A Case of Gloves and Socks Syndrome and Related Eruptions Caused by Coxsackievirus A4 Infection Mimicking Adult-onset Still's Disease.

Sir,

Gloves and socks syndrome (GSS) is an acute purpuric and papular eruption of the hands and feet that has been associated with several viral infections.[1] Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology characterized by spiking fever, evanescent skin rash, arthralgia, and neutrophilic leukocytosis.[2] Here, we report the first case of GSS and related eruptions caused by coxsackievirus A4 infection mimicking AOSD.

A 40-year-old man was referred to for diagnosis of faint nonpruritic erythema on the trunk [Figure 1a] and extremities in association with spiking fever (>39°C) and arthralgia in the knees and elbows that had been present for 3 days. Swollen axillary and inguinal lymph nodes were confirmed. A skin biopsy obtained from erythema on the abdomen showed superficial dermal edema and a mild perivascular lymphocytic infiltrate with scattered neutrophils in the superficial dermis, which was consistent with salmon-pink erythema of AOSD. [Figure 2] Abnormal laboratory examination included leukocytosis (leukocyte, 9900/μl; neutrophils, 9009/μl), liver and biliary tract dysfunctions (aspartate aminotransferase, 157 U/L; alanine aminotransferase, 270 U/L; gamma-glutamyl transpeptidase, 426 U/L), and elevated serum C-reactive protein (14.94 mg/dl) and ferritin (1169 ng/ml) levels. The serum antinuclear antibodies and rheumatoid factor were negative, and collagen disease and internal malignancies were excluded. AOSD was considered. However, on day 4, painful and pruritic erythema appeared on his hands [Figure 1b] and feet. The paired serum samples were negative for IgM (day 7, 0.27; day 21, 0.20; normal, <0.8) and IgG (day 7, 0.75; day 21, 0.58; normal, <0.8) antibodies against parvovirus B19. Epstein-Barr virus (EBV) and cytomegalovirus showed serological past-infection patterns. The negative serum neutralizing antibody titers for coxsackievirus A7, A9, A10, and A16 and elevated serum level of neutralizing antibody titer for coxsackievirus A4 (4096; normal, <4) were confirmed. We diagnosed this case as GSS and related eruptions caused by coxsackievirus A4 infection. Oral administration of loxoprofen sodium (120 mg/day) and topical application of 0.05% betamethasone butyrate propionate were started. The spiking fever and eruptions on the trunk and extremities disappeared in 9 days, and the arthralgia and eruptions on the hands and feet disappeared in 3 weeks. The abnormal laboratory test results improved after 1 month.

Figure 1

Clinical photographs. (a) At the first visit, nonpruritic salmon-pink erythema was seen on the back. (b) On day 4, painful and pruritic erythema appeared on his hands

Figure 2

Histopathological study. A skin biopsy obtained from salmon-pink erythema on the abdomen showed superficial dermal edema and a mild perivascular lymphocytic infiltrate with scattered neutrophils in the superficial dermis (hematoxylin and eosin staining, original magnification ×200)

Parvovirus B19, coxsackievirus B6, cytomegalovirus, and EBV have been shown to cause GSS.[34] In our case, the serum level of neutralizing antibody titer for coxsackievirus A4 was examined on day 21 and it was not examined in acute phase. Because GSS caused by coxsackievirus A4 had never been reported, we could not think of measurement of the titer in the acute phase. SRL, Inc., a laboratory testing company, estimated the frequency of the titer of 1:1024> to be about 0.7% among 2080 cases in one year. In our case, the titer of 1:4096 meant extremely high and rare. Further, the patient was perfectly healthy before the clinical symptoms appeared. Therefore, the result of the titer was considered current infection. This case illustrates the importance of medical practitioners being aware of the fact that coxsackievirus A4 infection may cause GSS.