Differential diagnosis
The differential diagnosis of HFMD includes conditions with oral lesions and maculopapular, vesicular lesions involving the palms and/or soles, as well as erythroderma.
Oral lesions. Aphthous ulcers are shallow, painful oral lesions not accompanied by skin rashes. Herpes gingivostomatitis, caused by herpes simplex virus (HSV), is often preceded by a prodrome of fever. The associated lesions manifest as vesicular clusters on a red base that evolve into large, painful ulcers. HSV mouth lesions can populate the gingivae, pharynx, hard palate, lips, and perioral skin. Skin lesions may occur unilaterally.
Rashes involving palms and soles. A number of conditions manifest with skin lesions similar to those of HFMD. An autoeczematization reaction consisting of a pruritic, papulovesicular eruption secondary to dermatophyte infection (eg, tinea pedis, tinea manuum, tinea cruris, tinea corporis, tinea capitis) should be ruled out. This type of reaction is thought to be a delayed hypersensitivity response to fungal antigens. Pruritus and the absence of mouth sores distinguishes this reaction from HFMD.7
Secondary syphilis can manifest with a short-lived macular rash involving the palm and soles, as well as oral mucous patches and generalized lymphadenopathy. Syphilis testing, including rapid plasma reagin or Venereal Disease Research Laboratory test with fluorescent treponemal antibody absorption, can rule out this diagnosis.
Erythema multiforme, which is more common in young adults, is characterized by target lesions on the palms and soles and erosions and/or bullae in the mouth and mucous membranes. It is usually preceded by a trigger, such as HSV infection.
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