Eosinophilic Fasciitis 

  • Author: Peter M Henning, DO, MAJ, MC; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Jan 18, 2012
 

Background

Eosinophilic fasciitis (EF) is a rare, localized fibrosing disorder of the fascia. The etiology and pathophysiology are unclear.

In 1974, Shulman provided an early description of eosinophilic fasciitis as a disorder characterized by peripheral eosinophilia and fasciitis that could be differentiated from scleroderma by the distinctive pattern of skin involvement that spares the digits, involves fascia rather than dermis, and is not accompanied by Raynaud phenomenon.[1, 2, 3]

Since 1974, over 250 patients with eosinophilic fasciitis have been reported.[4] Despite this, the current understanding of the disease relies on a relatively few large case series and multiple case reports. Therefore, the understanding of key aspects of the disease continues to evolve.

The etiology of eosinophilic fasciitis remains unknown, although many possible triggers and disease associations have been suggested. Some aspects of pathophysiology have been elucidated; however, a more complete understanding has yet to develop.

The available literature has generated a broader clinical image of the condition, but fascial thickening in the setting of eosinophilia, elevated sedimentation rate, and hypergammaglobulinemia remain critical elements of the syndrome. Visceral involvement in eosinophilic fasciitis is generally absent, a finding that helps differentiate eosinophilic fasciitis from systemic sclerosis and other differential considerations. However, an association with several hematologic diseases is recognized and frequently carries a grave prognosis.

The diagnosis of eosinophilic fasciitis is suspected in a patient presenting with characteristic skin changes and consistent laboratory findings. It is confirmed with full-thickness biopsy or characteristic MRI findings.

Eosinophilic fasciitis is generally corticosteroid-responsive, and initial treatment regimens are based on this therapy. Multiple additional agents have been used in steroid-refractory disease. The evidence for many of these agents is anecdotal, and there is no general consensus regarding the best agent for treatment of steroid-resistant disease or cases refractory to steroid withdrawal.

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Pathophysiology

Although the etiology of eosinophilic fasciitis is unknown, studies have shed light on some of the mechanisms involved in its pathogenesis.

In general, the pathophysiology underlying eosinophilic fasciitis is postulated to involve an inflammatory response resulting in an activated inflammatory cell infiltrate of affected tissues and subsequent dysregulation of extracellular matrix production by lesional fibroblasts.

Viallard et al (2001) demonstrated that, when stimulated, peripheral blood mononuclear cells of eosinophilic fasciitis patients produce significantly higher amounts of 5 cytokines, including interleukin (IL)–5 and interferon (IFN)–gamma.[5] IL-5 is known to activate mature eosinophils and to stimulate eosinophil chemotaxis, growth, and differentiation. IFN-gamma activates tissue macrophages and T cells. The findings of Dziadzio et al (2003) support increased levels of IL-5 in eosinophilic fasciitis, in addition to increased levels of transforming growth factor (TGF)–beta, another fibrogenic cytokine.[6]

Toquet et al (2003) investigated the phenotype of the lesional inflammatory cell infiltrate in patients with eosinophilic fasciitis and demonstrated a predominance of macrophages, CD8+ lymphocytes, and few eosinophils.[7] Pathologic specimens from patients with eosinophilic fasciitis demonstrate increased numbers of eosinophils, especially early in the disease course.

Taken together, the findings of these studies suggest a mechanistic framework marked by a proinflammatory and fibrogenic cytokine response with resultant tissue inflammatory cell infiltration.

In the tissues, the end effector cell of fibrosis is the fibroblast. Fibroblasts from lesional tissue of patients with eosinophilic fasciitis produce excess collagen in vitro and display elevated TGF-beta and type 1 collagen mRNA levels when examined via in situ hybridization with specific cDNA.[8, 9] Therefore, the pathogenesis appears to involve the concomitant increase in the expression of genes for TGF-beta and extracellular matrix proteins in fibroblasts in the affected tissues.

Mori et al (2002) suggested that an autocrine stimulatory loop involving major basic protein, a product of eosinophil degranulation, IL-6, which enhances collagen production and is induced my major basic protein, and TGF-beta could account for the progressive fibrosis seen in several eosinophil prominent disorders.[10]

Other studies showed elevated levels of serum manganese superoxide dismutase and tissue metalloproteinase 1 (TIMP-1) in eosinophilic fasciitis, suggesting a role in pathogenesis and providing a possible marker of disease activity.[11]

Fasciitis may be a common manifestation of various pathophysiologic processes associated with eosinophilia. The existence of primary and secondary forms of fasciitis has recently been suggested.

