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