Coxsackievirus A6 and Hand, Foot and Mouth Disease: Three Case Reports of Familial Child-to-Immunocompetent Adult Transmission and a Literature Review
Case 1: A 35-year-old man, computer technician, with irrelevant past medical history, was admitted to our outpatient clinic at the beginning of October 2012 with a 2-day history of papular and vesicular skin rash. He complained of fever with chills, malaise and sore throat 1 day before the onset of cutaneous symptoms. Moreover, the patient reported close contact with a child suffering from HFMD, during a family party, 1 week before symptoms developed.\nPhysical examination revealed erythematous papulovesicular lesions on the posterior oropharyngeal structures and multiple erythematous papules followed by vesicular lesions on his palms, soles and perioral zone (fig. , fig. ). A complete blood count revealed no abnormalities. The erythrocyte sedimentation rate was increased to 20 mm/h. Blood chemistry tests were normal, except for the level of C-reactive protein (CRP), which was elevated to 12 mg/l. Syphilis, HIV and hepatitis B and C serologies were negative. The pattern of serum protein electrophoresis was normal, and the initial chest X-ray and ECG demonstrated no pathologic findings.\nViral ribonucleic acid was extracted from vesicular fluid samples (both from the throat and skin) and from plasma. Afterwards, it was amplified with reverse transcription-seminested polymerase chain reaction (PCR) assay as described elsewhere [], using primers that allow amplification of all known human enteroviruses and identification of the serotypes by amplicon sequencing. The primers used for the seminested step amplified a 376-bp portion of the capsid viral protein 1 (VP1) gene. The amplicon sequencing and comparison to gene database identified Coxsackievirus A6, both from vesicles and plasma.\nHistological examination of the skin biopsy from a palmar papule showed orthokeratotic hyperkeratosis with areas of confluent parakeratosis and presence of singular basal and suprabasal keratinocyte necrosis. Moreover, a lymphocytic inflammatory infiltrate was present in the superficial dermis up to dermo-epidermal junction. The histological features were consistent with a viral infection.\nThe patient was diagnosed with HFMD based on characteristic clinical manifestations, positive results of enterovirus PCR analysis, molecular typing for Coxsackievirus A6 and histological findings. Symptomatic treatment with oral paracetamol and lidocaine oral spray was introduced. During a 7-month follow-up, no complications were observed. Skin and mucosal lesions resolved completely. No nail changes have been observed so far, but the child who infected the patient with Coxsackievirus A6 developed onychomadesis 2 months later (fig. ).