United States

Background 
Hand-foot-mouth disease (HFMD) is a viral illness that typically presents in children under the age of five with fevers and characteristic papulovesicular lesions of the hands, feet, and oral mucosa. With the rise of coxsackievirus-A6 and atypical Hand-foot-mouth disease (HFMD) presentations with ear lesions, providers need to consider a broad differential for external ear lesions that includes HFMD.
Case Presentation
A 3-year-old previously healthy male patient presents to his primary care clinic with a worsening rash. Three days ago, he developed fever, congestion, and rhinorrhea, and two days later, he developed a rash. The rash initially started on his hands, feet, and perioral region, but has since developed ear lesions. He has known sick contacts with fever and rash only on their hands and feet. On exam, he is afebrile. Skin exam is notable for pruritic, crusting, erythematous papulovesicular eruption concentrated on his palms, soles, and perioral regions. He has multiple, similarly-appearing lesions on the auricles of both ears, but no lesions within the helix or external canal. Oral exam is notable for erythematous macules on the soft palate, posterior oropharynx, and lower inner lip with normal gingiva and tongue.

Discussion
With the patient’s ear lesions, causes such as vascular, inflammatory, neoplastic, and traumatic causes were considered. However, because of his associated symptoms, an infection was more likely. Infections such as CV-A6, Rocky Mountain Spotted Fever, impetigo, Herpes Simplex Virus, Varicella Zoster Virus, and Monkeypox are all potential causes of papulovesicular ear lesions. Given the patient’s age and exposure to known sick contacts with typical HFMD presentation, CV-A6 was the most likely. In recent years CV-A6 has been associated with outbreaks of more severe disease and atypical HFMD worldwide – including China, Spain, Taiwan, the United States, and the UK.

External ear lesions are a rare atypical presentation of HFMD. When patients have no other symptoms, clinicians must consider the broad differential for papulovesicular ear lesions. 


AMA Research Challenge 2024 

Atypical Hand-Foot-Mouth Disease - The Need to Consider the Various Causes of Pediatric Papulovesicular Ear Lesions ​

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Background
The life cycle of Plasmodium parasites, the parasites responsible for the transmission of malaria, depends on the parasites’ ability to invade red blood cells. Mutations that alter the structure of red blood cells, including the mutation that causes sickle cell disease (Hb-SS), interfere with the life cycle of Plasmodium parasites and provide protection against malaria. Patients with Hb-SS rarely develop severe anemia that requires blood transfusions before 6 months of age.
Case Presentation
A female infant with Hb-SS discovered on routine newborn screening began needing monthly transfusions to maintain hemoglobin levels above 7 g/dl at the age of 6 weeks of life. Due to the severity of her anemia, hemolytic anemia gene sequencing was performed and revealed the presence of hereditary elliptocytosis and heterozygosity for G6PD deficiency. Splenectomy, performed at 2 years of age due to splenic sequestration, resulted in decreased frequency of transfusions, highlighting the role of hereditary elliptocytosis in her presentation.
Discussion
Hereditary elliptocytosis modifies the severity of Hb-SS; coexistence of hereditary elliptocytosis with Hb-SS can result in severe, early-onset anemia. Infants with Hb-SS and severe anemia need genetic testing to investigate for other causes of anemia.

Hereditary Elliptocytosis as a Modifier of Sickle Cell Disease Severity

Background
Blisters in children are typically attributed to common causes such as impetigo, herpes zoster, burns, sunburn, friction, contact dermatitis, bug bites, and thumb-sucking. However, less common causes like suction blisters from pacifiers are seldom reported. This case highlights a rare presentation of a suction blister on the thumb caused by a pacifier, emphasizing the need for vigilant monitoring of pacifier use in young children.

Case Presentation
A 21-month-old male with no significant past medical history presented with a suction blister on the left thumb. The blister was discovered after the child woke up crying in the crib, with the pacifier suctioned over the thumb. The thumb exhibited a circumferential pale appearance from the proximal interphalangeal joint to the distal thumb, with an intact, oval bulla filled with clear fluid on the volar thumb pad. The surrounding skin turned erythematous after removing the pacifier. The child was treated with ibuprofen for perceived pain and brought to the clinic. Physical examination confirmed the blister as approximately 8 mm in diameter, with no signs of infection or complications. The blister was managed conservatively. Parents were advised to keep the area clean, avoid puncturing the blister, and follow anticipatory guidance for care. The parents chose to discontinue pacifier use.

