Dermatologic Manifestations of Eosinophilic Fasciitis: Background, Pathophysiology, Epidemiology (original) (raw)

Background

Eosinophilic fasciitis is an idiopathic, fibrotic disorder with the histopathologic hallmark of fascial fibrosis. The presentation of eosinophilic fasciitis is acute with painful, swollen extremities progressing to disabling cutaneous fibrosis. Joint contractures, arthritis, neuropathy, and myositis may be associated with eosinophilic fasciitis. Many authors consider eosinophilic fasciitis to be a variant of morphea; others consider it a distinct entity.

eMedicine Logo

Pathophysiology

The etiology of eosinophilic fasciitis is unknown, but aberrant immune responses may play a role because hypergammaglobulinemia and antinuclear antibodies are associated. In addition, toxic, environmental, or drug exposures have been implicated in causing eosinophilic fasciitis. A 2006 case report implicated atorvastatin in a temporal relationship as the cause of a patient's eosinophilic fasciitis. [1] Simvastatin has also been reported temporally to the onset of eosinophilic fasciitis. [2] One report described eosinophilic fasciitis in association with the immune checkpoint inhibitor cemiplimab. [3]

Reports indicate that Borrelia burgdorferi may be a possible etiologic agent in some cases of eosinophilic fasciitis. However, one report of a patient with eosinophilic fasciitis and a review of the literature of cases in which Borrelia species were implicated in the pathogenesis failed to show a relationship between eosinophilic fasciitis and Borrelia infection. Borrelia species were not identified by direct microscopic examination of tissue samples or by polymerase chain reaction amplification of tissue samples in any of these reported cases of eosinophilic fasciitis. The conclusion was that positive serology alone for Borrelia does not implicate Borrelia infection in the pathogenesis of eosinophilic fasciitis in the absence of the positive demonstration of Borrelia by histochemical stains, immunohistochemical stains, or polymerase chain reaction amplification in tissue samples. [4]

In vitro fibroblasts from involved fascia produce increased levels of mRNA for collagen types I, III, and IV compared with adjacent dermal fibroblasts. In addition, fascial fibroblasts express transforming growth factor-beta I and connective-tissue growth factor mRNA, which may account for the clinical fibrosis. Eosinophil degranulation may lead to fibroblast activation.

Further research into eosinophilic fasciitis has shown elevations of transforming growth factor-beta and interleukin 5, which normalize with corticosteroid therapy. Another study has show that the fascial inflammatory infiltrate is predominately composed of CD8+ T lymphocytes, macrophages, and fewer eosinophils, suggesting a possible cytotoxic immune reaction in response to possible infectious or environmental agents. Other studies have shown elevated serum levels of manganese superoxide dismutase and tissue inhibitor of metalloproteinase (TIMP-1). Serum TIMP-1 may also serve as a marker of disease severity. [5, 6]

One report describe of diffuse eosinophilic fasciitis developing after local radiation therapy for breast cancer, implicating radiation injury as a possible traumatic trigger for the development of eosinophilic fasciitis. [7]

An additional case report in 2010 identified a patient with a temporal and anatomic relationship with the development of localized eosinophilic fasciitis after intravenous iron infusions for correction of anemia. [8]

A 2012 case report describes of a young male with eosinophilic fasciitis, recurrent fever, a sclerotic prepuce, and urethritis. Urethral and blood cultures were positive for Mycoplasma arginini. In addition, M arginini DNA was isolated in skin biopsy specimens of sclerotic skin by polymerase chain reaction (PCR). The authors suggested that the Mycoplasma infection may have contributed to the development of the sclerotic process. [9]

A case report in 2016 discussed a male patient with the development of eosinophilic fasciitis following an intestinal parasitic infection. Treatment with antiparasitic drugs, however, did not lead to resolution of symptoms. [10]

eMedicine Logo

Epidemiology

Frequency

Eosinophilic fasciitis is uncommon.

Race

Whites are primarily affected by eosinophilic fasciitis.

Sex

Eosinophilic fasciitis occurs equally in males and females.

Age

Most eosinophilic fasciitis patients are in their third to sixth decades of life; however, cases in children have been reported.

eMedicine Logo

Prognosis

The prognosis for eosinophilic fasciitis is good. Most patients experience partial or complete recovery.

