. Lancet Infect Dis. 2009;9(5):281-290. (Review) 17. Sika-Paotonu D, Beaton A, Raghu A, et al. Acute rheumatic 35. United States Centers for Disease Control and Prevention. fever and rheumatic heart disease. In: Ferretti JJ, Stevens Toxic shock syndrome (other than streptococcal) (TSS). 2011 DL, Fischetti VA, eds. Streptococcus pyogenes: Basic Biology Case Definition. Accessed December 15, 2019. Available at: to Clinical Manifestations. Oklahoma City, OK: University of https://wwwn.cdc.gov/nndss/conditions/toxic-shock- Oklahoma Health Sciences Center; 2016. (Textbook chapter) syndrome-other-than-streptococcal/case-definition/2011/. 18. Global Burden of Disease Collaborative Network. Global (CDC data) Burden of Disease Study 2017 (GBD 20176) Data Resources. 36. United States Centers for Disease Control and Prevention. Institute for Health Metrics and Evaluation (IHME): Seattle, Streptococcal toxic shock syndrome (STSS) (Streptococcus WA. Accessed December 15, 2019. Available at: http://ghdx. pyogenes). 2010 Case Definition. Accessed December 15, 2019. healthdata.org/gbd-2017. (Population study) Available at: https://wwwn.cdc.gov/nndss/conditions/ 19. Heininger U, Seward JF. Varicella. Lancet. 2006;368(9544): streptococcal-toxic-shock-syndrome/case-definition/2010/. 1365-1376. (Review) (CDC data) 20. National Center for Immunization and Respiratory Diseases. 37. Grama A, Marginean OC, Melit LE, et al. Staphylococcal Chickenpox (varicella). United States Centers for Disease scalded skin syndrome in child. A case report and a review Control and Prevention; 2018. Accessed December 15, 2019. from literature. J Crit Care Med (Targu Mures). 2016;2(4):192- Available at: https://www.cdc.gov/chickenpox/hcp/index. 197. (Case report, review) html. (CDC data) 38. Bukowski M, Wladyka B, Dubin G. Exfoliative toxins of 21. Kim KS, Hufnagel G, Chapman NM, et al. The group B cox- Staphylococcus aureus. Toxins (Basel). 2010;2(5):1148-1165. sackieviruses and myocarditis. Rev Med Virol. 2001;11(6):355- (Review) 368. (Review) 39. Mishra AK, Yadav P, Mishra A. A systemic review on 22. Xing W, Liao Q, Viboud C, et al. Hand, foot, and mouth staphylococcal scalded skin syndrome (SSSS): a rare and disease in China, 2008-12: an epidemiological study. Lancet critical disease of neonates. Open Microbiol J. 2016;10:150-159. Infect Dis. 2014;14(4):308-318. (Retrospective, population- (Review) based study; 267,942 confirmed cases) 40. Thomas AE, Baird SF, Anderson J. Purpuric and petechial 23. Dietz SM, van Stijn D, Burgner D, et al. Dissecting Kawasaki rashes in adults and children: initial assessment. BMJ. disease: a state-of-the-art review. Eur J Pediatr. 2017;176(8):995- 2016;352:i1285. (Review) 1009. (Review) 41.* United States Centers for Disease Control and Prevention. 24. Kato H, Ichinose E, Yoshioka F, et al. Fate of coronary aneu- Epidemiology and Prevention of Vaccine-Preventable Dis- rysms in Kawasaki disease: serial coronary angiography and eases. Hamborsky J, Kroger A, Wolfe S, eds. 13th ed. Wash- long-term follow-up study. Am J Cardiol. 1982;49(7):1758- ington D.C.: Public Health Foundation; 2015. (Textbook) 1766. (Follow-up study; 42 patients) 42. Olbrich KJ, Muller D, Schumacher S, et al. Systematic review 25. Holman RC, Belay ED, Christensen KY, et al. Hospitaliza- of invasive meningococcal disease: sequelae and quality of tions for Kawasaki syndrome among children in the United life impact on patients and their caregivers. Infect Dis Ther. States, 1997-2007. Pediatr Infect Dis J. 2010;29(6):483-488. 2018;7(4):421-438. (Systematic review; 31 studies) (Retrospective analysis) 43.* Waterfield T, Lyttle MD, Fairley D, et al. The “Petechiae in