Discussion
Pacifiers, while beneficial for soothing young children, can pose risks such as suction blisters from prolonged negative pressure. This case report of a suction blister on the thumb caused by a pacifier highlights the importance of considering uncommon causes of blisters in pediatric patients and underscores the need for careful monitoring of pacifier use. Educating parents on the potential risks and proper usage of pacifiers is crucial to prevent similar injuries. Recommendations include ensuring pacifiers are appropriately sized, made of safe materials, and not left with children unsupervised for extended periods. Improved education and product design may help mitigate these risks.


Pacifiers: Blissful or Blister? Suction Blister on the Thumb

Background: NMDA receptor encephalitis is a rare autoimmune disorder characterized by the production of antibodies against the N-methyl-D-aspartate (NMDA) receptors in the brain. It often presents with a variety of neurological and psychiatric symptoms, including seizures, speech impairment, and behavioral changes. 

Patient: We present the case of a 4-year-old girl initially diagnosed with focal epilepsy of unknown etiology, who exhibited speech regression and behavioral changes. Despite treatment with antiepileptic medication, her symptoms persisted and worsened over time. 

Results: Further evaluation, including imaging studies and EEG monitoring, did not reveal any significant abnormalities. However, autoimmune encephalitis was suspected due to the atypical presentation and lack of response to conventional treatments. Serum testing confirmed the presence of NMDA receptor antibodies. The patient was subsequently treated with high-dose steroids for 5 days, which led to a remarkable improvement in her condition. Within a week of discharge, she began speaking in full sentences again. 

Conclusion: This case highlights the importance of considering autoimmune encephalitis in children presenting with atypical seizure manifestations and behavioral changes. Prompt recognition and treatment with immunomodulatory therapy, such as high-dose steroids, can result in significant clinical improvement and better outcomes for these patients.

Pediatric NMDA Receptor Encephalitis: a Case of Speech Regression and Behavioral Changes

Background
Pericardial effusions have a variety of causes ranging from malignancy and trauma to lymphatic obstruction1. Infection is the most common cause of pericardial effusions in children, with serous effusions being the most common type2. Here we report a case of a post-viral hemorrhagic pericardial effusion with tamponade physiology in a pediatric patient with no history of trauma.

Case Presentation
A 12-year-old female with no past medical history presented to the pediatric emergency department with a two-week history of worsening shortness of breath on exertion. Two weeks prior, she had experienced a viral illness with fevers up to 102ºF and inspiratory chest pain. She tested negative for flu, strep throat, and COVID; she was given azithromycin, which initially improved her symptoms. About one week after her initial presentation, she developed shortness of breath, non-productive cough on exertion, and some congestion. At that time, she was given amoxicillin/clavulanic acid at an after-hours clinic, which her mother supplemented with home prednisolone and an albuterol inhaler. None of these improved her symptoms. She was then discovered to have cardiomegaly on an outside chest x-ray, which prompted a trip to the pediatric emergency department. On presentation to the emergency department, the patient had normal vital signs. In the emergency department, a bedside echocardiogram showed a large pericardial effusion with tamponade physiology, right ventricle diastolic collapse, and >30% mitral valve inflow variation. Cardiology was consulted and the patient was taken to the PICU for urgent pericardiocentesis. A pericardiocentesis and drain placement was performed at bedside in the PICU and drained 1200cc of hemorrhagic fluid, with cultures obtained and showing no growth. Hematology/Oncology was consulted due to concern for malignancy; however, CT and tumor marker labs showed no evidence of malignancy. Rheumatology was also consulted to rule out an autoimmune process, with autoimmune markers returning normal. The patient was given furosemide for the effusion, and repeat echocardiograms showed no accumulation, prompting the drain to be removed. The patient was discharged with ibuprofen and a close cardiology follow-up. Since then, the patient had a normal chest x-ray two weeks after admission, and an echo one month after admission showed no significant residual pericardial effusion, valvular dysfunction, and normal systolic motion.

