Symptom-Based Diagnosis in Pediatrics (CHOP Morning Report) 1st Ed.

CASE 9-6

Eighteen-Month-Old Girl



An 18-month-old girl was brought to the office by her mother for evaluation of a rash and low-grade fevers. The mother reported that the child was a bit fussy and not eating quite as well as usual. There was no history of irritability, vomiting, or loose stools. The infant did attend daycare but there were no known sick contacts.


There was no significant medical history. Immunizations were up-to-date.


T 39.5°C; RR 24/min; HR 120 bpm; BP 95/50 mmHg

Height 50th percentile; Weight 50th percentile

Physical examination revealed a well-appearing, playful toddler. Numerous 2-3 mm nontender erythematous papules and oval vesicles on an erythematous base were diffusely scattered on the torso and extremities with increased concentration on the hands, knees, and buttocks (Figure 9-6). The mucous membranes were normal. Of note, the mother was noted to have a few discrete inflammatory vesicles on her hands (Figure 9-7).


FIGURE 9-6. Typical cutaneous manifestations of hand, foot, and mouth disease on a toddler. A. Inflammatory vesicles on the hand. B. Inflammatory vesicle on the foot; C, D. Numerous small erythematous papules and vesicles on the knees and buttocks.


FIGURE 9-7. Typical small inflammatory vesicles on the hand of an adult.


No laboratory testing was performed.


The rash and fever resolved without treatment over the course of 7 days.



The differential diagnosis of a diffuse papulovesicular exanthem in a young child includes viral exanthems such as primary varicella, herpes simplex virus, and enterovirus infection, most commonly hand, foot, and mouth disease; scabies; and an id hypersensitivity reaction. Unusual causes include Gianotti-Crosti syndrome, also called papular acrodermatitis of childhood, and acropustulosis of infancy.

Primary varicella typically presents with low-grade fever, malaise, cough, coryza, and sore throat. The classic dewdrop on a rose petal exanthem presents first on the face and trunk, then spreads centripetally and appears as crops of red macules that progress to papules, vesicles, and pustules before crusting and resolving over 2-3 weeks. An enanthem with shallow oral ulcers may occur. The hallmark of the disease is the simultaneous presence of different clinical stages of the exanthem. With the initiation of routine immunization to the varicella-zoster virus in children, primary varicella is uncommon in immunocompetent children. Transmission occurs via respiratory droplets.

In children under age 5 years, the most common clinical presentation of primary herpes simplex virus (HSV) infection is acute herpetic gingivostomatitis, which usually presents with fever, irritability, gingival inflammation, and painful grey vesicles and shallow ulcers on the tongue, buccal mucosa, and palate which may extend to the lips and face. Drooling and decreased oral intake are common, and tender submandibular or cervical adenopathy may be seen. Symptoms usually resolve over 10-14 days. Infection is usually caused by HSV-1. Reactivation usually presents as more localized, grouped vesicles on an erythematous base localizing on the vermil-lion border of the lips or less frequently on the face and associated with pain, pruritus, burning, or tingling. Primary and recurrent cutaneous HSV infection without mucosal involvement may also occur, typically with involvement localized to a single area and manifest as grouped vesicles on an inflammatory base that quickly rupture, leaving shallow ulcerations. In children, transmission of herpes simplex virus typically occurs via oral contact from adult caregivers such as may occur from kissing or sharing of cups; caregivers may have obvious colds sores or may be asymptomatically shedding the virus. Disseminated HSV infection is usually seen only in neonates or immunocompromised individuals. Affected patients are generally ill-appearing and multiorgan involvement is common.

Gianotti-Crosti syndrome, also known as papular acrodermatitis of childhood, is an exanthem seen most commonly in association with EBV infection, although association with other viruses and with some bacteria, including influenza, coxsackievirus A16, enteroviruses, and group A Streptococcus has been reported and the entity was first described in association with acute hepatitis B virus infection. Gianotti-Crosti presents with an asymptomatic, acute, cutaneous eruption that develops over several days and appears as monomorphous pale, pink-to-flesh-colored or erythematous 1- to 10-mm papules or papulovesicles localized symmetrically and acrally over the extensor surfaces of the extremities, the buttocks, and the face. The number of lesions ranges from few to many. The trunk, knees, elbows, palms, and soles are rarely involved, and, in general, extensive involvement of the trunk is not consistent with a diagnosis of Gianotti-Crosti syndrome. Complete resolution typically takes more than 2 months, and the condition is self-limited. Fever and other signs and symptoms related to the primary infection may be seen, but in general children are well appearing.

Enteroviruses may cause a number of cutaneous manifestations, including a morbilliform exanthem, petechiae, and vesicular exanthems, which classically present as herpangina and hand, foot, and mouth disease. Herpangina manifests as shallow oral aphthae on the buccal mucosa and palate, lacks the gingival involvement of primary herpetic gingivostomatitis, and is milder in severity. Enteroviruses are transmitted by oral-oral and fecal-oral transmission; presumably, entero-virus infection may also be transmitted through direct contact with fluid from these cutaneous and mucosal lesions. Of the many enteroviral subtypes, coxsackieviruses, echoviruses, and enterovirus-71 are the subtypes which have been associated with cutaneous manifestations. Coxsackie A4 and echovirus 11 have been associated with a diffuse vesicular exanthem; echoviruses 2 and 9 with a rubelliform eruption; echoviruses 6, 9, 11, and 25 with a morbilliform eruption; echoviruses 11 and 19 with a petechiae exanthema, and echovirus 19 with a macular eruption.