The end stage of the fibrotic process leads to substantial morbidity due to skin sclerosis and joint contractures. In addition, arthritis, neuropathies, and myositis may be present. Ten percent of cases may result in myelodysplasia, such as aplastic anemia, which portends a poor prognosis. Spontaneous resolution is possible, and treatment with corticosteroids usually results in recovery; however, skin sclerosis and joint contractures may persist.

A 2007 study reported that the risk of residual fibrosis/contractures after therapy was much higher with an age younger than 12 years at presentation, trunk involvement, associated morphealike, and dermal fibrosis in addition to the subcutaneous fat/fascial fibrosis. [11]

eMedicine Logo

  1. DeGiovanni C, Chard M, Woollons A. Eosinophilic fasciitis secondary to treatment with atorvastatin. Clin Exp Dermatol. 2006 Jan. 31(1):131-2. [QxMD MEDLINE Link].
  2. Serrano-Grau P, Mascaró-Galy JM, Iranzo P. Eosinophilic fasciitis after taking simvastatin. Actas Dermosifiliogr. 2008 Jun. 99(5):420-1. [Full Text].
  3. Boppana SH, Dulla NR, Beutler BD, Gullapalli N, Kaur R. Drug-Associated Eosinophilic Fasciitis: A Case of Eosinophilic Fasciitis Secondary to Cemiplimab Therapy. Am J Case Rep. 2021 Aug 17. 22:e932888. [QxMD MEDLINE Link].
  4. Anton E. Failure to demonstrate Borrelia burgdorferi-specific DNA in lesions of eosinophilic fasciitis. Histopathology. 2006 Jul. 49(1):88-90. [QxMD MEDLINE Link].
  5. Jinnin M, Ihn H, Yazawa N, Asano Y, Yamane K, Tamaki K. Elevated serum levels of manganese superoxide dismutase in patients with eosinophilic fasciitis. Clin Rheumatol. 2003 Dec. 22(6):505. [QxMD MEDLINE Link].
  6. Jinnin M, Ihn H, Yamane K, Asano Y, Yazawa N, Tamaki K. Serum levels of tissue inhibitor of metalloproteinase-1 and 2 in patients with eosinophilic fasciitis. Br J Dermatol. 2004 Aug. 151(2):407-12. [QxMD MEDLINE Link].
  7. Sherber NS, Wigley FM, Paget SA. Diffuse fasciitis with eosinophilia developing after local irradiation for breast cancer. Clin Rheumatol. 2009 Jun. 28(6):729-32. [QxMD MEDLINE Link].
  8. Firoz BF, Goldberg LH, Landau J, Kaye V, Berman L. Eosinophilic fasciitis secondary to intravenous iron infusions. Dermatol Online J. 2010 May 15. 16(5):5. [QxMD MEDLINE Link].
  9. Silló P, Pintér D, Ostorházi E, Mazán M, Wikonkál N, Pónyai K, et al. Eosinophilic Fasciitis associated with Mycoplasma arginini infection. J Clin Microbiol. 2012 Mar. 50(3):1113-7. [QxMD MEDLINE Link]. [Full Text].
  10. Oliveira M, Patinha F, Marinho A. Eosinophilic fasciitis after parasite infection. Reumatologia. 2016. 54 (1):38-41. [QxMD MEDLINE Link].
  11. Endo Y, Tamura A, Matsushima Y, Iwasaki T, Hasegawa M, Nagai Y. Eosinophilic fasciitis: report of two cases and a systematic review of the literature dealing with clinical variables that predict outcome. Clin Rheumatol. 2007 Sep. 26(9):1445-51. [QxMD MEDLINE Link].
  12. Kroft EB, de Jong EM, Evers AW. Physical burden of symptoms in patients with localized scleroderma and eosinophilic fasciitis. Arch Dermatol. 2008 Oct. 144(10):1394-5.
  13. Mourad AI, Lehman JS, Mydlarski PR. Groove Sign in Eosinophilic Fasciitis. Mayo Clin Proc. 2021 Aug. 96 (8):2184. [QxMD MEDLINE Link].
  14. Daniel RS, Brown AN. Case report of unilateral eosinophilic fasciitis in a Vietnamese woman. Am J Med Sci. 2009 Feb. 337(2):153-4. [QxMD MEDLINE Link].
