Hand Foot and Mouth Disease

Hand, foot, and mouth disease (HFMD) is a common, typically self-limited viral syndrome in children. HFMD is seasonal with individual cases and regional outbreaks usually occur in the spring, summer, and fall. In the United states, most cases involve children less than 4 years of age. Adults can also be affected, especially if they were in contact with children in childcare. Infected patients continue to shed the virus for a long time, making hand hygiene and environmental control measures in health care settings and daycare centers of vital importance, to prevent spread of the infection. 

HFMD is marked by fever, oral ulcers and papulovesicular rash affecting the palms of the hands, soles of the feet and buttocks. Skin lesions can be either asymptomatic or tender and painful. Desquamation can follow the rash. Symptoms usually last less than one week. Incubation period is 3 to 5 days with a prodrome that may include fever, malaise, abdominal pain, and myalgia 

HFMD is caused by infection with a variety of viruses in the genus Enterovirus. The most common strains that cause HFMD are coxsackievirus A16 and enterovirus 71. The rash of coxsackievirus A16 HFMD may be more extensive and severe. Clinical characteristics of HFMD caused by enterovirus 71 may be somewhat different, with smaller vesicles, diffuse erythema of the trunk and limbs, and higher fever (temperature ≥ 39°C [102.2°F] for more than 3 days).  Many other coxsackievirus strains have been detected, including A5, A7, A9, A10, B2, and B5. 

Neurologic and cardiopulmonary complications are more often associated with enterovirus 71 infection. Neurologic manifestations associated with enterovirus 71 infection include aseptic meningitis, a poliomyelitis-like syndrome, brainstem encephalitis, neurogenic pulmonary edema, opsoclonus-myoclonus syndrome, cerebellar ataxia, Guillain-Barré syndrome, and transverse myelitis. 

Atypical HFMD associated with coxsackievirus A6 has been increasingly occurring in audlts worldwide. It often presents with atypical cutaneous features, less oral involvement, and a more severe and prolonged disease course compared with classic HFMD. The disease is usually self-limiting, resolving within 2 to 3 weeks. However, it may be followed by potential complications such as eczema coxsackium and nail dystrophy. 

In mild cases of HFMD, particularly in patients with a high probability of having the disease based on their clinical characteristics and sick contacts, laboratory testing is not necessary. Testing is usually reserved for severe cases and public health investigation of outbreaks. IgM-capture enzyme-linked immunosorbent assays (ELISAs) for coxsackievirus A16 and enterovirus 71 are available. Enteroviruses initially replicate in the gastrointestinal tract. Viremia precedes invasion of the skin and mucous membranes. Plasma can be tested for IgM antibody testing. Throat and vesicle specimens are preferred for culture and PCR. In the first week of disease, the IgM detection rate is 90.2% for enterovirus 71 and 68% for coxsackievirus A16. In cases with atypical manifestations, RT-PCR testing of vesicular fluid, throat swabs, or stool samples can aid in the diagnosis.

References

Repass G, etal. Hand Foot and Mouth Disease. Cleveland Clinic Journal of Medicine September 2014 vol. 81 9 537-543

Enterovirus, Molecular Detection, PCR, Plasma. www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/89893. Accessed June 10, 2014. 

Yu N, etal. Evaluation of human enterovirus 71 and coxsackievirus A16 specific immunoglobulin M antibodies for diagnosis of hand-foot-and-mouth disease. Virol J 2012; 9:12. 

Wang W, Chiu S. Coxsackievirus A6–Induced Atypical Hand-Foot-Mouth Disease. JAMA Dermatol. Published online May 22, 2024. doi:10.1001/jamadermatol.2024.1029.