Wells Syndrome in Adults and Children: A Report of 19 Cases

Background  Wells syndrome, an uncommon inflammatory dermatosis, is characterized by protean cutaneous manifestations, suggestive but not specific histopathologic findings, and usually a recurrent course. Because of its original description as a distinct entity, it has come to be regarded as an abnormal eosinophilic response to a number of causative agents.

Observations  The medical records of 19 patients (12 adults and 7 children) with Wells syndrome referred to the Institute of Dermatological Sciences from 1990 to 2005 were evaluated for the type and prevalence of skin lesions, clinical course and response to treatment, and possibly associated systemic symptoms, as well as histologic, laboratory, and immunofluorescence findings. The classic plaque-type variant proved to be the most common presentation in children but not in adults, who more frequently had the annular granuloma–like variant. Unilesional forms were found to occur more frequently in children. The course was recurrent, although slowly progressing, with a mean duration of disease of 5 years for adults and 3 years for children.

Conclusions  We emphasize the concept that the diagnosis of Wells syndrome is a clinicopathologic diagnosis. Although it should be classified within a spectrum that includes multisystem eosinophilic disorders, such as Churg-Strauss and hypereosinophilic syndromes, Wells syndrome, which has 7 variants, is a distinct cutaneous disease lacking systemic involvement.

Wells syndrome,¹ or eosinophilic cellulitis, first described by Wells in 1971 as recurrent granulomatous dermatitis with eosinophilia,² is an uncommon inflammatory dermatosis of uncertain pathogenesis characterized by clinical polymorphism, suggestive but nonspecific histopathologic traits, usually a recurrent course, and inconstant response to therapy.

We describe the clinical and histopathologic features and courses of 19 patients (12 adults and 7 children) with Wells syndrome.

The medical records of 19 patients seen in the Institute of Dermatological Sciences from 1990 to 2005 were reviewed on the basis of an established diagnosis of Wells syndrome.

Diagnostic criteria included (1) protean cutaneous manifestations that showed spontaneous resolution or response to nonaggressive treatments; (2) a recurrent course; (3) benign clinical behavior; (4) no evidence of systemic illness; (5) lack of evidence of triggering factors, including insect bites, bacterial, viral, and parasitic infections or infestations, as well as any kind of drug intake; (6) histopathologic changes of eosinophilic dermatosis, with or without granulomatous features, with possible presence of typical flame-shaped figures; (7) negative direct immunofluorescence findings; and (8) inconsistent blood eosinophilia.

The clinical features of the patients are summarized in Table 1. The onset of the disease was acute in all cases, but only 1 adult patient (case 1) presented with a fever.

The skin lesions were single or multiple, and unilesional presentation occurred much more frequently in children than in adults. We categorized 7 clinical variants (Table 2). The classic plaque-type variant proved to be the most common clinical presentation in the group of children but not in the adult group. In the adult group, erythematous annular lesions resembling annular granuloma were the most frequently recognized (Figure 1). Bullous lesions (Figure 2) were found in 2 adult patients but were not observed in children. Resolution, generally spontaneous, was complete within 4 to 6 weeks. Different skin lesions might be simultaneously present in the same patient (Figure 3), more commonly during the disease's course rather than at onset; this occurred more frequently in adults than in children. The clinical course was recurrent over several years (mean number of relapses, 4 in adults and 3 in children).

Considering the good prognosis of the disease and its tendency to resolve spontaneously, systemic corticosteroids, sometimes in association with dapsone, were necessary only in cases presenting with widespread and persistent skin lesions. Children, in whom the disease showed a more indolent course and in whom localized forms were common, usually received only topical corticosteroids.

Blood eosinophilia was found in approximately 50% of the cases; in these patients, the levels of eosinophils fluctuated with the course of the disease, returning to reference range on clinical remission. The erythrocyte sedimentation rate was markedly elevated only in 2 adult patients, paralleling the clinical activity of the disease and reverting to normal levels between attacks; these patients had particularly severe disease.

Three phases can be differentiated: acute, subacute, and regressive. The acute phase was characterized by edema of the superficial dermis and middermis with a dense eosinophilic infiltrate and without signs of vasculitis. In the subacute granulomatous phase, flame-shaped areas were observed in the dermis, consisting of eosinophils and histiocytes around amorphous depositions of collagen (Figure 4). Indeed, typical flame-shaped areas were seen in only about 50% of the cases. The regressive phase showed the gradual disappearance of eosinophils with the persistence of histiocytes and appearance of giant cells around collagen deposits, forming microgranulomas.

The concept of Wells syndrome has become somewhat blurred in the recent past because of its clinical polymorphism and suggestive, but not distinctive, histopathologic characteristics. More recently, some reports of Wells syndrome in association with rare multisystem eosinophilic disorders, such as Churg-Strauss syndrome³ and hypereosinophilic syndrome,⁴ further brought into question the existence of Wells syndrome as a distinct entity. A common pathogenesis with activated eosinophils playing a pivotal role has also been suggested for all of these forms.^3,4 We defend the view of Wells syndrome as a distinct disease, although one that represents the benign cutaneous end of a spectrum of conditions linked to the immunobiologic characteristics of eosinophils.⁵ We categorized 7 clinical variants of the disease, which possibly represent eosinophilic dermatoses different from Wells' original definition.² Thus, we propose unifying criteria to lump polymorphic cutaneous patterns under the label of Wells syndrome.

Correspondence: Ruggero Caputo, MD, Institute of Dermatological Sciences, University of Milan, Via Pace 9, 20122, Milan, Italy (ruggero.caputo@unimi.it).

Financial Disclosure: None reported.

Accepted for Publication: February 17, 2006.

Author Contributions:Study concept and design: Caputo and Marzano. Acquisition of data: Caputo, Marzano, Vezzoli, and Lunardon. Analysis and interpretation of data: Caputo and Marzano. Drafting of the manuscript: Caputo and Marzano. Critical revision of the manuscript for important intellectual content: Caputo and Marzano. Administrative, technical, and material support: Caputo, Marzano, Vezzoli, and Lunardon. Study supervision: Caputo and Marzano.