Approach Considerations

Wells Syndrome (eosinophilic cellulitis) is usually diagnosed on the basis of the characteristic histopathologic findings in a skin biopsy specimen.

Peripheral blood and bone marrow eosinophilia are usually present. In peripheral blood, an increase in eosinophil cation protein (ECP) and IL-5 levels can be detected. The levels of ECP and IL-5 seem to be correlated with the severity of the disease.

Histologic Findings

Skin biopsy specimens of Wells Syndrome (eosinophilic cellulitis) show a dermal infiltrate of eosinophils, histiocytes, and eosinophil debris between collagen bundles that forms flame figures. During the acute early phase, the dense infiltrate of degranulating eosinophils is usually located in the epidermis and the dermis, although it occasionally extends into the subcutaneous tissue and the underlying muscle.^{[49, 50, 51]} See the images below.

A superficial and deep perivascular and interstitial inflammatory pattern. Courtesy of DermNet New Zealand (https://www.dermnetnz.org/assets/Uploads/pathology/t/wellsfigure2.jpg).

View Media Gallery

Superficial and deep perivascular and interstitial inflammatory pattern extending into the subcutaneous tissue. Courtesy of DermNet New Zealand (https://www.dermnetnz.org/assets/Uploads/pathology/t/wellsfigure3.jpg).

View Media Gallery

Vesiculation can occur. The blisters contain eosinophils and are predominantly subepidermal and, occasionally, multiloculated and spongiotic. The location of the infiltrate is correlated with the different clinical features.

After weeks, the flame figures are seen, along with a palisade of histiocytes and giant cells around some collagen fibers. With immunofluorescent stains, eosinophil major basic protein is identified in the granules of the flame figures.^[52]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.

Although the histopathologic findings of eosinophilia, histiocytes, and flame figures are characteristic of Wells syndrome, they are also found in other conditions, including bullous pemphigoid, eczema, tinea infection, dermatitis herpetiformis, scabies, and insect bites.^{[53, 54]}