Copyright © 2020 EB Medicine. All rights reserved. 20 Reprints: www.ebmedicine.net/pempissues children” (PiC) study: evaluating potential clinical decision CME Questions rules for the management of feverish children with nonblanching rashes, including the role of point of care testing for procalcitonin & Neisseria meningitidis DNA - a study Take This Test Online! protocol. BMC Pediatr. 2018;18(1):246. (Prospective diagnostic accuracy study) Current subscribers receive CME credit absolutely 44. Ang E, Sundel R. Henoch-Schönlein purpura. In: Chang V, Zaoutis L, eds. Comprehensive Pediatric Hospital Medicine. 2nd free by completing the following test. Each issue TM ed. New York, NY: McGraw-Hill Education; 2017:832-835. includes 4 AMA PRA Category 1 Credits , 4 ACEP (Textbook chapter) Category I credits, 4 AAP Prescribed credits, or Take This Test Online! 45. Friedman M, Mendoza C. Petechiae and purpura. In: Tenen- 4 AOA Category 2-A or 2-B credits. Online testing bein M, Macias C, Sharieff G, et al, eds. Strange and Schafer- is available for current and archived issues. To meyer’s Pediatric Emergency Medicine. 5th ed. New York, NY: receive your free CME credits for this issue, scan McGraw-Hill Education; 2018:549-552. (Textbook chapter) the QR code below with your smartphone or visit 46. McCarthy HJ, Tizard EJ. Clinical practice: diagnosis and management of Henoch-Schönlein purpura. Eur J Pediatr. www.ebmedicine.net/P0120. 2010;169(6):643-650. (Review) 47. Saulsbury FT. Henoch-Schönlein purpura in children. Report of 100 patients and review of the literature. Medicine (Baltimore). 1999;78(6):395-409. (Case reports, review; 100 patients) 48. Burks M, Usatine R. Henoch-Schönlein purpura. In: Usatine R, Sabella C, Smith M, et al., eds. The Color Atlas of Pediatrics. 1st ed. New York, NY: McGraw-Hill Pediatrics; 2015:1012- 1. Which of the following is a red flag in the his- 1017. (Textbook chapter) tory of a pediatric patient with a fever and rash? 49. Rajput R, Sehgal A, Jain D, et al. Acute parvovirus B19 infection leading to severe aplastic anemia in a previously a. The patient’s temperature at home was healthy adult female. Indian J Hematol Blood Transfusion. 40.3°C (104.6°F), measured rectally. 2012;28(2):123-126. (Case report) b. The patient has been eating and drinking 50. Woods-Hill CZ, Fackler J, Nelson McMillan K, et al. Associa- less than normal. tion of a clinical practice guideline with blood culture use c. The patient returned from a trip to the in critically ill children. JAMA Pediatr. 2017;171(2):157-164. Middle East 6 days ago. (Retrospective cohort study; 2356 patients) d. The rash has been itching. 51. Ronkainen J, Koskimies O, Ala-Houhala M, et al. Early prednisone therapy in Henoch-Schönlein purpura: a randomized, double-blind, placebo-controlled trial. J Pediatr. 2. Your intern discusses a patient with you. The 2006;149(2):241-247. (Randomized double-blind placebo- patient is a 15-year-old boy who has had a controlled trial; 171 patients) fever for 1 day and has now developed a rash. 52. Delbet JD, Hogan J, Aoun B, et al. Clinical outcomes in The intern describes the rash as nonpainful, children with Henoch-Schönlein purpura nephritis without nonpruritic, sparing the palms and soles, but crescents. Pediatr Nephrol. 2017;32(7):1193-1199. (Retrospec- tive multicenter study; 92 patients) including the face and genitals, and it is dif- 53. Hahn D, Hodson EM, Willis NS, et al. Interventions fusely erythrodermic. The patient’s vital signs for preventing and treating kidney disease in Henoch- are: temperature, 38.9°C (102°F); heart rate, 120 Schönlein purpura (HSP). Cochrane Database Syst Rev. beats/min; and blood pressure, 115/75 mm Hg. 2015(8):CD005128. (Systematic review; 13 randomized Which of the following should be considered a controlled trials) red flag for serious infection? 54. Dudley J, Smith G, Llewelyn-Edwards A, et al. Randomised, a. The fever does not improve with an double-blind, placebo-controlled trial to determine whether steroids reduce the incidence and severity of nephropa- antipyretic. thy in Henoch-Schönlein purpura (HSP). Arch Dis Child. b. The rash spares the palms and soles. 2013;98(10):756-763. (Randomized controlled trial; 352 c. The patient has diffuse erythroderma. patients) d. The fever presented prior to the rash. 55. Jauhola O, Ronkainen J, Koskimies O, et al. Outcome of Henoch-Schönlein purpura 8 years after treatment with a placebo or prednisone at disease onset. Pediatr Nephrol. 2012;27(6):933-939. (Randomized trial; 160,138 patients) 56. Wardle AJ, Connolly GM, Seager MJ, et al. Corticosteroids for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2017;1:Cd011188. (Systematic review)

