First described in 1971 by George Wells, Wells syndrome (or eosinophilic cellulitis) is an uncommon, recurrent inflammatory dermatosis of unknown etiology. Clinically, individual lesions resemble cellulitis, and “flame figures” with a diffuse eosinophilic infiltrate are seen histologically.

Wells syndrome appears to be a hypersensitivity reaction to a variety of triggers. Myeloproliferative disorders including chronic myeloid leukemia,^1,2 chronic eosinophilic leukemia,³ and mantle zone lymphoma⁴ have been associated with Wells syndrome. Other associated malignancies, such as gastric cancer,⁵ adenocarcinoma of the lung,⁶ renal cell carcinoma,⁷ and colon carcinoma,⁸ have also been reported. A variety of other inciting agents have been associated with Wells syndrome, including infections, infestations, arthropod bites, and medications. Reported inciting medications include etanercept,⁹ adalimumab,¹⁰ vaccines,^11,12,13 and hydrochlorothiazide.¹⁴

The exact pathogenesis of Wells syndrome is unclear, but there is evidence that cytokines such as interleukins 2 and 5 (IL-2 and IL-5) expressed by T cells prime eosinophils for degranulation.^15,16,17 T-cell sensitivity to mosquito salivary gland extract has been shown in some patients with Wells syndrome.¹⁸

Wells syndrome classically presents with sudden onset of pruritic, erythematous, edematous papules, and plaques that rapidly evolve over days (Fig. 59-1). Seven clinical variants have been described: plaque-type, annular granuloma-like, urticaria-like, papulovesicular, bullous, papulonodular, and fixed drug eruption–like.¹⁹ Children most commonly present with the classic plaque-like lesions, whereas adults more commonly present with annular granuloma-like lesions.¹⁹ Itching or burning can precede the appearance of lesions. The extremities are more commonly affected, though the trunk and face can also be involved. Lesions resolve within weeks, leaving hyperpigmentation and atrophy. Recurrence is common. The disease tends to wax and wane over years before resolving. Systemic findings such as fever, malaise, lymphadenopathy, and arthralgias can be seen.

An elevated white blood cell count with peripheral eosinophilia is frequently seen, especially during the active phases of the disease, but can be normal during quiescent periods. An elevated erythrocyte sedimentation rate can be seen with acute flares.

The histopathology of Wells syndrome will vary by the stage of the lesion. A constant feature over the acute and subacute stages is the presence of eosinophils. There is generally an intense infiltrate of eosinophils which are present in the superficial and deep dermis. Extension of eosinophils into the subcutaneous fat is possible, as well as the fascia and skeletal muscle.²⁰ The eosinophils are often placed in a perivascular distribution, with involvement of the interstitial dermis as well. The eosinophils can form a band in the upper dermis, or be focused in the deeper dermis.²⁰ In addition to eosinophils, other mixed inflammation including histiocytes and lymphocytes can also be present. The epidermis can show variable changes, ranging from minimal change to the development of intraepidermal spongiotic vesicles (Figs. 59-2 and 59-3).