Background
Wells syndrome (eosinophilic cellulitis) is an uncommon condition of unknown etiology. In 1971, George Wells first described this syndrome as a recurrent granulomatous dermatitis with eosinophilia. [1] In 1979, he and Neil Smith renamed it eosinophilic cellulitis.
The presentation of Wells syndrome usually involves a mildly pruritic or tender cellulitislike eruption with typical histologic features characterized by edema, flame figures, and a marked infiltrate of eosinophils in the dermis. [2] Papular and nodular eruptions at the clinical presentation have also been reported. The condition can recur and may be preceded by a pruritic papular eruption. Although the syndrome is usually sporadic, some familial cases have been reported.
In a small retrospective study (N = 9), vasculitis, Wells syndrome, and Sweet syndrome occurred in succession in one patient, suggests that these diseases may overlap each other. [3] Another report described a dominant syndrome consisting of eosinophilic cellulitis, intellectual disability, and abnormal body habitus in one family. [4]
Of the numerous treatment options available for Wells syndrome, [5] systemic corticosteroids are the most effective, though they carry a risk of corticosteroid dependence. Other options include topical corticosteroids, calcineurin inhibitors, griseofulvin, H1-receptor antagonists, cyclosporine, and dapsone.
Pathophysiology
At least some cases of Wells syndrome may involve hypersensitivity to an arthropod bite or sting. An impressive response of peripheral lymphocytes to mosquito salivary gland extracts has been documented in some patients with this syndrome. [6] A dermal infiltrate of histiocytes, eosinophils, and eosinophilic granules occurs between collagen bundles, which forms the classic flame figures. The eosinophilic infiltrate is almost always restricted to the epidermis and the dermis, but it has also been found in the subcutaneous tissue and the underlying muscle. The location of the infiltrate is correlated with the different clinical features.
Type 2 T helper cell (Th2)-skewing immune dysregulation may be evident, as may a strong CD4+ T-cell proliferation in response to mosquito salivary gland extracts, probably reflecting a significant association between Wells syndrome and mosquito bites in some patients. [7] In one study, immunophenotyping of peripheral T cells revealed an increased proportion of CD3+ and CD4+ T cells. [8] These lymphocytes spontaneously release significant amounts of interleukin (IL)-5, suggesting that activated T cells may be involved in the pathogenesis of blood and tissue eosinophilia. The eosinophils then degranulate in the dermis, causing edema and inflammation. [9]
With immunofluorescent stains, eosinophil major basic protein is identified in the granules of the flame figures. On electron microscopy, the collagen fibers are intact; this finding suggests that an initial degeneration of collagen is not a factor in initiating the formation of the flame figures.
Etiology
The etiology of Wells syndrome is unknown. Drugs, various infections, and, possibly, nonhematologic malignancies may act as as trigger events. [10, 11] Medications linked include antibiotics, anticholinergic agents, anesthetics, nonsteroidal anti-inflammatory drugs (NSAIDs), thyroid medications, chemotherapeutic agents, thiomersal-containing vaccinations, anti–tumor necrosis factor (TNF) agents, and thiazide diuretics. [12, 13] Vaccines implicated include hepatitis B vaccine, influenza vaccine, tetanus vaccine, tetanus-diphtheria vaccine, human papillomavirus (HPV) vaccine, and triple-antigen vaccine. [14, 13, 15, 16]
Although some familial cases have been described, eosinophilic cellulitis is usually sporadic. Suggested precipitating factors include the following:
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Arthropod bites and stings, including those of the honeybee [17]
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Cutaneous viral infections - There may be a link between parvoviral infection and Wells syndrome [18]
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Leukemia [23]
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Myeloproliferative disorders
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Atopic dermatitis
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Fungal infections
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Giardiasis [24]
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Hypersensitivity reactions to medications or metals, including metallic alloy implants [25]
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Churg-Strauss syndrome - This association has been noted in a few patients [26] ; the reports are noteworthy for the presence of bullae and antineutrophil cytoplasmic antibodies [27] ; only a few other autoimmune diseases have been associated with Wells syndrome, including a case report of systemic lupus erythematosus (SLE) [28]
Differentiating Wells syndrome from Churg-Strauss syndrome can be challenging. [29] Both syndromes may be characterized by eosinophils and flame figures. It has been postulated that Wells syndrome might represent the initiation of a pathogenetic process that is fully developed as Churg-Strauss syndrome. [30] Thus, the two syndromes may occur together or appear to do so, possibly in association with the hypereosinophilic syndrome. [31]
Epidemiology
Wells syndrome is rare, with only a couple of hundred reported cases in the literature. [1]
Wells syndrome usually affects adults but has been known to occur in children. [32, 33, 34] In one case series of 19 patients, the classic plaque-type presentation was the most common variant in children, whereas the annular granuloma–like variant was the most common variant in adults. [35]
Prognosis
The prognosis for patients with Wells syndrome is excellent. The condition tends to resolve in weeks or months, usually without scarring; however, it occasionally recurs, and in these recurrent cases, it can take years to resolve.
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Superficial and deep perivascular and interstitial inflammatory pattern. Image from DermNet New Zealand (https://www.dermnetnz.org/assets/Uploads/pathology/t/wellsfigure2.jpg).
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Superficial and deep perivascular and interstitial inflammatory pattern extending into subcutaneous tissue. Image from DermNet New Zealand (https://www.dermnetnz.org/assets/Uploads/pathology/t/wellsfigure3.jpg).
Tables
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