January 2020 • www.ebmedicine.net 21 Copyright © 2020 EB Medicine. All rights reserved. 3. A 7-year-old boy presents with fever for 2 days, 8. A 2-year-old boy is brought in to the ED by sore throat, anterior lymphadenopathy, head- his babysitter who is watching him for the ache, and a spreading “rough feeling” rash. On week. She is unsure of his past medical his- examination, his lips and tongue are red, he still tory or vaccination status. She brings him in complains of headache, and you notice the coarse after 3 days of high fever, tearing red eyes, rash on his torso and arms, with linear areas of nonproductive cough, and a new morbilliform petechiae in his arm folds and the fold on the rash. On examination, you notice bluish-white back of his neck. After the physical examination, spots on the inside of his cheeks. According to what is the next BEST step in management? the CDC, what kind of precautions should be a. Order blood work and blood cultures, taken? and begin treatment to cover for a. Airborne meningococcemia. b. Contact b. Obtain a rapid strep throat swab, and treat c. Neutropenic the headache and fever with an antipyretic. d. Contact plus c. Admit the patient due to concern for Kawasaki disease, and order appropriate 9. A 16-year-old boy presents with a severe blood work. headache, a temperature of 40°C (104°F), blood d. Check coagulation studies and platelets for pressure of 98/45 mm Hg, and a nonblanching an underlying bleeding disorder. rash on both legs. Which of the following is the BEST first step in management? 4. According to the Jones criteria, which of the a. Order a variety of blood work and a rapid following patients with a known recent history lumbar puncture to determine the etiology of culture-confirmed strep throat could be diag- of the rash. nosed with acute rheumatic fever? b. Order coagulation studies, including a. A child with temperature of 38.2°C (100.8°F), fibrinogen and D-dimer. a CRP of 4 mg/L, and a rash c. Order blood work, rapidly obtain IV access, b. A child with temperature of 38.4°C (101.1°F), and administer IV ceftriaxone prior to polyarthritis, subcutaneous nodules, and receiving the results of testing. generalized rash d. Administer corticosteroids for treatment of c. A child with a prolonged PR interval on potential HSP. electrocardiogram and a generalized rash d. A child with a temperature of 38.6°C 10. A 2-year-old boy presents in July with 2 days (101.5°F), an ESR of 75 mm/hr, and diffuse of fever. He now refuses to eat and has de- arthralgias creased urine output. His mother is concerned that he has something transmitted by an insect, 5. Special care must be taken with pregnant as she has noted what she believes are bug individuals, as well as family members and bites on his feet and hands. She last gave him healthcare workers, in the setting of TORCH ibuprofen the evening before, and he has not diseases. Which of the following is a TORCH had any acetaminophen. On examination, you disease? note vesicles in the posterior oropharynx. He a. Measles b. Meningococcemia is febrile and mildly tachycardic in proportion c. Lyme disease d. Parvovirus B19 to temperature; however, his blood pressure is within normal limits. What is the BEST first 6. What study is important to obtain in a patient step in management? with presumed HSP who has emesis and ab- a. Administer weight-based dosing of dominal discomfort? ibuprofen and acetaminophen, and attempt a. Liver function tests oral rehydration with cold or frozen fluids. b. Lipase levels b. Order a CBC and comprehensive metabolic c. Abdominal ultrasound panel, and place an IV line to administer 20 d. Upright and decubitus abdominal x-rays mL/kg of normal saline. c. Test the patient for tick- and mosquito-borne 7. Which of the following is considered one of the diseases, given parental concern. clinical diagnostic criteria for Kawasaki disease? d. Prescribe a topical corticosteroid cream a. Inguinal lymphadenopathy for the lesions on the hands and feet, and b. Conjunctival injection discharge the patient to follow up with his c. Small bluish-white patches along the buccal primary care provider. mucosa d. Electrocardiographic changes

