Wells described the first patient in 1971 as “recurrent granulomatous dermatitis with eosinophilia.” He later renamed the disease “eosinophilic cellulitis.”[1] In 1979, Spiegel and Winkelmann proposed the eponym "Wells syndrome."

Wells syndrome has a sudden onset. In the classic form, symptomatology is marked by large well limited inflammatory erythematous and edematous patches that are often covered with vesicles or bullae. The lesions are located preferentially on the trunk and the extremities. The eruption is preceded by sensations of itching or burning. General signs are rare. A low fever can be associated with cutaneous symptoms. The evolution in the following days is marked by an extension of the patches, which take an annular configuration, with the center healing while the border becomes purple. Inflammatory signs regress within approximately 10 days while the plaques become indurated. Restitutio ad integrum usually occurs in 4 to 6 weeks. Recurrence is the rule, with variable locations. The period between recurrences varies from a few months to several years; however, the prognosis remains good with long-term recovery.

Biologically, the main element is peripheral blood eosinophilia which is found in about 50% of cases during the acute phase.

The treatment of Wells syndrome is not codified. Apart from the etiological treatment of a triggering or associated disease, corticosteroids and dapsone are the two main treatments for Wells syndrome.

Therapeutic Agents

• Corticosteroids: It is the reference treatment for all reactional dermatoses whether neutrophilic or eosinophilic. General corticotherapy reduces the duration and importance of relapses in 10% of cases.[2] Initial doses range from 0.5 to 1 mg/kg/day, with rapid tapering. During the decrease of the treatment, it is not uncommon to observe a relapse of the lesions, which can lead, in certain cases, to a real corticosteroid dependence. Local corticosteroids represent an interesting alternative to general corticosteroids, especially in superficial forms, with inconsistent results of the order of 50%.[2] However, it should not be used in deep hypodermic or extended forms.
• Dapsone: Dapsone is an interesting therapeutic alternative to corticosteroids, with doses ranging from 50 to 200 mg daily. It would reduce the duration of relapses. The optimal duration of treatment is not clearly defined but can be several months in the absence of adverse effects requiring discontinuation of treatment. It can be used alone or in combination with other treatments, including corticosteroids. It can also serve as a relay for general corticosteroids, especially in cases of corticosteroid dependence.
• Antihistamines: Antihistamines, especially hydroxyzine if pruritus, is important and maybe tried as a first intention, because of their excellent tolerance even if their effectiveness does not seem to exceed 25% of the cases.[2] They sometimes allow the practitioner to avoid the use of general steroid treatment. The dosage varies from 50 to 100 mg/day. Hydroxyzine can be combined with other antihistamines.
• Other treatments: These are all anecdotal, with their interest being reported in only a few clinical cases.[16] Colchicine, PUVA (psoralen and ultraviolet A) therapy, interferon-alpha, cyclins [17], synthetic antimalarials, ciclosporin, and anti-TNF agents can be mentioned.[18]

Therapeutic Strategy

In most cases, general corticosteroids (10 to 80 mg daily) allow rapid healing. Tapering the dose over one month is generally well tolerated. Continued low-dose therapy with corticosteroids allows preventing recurrences. Dapsone may be prescribed as first-line treatment in low inflammatory forms. It also seems to give good results in case of corticosteroids resistance [13]. IFN-alpha and IFN-beta could represent interesting alternatives.[19][20] For mild cases, topical corticosteroids may be sufficient. Finally, the treatment of an associated disease, when it is found, is essential. It must be prescribed as a first-line treatment and can cure Wells syndrome.[21]

Acute bacterial cellulitis is eliminated in front of the absence of infectious context (fever, leukocytosis) and recurrent evolution. The histopathologic findings of bacteria cellulitis can also include significant edema, but neutrophils are the predominant inflammatory cell in these infections. In rare cases, clinical and histological similarities have been described with chronic erythema migratory. Eosinophilic annular erythema is also a differential diagnosis, but this entity is considered by many to be a subset of Wells syndrome.

Wells syndrome can be easily mistaken for acute bacterial cellulitis; therefore, first-line practitioners should be well aware of this dermatosis.

Moreover, Wells syndrome can be associated with other diseases such as hematologic malignancies (chronic myeloid leukemia,[5] chronic lymphocytic leukemia, polycythemia vera, non-Hodgkin lymphoma), malignant tumors, ulcerative colitis,[6] eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome),[7] hypereosinophilic syndrome,[8] which implies cooperation with dermatologists, hematologists, oncologists, and internists to improve patient-centered care.

Furthermore, the diagnosis of Wells syndrome is mainly based on the histological study and the identification of flame-figures, but these findings are not specific to Wells syndrome and can be observed in many other skin conditions such as prurigo, eczema, arthropod bite, scabies, bullous pemphigoid, pemphigus vegetans, and eosinophilic granulomatosis with polyangiitis. Therefore, clinicopathologic conferences are highly recommended to establish the correct diagnosis.