Hand-foot-and-mouth disease 

 

·       Systemic viral infection characterized by ulcerative enanthem; vesicular exanthem on the distal extremities; mild constitutional symptoms.

·       Etiology.

Ø Enterovirus (picornavirus group, single-stranded RNA, nonenveloped). Commonly: Coxsackie virus A 1 6 and EV7 1. Coxsackie A6 associated with eczema coxsackium.

·       Demography.

Ø Most common in first decade. Outbreaks during warmer months (late summer, or early fall) in temperate climates. Highly contagious, spread from person to person by oral-oral and fecal-oral routes.

·       Pathogenesis.

Ø Enteroviral implantation in the Gl tract (buccal mucosa and ileum) with extension into regional lymph nodes. Seventy-two hours later viremia occurs with seeding of the oral mucosa and skin of the hands and feet.

 

Epidemiology

 

Hand-foot-and-mouth disease is the best recognized enteroviral exanthema with worldwide distribution that is usually self-limited. This disorder is characterized by a vesicular eruption on the palms and soles in conjunction with an erosive stomatitis. It is transmitted human-to-human via fecal–oral route and, less commonly, respiratory inhalation, usually with a 3–6-day incubation period, and viral shedding lasting up to 5 weeks. Exposure to virus in fecally contaminated water in swimming pools or via ingestion of oysters may be responsible for some infections. Once inhaled or ingested, virus replication ensues in the oropharynx and/or gastrointestinal tract with subsequent viremia.

Children less than 10 years of age are most frequently affected and infections occur more frequently in lower socioeconomic groups. 

Infections are most common in the spring, summer and autumn months. However, coxsackie virus A6 outbreaks frequently affect adults and can occur in the winter.

 

Etiology

 

HFMD is caused by a number of non-polio enteroviruses, most commonly coxsackie virus type A16 and enteroviruse 71.

 

Pathology

 

Histology is not usually performed, but shows spongiosis, intra epidermal splits progressing to vesicle formation, mononuclear cells entering the epidermis and necrosis of individual keratinocytes. There is a lymphocytic upper dermal and perivascular infiltrate. Viral particles are detectable with electron microscopy

 

 

Clinical features

 

History

HFMD usually begins with a non-specific prodrome, including low grade fever (38-39 degree C) that last 1-2 days, malaise, and occasionally, abdominal pain or upper respiratory tract symptoms. Sore throat or sore mouth is common and may lead to poor oral intake and dehydration. Cervical and mandibular lymphadenopathy may be present.

 

Cutaneous lesions

Nearly all cases of HFMD have painful oral lesions. These are generally few in number and are found on the tongue, buccal mucosa, hard palate, and less frequently, the oropharynx. The lesion starts as bright pink macules and papules that progress to small 4-8 mm grayish vesicles with surrounding erythema. These quickly erode and form yellow to grey erosions surrounded by an erythematous halo. The time between vesicles and erosion is short, so most patient present with erosions. Frequently 5 to 10 painful erosive oral lesions are present.

Cutaneous peripheral lesions are present in two third of patients and appear soon after the oral lesions. The lesions are most common on the palms, soles, sides and dorsum of the hands and feet, buttocks and, occasionally, external genitalia, and on the face and legs. They evolve similar to the oral lesions, starting as red macules that become clear oval, elliptical (football shaped), or triangular greyish vesicles with surrounding red halos. The number of lesions ranges from few to up to 50 and run parallel to the skin lines on fingers and toes. After crusting, they heal in 7-10 days without scarring.

Onychomadesis occasionally occurs 1–2 months after HFMD as a consequence of temporary nail matrix arrest related to the viral infection.

 

Coxsackievirus A6 (CVA6) has emerged as a cause of both outbreaks and sporadic cases of severe and atypical HFMD. This variant is characterized by more widespread vesicular, papulovesicular, and sometimes bullous or petechial eruptions, frequently involving the perioral area, extremities and trunk, as well as the palms, soles, and buttocks. Oral lesions develop in approximately half of patients, and delayed acral desquamation and onychomadesis are common. The eruption may be accentuated in areas of pre-existing skin injury or eczematous dermatitis, with the latter referred to as “eczema coxsackium”. In addition, patients with HFMD due to CVA6 are often febrile but do not usually have neurologic or other complications.

Enterovirus 71 infection may have associated CNS involvement (aseptic meningitis, encephalitis, meningoencephalitis, or flaccid paralysis), and pulmonary edema.

 

Laboratory teats

 

Confirmation of an enteroviral infection can be done by viral culture or reverse transcription polymerase chain reaction (RT-PCR)-based assays. Virus can be recovered from vesicular fluid, as well as throat and stool swabs. PCR is most widely employed for cerebrospinal fluid (CSF) sample and can help to identify serotypes in severe enteroviral infection.

 

Differential diagnosis

A sudden outbreak of oral and distal extremity lesions is pathognomonic for hand foot and mouth disease. However, if only the oral lesions are present, the differential diagnosis would include HSV infection, aphthous stomatitis, herpangina, erythema multiforme and adverse drug reaction.

 

Prognosis and clinical course

HFMD is usually a benign and self-limited illness. Rise in serum antibodies eliminates the viremia in 7 to 10 days.

 

Treatment

 

For most enteroviral exanthems, the course is self-limited, the prognosis is excellent, and supportive care suffices. However, in certain patient populations, e.g. immunosuppressed individuals or neonates, an enteroviral infection may be associated with potentially life-threatening complications. Pleconaril, a drug that interferes with enterovirus attachment and uncoating by binding to the protein capsid, has been demonstrated to be effective both in vitro and in clinical studies, including a recent randomized, placebo-controlled trial in neonates with enteroviral sepsis; it therefore holds promise as a specific antiviral therapy for serious enteroviral infections.