Approach to the patient with suspected HFMD


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HFMD is usually diagnosed by history and physical examination. In the presented case, Jeff had frequent contact with his grandchild, who was younger than 4 years of age, so the grandson was the likely source of the illness. The rash usually consists of papules and vesicles, 2 to 6 mm in size, on the gingiva, buccal mucosa, tongue, and pharynx. Lesions may also be found on the skin of the hands, feet, buttocks, and genitalia.11 Of note, the presentation of CV A6 HFMD has some atypical features: lesions on the dorsal surfaces of the hands, areas of eczema, and large purpuric vesicles/bullae.18 Fever and malaise are often present. CV A6 HFMD has been reported to present with more bothersome symptomatology.

Cases of HFMD caused by CV A6 may occur seasonally and have the appearance of typical cases caused by other strains; however, clustered cases of CV A6 HFMD in Scotland and the United States were noted between October and February, whereas typical HFMD outbreaks take place in the summer and early autumn. Untimely presentations may cause providers to miss the diagnosis. Four children were admitted to a hospital in Edinburgh, United Kingdom, during winter. Initially, these patients were treated with acyclovir for a feared diagnosis of eczema herpeticum; afterward, however, molecular typing identified CV A6.19

What about the rash on Jeff’s trunk and buttocks? Some literature emphasizes that HFMD should be recognized as hand-foot-and-mouth and buttock disease because lesions appear on the buttocks in one-third of cases. Jeff’s illness occurred in winter.11 As noted, HFMD occurs more commonly in temperate climates during the summer and fall, but outbreaks of CV A6 HFMD can occur in winter. A cluster of cases of CV A6 HFMD was noted in the United States between November 2013 and December 2014.1,19 CV A6 HFMD also tends to have a more severe course that includes erosive lesions that may be purpuric, and it affects the buttocks.15 In late disease, desquamation of the hands and feet may have a clinical presentation similar to that of certain fungal infections.16

A culture specimen can be sent for laboratory analysis, but this is not always readily available and is rarely done. The virus is found and can be cultured from skin  or oral lesions or from stool specimens. The best place to swab for a sample is an oral lesion; however, if there are no vesicles, a rectal swab can be performed.20 The culture result may take longer than 2 weeks, at which point the patient should be recovering.21 A culture can be helpful to determine the strain, guide the care of household contacts, and determine whether an outbreak is occurring. Polymerase chain reaction (PCR) and microarray technology can be used to identify the causative virus. Different healthcare settings may have a variety of specific assays.20 An infectious disease consult is rarely necessary but is nevertheless recommended in questionable cases or when the patient is known to be immunosuppressed. 

Differential diagnosis

HFMD can be confused with another vesicular eruption, such as herpes simplex or varicella-zoster virus infection.17 The differential diagnosis in an adult can include a variety of conditions with cutaneous manifestations, including varicella-zoster virus infection, drug reaction, eczema herpeticum, secondary syphilis, and bullous impetigo.18, 22, 23 Other viral infections caused by CV strains or versions of the echovirus can present with herpangina but are usually accompanied by a high fever. Aphthous stomatitis may have the appearance of HFMD with oral ulcerations, but the ulcerations are larger than those in HFMD, are not associated with fever, and may be recurrent.20,21

Eczema herpeticum is a serious skin infection that occurs as a secondary herpesvirus infection within preexisting lesions of atopic dermatitis or another erosive dermatosis. It usually occurs in children and young adults with a history of eczema in which the skin has become compromised and is easily invaded by the herpesvirus. The rash spreads and appears as scattered umbilicated lesions. Eczema herpeticum can become a fulminant disease with systemic symptoms and involvement. Those most at risk are children who have atopic dermatitis or who are immunocompromised. It carries a 10% mortality rate.24

A drug reaction typically presents in the form of pruritic skin lesions. Stevens-Johnson syndrome can be due to a drug reaction. The characteristic features of Stevens-Johnson syndrome include a rapidly developing blistering exanthema and target-like lesions accompanied by mucosal involvement and skin detachment.25 In 2010–2012 in Taiwan, 21 cases of CV A6 HFMD were initially treated as suspected severe drug reactions affecting the skin.25 A drug may be responsible for skin reactions and should always be considered, especially in cases with an atypical clinical presentation, such as that of CV A6 HFMD.25 Drug-induced hypersensitivity syndrome (DIHS) is a multiple-organ drug reaction previously known as drug reaction with eosinophilia and systemic symptoms (DRESS). The former term is now used because eosinophilia is not always present. HFMD is usually limited, milder than DIHS, does not involve organs, other than the skin and mucus membranes and does not lead to full-thickness epidermal necrosis.25

Other childhood illnesses can present with a rash and may be included in the differential diagnosis. A 43-year-old patient in Connecticut developed 2- to 9-mm pink-red papules and papulovesicles on the left forearm, dorsal surfaces of the hands, palms, fingers, and one toe. Small vesicles and erosions were also present on the hard palate and soft palate. The provider ordered a complete blood cell count and PCR of serum for parvovirus B19. The blood cell count was normal, and the result of the test for parvovirus B19 was negative. However, the result of reverse transcriptase (RT)-PCR4 of plasma for enterovirus was positive. A test for viral typing sent to the Centers for Disease Control and Prevention confirmed CV A6 infection.26


The treatment of HFMD is supportive and includes consideration of reducing transmission. In Jeff’s case, the primary symptoms were itching and pain from the lesions. He was treated with analgesics and antihistamines for symptom control. He was encouraged to rest, stay away from the workplace with his active lesions and fever, and increase his fluid intake. Cool liquids and the avoidance of acidic and spicy foods are preferred. If lesions in the mouth are severe to the point that they limit intake, intravenous hydration may be necessary.20 To prevent transmission, Jeff should practice frequent handwashing, especially after touching any blisters or using the bathroom and before eating. Although it is assumed that Jeff was exposed to HFMD via his grandchild, he should stay away from children while he is febrile with active lesions. Institutional outbreaks are possible with children, and contact precautions are recommended in healthcare settings. As new cases of CV A6 HFMD appear and affect adults with an atypical presentation, increased vigilance may become necessary to recognize outbreaks.17 

At Jeff’s home, contaminated surfaces and items should be washed and disinfected with dilute chlorine bleach. Jeff should avoid close contact with others while infected—refraining from hugging, kissing, and sharing utensils. Contacts should be observed for the development of symptoms.27 At this time, there is no vaccine for the viruses responsible for HFMD3; however, research is ongoing to develop small-animal models for testing possible vaccines.28


HFMD may often go undiagnosed in adults because the clinicians who treat them are relatively inexperienced in identifying childhood illnesses. This case, diagnosed as HFMD on the basis of the clinical presentation, deviated from what has been commonly seen in the past. Jeff’s lesions were larger and clinically more symptomatic than those commonly seen in children. Fortunately, with some symptomatic support, Jeff’s lesions healed, and he experienced no sequelae. Perhaps he did have HFMD from CV A6. As outbreaks occur, it will be essential for primary care providers to be aware of the adult presentation of HFMD and the newer strain of CV A6. 

Susan Renda, DNP, ANP-BC, CDE, FNAP, is an assistant professor and AGNP primary care track coordinator at the Johns Hopkins University School of Nursing, and Michael Sanchez, DNP, CRNP, NP-C, FNP-BC, AAHIVS, is an assistant professor at the Johns Hopkins University School of Nursing in Baltimore.


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