Discussion
Pericardial effusions are most often serous but can sometimes be hemorrhagic. Hemorrhagic pericardial effusions are usually due to trauma but should not be excluded as a possibility when dealing with viral illnesses or other causes. It is also important to rule out other pathological processes, such as malignancy and autoimmune conditions, when working up hemorrhagic effusions. It is also important to gather a thorough history from patients, including potential trauma or prior infections. Life threatening cardiac tamponade occurs when a patient develops an obstructive shock due to buildup of fluid in the pericardium. Cardiac tamponade is diagnosed with echocardiogram showing right ventricle diastolic collapse. Definitive treatment is pericardiocentesis, which removes pericardial fluid and relieves the obstructive shock.

Serious but Not Serous: a case of infectious, non-traumatic hemorrhagic effusion in pediatric cardiac tamponade

Background
VACTERL Association is a group of birth defects that can present as a combination of Vertebral, Anal, Cardiac, Tracheal, Esophageal, Renal and Limb abnormalities. It is a diagnosis of exclusion requiring at least three of these features to be present. There is no true explanation for VACTERL from either a causation or embryo-pathogenesis standpoint, but risk factors include gene mutations, chromosomal anomalies and maternal diabetes. VACTERL occurs in 1 out of 10,000 to 40,000 births, though it is likely underdiagnosed due to its variability in presentation.

Case Presentation
Patient is a 4-month-old male with history of VACTERL association status-post tracheoesophageal fistula ligation, esophageal atresia repair and G-Tube dependency, presenting for follow-up after 118-day NICU stay for prematurity and fetal anomaly workup. Hospital course was complicated by respiratory distress, sepsis rule out, cardiac resuscitation, pneumothorax, and hemidiaphragmatic paralysis. Patient was born at 35w6d to a refugee mother from Venezuela via spontaneous vaginal delivery. Pregnancy was complicated by polyhydramnios, abnormal prenatal ultrasound and late prenatal care. Delivery was complicated by premature prolonged rupture of membranes. Patient currently presents with global developmental delays and requires follow-up with surgery, gastroenterology, pulmonology, nephrology, cardiology, genetics, ENT and ophthalmology.

Discussion
Early signs of VACTERL association included (1) multicystic left kidney seen on prenatal ultrasound, and (2) polyhydramnios and lack of gastric bubble indicating tracheoesophageal fistula (TEF) or imperforate anus. While not present in this patient, a single umbilical artery also frequently accompanies VACTERL. Since VACTERL is a diagnosis of exclusion, the differential included Fanconi anemia, CHARGE syndrome, DiGeorge syndrome and Alagille syndrome, all of which share features with VACTERL.
From “VACTERL,” the patient presented with: (V) supernumerary ribs, S1 defect and rib hypoplasia; (C) patent foramen ovale, atrial septal defect and patent ductus arteriosus; (TE) TEF Type C, and (R) left multicystic kidney. As outlined in a new Pediatric Research (2020) guideline, VACTERL phenotypes fall under four subtypes—STRICT-VACTERL, VACTERL-LIKE, VACTERL-PLUS and NO-VACTERL—based on major and minor criteria. The patient was classified as STRICT-VACTERL.
Treatment required careful coordination of care from the neonatology team, and despite surgical interventions, long-term care from various specialists throughout childhood will likely be necessary. Prognosis for VACTERL is generally good, though chronic health issues into adulthood are common. While early identification of anomalies through antenatal care is key for early coordination of care and birth plan, further research is needed to identify and correct modifiable causes for future prevention.

The 118 Day NICU Voyage of a VACTERL Baby from Venezuela

Abstract Title: Under Pressure: Brain Abscess and Meningitis Complicated by Orbital and Ethmoidal Encephaloceles-A Pediatric Case Report

Alisa Liberman, BS1, Timur Raghib, MD2
1Midwestern University Arizona College of Osteopathic Medicine, Glendale, AZ; 2Phoenix Children’s Hospital, Phoenix, Arizona

Background
An encephalocele is a herniated sac containing meninges and brain tissue that protrudes out of a skull defect. The majority of primary encephaloceles are congenital. Secondary encephaloceles can arise due to trauma, tumors, surgery, and chronic sinusitis. Literature review of infectious pathology associated with encephaloceles yielded documented cases of different type of encephaloceles associated with meningitis and/or empyema in both adult and pediatric populations. Here we present, to our knowledge, the first documented case of brain abscess and
meningitis complicated by concurrent orbital and ethmoidal encephaloceles in the pediatric population.