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January 2020 • www.ebmedicine.net 23 Copyright © 2020 EB Medicine. All rights reserved. CME Information Date of Original Release: January 1, 2020. Date of most recent review: December 15, 2019. Termination date: January 1, 2023. Accreditation: EB Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. This activity has been planned and implemented in accordance with the accreditation requirements and policies of the ACCME. November 2019 Volume 16, Number 11

Authors Credit Designation: EB Medicine designates this enduring material for a maximum of 4 AMA Amy Buckowski, MD TM Pediatric Stroke: Diagnosis Department of Emergency Medicine, Los Angeles County + USC PRA Category 1 Credits . Physicians should claim only the credit commensurate with the Medical Center, Los Angeles, CA Emily Rose, MD, FAAP, FAAEM, FACEP and Management in the Director for Pre-Health Undergraduate Studies, Director of the Minor extent of their participation in the activity. in Health Care Studies, Keck School of Medicine of the University of Southern California; Associate Professor of Clinical Emergency Medicine Emergency Department (Educational Scholar), Department of Emergency Medicine, Los Angeles County + USC Medical Center, Los Angeles, CA Specialty CME: Included as part of the 4 credits, this CME activity is eligible for 4 Infectious Abstract Peer Reviewers Lauren A. Beslow, MD, MSCE, FAHA Disease CME credits and 0.5 Pharmacology CME credits. Although pediatric stroke is rare, it is a leading cause of Assistant Professor of Neurology and Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Division of Child Neurology, morbidity and mortality in children. The diagnosis of stroke Children's Hospital of Philadelphia, Philadelphia, PA is often delayed in children, which can contribute to death Meghan Gilley, MD, FRCPC and disability. Management of pediatric stroke is challenging Pediatric Emergency Medicine Staff, BC Children’s Hospital; Clinical ACEP Accreditation: Pediatric Emergency Medicine Practice is also approved by the Instructor, Department of Pediatrics, University of British Columbia, because there are few data to support the efficacy of interven- Vancouver, Canada American College of Emergency Physicians for 48 hours of ACEP Category I credit per annual tions, and management is based on society guidelines and Prior to beginningon this the activity, back page.see “CME Information” expert opinion, as well as extrapolation from adult stroke

management. This issue reviews the most common causes of This issue is eligible for 4 Stroke CME credits and subscription. pediatric stroke, provides guidance for distinguishing stroke 0.25 Pharmacology CME credits. from stroke mimics, discusses the indications for laboratory David M. Walker, MD, FACEP, FAAP studies and imaging modalities, and offers evidence-based Chief, Pediatric Emergency AAP Accreditation: This continuing medical education activity has been reviewed by the Garth Meckler, MD, MSHS Medicine, Department of Pediatrics, recommendations for treatment. Associate Professor of Pediatrics, Joseph M. Sanzari Children's Alson S. Inaba, MD, FAAP University of British Columbia; Hospital, Hackensack University Pediatric Emergency Medicine Division Head, Pediatric Emergency Medical Center, Hackensack, NJ American Academy of Pediatrics and is acceptable for a maximum of 48 AAP credits per Ari Cohen, MD, FAAP Specialist, Kapiolani Medical Center Medicine, BC Children's Hospital, Chief of Pediatric Emergency for Women & Children; Associate Vancouver, BC, Canada Vincent J. Wang, MD, MHA Editors-in-Chief Medicine, Massachusetts General Professor of Pediatrics, University Professor of Pediatrics and Hospital; Instructor