Scabies is not an uncommon infestation caused by the Sarcoptes scabei mite. Transmission occurs via contact, and infestation of several household or other close contacts is not uncommon. Scabies classically presents as diffusely distributed, intensely pruritic inflammatory papules, vesicles, and burrows, which are often excoriated. The palms, soles, axillae, and scalp are often involved preferentially in infants, whereas in older children and adults, areas of involvement typically include the web spaces between the fingers and of the wrists, axillae, and waist.

Id hypersensitivity reactions (autoeczematization) occur as an immunologic reaction to a primary cutaneous infection or inflammatory disease. Id reactions present as a symmetric eruption of small erythematous, pruritic papules, and vesicles which may favor an acral distribution or may involve the head, torso, and extremities more diffusely. In children, id reactions typically are seen in association with dermatophyte skin infections, such as tinea capitis, or in association with a contact dermatitis, other eczematous dermatitis, or bacterial skin infection such as cellulitis.

Acropustulosis of infancy, also known as infantile acropustulosis, is a recurrent, pruritic vesicopustular dermatitis that typically involves the hands and feet, although milder involvement of the torso, face, arms, or legs is occasionally seen. It classically presents in infants and toddlers, with each episode lasting 1-2 weeks and recurring every 3-4 weeks, and generally resolves by age 3 years. Although the etiology is unknown, some cases appear to begin after scabies infestation, suggesting that acropustulosis may represent a hypersensitivity reaction to scabies.


On the basis of the clinical presentation, a diagnosis of hand, foot, and mouth disease (HFMD) was carried out.


HFMD is a common and mild, self-limited disease usually seen in children under 10 years of age. The most common cause of HFMD is Coxsackievirus A type 16, although HFMD has also been associated with coxsackievirus A5, A7, A9, A10, B2, and B5 infection. In Japan and other Pacific countries, enterovirus 71 infection has been associated with HFMD and neurologic complications, including a polio-like syndrome, aseptic meningitis, encephalitis, encephalomyelitis, and acute cerebellar ataxia. HFMD most commonly occurs in epidemics during the summer and fall, although low levels of endemic cases occur throughout the year. Coxsackievirus is a subgroup of the enteroviruses and is a member of the Picornaviridae family consisting of small, nonenveloped, single-stranded RNA viruses. The virus is transmitted via the fecal-oral route or via contact with skin lesions and oral secretions. Viremia develops, followed by invasion of the skin and mucous membranes.


The cutaneous manifestations of HFMD present as anywhere from several to over 100 erythematous macules and papules that evolve into oral, gray vesicles on an erythematous base. As suggested by the name, involvement of the hands and feet is characteristic, and lesions favor the lateral aspects on the fingers and toes as well as periungual. Mucosal involvement characteristically involves the hard palate, tongue, buccal mucosa, and gums and presents as erythematous macules, papules, and fragile vesicles that rupture easily, resulting in shallow painful ulcers surrounded by an erythematous halo; associated pain may interfere with oral intake, and irritability is common. Both the cutaneous and oral lesions typically resolve over 7-10 days without intervention and without sequelae, although aseptic meningitis may also be seen with enteroviral infection.


HFMD is usually diagnosed clinically, although the virus can be detected from appropriate samples, including blood, stool, and skin lesions. Identification methods include culture, immunoassay, polymerase chain reaction (PCR), and microarray technology. PCR may also be performed on urine and will remain positive for longer than PCF of blood specimens.


Management of HFMD is symptomatic. Affected children should be encouraged to drink cool, soothing liquids to maintain hydration and to avoid hot and spicy foods and drinks. Appropriate pain control medications, such as oral acetominophen or ibuprofen, and use of topical analgesics should be provided as necessary. Topical analgesic preparations include “Magic Mouthwash,” which is typically composed of equal volume of liquid diphenhydramine and Maalox® 2% viscous lido-caine may be added if the child is old enough to swish and spit the medication but is best avoided in infants and younger children to avoid swallowing of medication and risk of lidocaine toxicity. Topical benzocaine gel is also helpful.


1. Cherry JD, Krogstad P. Enteroviruses and parechoviruses. In: Feigin RD, Cherry JD, Demmler-Harrison GJ, Kaplan SL, eds. Feigin and Cherry’s Textbook of Pediatric Infectious Diseases. 6th ed. Philadelphia, PA: Saunders Elsevier; 2009:2110-2169.

2. Modlin JF. Enteroviruses: coxsackieviruses, echoviruses, and newer enteroviruses. In: Long SS, Pickering LK, Prober CG, eds. Principles and Practice of Pediatric Infectious Diseases. 3rd ed. Philadelphia, PA: Churchill Livingstone Elsevier; 2008:1149-1157.