Case Presentation
A 10-year-old male with a history of headaches presented to an emergency department with fever, altered mental status, swelling near his right eye and mid-forehead, vomiting, and worsening headaches. One year prior, the patient suffered unspecified skull fractures after a motor vehicle accident and subsequently developed headaches. One week prior to presentation his headaches increased in intensity and frequency. In the emergency department, CT of the head showed pansinusitis, and lumbar puncture showed a leukocyte count 12694, glucose 7, and
protein 307. The patient was started on Vancomycin and Ceftriaxone. He was transferred to another hospital, where repeat CT and MRI showed a right inferior frontal lobe abscess with intraventricular extension, right anterior cranial fossa bony defect with an encephalocele protruding into the right superior orbit and a small component extending into right ethmoid, in addition to pansinusitis. The patient underwent endoscopic sinus surgery, cerebral abscess drainage, and external ventricular drain catheter placement. CSF and brain abscess cultures were positive for Streptococcus Pneumoniae and Staphylococcus Aureus/Staphylococcus Epidermis, respectively. The patient was treated with culture-sensitive antibiotics and transitioned to Ceftriaxone and Metronidazole for an additional six weeks.

Discussion
This case describes an uncommon presentation of brain abscess and meningitis complicated by worsening orbital and ethmoidal encephaloceles. In our patient, we propose that the encephaloceles initially developed secondary to the patient’s traumatic skull fractures and expanded due to increased intracranial pressure and mass effect from the frontal brain abscess. From this case we learn that even before obtaining imaging, it may be important for clinicians to keep infectious intracranial pathology complicated by encephaloceles on the differential in a patient with a history of skull trauma presenting with fever, altered mental status, forehead and
eye swelling, and worsening headaches. Additionally, while clinicians may be cautious in repeating CT/MRI given the radiation/cost, our case illustrates that it may be necessary to prevent diagnostic delay.

Under Pressure: Brain Abscess and Meningitis Complicated by Orbital and Ethmoidal Encephaloceles-A Pediatric Case Report

Epstein-Barr Virus (EBV), a member of the Herpesviridae family, is globally prevalent. While most children infected are asymptomatic, around 25% develop infectious mononucleosis (IM) characterized by fever, sore throat, and lymphadenopathy. IM can lead to multisystem involvement, including rare pulmonary manifestations like pneumonia. In literature, pulmonary nodules are exceedingly rare in immunocompetent children. Here we discuss a unique case of nodular lung findings in a patient with IM to highlight the diverse clinical manifestations of EBV infection.

An 11-year-old male previously healthy male presented to the emergency room (ER) with one week of fever, neck pain and sore throat. In the ER, vitals were unremarkable. Physical examination revealed a non-fluctuant, right larger than left submandibular lymphadenopathy with mild tenderness to palpation. CT soft tissue and neck with IV contrast revealed bilateral cervical and supraclavicular lymphadenopathy. CT chest noted multiple small scattered noncalcified pulmonary nodules. Clinical symptoms work-up was significant for WBC 15.4 TH/cmm, CRP 3.00 mg/dL, LDH mildly elevated at 394 U/L, and uric acid 6.0 mg/dL. Histoplasmosis and Bartonella antibody panels were negative. ENT was consulted and he was started on 0.15 mg/kg of Decadron for four doses to minimize airway swelling and IV Unasyn for infectious coverage. EBV serologies were also obtained showing IgG positive, IgM positive, Nuclear Ag IgG negative, and Early Ag IgG positive, indicating the patient’s lymphadenitis and suspicious apical pulmonary nodules were secondary to infectious mononucleosis. The patient’s family was notified of the diagnosis and strict return precautions and counseling were given.

Pulmonary manifestations in EBV-related illnesses are relatively uncommon, but can present as pneumonia. In immunosuppressed patients, EBV can cause lymphoproliferative disorders (PTLD) or lymphoma which can present as pulmonary nodules. In literature, pulmonary nodules rarely occur in an immunocompetent child. Pulmonary nodules could be part of the clinical presentation of IM in otherwise healthy children and in an appropriate setting, a close follow-up with complete resolution is adequate to rule out malignancy. Our patient was managed conservatively with close monitoring and regular follow- up. The decision on follow up imaging should be individualized based on clinical signs and symptoms and imaging characteristics. The discussed case emphasizes the importance of understanding and recognizing the variable presentations of EBV even in the most unlikely of patients.

