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Wells Syndrome

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD  more...
Updated: Jun 02, 2016


In 1971, George Wells first described this syndrome as a recurrent granulomatous dermatitis with eosinophilia.[1] Wells and Smith renamed it eosinophilic cellulitis in 1979.[2]

Wells syndrome (eosinophilic cellulitis) is an uncommon condition of unknown etiology. The presentation usually involves a mildly pruritic or tender cellulitis-like eruption with typical histologic features characterized by edema, flame figures, and a marked infiltrate of eosinophils in the dermis.[3] Papular and nodular eruptions at the clinical presentation have also been reported.[4, 5] The condition can recur and may be preceded by a pruritic papular eruption. Although Wells syndrome is usually sporadic, some familial cases have been reported.

One study showed the successive occurrence of vasculitis, Wells syndrome, and Sweet syndrome in a patient. This finding suggests that there is an overlap between these diseases.[6] Another report describes a dominant syndrome consisting of eosinophilic cellulitis, mental retardation, and abnormal body habitus in one family.[7]



At least some cases of Wells syndrome (eosinophilic cellulitis) may represent 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 Wells syndrome.[8] 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.

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.[9] In one study, immunophenotyping of peripheral T cells revealed an increased proportion of CD3+ and CD4+ T cells.[10] These lymphocytes spontaneously release significant amounts of interleukin 5 (IL-5); this finding suggests 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.[11]

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 flame figures.



The etiology of Wells syndrome (eosinophilic cellulitis) is unknown. Wells syndrome may be due to drugs, various infections, and, possibly, nonhematologic malignancies as trigger events.[12, 13] Medications linked include antibiotics, anticholinergic agents, anaesthetics, nonsteroidal anti-inflammatory agents, thyroid medications, chemotherapeutic agents, thiomersal-containing vaccinations, antitumor necrosis factor agents, and thiazide diuretics.[14] Vaccines implicated include hepatitis B vaccine, influenza vaccine, tetanus vaccine, tetanus-diphtheria vaccine, and triple-antigen vaccine.[15, 16]

Wells syndrome is usually sporadic, but some familial cases have been described. Suggested precipitating factors include the following:

  • Arthropod bites and stings, including those of the honeybee [17]
  • Cutaneous viral infections; there is a possible link between parvoviral infection and Wells syndrome [18]
  • Cutaneous parasitic infestations, including toxocariasis, [19, 20] ascariasis, [21] and onchocerciasis [22]
  • Leukemia
  • Myeloproliferative disorders
  • Atopic dermatitis
  • Fungal infections
  • Giardiasis [23]
  • Hypersensitivity reactions to medications or metals, including metallic alloy implants [24]
  • Churg-Strauss syndrome: This syndrome has been associated in a few patients [25] ; these reports are noteworthy for the presence of bullae and of antineutrophil cytoplasmic antibodies [26] ; only a few other autoimmune diseases have been associated, including a case report of systemic lupus erythematosus [27] ; sometimes, differentiating between these disorders can be challenging [28] Both Wells syndrome and Churg-Strauss syndrome may have eosinophils and flame figures. It has been postulated that Wells syndrome could represent the initiation of a pathogenetic process fully developed as Churg-Strauss syndrome. [29]


Wells syndrome (eosinophilic cellulitis) is rare. Only about 80 cases have been reported worldwide.

Wells syndrome usually affects adults, but it has been known to occur in children.[30, 31, 32, 33] In one case series of 19 patients, the classic plaque-type presentation was the most common variant found in children, whereas the annular granuloma–like variant was the most common variant in adults.[34]



The prognosis for patients with Wells syndrome (eosinophilic cellulitis) is excellent. It tends to resolve in weeks or months, usually without scarring. It occasionally recurs. In these recurrent cases, it can take years to ultimately resolve.

Contributor Information and Disclosures

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.


Justin Brown, MD Dermatologist, The Dermatology Group

Justin Brown, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society for MOHS Surgery, Sigma Xi

Disclosure: Received honoraria from Medicis for review panel membership; Received honoraria from Triax for review panel membership.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.


David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Rosalie Elenitsas, MD Herman Beerman Associate Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System

Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology and American Society of Dermatopathology

Disclosure: Lippincott Williams Wilkins Royalty Textbook editor; DLA Piper Consulting fee Consulting

Takeji Nishikawa, MD Emeritus Professor, Department of Dermatology, Keio University School of Medicine; Director, Samoncho Dermatology Clinic; Managing Director, The Waksman Foundation of Japan Inc

Disclosure: Nothing to disclose.

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