in Pediatrics, Joshua Nagler, MD, MHPEd Ilene Claudius, MD of Hawaii John A. Burns School of Emergency Medicine; Division year. These credits can be applied toward the AAP CME/CPD Award available to Fellows and Harvard Medical School, Boston, MA Assistant Professor of Pediatrics Associate Professor; Director, Medicine, Honolulu, HI Chief, Pediatric Emergency and Emergency Medicine, Harvard Process & Quality Improvement Medicine, UT Southwestern Jay D. Fisher, MD, FAAP, FACEP Madeline Matar Joseph, MD, FACEP, Medical School; Associate Division Program, Harbor-UCLA Medical Clinical Professor of Emergency Medical Center; Director of FAAP Chief and Fellowship Director, Division Center, Torrance, CA Medicine and Pediatrics, University Emergency Services, Children's Candidate Fellows of the American Academy of Pediatrics. Professor of Emergency Medicine of Emergency Medicine, Boston of Nevada, Las Vegas School of Health, Dallas, TX Tim Horeczko, MD, MSCR, FACEP, and Pediatrics, Assistant Chair, Children’s Hospital, Boston, MA FAAP Medicine, Las Vegas, NV Pediatric Emergency Medicine International Editor James Naprawa, MD Associate Professor of Clinical Quality Improvement, Pediatric Marianne Gausche-Hill, MD, FACEP, Attending Physician, Emergency Lara Zibners, MD, FAAP, FACEP, Emergency Medicine, David Geffen FAAP, FAEMS Emergency Medicine Division, Department USCF Benioff MMed School of Medicine, UCLA; Core Medical Director, Los Angeles University of Florida College of AOA Accreditation: Pediatric Emergency Medicine Practice is eligible for up to 48 American Children's Hospital, Oakland, CA Honorary Consultant, Paediatric Faculty and Senior Physician, Los Medicine-Jacksonville, County EMS Agency; Professor of Emergency Medicine, St. Mary's Angeles County-Harbor-UCLA Jacksonville, FL Clinical Emergency Medicine and Joshua Rocker, MD Hospital Imperial College Trust, Medical Center, Torrance, CA Associate Chief and Medical Pediatrics, David Geffen School Stephanie Kennebeck, MD London, UK; Nonclinical Instructor Osteopathic Association Category 2-A or 2-B credit hours per year. Director, Assistant Professor of of Medicine at UCLA; Clinical Associate Professor, University of of Emergency Medicine, Icahn Editorial Board Pediatrics and Emergency Medicine, Faculty, Harbor-UCLA Medical Cincinnati Department of Pediatrics, School of Medicine at Mount Sinai, Cohen Children's Medical Center of Jeffrey R. Avner, MD, FAAP Center, Department of Emergency Cincinnati, OH New York, NY Chairman, Department of Medicine, Los Angeles, CA New York, New Hyde Park, NY Pediatrics, Professor of Clinical Anupam Kharbanda, MD, MSc Michael J. Gerardi, MD, FAAP, Steven Rogers, MD Pharmacology Editor Pediatrics, Maimonides Children's Chief, Critical Care Services, Needs Assessment: The need for this educational activity was determined by a survey of FACEP, President Associate Professor, University of Hospital of Brooklyn, Brooklyn, NY Children's Hospital Minnesota, Aimee Mishler, PharmD, BCPS Associate Professor of Emergency Minneapolis, MN Connecticut School of Medicine, Emergency Medicine Pharmacist, Steven Bin, MD Medicine, Icahn School of Medicine Attending Emergency Medicine Program Director – PGY2 Associate Clinical Professor, UCSF at Mount Sinai; Director, Pediatric Tommy Y. Kim, MD, FAAP, FACEP Physician, Connecticut Children's Emergency Medicine Pharmacy medical staff, including the editorial board of this publication; review of morbidity and mortality Associate Professor of Pediatric School of Medicine; Medical Director, Emergency Medicine, Goryeb Medical Center, Hartford, CT Residency, Valleywise Health Emergency Medicine, University of Pediatric Emergency Medicine, UCSF Children's Hospital, Morristown Medical Center, Phoenix, AZ Emergency Department California Riverside School of Medicine, Christopher Strother, MD Benioff Children's Hospital, San Medical Center, Morristown, NJ Riverside Community Hospital, Associate Professor, Emergency Francisco, CA Medicine,December Pediatrics, and Medical 2019 APP Liaison data from the CDC, AHA, NCHS, an