Unusual Suspect: EBV's Role in Pediatric Pulmonary Nodules

Background 
Arterial thoracic outlet syndrome (TOS) is extremely difficult to diagnose as the symptoms appear benign until a stroke occurs. Ischemic strokes are rare in adolescents, with a prevalence of 0.54 to 2.4 per 100,000. The burden of stroke on children, however, is tremendous. Among adolescents with stroke, nearly half of them have an unknown etiology. Therefore, a good review of the patients’ symptoms, along with a thorough history, can help with early diagnosis and treatment of arterial TOS, a known critical cause of ischemic strokes in children and adolescents.

Case Presentation 
We report an atypical case of a 16-year-old female who had an acute ischemic stroke due to arterial TOS. The patient’s mother reported a three-year history of syncopal episodes, headaches, and diminished blood flow to her right hand. The syncopal episodes occurred during activities with arm elevation, such as styling her hair or playing softball. Sports or occupations with repetitive arm elevation are a risk factor for TOS as they lead to increased thoracic outlet compression. Her headaches increased in frequency and severity leading up to the stroke. Her right hand would turn white and cold, and her grip strength decreased. The patient saw a 
physician a few months before the stroke for her syncopal episodes; her bloodwork came back normal, and she was sent home. A brain Magnetic Resonance Imaging showed diffusion restriction in the pons, basilar artery thrombus, and suspected right cerebellar hemisphere infarct. During an emergency thrombectomy, an incidental right cervical rib was found compressing the subclavian artery. Right upper extremity Doppler ultrasound found axillary, brachial, and radial arteries occlusive thrombi, with retrograde thromboembolism a likely etiology of her infarcts. 

Discussion 
Treatments of arterial TOS include cervical rib resection and anticoagulant therapy. It causes compression of the subclavian artery. This can damage the artery and lead to clot formation, as well as, in this case, retrograde thromboembolism, in which a distal vein thrombosis travels up the artery to the brain, causing a stroke. The most common cause of arterial TOS is the presence of a cervical rib, which is present in 0.5-1% of the population. This case report aims to highlight the clinical symptoms and an important risk factor that should raise suspicion of arterial TOS before a major debilitating event such as a stroke occurs and to raise awareness these symptoms may present in children or adolescents. 






Arterial Thoracic Outlet Syndrome: A Case Report on Stroke in an Adolescent

Abstract Title
Management of Complex Regional Pain Syndrome Exacerbation After Unilateral Total Knee Arthroplasty: A Case Study
Authors: Linares AD, Joohee Y, Qiu C, Ehsan A, Kim K

Background (141)
Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by pain most commonly in the distal extremities after surgery or injury like fracture or sprain, where the pain is disproportionately greater than typically experienced after similar tissue trauma. CRPS most commonly affects the arms, hands, legs or feet. Symptoms include severe pain, swelling, restricted range of motion, temperature and skin changes. CRPS is divided into two groups: Type 1, lacking known nerve damage, and Type 2, resulting from specific nerve damage. As in this case, CRPS has been reported as a rare side effect of elective total knee arthroplasty, affecting daily functioning and work, and decreasing quality of life. Treatment is multidisciplinary, including physiotherapy, psychology, and pain management. Pharmacotherapy is aimed at primary mechanisms involved, such as vasomotor disturbances, inflammation, pain or sensory dysfunction, muscular involvement, and psychological factors.

Case Presentation (124)
A 53-year-old woman with PMH of chronic pain syndrome, osteoarthritis, and CRPS ten months after left total knee arthroplasty presented to the emergency department with worsening left knee pain radiating to the left hip and limited mobility. Physical examination revealed edema of the left knee without other deformities. Imaging revealed intact hardware with no abnormalities. Lack of fever or leukocytosis effectively ruled out a septic joint. Subsequent pain management included methadone, IV morphine, methocarbamol, acetaminophen, pregabalin, amitriptyline and Lidoderm patch. Her pain remained refractory to the treatment, therefore dexamethasone, capsaicin cream and hydromorphone were added. Even then, continuing pain led to replacing hydromorphone with morphine. Excessive drowsiness complicated treatment, thus adjustments to the pregabalin, methocarbamol and morphine dosages were made.