Treatment & Management

Wells GC. Recurrent granulomatous dermatitis with eosinophilia. Trans St Johns Hosp Dermatol Soc. 1971. 57(1):46-56. [QxMD MEDLINE Link].
Wells GC, Smith NP. Eosinophilic cellulitis. Br J Dermatol. 1979 Jan. 100(1):101-9. [QxMD MEDLINE Link].
Brehmer-Andersson E, Kaaman T, Skog E, Frithz A. The histopathogenesis of the flame figure in Wells' syndrome based on five cases. Acta Derm Venereol. 1986. 66(3):213-9. [QxMD MEDLINE Link].
Ghislain PD, Van Eeckhout P. Eosinophilic cellulitis of papulonodular presentation (Wells' syndrome). J Eur Acad Dermatol Venereol. 2005 Mar. 19(2):226-7. [QxMD MEDLINE Link].
Holme SA, McHenry P. Nodular presentation of eosinophilic cellulitis (Wells' syndrome). Clin Exp Dermatol. 2001 Nov. 26(8):677-9. [QxMD MEDLINE Link].
Consigny S, Courville P, Young P, et al. [Histological and clinical forms of the eosinophilic cellulitis]. Ann Dermatol Venereol. 2001 Mar. 128(3 Pt 1):213-6. [QxMD MEDLINE Link].
Davis MD, Brown AC, Blackston RD, et al. Familial eosinophilic cellulitis, dysmorphic habitus, and mental retardation. J Am Acad Dermatol. 1998 Jun. 38(6 Pt 1):919-28. [QxMD MEDLINE Link].
Koga C, Sugita K, Kabashima K, Matsuoka H, Nakamura M, Tokura Y. High responses of peripheral lymphocytes to mosquito salivary gland extracts in patients with Wells syndrome. J Am Acad Dermatol. 2010 Jul. 63(1):160-1. [QxMD MEDLINE Link].
Tatsuno K, Fujiyama T, Matsuoka H, Shimauchi T, Ito T, Tokura Y. Clinical categories of exaggerated skin reactions to mosquito bites and their pathophysiology. J Dermatol Sci. 2016 Jun. 82 (3):145-52. [QxMD MEDLINE Link].
Plotz SG, Abeck D, Behrendt H, Simon HU, Ring J. [Eosinophilic cellulitis (Wells syndrome)]. Hautarzt. 2000 Mar. 51(3):182-6. [QxMD MEDLINE Link].
Espana A, Sanz ML, Sola J, Gil P. Wells' syndrome (eosinophilic cellulitis): correlation between clinical activity, eosinophil levels, eosinophil cation protein and interleukin-5. Br J Dermatol. 1999 Jan. 140(1):127-30. [QxMD MEDLINE Link].
Kaufmann D, Pichler W, Beer JH. Severe episode of high fever with rash, lymphadenopathy, neutropenia, and eosinophilia after minocycline therapy for acne. Arch Intern Med. 1994 Sep 12. 154(17):1983-4. [QxMD MEDLINE Link].
Hirsch K, Ludwig RJ, Wolter M, et al. Eosinophilic cellulitis (Wells' syndrome) associated with colon carcinoma. J Dtsch Dermatol Ges. 2005 Jul. 3(7):530-1. [QxMD MEDLINE Link].
Heelan K, Ryan JF, Shear NH, Egan CA. Wells syndrome (eosinophilic cellulitis): Proposed diagnostic criteria and a literature review of the drug-induced variant. J Dermatol Case Rep. 2013. 7(4):113-20. [QxMD MEDLINE Link]. [Full Text].
Fournier C, Auger I, Houle MC. Wells syndrome (eosinophilic cellulitis) following vaccination: Two pediatric cases with positive patch test to aluminium salts. Contact Dermatitis. 2020 Feb 7. [QxMD MEDLINE Link].
Simpson JK, Patalay R, Francis N, Roberts N. Influenza Vaccination as a Novel Trigger of Wells Syndrome in a Child. Pediatr Dermatol. 2015 Apr 20. [QxMD MEDLINE Link].
Brun J, Chiaverini C, Bessis D, Bourrat E, Lasek-Duriez A, Hadj-Rabia S, et al. [Wells Syndrome in children and atopy: Retrospective study of 11 cases and review of the literature]. Ann Dermatol Venereol. 2015 Apr 3. [QxMD MEDLINE Link].
Lin HL, Lin JN, Chen CW, Kuo LC, Lee WC. Eosinophilic cellulitis after honeybee sting. J Formos Med Assoc. 2009 Dec. 108(12):964-6. [QxMD MEDLINE Link].
Cherng E, McClung AA, Rosenthal HM, Hicks J, Levy ML. Wells' Syndrome Associated with Parvovirus in a 5-Year Old Boy. Pediatr Dermatol. 2011 Dec 9. [QxMD MEDLINE Link].
Hurni MA, Gerbig AW, Braathen LR, Hunziker T. Toxocariasis and Wells' syndrome: a causal relationship?. Dermatology. 1997. 195(4):325-8. [QxMD MEDLINE Link].