ACEP; and evaluation of prior activities for emergency Sandip Godambe, MD, PhD Department of Emergency Medicine, Richard M. Cantor, MD, FAAP, FACEP Chief Quality and Patient Safety Officer, Riverside, CA Education;Volume Director, 16, Pediatric Number 12Brittany M. Newberry, PhD, MSN, Management of Pediatric MPH, APRN, ENP-BC, FNP-BC Professor of Emergency Medicine Professor of Pediatrics, Attending Authors Emergency Medicine; Director, and Pediatrics; Section Chief, Physician of Emergency Medicine, Melissa Langhan, MD, MHS Simulation; Icahn School of Medicine Faculty, Emory University School Associate Professor of Pediatrics and physicians. at Mount Sinai, New York, NY of Nursing, Emergency Nurse Pediatric Emergency Medicine; Children's Hospital of The King's Prakriti Gill, MD Septic Arthritis andDaughters HealthOsteomyelitis System, Norfolk, VA Emergency Medicine; Fellowship Practitioner Program, Atlanta, GA; Medical Director, Upstate Poison Adam E. Vella, MD, FAAP Control Center, Golisano Children's Director, Director of Education,Pediatric Emergency Medicine Fellow, Department of EmergencyNurse Practitioner, Fannin Regional Ran D. Goldman, MD Director of Quality Assurance, Hospital, Syracuse, NY Pediatric EmergencyMedicine, Medicine, Yale Icahn School of Medicine at Mount Sinai, NewHospital York, EmergencyNY Department, Professor, Department of Pediatrics, University School of Medicine, New Pediatric Emergency Medicine, Jennifer E. Sanders, MD Blue Ridge, GA AbstractSteven Choi, MD, FAAP University of British Columbia; Haven, CT New York-Presbyterian, Target Audience: This enduring material is designed for emergency medicine physicians, Chief Quality Officer and Associate Research Director, Pediatric Assistant Professor,Weill Departments Cornell, New of York,Pediatrics NY and Emergency Dean for Clinical Quality, Yale Emergency Medicine, BC Children's Robert Luten, MD Medicine, Icahn School of Medicine at Mount Sinai, New York, NY Septic arthritisMedicine/Yale and School osteomyelitis of Medicine; Hospital,in pediatric Vancouver, patients BC, Canada represent Professor, Pediatrics and Vice President, Chief Quality Officer, Emergency Medicine,Peer University Reviewers of Joseph Habboushe, MD, MBA physician assistants, nurse practitioners, and residents. true emergencies,Yale New Haven and Health can System, quickly threaten life and limb. A Florida,high Jacksonville, FL Assistant Professor of Emergency Richard M. Cantor, MD, FAAP, FACEP index of Newsuspicion Haven, CT should be maintained,Medicine, NYU/Langone as these andconditions of Bellevue Medical Centers, New Professor of Emergency Medicine and Pediatrics; Section Chief, ten present with a subacute course York,of illness NY; CEO, andMD Aware vague LLC signs and- Pediatric Emergency Medicine; Medical Director, Upstate Poison Control symptoms. Septic arthritis and osteomyelitis can occur concur Center, Golisano Children’s Hospital, Syracuse, NY Goals: Upon completion of this activity, you should be able to: (1) demonstrate medical decision- Susan Fraymovich, DO rently, so suspicion for one should also prompt investigation for- Assistant Professor of Clinical Emergency Medicine, Assistant Professor the other. The diagnostic evaluation should include blood work of Clinical Pediatrics, New York Presbyterian Hospital, Weill Cornell making based on the strongest clinical evidence; (2) cost-effectively diagnose and treat the as well as samples from the infected joint or bone for culture. Medicine, New York, NY Management with antibiotics is a standard approach, but the du- Prior to beginning this activity, see “CME Information” most critical ED presentations; and (3) describe the most common medicolegal pitfalls for each ration of antibiotic therapy is controversial. This issue reviews the on the back page. current literature and provides an evidence-based approach for This issue is eligible for 4 Infectious Disease CME credits the evaluation and management of pediatric patients with septic and 0.5 Pharmacology CME credits. topic covered. arthritis and osteomyelitis.

