SHORT COMMUNICATION
791 Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV
Wells’ Syndrome Associated with Coxsackievirus A6 Infection
Yuta YOSHII, Takahiro ISHIKAWA, Takichi MUNETSUGU, Aya NISHIZAWA, Norihiro FUJIMOTO and Takahiro SATOH * Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Japan. * E-mail: tasaderm @ ndmc. ac. jp Accepted Jun 5, 2018; Epub ahead of print Jun 8, 2018
Wells’ syndrome, also known as eosinophilic cellulitis, is a skin disease originally described as erythematous indurated plaques resembling bacterial cellulitis characterized by tissue eosinophilia and so-called“ flame figures”( 1). Pathological aetiologies have yet to be clarified, but insect bites, parasitic infections, and drugs have been implicated as trigger factors( 2 – 6). Viral agents, such as human parvovirus B19, herpes simplex virus, and even influenza virus vaccination, have also been reported to trigger Wells’ syndrome( 7 – 9).
CASE REPORT
A 45-year-old man presented with a 5-day history of fever( 38 ° C) and erythema of the extremities. Physical examination demonstrated various-sized erythematous lesions on his swollen hands and feet( Fig. 1A). Vesicle and bulla formation was observed on the dorsal aspects of his hands and feet. He also had urticarial erythema on the upper arms and trunk( Fig. 1B). No oral lesions or cervical lymphadenopathy were detected. Laboratory findings demonstrated blood neutrophilia( 11,220 / μl) and increased C- reactive protein( 12.0 mg / dl; normal: < 0.3 mg / dl). Histopathological examination of an upper arm erythematous lesion on day 6 showed relatively moderate levels of cellular infiltrate, comprising lymphocytes and eosinophils in the entire dermis with dilated capillaries. In the ery thematous vesicular lesions, marked oedema in the papillary dermis and intra-epidermal vesicle formation were observed( Fig. 1C – E), in addition to dermal cellular infiltrates. No reticular or ballooning degeneration of keratinocytes was found. Within 10 days, the fever, erythema and vesicles / bullae had partially resolved, but swelling of the dorsal aspects of the hands persisted with severe pruritus( Fig. 2A). In addition, the patient had marked blood eosinophilia, up to 14,945 / μl. A second biopsy specimen of the dorsum of the hand on day 14 showed a dense cellular infiltrate in the entire dermis and subcutaneous tissues, consisting of many eosinophils( Fig. 2B). Small foci of“ flame figures” were also observed( Fig. 2C). The FIP1L1-PDGFRA fusion gene was negative. The patient was treated with oral prednisolone( 40 mg / day), resulting in a dramatic improvement in the skin manifestations and blood eosinophilia. No recurrence has been observed. Investigations for viral titres demonstrated an increase in anti-coxsackievirus A6( from × 8 up to × 128 within 2 weeks)( Fig. 2D). There were no significant changes in titres suggestive of other infectious agents, such as cytomegalovirus( CMV), Epstein-Barr virus( EBV), herpes simplex virus( HSV), adenovirus, human parvovirus B19, or Mycoplasma pneumoniae.
DISCUSSION
Fig. 1. Clinical and histopathological features of initial skin lesions on day 6.( A) Dorsal aspects of the hands are swollen with erythema and vesicles / bullae.( B) Urticarial erythema on the upper arms.( C) A weak or moderate cellular infiltrate and oedema are observed in the entire dermis( original magnification × 40).( D) Intraepidermal vesicles and marked oedema in the papillary dermis( original magnification × 40).( E) Lymphocytes and eosinophils around deep dermal vessels and eccrine glands( original magnification × 400).
This case showed bilateral erythematous swelling of the hands with pruritus or a burning sensation, which was histopathologically characterized by marked tissue eosinophilia in the entire dermis and subcutaneous tissues with flame figures. The patient also had severe blood eosinophilia. These manifestations appeared to be triggered by coxsackievirus A6 infection. The differential diagnosis should include the non-episodic type of angioedema with eosinophilia. We preferred to diagnose this patient with Wells’ syndrome because of the marked dermal tissue eosinophilia with flame figures. However, the present case may lie somewhere on the continuum between these 2 diseases.
One of the unusual features of the present case was that the initial symptoms on day 6, such as the vesicular erythema of the hands / feet and urticarial erythema on the trunk( Fig. 1), were not necessarily accompanied by marked tissue eosinophilia. In this stage, he showed blood neutrophilia, but not eosinophilia. Thus, whether these initial symptoms can be regarded as an early stage of Wells’ syndrome is unclear. One may assume that these were atypical forms of hand-foot-mouth disease or erythema exudativum multiforme associated with coxsackievirus A6 infection, as coxsackievirus A6 has recently been repor-
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2018 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2985 Acta Derm Venereol 2018; 98: 791 – 792