Bassukas ID, Gaitanis G, Zioga A, Boboyianni C, Stergiopoulou C. Febrile "migrating" eosinophilic cellulitis with hepatosplenomegaly: adult toxocariasis - a case report. Cases J. 2008 Nov 28. 1(1):356. [QxMD MEDLINE Link].
Tsuda S, Tanaka K, Miyasato M, Nakama T, Sasai Y. Eosinophilic cellulitis (Wells' syndrome) associated with ascariasis. Acta Derm Venereol. 1994 Jul. 74(4):292-4. [QxMD MEDLINE Link].
van den Hoogenband HM. Eosinophilic cellulitis as a result of onchocerciasis. Clin Exp Dermatol. 1983 Jul. 8(4):405-8. [QxMD MEDLINE Link].
Omigawa C, Namiki T, Ueno M, Ugajin T, Miura K, Yokozeki H. Case of Wells' syndrome: A rare association with the clinical course of chronic lymphocytic leukemia. J Dermatol. 2019 Feb. 46 (2):e57-e59. [QxMD MEDLINE Link].
Aslam A, Salman W, Chaudhry IH, Coulson IH, Owen CM. Bullous eosinophilic cellulitis associated with giardiasis. Clin Exp Dermatol. 2013 Jul 23. [QxMD MEDLINE Link].
Zhu L, Hu D, Wang Q, Hou J, Li M. Diffuse polymorphic eosinophilic cellulitis in a patient with metallic alloy implants: a possible association?. Int J Dermatol. 2011 Dec. 50(12):1535-7. [QxMD MEDLINE Link].
Lee SH, Roh MR, Jee H, Chung KY, Jung JY. Wells' syndrome associated with churg-strauss syndrome. Ann Dermatol. 2011 Nov. 23(4):497-500. [QxMD MEDLINE Link]. [Full Text].
Fujimoto N, Wakabayashi M, Kato T, Nishio C, Tanaka T. Wells syndrome associated with Churg–Strauss syndrome. Clin Exp Dermatol. 2011 Jan. 36(1):46-8. [QxMD MEDLINE Link].
Yin G, Xie Q. Systemic lupus erythematosus associated with Wells' syndrome. Rheumatol Int. 2011 Feb 22. [QxMD MEDLINE Link].
Omiya W, Fujita Y, Baba K, Shibaki A, Odani T, Shimizu H. Unusual cutaneous manifestations of Churg-Strauss syndrome mimicking Wells' syndrome. Eur J Dermatol. 2012 Jun 15. [QxMD MEDLINE Link].
Ratzinger G, Zankl J, Zelger B. Wells syndrome and its relationship to Churg-Strauss syndrome. Int J Dermatol. 2013 Aug. 52(8):949-54. [QxMD MEDLINE Link].
Anderson CR, Jenkins D, Tron V, Prendiville JS. Wells' syndrome in childhood: case report and review of the literature. J Am Acad Dermatol. 1995 Nov. 33(5 Pt 2):857-64. [QxMD MEDLINE Link].
Nielsen T, Schmidt H, Sogaard H. Eosinophilic cellulitis. (Well's syndrome) in a child. Arch Dermatol. 1981 Jul. 117(7):427-9. [QxMD MEDLINE Link].
Shams M, Hudgens J, Lesher JL Jr, Florentino F. Wells' syndrome presenting as a noninfectious bullous cellulitis in a child. Pediatr Dermatol. 2012 Mar. 29(2):224-6. [QxMD MEDLINE Link].
Powell JG, Ramsdell A, Rothman IL. Eosinophilic cellulitis (Wells syndrome) in a pediatric patient: a case report and review of the literature. Cutis. 2012 Apr. 89(4):191-4. [QxMD MEDLINE Link].
Caputo R, Marzano AV, Vezzoli P, Lunardon L. Wells syndrome in adults and children: a report of 19 cases. Arch Dermatol. 2006 Sep. 142(9):1157-61. [QxMD MEDLINE Link].
Spinelli M, Frigerio E, Cozzi A, Garutti C, Garavaglia MC, Altomare G. Bullous Wells' syndrome associated with non-Hodgkin's lymphocytic lymphoma. Acta Derm Venereol. 2008. 88(5):530-1. [QxMD MEDLINE Link].
Odia SG, Purschel W, Worret WI, Rakoski J. Hypereosinophilic cellulitis(Wells' syndrome) resembling urticaria. Acta Derm Venerol (Ljubljana). 1994. 6:193-195.
Mutasim DF, Cooper CH. A case of Wells' syndrome in a patient with lymphocytic lymphoma. Geriatr Dermatol. 1996. 4(1):11-14.
Pessach I, Petevi K, Gkirkas K, Stamouli M, Constantinou P, Rontogianni D, et al. Wells' syndrome with a clinicopathological correlation associated with mantle-cell lymphoma. Leuk Lymphoma. 2016 Mar 21. 1-3. [QxMD MEDLINE Link].
Kettani F, Baline K, Hali F, Azzouzi S, Chiheb S. [Wells syndrome misdiagnosed as bacterial cellulitis]. Rev Med Interne. 2020 Feb 20. [QxMD MEDLINE Link].