Discussion (134)
Managing CRPS can be extremely complicated due to the varying presentations and responses to treatment for each patient. For each patient that presents with CRPS, a thorough initial evaluation should be done in order to gain a comprehensive understanding of the range of their symptoms. This questioning can often help guide therapy as it may reveal the extent of nerve or muscle involvement in the etiology of pain, as well how much swelling can contribute to their symptoms. With this understanding, a pain control regimen can include muscle relaxants, opioids, and nerve pain medications . As seen with this patient, it is then necessary to closely monitor these patients and adjust the initial regimen in response to any side effects, allowing for effective pain control. 


Management of Complex Regional Pain Syndrome Exacerbation After Unilateral Total Knee Arthroplasty: A Case Study

Background:
Myotonic Dystrophy is an autosomal dominant neuromuscular disease with a global incidence of 1 in 8000 worldwide. This condition can be further categorized into myotonic dystrophy type 1 (DM1), having childhood onset, and myotonic dystrophy type 2 (DM2). The DM2 subtype is generally milder and often presents with proximal muscle weakness, especially in the hip girdle musculature, and disabling myalgic pain. Weakness in the neck flexion, finger flexion and tricep extension are also common symptoms. Genetic testing is the gold standard for DM2 diagnosis. Electromyography studies and muscular biopsies provide additional evidence in support of the diagnosis of DM compared to other inflammatory/metabolic myopathies. Despite these multiple diagnostic strategies, current practice lacks guidelines for efficient diagnosis and treatment initiation especially when clinical presentation is unclear.

Case Presentation:
A 65-year-old woman of Korean descent with a past medical history of hypothyroidism presented to her primary care physician for upper and lower extremity swelling, upper extremity weakness, and a positive antinuclear antibody. After ruling out deep-vein thrombosis, furosemide improved her lower extremity edema. However, she continued to experience fatigue, poor appetite, nausea, intermittent dyspnea on exertion, and difficulty with ambulation. The patient went to the emergency department and was started on moderate-dose prednisone. Symptoms improved for two weeks. Then, the patient visited her rheumatologist, and was given an increased dose of oral prednisone with the suspicion of polymyositis, yet little benefit was gained. Muscle biopsy was not ordered due to prior use of corticosteroids. Instead, the patient underwent a nerve conduction study (NCS) and electromyography (EMG). Results from the EMG revealed signs of DM2, including myotonic discharges and positive sharp waves.

Discussion:
During initial evaluation of extremity muscle weakness, current practice often begins with noninvasive measures including laboratory testing and imaging, followed by EMG if suspecting neurological involvement. Muscle biopsy can be done if the diagnosis remains unclear. However, biopsy may be complicated by corticosteroid treatment due to corticosteroid-induced myopathy of type II muscle fibers, delaying definitive diagnosis and pathology-specific management. Especially with this patient’s atypical presentation, deferring glucocorticoid treatment until after muscle biopsy may have improved access to diagnostic testing and earlier initiation of treatments appropriate for the pathology at play. Muscle weakness can encompass numerous etiologies, so early EMG and muscle biopsy may be useful tools in distinguishing the cause of symptoms and guiding management to bring greater and longer-lasting symptom relief to patients.


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Atypical Hand-Foot-Mouth Disease - The Need to Consider the Various Causes of Pediatric Papulovesicular Ear Lesions

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Hereditary Elliptocytosis as a Modifier of Sickle Cell Disease Severity

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Premium content

Atypical Hand-Foot-Mouth Disease - The Need to Consider the Various Causes of Pediatric Papulovesicular Ear Lesions ​

Next from AMA Research Challenge 2024

Hereditary Elliptocytosis as a Modifier of Sickle Cell Disease Severity

Stay up to date with the latest Underline news!

PRESENTATIONS

CONFERENCES

COMPANY

RESOURCES

Atypical Hand-Foot-Mouth Disease - The Need to Consider the Various Causes of Pediatric Papulovesicular Ear Lesions