Understanding the mechanisms involved in the development of fascial inflammation and fibrosis in these conditions may yield insights into the pathogenesis of other fibrotic skin diseases.

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Epidemiology

Frequency

United States

Eosinophilic fasciitis is very rare.

Mortality/Morbidity

No data are available on morbidity or mortality rates associated with eosinophilic fasciitis. Morbidity may result from joint contractures or carpal tunnel syndrome associated with fascial fibrosis. Rarely, a fatal aplastic anemia may develop.

Race

Eosinophilic fasciitis affects whites more often than it affects other races. It has been reported in African Americans, Africans, and Asians.[12, 13, 14, 15, 16]

Sex

In adults, eosinophilic fasciitis affects women more often than men.[17, 18, 19]

Age

The age range in eosinophilic fasciitis is 1-88 years, although most patients present during the third to sixth decades of life.[18] The average age of onset in two recent case series was 54.4 and 49.8 years.[18, 19]

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Contributor Information and Disclosures
Author

Peter M Henning, DO, MAJ, MC  Fellow, Department of Rheumatology, Walter Reed Army Medical Center, Washington, DC

Peter M Henning, DO, MAJ, MC is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

George R Mount, MD, MAJ USA MC  Assistant Professor of Medicine, Uniformed Services University of the Health Sciences; Attending Physician, Department of Rheumatology, Madigan Army Medical Center, Tacoma, WA

George R Mount, MD, MAJ USA MC is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Nicholas David Kortan, DO, CPT, MC,  Resident Physician, Department of Internal Medicine, Walter Reed Army Medical Center, Washington, DC

Nicholas David Kortan, DO, CPT, MC, is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Sherif Nasef, MD  Consulting Staff, Department of Internal Medicine, Division of Rheumatology, Lake Havasu Regional Medical Center

Sherif Nasef, MD is a member of the following medical societies: American College of Physicians, American College of Physicians-American Society of Internal Medicine, American College of Rheumatology, and American Medical Association

Disclosure: Nothing to disclose.

Kristine M Lohr, MD, MS  Professor, Department of Internal Medicine, Center for the Advancement of Women's Health and Division of Rheumatology, Director, Rheumatology Training Program, University of Kentucky College of Medicine

Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians and American College of Rheumatology

Disclosure: Nothing to disclose.

Specialty Editor Board

John Varga, MD  Professor, Department of Internal Medicine, Division of Rheumatology, Northwestern University

John Varga, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, Central Society for Clinical Research, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Lawrence H Brent, MD  Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, and American College of Rheumatology

Disclosure: Abbott Honoraria Speaking and teaching; Centocor Consulting fee Consulting; Genentech Grant/research funds Other; HGS/GSK Honoraria Speaking and teaching; Omnicare Consulting fee Consulting; Pfizer Honoraria Speaking and teaching; Roche Speaking and teaching; Savient Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

Additional Contributors

The opinions or assertions contained here are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

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The arm of this patient demonstrates the puckered, so-called orange-peel or cobblestone skin that may occur in eosinophilic fasciitis.
The skin of the patient's back appears shiny due to the stretched dermis overlying an inflamed fascia. Mild diffuse hyperpigmentation is present, along with a U-shaped area of hypopigmentation extending approximately from T10 to L4.
The skin of the abdomen and breasts is shiny and taut. The thigh reveals puckering or cobblestoning of the overlying dermis due to scattered retraction from scarred fascia.
Eosinophilic fasciitis. Top: In this gross specimen, the dermis (A), subcutaneous adipose tissue (B), and skeletal muscle do not appear unusual. However, the fascia (D) is markedly thickened. Bottom left: The gross findings are recapitulated in this low-power photomicrograph. The epidermis, dermis (A), and subcutaneous adipose tissue are not remarkable in this case. The fascia (D) is markedly thickened and focally infiltrated by inflammatory cells (E). The small amount of skeletal muscle (C) appears normal (hematoxylin and eosin stain at low power). Bottom right: A close-up photograph of a portion of the fascia showing mostly edematous cellular connective tissue (F). It is focally infiltrated by inflammatory cells, including lymphocytes, plasma cells, and histiocytes. The more intensely stained hypocellular pink bands across the top of the field (G) are part of an interstitial exudate of fibrin (hematoxylin and eosin stain at medium power).
 
 
 
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