Wells' syndrome

ARTICLE

A 29-year-old, West-Indian woman presented a two year history of widespread, pruritic urticarial lesions which developed into indurated plaques, persisting for weeks. The first eruption occurred in the West Indies. There was neither previous history of atopy, insect bites nor preceding illness. She received a systemic steroid (prednisone 0.5 mg/kg/day), that resulted in complete clearing of the lesions within fifteen days. Another flare-up occurred a few days after giving birth. A topical steroid (clobetasol) was effective this time.

She was seen in our department for the third recurrence. Her general health was good and she was apyretic. The urticarial papules had a centrifugal extension, forming annular, erythematous and indurated plaques on the arms and thighs (Fig. 1) with erythematous borders and occasional blistering (Fig. 2). Routine blood tests were within normal limits.

A biopsy specimen of an erythematous plaque revealed in the whole dermis, a diffuse infiltration of eosinophils. There were collagen bundles encrusted with eosinophilic granules characteristic of "flame figures" (Fig. 3).

Wells' syndrome

This clinico-pathological picture is consistent with Wells' syndrome. The patient received a topical steroid (clobetasol once a day for fifteen days) and the lesions gradually resolved. Treatment was progressively tapered over the next month. Then however, the eruption evolved into pigmented and infiltrated morphea-like lesions. She had no further recurrence after an eight month follow-up.

Comments

Wells' syndrome (WS) is a rare and benign disease, first described in 1971 as recurrent granulomatous dermatitis with eosinophils [1]. Its diagnosis is based on the combination of typical clinical manifestations and characteristic, but aspecific "flame figures". There is no age or sex predominance [2, 3]. WS is characterized by recurrent episodes of erythematous, oedematous swellings resembling bacterial cellulitis, but with minimal systemic disturbance. Fever may be observed. Lesions can occur anywhere on the body but the face is rarely involved [3]. After prodromal burning sensations or itching, urticarial eruption evolves to infiltrated, erythematous plaques, spreading outward rapidly within a few days. Blistering due to the oedematous swelling may be observed as in our case, and may be major, especially in childhood [4, 5]. Moreover, the distinct rosy, oedematous and violaceous border may resemble granuloma annulare [1]. A second stage is characterized by gradual centrifugal resolution of the erythema with blue-green coloration. It usually results in morphea-like lesions [2, 4], with a slowly resolving hyperpigmentation without scarring. As in our case, recurrences are common, at intervals of a few months over many years [6]. Spontaneous remission after months to several years is the rule.

Peripheral hypereosinophilia is found in over half the cases at the beginning of the eruption [6], sometimes reaching 26,000 cells/mm³ [4]. Medullar hypereosinophilia [6] may be present and total IgE may be raised [3, 7].

In the acute stage, histological examination does not reveal any cellulitis but a dense dermal infiltrate of eosinophils associated with dermal oedema [2]. In the subacute stage, eosinophils and pale histiocytes infiltrate connective tissue bundles, forming "flame figures". These consist of a central core of collagen bundles coated with eosinophilic debris [2, 3]. However, flame figures are not specific and may be observed in others conditions such as eczema, prurigo and pemphigoid [1, 2]. In the later stages, flame figures become surrounded by a palisade of large histiocytes and giant cells of the foreign body type, forming microgranulomas, without vasculitis [2].

WS must be distinguished from hypereosinophilic syndrome [1], associated with a high incidence of endocarditis and mortality, and characterized by sustained peripheral eosinophilia (at least 1,500 cells/mm³ for more than 6 months) with no aetiology. About half of these syndromes display skin manifestations such as pruritic erythematous eruptions, urticaria or angioedema. Skin biopsies show perivascular infiltrates of eosinophils [1, 2].

The pathogenesis of WS is unclear. It may correspond to a peculiar response to unspecific trigger factors such as insect bites [1, 2], varicella infection [5] or drug administration [1, 3]. Exposure to such factors may also explain recurrences. Hormonal influences may result in flares after parturition as in our case, as previously reported [8]. Moreover, allergic manifestations such as urticaria, asthma or atopic dermatitis [3] can be associated with WS.

Peripheral blood mononuclear cells and dermal infiltrating cells have been recently shown to be mostly CD4⁺CD7^­ cells expressing mRNA for IL-5 in one case. Since this cytokine is known to play a role in the development of eosinophilia, it may play a pathogenic role [7]. Eosinophils may degranulate, spreading major basic protein on collagen bundles, leading to damaged collagen and the formation of flame figures and granulomas [9].

Systemic steroids (from 0.5 to 2 mg/kg/day) are the first line treatment, resulting in rapid healing in most cases. In the case of recurrences, the prolonged use of low dose (5 mg) alternate-day prednisone may be useful [8]. Topical steroids may also be effective as was seen in our case [5]. Colchicine, grisefulvine and dapsone are not consistently effective [1, 2, 8]. PUVA therapy has been tried successfully in one case of corticoresistant, widespread WS [10]. Interferon-alpha has brought about a dose-dependent improvement of the swelling in one case [11]. Lastly, intravenous interferon gamma was effective in one case, reducing by 50% the severity of the eruption [7], but its use is debatable in a benign dermatitis.

REFERENCES

1. Wells GC, Smith NP. Eosinophilic cellulitis. Br J Dermatol 1979; 100: 101-9.

2. Aberer W, Konrad K, Wolff K. Wells' syndrome is a distinctive disease entity and not a histologic diagnosis. J Am Acad Dermatol 1988; 18: 105-14.

3. Paquet P, Laso-Dosal F, de La Brassinne M. Well's syndrome : report of two cases. Dermatology 1992; 184: 139-41.

4. Lindskov R, Illum N, Weismann K, Thomsen OF. Eosinophilic cellulitis : five cases. Acta Derm Venereol 1988; 68: 325-30.

5. Anderson CR, Jenkins D, Tron V, Prendiville JS. Wells' syndrome in childhood: case report and review of the literature. J Am Acad Dermatol 1995; 33: 857-64.

6. Horn HM, Hepburn NC, McLaren KM, Tidman MJ. Recrudescent tumorous eosinophilic cellulitis. Br J Dermatol 1995; 133: 143-4.

7. Yagi H, Tokura Y, Matsushita K, Hanaoka K, Furukawa F, Takigawa M. Wells' syndrome : a pathogenic role for circulating CD4⁺CD7^­ T cells expressing interleukine-5 mRNa. Br J Dermatol 1997; 136: 918-23.

8. Coldiron JK, Robinson JK. Low-dose alternate-day prednisone for persistent Wells' syndrome. Arch Dermatol 1989; 125: 1625-6.

9. Peters MS, Schroeter AL, Gleich GJ. Immunofluorescence identification of eosinophil granule major basic protein in the flame figures of Wells' syndrome. Br J Dermatol 1983; 109: 141-8.

10. Diridl E, Hsnigsmann H, Tanew A. Wells' syndrome responsive to PUVA therapy. Br J Dermatol 1997; 137: 479-80.

11. Husak R, Goerdt S, Orfanos CE. Interferon alfa treatment of a patient with eosinophilic cellulitis and HIV infection. N Engl J Med 1997; 337: 641-2.