CME Objectives: Upon completion of this activity, you should be able to: (1) distinguish benign Editors-in-Chief Ari Cohen, MD, FAAP Alson S. Inaba, MD, FAAP Ilene Claudius, MD Chief of Pediatric Emergency Garth Meckler, MD, MSHS Associate Professor; Director, Medicine, Massachusetts General Pediatric Emergency Medicine David M. Walker, MD, FACEP, FAAP Specialist, Kapiolani Medical Center Associate Professor of Pediatrics, versus life-threatening causes of rash in febrile pediatric patients; (2) identify red flags in Process & Quality Improvement Hospital; Instructor in Pediatrics, Chief, Pediatric Emergency for Women & Children; Associate University of British Columbia; Program, Harbor-UCLA Medical Harvard Medical School, Boston, MA Division Head, Pediatric Emergency Medicine, Department of Pediatrics, Center, Torrance, CA Professor of Pediatrics, University Jay D. Fisher, MD, FAAP, FACEP Medicine, BC Children's Hospital, Joseph M. Sanzari Children's of Hawaii John A. Burns School of Hospital, Hackensack University Tim Horeczko, MD, MSCR, FACEP, Clinical Professor of Emergency Medicine, Honolulu, HI Vancouver, BC, Canada the history and physical examination; (3) broaden the differential diagnosis of rash in febrile Medical Center, Hackensack, NJ FAAP Medicine and Pediatrics, University Joshua Nagler, MD, MHPEd Madeline Matar Joseph, MD, FACEP, Associate Professor of Clinical of Nevada, Las Vegas School of Assistant Professor of Pediatrics Vincent J. Wang, MD, MHA FAAP Emergency Medicine, David Geffen Medicine, Las Vegas, NV and Emergency Medicine, Harvard Professor of Pediatrics and School of Medicine, UCLA; Core Professor of Emergency Medicine Marianne Gausche-Hill, MD, FACEP, Medical School; Associate Division Emergency Medicine; Division patients to include less commonly seen—but dangerous—condition and those that could be Faculty and Senior Physician, Los and Pediatrics, Assistant Chair, FAAP, FAEMS Chief and Fellowship Director, Division Chief, Pediatric Emergency Angeles County-Harbor-UCLA Pediatric Emergency Medicine Medical Director, Los Angeles of Emergency Medicine, Boston Medicine, UT Southwestern Medical Center, Torrance, CA Quality Improvement, Pediatric County EMS Agency; Professor of Children’s Hospital, Boston, MA Medical Center; Director of Emergency Medicine Division, Emergency Services, Children's potential public health threats; (4) correctly identify patients who can be discharged and those Editorial Board Clinical Emergency Medicine and University of Florida College of James Naprawa, MD Pediatrics, David Geffen School Health, Dallas, TX Jeffrey R. Avner, MD, FAAP Medicine-Jacksonville, Attending Physician, Emergency of Medicine at UCLA; Clinical Jacksonville, FL Department USCF Benioff International Editor Chairman, Department of Faculty, Harbor-UCLA Medical Pediatrics, Professor of Clinical Stephanie Kennebeck, MD Children's Hospital, Oakland, CA Lara Zibners, MD, FAAP, FACEP, who require diagnostic testing for further evaluation; and (5) determine appropriate treatment of Center, Department of Emergency Pediatrics, Maimonides Children's Medicine, Los Angeles, CA Associate Professor, University of Joshua Rocker, MD MMed Hospital of Brooklyn, Brooklyn, NY Cincinnati Department of Pediatrics, Associate Chief and Medical Honorary Consultant, Paediatric Michael J. Gerardi, MD, FAAP, Steven Bin, MD Cincinnati, OH Director, Assistant Professor of Emergency Medicine, St. Mary's FACEP, President Hospital Imperial College Trust, the febrile patient with rash and plan appropriate disposition and follow-up care. Associate Clinical Professor, UCSF Anupam Kharbanda, MD, MSc Pediatrics and Emergency Medicine, Associate Professor of Emergency Cohen Children's Medical Center of London, UK; Nonclinical Instructor School of Medicine; Medical Director, Medicine, Icahn School of Medicine Chief, Critical Care Services, Pediatric Emergency Medicine, UCSF Children's Hospital Minnesota, New York, New Hyde Park, NY of Emergency Medicine, Icahn at Mount Sinai; Director, Pediatric School of Medicine at Mount Sinai, Benioff Children's Hospital, San Minneapolis, MN Steven Rogers, MD Emergency Medicine, Goryeb New York, NY Francisco, CA Children's Hospital, Morristown Tommy Y. Kim, MD, FAAP, FACEP Associate Professor, University of Connecticut School of Medicine, Discussion of Investigational Information: As part of the journal, faculty may be presenting Richard M. Cantor, MD, FAAP, FACEP Medical Center, Morristown, NJ Associate Professor of Pediatric Pharmacology Editor Attending Emergency Medicine Professor of Emergency Medicine Sandip Godambe, MD, PhD Emergency Medicine, University of Aimee Mishler, PharmD, BCPS and Pediatrics; Section Chief, California Riverside School of Medicine, Physician, Connecticut Children's Chief Quality and Patient Safety Officer, Medical Center, Hartford, CT Emergency Medicine Pharmacist, Pediatric Emergency Medicine; Professor of Pediatrics, Attending Riverside Community Hospital, Program Director – PGY2 investigational information about pharmaceutical products that is outside Food and Drug Medical