Falagas ME, Vergidis PI. Narrative review: diseases that masquerade as infectious cellulitis. Ann Intern Med. 2005 Jan 4. 142(1):47-55. [QxMD MEDLINE Link].
Gallard C, Law-Ping-Man S, Darrieux L, Tisseau L, Safa G. [Wells syndrome mimicking facial cellulitis: Three cases]. Ann Dermatol Venereol. 2017 Apr. 144 (4):284-289. [QxMD MEDLINE Link].
Belfeki N, Gharbi E, Flateau C, Diamantis S. Erysipelas-like presentation of Wells' syndrome (eosinophilic cellulitis). Reumatismo. 2020 Jan 28. 71 (4):226-229. [QxMD MEDLINE Link].
Martin C, Debarbieux S, Rozieres A, Hilger C, Berard F. Wells' syndrome-like reaction following Argas reflexus bites. Eur J Dermatol. 2018 Feb 5. [QxMD MEDLINE Link].
Govoni M, Colina M, Cavazzini L, Trotta F. Churg-Strauss syndrome and Wells syndrome: coincidence or pathogenetic association? A new case report. Clin Exp Rheumatol. 2007 Jan-Feb. 25 (1 Suppl 44):S41. [QxMD MEDLINE Link].
Benzaquen M, Brajon D, Delord M, Yin N, Bittar F, Toga I, et al. Cutaneous and pulmonary dirofilariasis due to Dirofilaria repens. Br J Dermatol. 2015 Apr 27. [QxMD MEDLINE Link].
Rajagopal Srinivasan V, Singh S, Bharti JN, Vedant D. Terbinafine-induced DRESS syndrome mimicking eosinophilic cellulitis. J Eur Acad Dermatol Venereol. 2021 Feb. 35 (2):e145-e147. [QxMD MEDLINE Link].
Leiferman KM, Peters MS. Reflections on eosinophils and flame figures: where there's smoke there's not necessarily Wells syndrome. Arch Dermatol. 2006 Sep. 142(9):1215-8. [QxMD MEDLINE Link].
Moossavi M, Mehregan DR. Wells' syndrome: a clinical and histopathologic review of seven cases. Int J Dermatol. 2003 Jan. 42(1):62-7. [QxMD MEDLINE Link].
Stern JB, Sobel HJ, Rotchford JP. Wells' syndrome: is there collagen damage in the flame figures?. J Cutan Pathol. 1984 Dec. 11(6):501-5. [QxMD MEDLINE Link].
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 Aug. 109(2):141-8. [QxMD MEDLINE Link].
Aberer W, Konrad K, Wolff K. Wells' syndrome is a distinctive disease entity and not a histologic diagnosis. J Am Acad Dermatol. 1988 Jan. 18(1 Pt 1):105-14. [QxMD MEDLINE Link].
Haddad F, Helm TN. Wells syndrome. Cutis. 2014 Jan. 93(1):17, 38-9. [QxMD MEDLINE Link].
Herr H, Koh JK. Eosinophilic cellulitis (Wells' syndrome) successfully treated with low-dose cyclosporine. J Korean Med Sci. 2001 Oct. 16(5):664-8. [QxMD MEDLINE Link].
Church MK, Maurer M, Simons FE, et al. Risk of first-generation H(1)-antihistamines: a GA(2)LEN position paper. Allergy. 2010 Apr. 65(4):459-66. [QxMD MEDLINE Link].
Räßler F, Lukács J, Elsner P. Treatment of eosinophilic cellulitis (Wells syndrome) - a systematic review. J Eur Acad Dermatol Venereol. 2016 Sep. 30 (9):1465-79. [QxMD MEDLINE Link].
Brown J, Schwartz RA. Wells' syndrome (eosinophilic cellulitis). Cesko-Slovenska Dermatol. 2002. 77:261-263.

Media Gallery

A superficial and deep perivascular and interstitial inflammatory pattern. Courtesy of DermNet New Zealand (https://www.dermnetnz.org/assets/Uploads/pathology/t/wellsfigure2.jpg).
Superficial and deep perivascular and interstitial inflammatory pattern extending into the subcutaneous tissue. Courtesy of DermNet New Zealand (https://www.dermnetnz.org/assets/Uploads/pathology/t/wellsfigure3.jpg).

of 2

Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Coauthor(s)

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, The Scientific Research Honor Society

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.

Acknowledgements

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.

Wells Syndrome Workup

Approach Considerations

Histologic Findings

References

Tables

Contributor Information and Disclosures

What would you like to print?