  15. Dowden AM, Ballas ZK. Eosinophilic fasciitis masquerading as angioedema. Ann Allergy Asthma Immunol. 2009 Mar. 102(3):258-9. [QxMD MEDLINE Link].
  16. de Boysson H, Chèze S, Chapon F, Le Mauff B, Auzary C, Geffray L. Eosinophilic fasciitis with paroxysmal nocturnal hemoglobinuria. Joint Bone Spine. 2013 Mar. 80(2):208-10. [QxMD MEDLINE Link].
  17. Kitamura Y, Hatamochi A, Hamasaki Y, Ikeda H, Yamazaki S. Association between eosinophilic fasciitis and systemic lupus erythematosus. J Dermatol. 2007 Feb. 34(2):150-2. [QxMD MEDLINE Link].
  18. Khalifa M, Slim I, Ghannouchi N, et al. Eosinophilic fasciitis and toxic thyroid adenoma--a novel association. Acta Clin Belg. 2008 May-Jun. 63(3):197-9.
  19. Tahara K, Yukawa S, Shoji A, Hayashi H, Tsuboi N. Long-term remission by cyclosporine in a patient with eosinophilic fasciitis associated with primary biliary cirrhosis. Clin Rheumatol. 2008 Sep. 27(9):1199-201. [QxMD MEDLINE Link].
  20. Pardal-Fernández JM, Sáez-Méndez L, Rodríguez-Vázquez M, Godes-Medrano B, Iñíguez-De Onzoño L. [Multiple mononeuritis and eosinophilic fasciitis in a patient with idiopathic hypereosinophilic syndrome]. Rev Neurol. 2012 Jan 16. 54(2):100-4. [QxMD MEDLINE Link].
  21. Varga J, Griffin R, Newman JH, Jimenez SA. Eosinophilic fasciitis is clinically distinguishable from the eosinophilia-myalgia syndrome and is not associated with L-tryptophan use. J Rheumatol. 1991 Feb. 18(2):259-63. [QxMD MEDLINE Link].
  22. Varga J, Kahari VM. Eosinophilia-myalgia syndrome, eosinophilic fasciitis, and related fibrosing disorders. Curr Opin Rheumatol. 1997 Nov. 9(6):562-70. [QxMD MEDLINE Link].
  23. Ganta CC, Chatterjee S, Pohlman B, Hojjati M. Chronic graft-versus-host disease presenting as eosinophilic fasciitis: therapeutic challenges and an additional case. J Clin Rheumatol. 2015 Mar. 21 (2):86-94. [QxMD MEDLINE Link].
  24. Nashel J, Steen V. The use of an elevated aldolase in diagnosing and managing eosinophilic fasciitis. Clin Rheumatol. 2015 Aug. 34 (8):1481-4. [QxMD MEDLINE Link].
  25. Baumann F, Bruhlmann P, Andreisek G, Michel BA, Marincek B, Weishaupt D. MRI for diagnosis and monitoring of patients with eosinophilic fasciitis. AJR Am J Roentgenol. 2005 Jan. 184(1):169-74. [QxMD MEDLINE Link].
  26. Valencia IC, Chang A, Kirsner RS, Kerdel FA. Eosinophilic fasciitis responsive to treatment with pulsed steroids and cyclosporine. Int J Dermatol. 1999 May. 38(5):369-72. [QxMD MEDLINE Link].
  27. Romano C, Rubegni P, De Aloe G, et al. Extracorporeal photochemotherapy in the treatment of eosinophilic fasciitis. J Eur Acad Dermatol Venereol. 2003 Jan. 17(1):10-3. [QxMD MEDLINE Link].
  28. Tzaribachev N, Holzer U, Schedel J, Maier V, Klein R, Kuemmerle-Deschner J. Infliximab effective in steroid-dependent juvenile eosinophilic fasciitis. Rheumatology (Oxford). 2008 Jun. 47(6):930-2. [QxMD MEDLINE Link].
  29. Haiduc VF, Erkan D, Kirou K, Birchansky S, Park J, Danon MJ. Anti-neutrophil cytoplasmic antibody (c-ANCA) positive recurrent eosinophilic fasciitis responsive to cyclophosphamide: a clinical pathology conference held by the Division of Rheumatology at Hospital for Special Surgery. HSS J. 2008 Feb. 4(1):81-6. [QxMD MEDLINE Link]. [Full Text].
  30. Smith LC, Cox NH. Dapsone treatment for eosinophilic fasciitis. Arch Dermatol. 2008 Jul. 144(7):845-7. [QxMD MEDLINE Link].
