A 3-year-old boy with no medical history presents to your urgent care clinic with a 2-day history of “blisters all over.” His mother states that he has generally been feeling unwell for about 3 to 4 days with cough and general malaise. His oral intake has been slightly decreased, but he does not complain of pain with eating. His mother reports tactile temperatures but no documented fevers. His mother has not given him any medications, and his immunizations are current. Other children in his day care class were out last week with a “rash.”
Marissa J. Perman
In the office, he is a febrile and nontoxic-appearing. He has several crusted papules in the perioral region and on the cheeks with a few small erosions on the tongue and buccal mucosa. Involving the elbows, knees, buttocks, dorsum of the hands and feet, as well as palms and soles, are numerous 3 mm to 10 mm erythematous, hemorrhagic crusted papules, papulovesicles and discrete ovoid vesicles. His conjunctiva and genital mucosa are unremarkable.
What is the most likely etiology?
Diagnosis: Hand, foot and mouth disease
Hand, foot and mouth disease (HFMD) is a common childhood viral exanthem that usually affects children aged younger than 10 years. HFMD rarely occurs in adults, likely due to prior exposure and antibody development. Despite the name, HFMD often involves the buttocks and may also present more extensively on the face, arms and legs, especially the elbows and knees. HFMD is caused by enterovirus species, part of the Picornaviridae family. For most healthy children, HFMD is self-limited. Occasionally, enteroviruses that cause HFMD can lead to more serious sequelae such as pulmonary edema, encephalitis or myocarditis.
HFMD tends to follow a seasonal variation most commonly appearing in late summer and early fall. Outbreaks may be seen in day cares, schools and larger geographic regions, especially the Asia-Pacific region. Human enterovirus 71 (HEV-71) and coxsackievirus A16 (CV-A16) are the most common enteroviruses to cause HFMD. Other coxsackievirus, enterovirus and echovirus serotypes (also part of the enterovirus species) have been reported to cause HFMD.
Figure 1. Numerous erythematous focally crusted papules and papulovesicles on the knees and shins.
Images: Perman MJ
Patients infected with the viruses causing HFMD may be asymptomatic or present with a range of symptoms. Transmission is via the fecal-oral route in developing countries but more likely via respiratory droplets in developed countries. The incubation period lasts between 3 and 7 days, followed by 2 to 3 days of low-grade fevers, malaise, cough, sore throat, lymphadenopathy and, rarely, oral pain. This is followed 1 to 2 days later by, usually, asymptomatic oral erosions on the buccal, labial mucosa and tongue, and vesicles on the palms and soles and dorsum surface of the hands and feet. The enanthem may precede the exanthem, or they may occur simultaneously.
Hemorrhagic crusted papules, erosions and vesicles often develop on the buttocks and less commonly on the knees and elbows, occasionally with a more widespread eruption. The oral lesions have a thin, oval, gray-white vesicle with a surrounding red halo. Similarly, the lesions on the palms and soles tend to be elliptical or “football shaped” with a red halo. The long axis of these lesions is oriented parallel to skin lines and may aid in the diagnosis. The eruption tends to resolve in 5 to 7 days and may heal with dyspigmentation, but rarely scars.
Figure 2. Discrete pink papules and vesicles on the dorsum of the hand and digit. Note that the smaller lesions are oriented parallel to skin lines.
Most children with HFMD have mild disease. However, patients infected with HEV-71 may develop more severe disease. In particular, several reports of epidemics associated with HEV-71 in the Asia-Pacific region have led to hospitalization for complications, including pulmonary edema, pneumonia, meningoencephalitis, myocarditis and, rarely, death.
In one study from Taiwan, risk factors for central nervous system involvement without pulmonary edema included high fever (>39·C), fever lasting 3 days or longer and neurologic symptoms such as headache, lethargy, vomiting, seizures and hyperglycemia. Risk factors associated with pulmonary edema included leukocytosis, hyperglycemia and limb weakness.
Diagnosis of HFMD is usually clinical; however, enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) techniques may be available if needed. Higher viral loads may be found in oral secretions vs. stool, but do not persist as long as the viral load in stool, which can last for 3 to 11 weeks. Because of the prolonged shedding in the stool, HFMD is highly contagious and difficult to prevent spread.
The differential diagnosis for the oral erosions includes aphthous stomatitis, herpangina and herpes simplex virus (HSV), all of which are usually painful. For the cutaneous lesions, HSV, primary varicella and Gianotti-Crosti syndrome may be considered. Varicella may also involve the mucosa but tends to have a centripetal rather than acral pattern. There is an erythema multiforme-like pattern that can also rarely be seen. Buttock involvement may help distinguish HFMD from erythema multiforme.
Management is supportive, and most patients have self-limited disease without sequelae. Persistent, high fevers or other unusual symptoms may prompt more aggressive management. With the risk for severe sequelae, especially in the Asia-Pacific region, a vaccine may be available in the future. Although most physicians are familiar with the classic presentation of HFMD, certain outbreaks can lead to a more extensive distribution with more intense vesiculation and should be distinguished from HSV or primary varicella infection.
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- Dr. Perman reports no relevant financial disclosures.