Director, Upstate Poison Physician of Emergency Medicine, Department of Emergency Medicine, Christopher Strother, MD Emergency Medicine Pharmacy Control Center, Golisano Children's Children's Hospital of The King's Riverside, CA Associate Professor, Emergency Residency, Valleywise Health Hospital, Syracuse, NY Daughters Health System, Norfolk, VA Melissa Langhan, MD, MHS Medicine, Pediatrics, and Medical Medical Center, Phoenix, AZ Steven Choi, MD, FAAP Associate Professor of Pediatrics and Education; Director, Pediatric Administration approved labeling. Information presented as part of this activity is intended Ran D. Goldman, MD Emergency Medicine; Director, APP Liaison Chief Quality Officer and Associate Professor, Department of Pediatrics, Emergency Medicine; Fellowship Dean for Clinical Quality, Yale Director, Director of Education, Simulation; Icahn School of Medicine Brittany M. Newberry, PhD, MSN, University of British Columbia; at Mount Sinai, New York, NY Medicine/Yale School of Medicine; Research Director, Pediatric Pediatric Emergency Medicine, Yale MPH, APRN, ENP-BC, FNP-BC Vice President, Chief Quality Officer, University School of Medicine, New Adam E. Vella, MD, FAAP Faculty, Emory University School solely as continuing medical education and is not intended to promote off-label use of any Emergency Medicine, BC Children's Yale New Haven Health System, Hospital, Vancouver, BC, Canada Haven, CT Director of Quality Assurance, of Nursing, Emergency Nurse New Haven, CT Pediatric Emergency Medicine, Practitioner Program, Atlanta, GA; Joseph Habboushe, MD, MBA Robert Luten, MD Professor, Pediatrics and New York-Presbyterian, Nurse Practitioner, Fannin Regional Assistant Professor of Emergency Hospital Emergency Department, pharmaceutical product. Emergency Medicine, University of Weill Cornell, New York, NY Medicine, NYU/Langone and Blue Ridge, GA Bellevue Medical Centers, New Florida, Jacksonville, FL York, NY; CEO, MD Aware LLC Faculty Disclosure: It is the policy of EB Medicine to ensure objectivity, balance, independence, transparency, and scientific rigor in all CME-sponsored educational activities. All faculty participating in the planning or implementation of a sponsored activity are expected to disclose to the audience any relevant financial relationships and to assist in resolving any conflict of interest that may arise from the relationship. Presenters must also make a meaningful disclosure to the audience In upcoming issues of of their discussions of unlabeled or unapproved drugs or devices. In compliance with all ACCME Essentials, Standards, and Guidelines, all faculty for this CME activity were asked to complete a full disclosure statement. The information received is as follows: Dr. Philopena, Dr. Hanley, Dr. Pediatric Emergency Medicine Dueland-Kuhn, Dr. Avner, Dr. Gerber, Dr. Mishler, Dr. Claudius, Dr. Horeczko, and their related parties report no significant financial interest or other relationship with the manufacturer(s) Practice.... of any commercial product(s) discussed in this educational presentation. Commercial Support: This issue of Pediatric Emergency Medicine Practice did not receive any • Eating Disorders commercial support. • Neonatal Seizures Earning Credit: Two Convenient Methods: (1) Go online to www.ebmedicine.net/CME and click on the title of this article. (2) Mail or fax the CME Answer And Evaluation Form with your June • Mild TBI/Concussion and December issues to Pediatric Emergency Medicine Practice. Hardware/Software Requirements: You will need a Macintosh or PC with Internet capabilities to access the website. Additional Policies: For additional policies, including our statement of conflict of interest, source of funding, statement of informed consent, and statement of human and animal rights, visit http://www.ebmedicine.net/policies.

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Pediatric Emergency Medicine Practice (ISSN Print: 1549-9650, ISSN Online: 1549-9669, ACID-FREE) is published monthly (12 times per year) by EB Medicine (PO Box 1671, Williamsport, PA 17703). Opinions expressed are not necessarily those of this publication. Mention of products or services does not constitute endorsement. This publication is intended as a general guide and is intended to supplement, rather than substitute, professional judgment. It covers a highly technical and complex subject and should not be used for making specific medical decisions. The materials contained herein are not intended to establish policy, procedure, or standard of care. Pediatric Emergency Medicine Practice is a trademark of EB Medicine. Copyright © 2020 EB Medicine All rights reserved. No part of this publication may be reproduced in any format without written consent of EB Medicine. This publication is intended for the use of the individual subscriber only, and may not be copied in whole or in part or redistributed in any way without the publisher’s prior written permission – including reproduction for educational purposes or for internal distribution within a hospital, library, group practice, or other entity.