  31. Weber HO, Schaller M, Metzler G, Röcken M, Berneburg M. Eosinophilic fasciitis and combined UVA1--retinoid--corticosteroid treatment: two case reports. Acta Derm Venereol. 2008. 88(3):304-6. [QxMD MEDLINE Link].
  32. Horacek E, Sator PG, Gschnait F. Venous furrowing': a clue to the diagnosis of eosinophilic fasciitis. A case of eosinophilic fasciitis ultimately treated with oral PUVA therapy. Dermatology. 2007. 215(1):89-90. [QxMD MEDLINE Link].
  33. Khanna D, Agrawal H, Clements PJ. Infliximab may be effective in the treatment of steroid-resistant eosinophilic fasciitis: report of three cases. Rheumatology (Oxford). 2010 Jun. 49(6):1184-8. [QxMD MEDLINE Link]. [Full Text].
  34. Hariman R, Patel P, Strouse J, Collins MP, Rosenthal A. Development of Eosinophilic Fasciitis during Infliximab Therapy for Psoriatic Arthritis. Case Rep Rheumatol. 2016. 2016:7906013. [QxMD MEDLINE Link].
  35. Pimenta S, Bernardes M, Bernardo A, Brito I, Castro L, Simões-Ventura F. Intravenous immune globulins to treat eosinophilic fasciitis: a case report. Joint Bone Spine. 2009 Oct. 76(5):572-4. [QxMD MEDLINE Link].
  36. Lebeaux D, Francès C, Barete S, Wechsler B, Dubourg O, Renoux J, et al. Eosinophilic fasciitis (Shulman disease): new insights into the therapeutic management from a series of 34 patients. Rheumatology (Oxford). 2012 Mar. 51(3):557-61. [QxMD MEDLINE Link].
  37. Manzini CU, Sebastiani M, Giuggioli D, Manfredi A, Colaci M, Cesinaro AM, et al. D-penicillamine in the treatment of eosinophilic fasciitis: case reports and review of the literature. Clin Rheumatol. 2012 Jan. 31(1):183-7. [QxMD MEDLINE Link].
  38. Espinoza F, Jorgensen C, Pers YM. Efficacy of Tocilizumab in the treatment of Eosinophilic fasciitis: Report of one case. Joint Bone Spine. 2015 Jul 7. [QxMD MEDLINE Link].
  39. Mertens JS, Zweers MC, Kievit W, Knaapen HK, Gerritsen M, Radstake TR, et al. High-Dose Intravenous Pulse Methotrexate in Patients With Eosinophilic Fasciitis. JAMA Dermatol. 2016 Nov 1. 152 (11):1262-1265. [QxMD MEDLINE Link].
  40. Oza VS, Walsh R, North J, Berger TG, Murase JE. Treatment of Eosinophilic Fasciitis With Sirolimus. JAMA Dermatol. 2016 Apr. 152 (4):488-90. [QxMD MEDLINE Link].

Author

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Emeritus Professor, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, American Contact Dermatitis Society, Association of Military Dermatologists, Association of Professors of Dermatology, American Dermatological Association, Women's Dermatologic Society, Medical Dermatology Society, Dermatology Foundation, Society for Investigative Dermatology, Washington DC Dermatological Society, Atlantic Dermatologic Society, Philadelphia Dermatological Society, Pennsylvania Academy of Dermatology, College of Physicians of Philadelphia

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier
Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

Ponciano D Cruz, Jr, MD Professor and Vice-Chair, Paul R Bergstresser Chair, Department of Dermatology, University of Texas Southwestern Medical Center

Ponciano D Cruz, Jr, MD is a member of the following medical societies: Texas Medical Association

Disclosure: Received consulting fee from RCTS for independent contractor; Received honoraria from Mary Kay Cosmetics for consulting; Received grant/research funds from Galderma for principal investigator.