Hand, foot and mouth disease can start with a low-grade fever, reduced appetite, and general malaise. The most common hand, foot, and mouth disease presenting symptom is usually mouth or throat pain secondary to the enanthem. The presence of vesicles surrounded by a thin halo of erythema, eventually rupturing and forming superficial ulcers with a grey-yellow base and erythematous rim. The exanthem can be macular, papular or vesicular. The lesions are non-pruritic, and typically not painful. The exanthem involves the dorsum of the hand, feet, buttocks, legs, and arms.

Hand, foot and mouth disease can also present with atypical features like concomitant aseptic meningitis. Enterovirus infections that cause hand, foot, and mouth disease are notorious for involving the central nervous system (CNS) and may cause encephalitis, polio-like syndrome, acute transverse myelitis, Guillain-Barre syndrome, benign intracranial hypertension and acute cerebellar ataxia.

The diagnosis of hand, foot, and mouth disease is usually made clinically. The virus can be detected in the stool for about 6 weeks after infection, however, shedding from oropharynx is usually less than 4 weeks. Light microscopy of biopsies or scrapings of vesicles will differentiate hand, foot, and mouth disease from varicella zoster virus and herpes simplex virus.[7][8]

While serology is not sensitive to make a diagnosis of hand, foot, and mouth disease, levels of IgG can be used to monitor recovery. In some centers, serology is used to differentiate enterovirus 71 from coxsackievirus as this has prognostic significance. Today, polymerase chain reaction assays are available in most centers to confirm the diagnosis of coxsackievirus.

Hand, foot, and mouth disease is a mild clinical syndrome and will resolve within 7 to 10 days. Treatment is primarily supportive. Pain and fever can be managed with NSAIDs and acetaminophen. Making sure the patient remains well hydrated is important. Additionally, a mixture of liquid ibuprofen and liquid diphenhydramine can be used to gargle with which helps coat the ulcers, ameliorating the pain.[9][10]

Ribavirin, quinacrine, and amantadine have all been used off-label to treat severe cases of enterovirus 71 induced hand, foot, and mouth disease disease.

Over the past decade, researchers have developed specific treatments to manage enterovirus 71 induced hand, foot, and mouth disease because of its severe neurological complications. So far, no drug has been approved, but promising novel agents include molecular decoys, translation inhibitors, receptor antagonists and replication inhibitors. One new antiviral agent that has shown promise in the treatment of enterovirus 71 is pleconaril.[11]

• Enteroviruses

• Erythema multiforme

• Herpangina

• Herpes simplex

• Herpes zoster

• Kawasaki disease

• Toxic epidermal necrolysis(TEN)

• Viral pharyngitis

The prognosis for the majority of patients with hand, foot, and mouth disease is excellent. Most patients recover within a  few weeks without any residual sequelae. The acute illness usually lasts 10 to 14 days, and the infection rarely recurs or persists. However, some patients with hand, foot, and mouth disease may develop serious complications which include the following:

• Persistent stomatitis which is associated with painful ulcers. The pain can be severe enough to limit intake of food and dehydration can result, especially in young children.
• Aseptic meningitis can occur, but this is more common with enterovirus 71. This particular virus is associated with a higher rate of neurological involvement compared to coxsackievirus. The individual may develop acute cerebellar ataxia, polio-like syndrome, encephalitis, benign intracranial hypertension and Guillain-Barre syndrome. It is believed that the virus induces damage to the gray matter which then results in the motor dysfunction.
• Very rarely coxsackievirus can cause interstitial pneumonia, myocarditis, and pulmonary edema.
• Some studies indicate that coxsackievirus infections may also be associated with spontaneous abortions.

The majority of patients with coxsackievirus-induced hand, foot, and mouth disease are treated as outpatients, but those who have CNS involvement may require admission for close monitoring. These patients often require imaging studies of the brain to guide treatment and recovery. Infants may develop dehydration, especially if they develop painful oral ulcers and may require Intravenous hydration. Admission is highly recommended in any infant with hand, foot, and mouth disease who shows signs of severe disease and lethargy. The virus is shed in the stools for a few weeks; hence, patients should be educated about hand washing and maintenance of good personal hygiene.

Cases of HFMD are on the rise and clinicians need to know how to make the diagnosis. Because many recent cases have involved the brain, an interprofessional team that includes a neurologist, internist and an infectious disease expert should be involved. Patients with signs of encephalitis need to be monitored by the nurses.

The outcomes for most patients with HFMD are excellent, with full recovery occurring within 7-21 days.