Epidemiology and Treatment of Eosinophilic Fasciitis: An Analysis of 63 Patients From 3 Tertiary Care Centers

Eosinophilic fasciitis (EF) is a rare fibrosing disorder of the fascia characterized by erythema, edema, and induration of the bilateral extremities. Joint contractures and related functional limitation commonly occur owing to fascial involvement overlying the joints. Hematologic abnormalities, including peripheral eosinophilia and monoclonal gammopathy, may occur. Systemic corticosteroids are considered first-line therapy; however, prolonged treatment is frequently required in patients with EF, and a standardized therapeutic protocol is lacking.^1,2 Given the dearth of systematic data guiding treatment, we evaluated the presentation and clinical response of EF in 63 patients at 3 tertiary care centers.

After institutional review board approval from Partners HealthCare and New York University Langone Medical Center, we performed a search of the Partners Research Patient Data Registry (January 1, 1995-May 31, 2015; Brigham and Women’s and Massachusetts General Hospitals) and 2 medical record databases at New York University Langone Medical Center (January 1, 2005-May 31, 2015), which together include more than 20 million patient visits. The search was based on the term fasciitis and EF-related International Classification of Diseases, Ninth Revision codes (728.89, 728.9, and 729.4). Data were extracted on patient demographics, disease presentation, treatment, and clinical response, defined as complete response (resolution of erythema and/or edema with no or minimal persistent induration), partial response (incomplete improvement of erythema, edema, and/or induration), or no response (lack of improvement). Each patient record, along with clinical photographs when available, was reviewed to ensure accurate diagnosis of EF. The 2 senior authors (A.N.F. and R.A.V.) independently confirmed the diagnosis of EF and assessment of clinical response. Categorical variables were compared using 2-tailed χ² tests, with P ≤ .05 considered statistically significant. Analysis was conducted from October 1, 2014, to May 31, 2015.

Of 1626 patients with fasciitis identified, 63 had confirmed EF (Table 1). Mean (SD) time from onset of EF to diagnosis was 11 (8) months. Seventy-nine percent of patients (37 of 47) were initially misdiagnosed, most frequently with systemic sclerosis (SSc), deep vein thrombosis, hypereosinophilic syndrome, or cellulitis. Most patients who were misdiagnosed with SSc underwent unnecessary evaluation for internal disease and failed to receive corticosteroids before the correct diagnosis. Four patients who were misdiagnosed with hypereosinophilic syndrome or eosinophilic leukemia underwent bone marrow biopsies and 1 patient received chemotherapy. Fifty percent of patients (31 of 62) had joint contractures, yet only 37% (23 of 62) were referred for physical therapy. In 28% of patients (8 of 29), trauma or intense exercise preceded the onset of EF. During a mean (SD) follow-up of 39 (43) months, complete response was more likely with the combination of corticosteroids and methotrexate (21 of 33 patients [64%]) compared with other treatment combinations (9 of 31 [29%]; P = .006), corticosteroid monotherapy (10 of 33 [30%]; P = .007), or treatment without corticosteroids (1 of 6 [17%]; P = .03) (Table 2). Complete response also occurred more frequently in patients diagnosed within 6 months of the onset of EF, but this finding was not statistically significant (10 of 15 [67%] vs 17 of 31 [55%]; P = .45).

To our knowledge, this study represents the largest cohort to date of patients with EF and underscores the diagnostic and therapeutic challenge that EF presents. Frequent misdiagnoses likely accounted for the mean diagnostic delay of almost 1 year and resulted in unnecessary, invasive procedures and inappropriate treatments. Furthermore, many patients were undertreated; more than 10% of patients did not receive the standard of care with corticosteroids, and only 37% were referred for physical therapy despite the high rate of joint contractures.

The most common misdiagnosis was SSc, likely because both EF and SSc frequently present with induration of the extremities. Distinguishing these 2 conditions is imperative because corticosteroids are first-line therapy for EF, whereas corticosteroids are generally avoided in patients with SSc, given a potential association with renal crisis. Furthermore, visceral involvement in EF is generally limited to hematologic abnormalities, and thus an extensive systemic workup is not indicated as it is in SSc. Clinically, nailfold capillary changes and Raynaud phenomenon are typically absent in EF, unlike in SSc, and skin tightening on the distal digits is lacking. In addition, the groove sign (linear depressions along the course of veins), pseudocellulitic or peau d’orange skin, concurrent plaque morphea, and peripheral eosinophilia may be present in EF. As only 28% of patients in our study had a history of recent trauma or exercise, this criterion may play a more limited role in the etiology and thus diagnosis of EF than traditionally thought.^1,3 Diagnostic criteria for EF incorporating these characteristics have been recently proposed but remain to be validated.³

Although corticosteroids remain first-line therapy for EF, their prolonged use in this and 2 other large studies^1,2 demonstrates the need for corticosteroid-sparing therapy. In our study, combination therapy with corticosteroids and methotrexate, which may have corticosteroid-sparing effects,^4,5 portended a higher rate of complete response. Furthermore, our study supports the notion that early treatment of EF results in improved outcomes.²

This study’s limitations include its retrospective nature, the possibility of spontaneous resolution rather than therapeutic effect, and the fact that initial therapeutic intervention occurred at various disease stages, thereby complicating assessment of clinical response. Despite the small sample size, this study represents the largest cohort to date of patients with EF. Further investigation is needed to determine an appropriate treatment algorithm for patients with EF.

Accepted for Publication: August 18, 2015.

Corresponding Author: Ruth Ann Vleugels, MD, MPH, Department of Dermatology, Brigham and Women’s Hospital, 221 Longwood Ave, Boston, MA 02115 (rvleugels@partners.org).

Published Online: November 11, 2015. doi:10.1001/jamadermatol.2015.3648.

Author Contributions: Dr Wright and Mr Mazori had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Dr Wright and Mr Mazori are co–first authors and Dr Vleugels and Dr Femia are co–last authors.

Study concept and design: Wright, Mazori, Patel, Femia, Vleugels.

Acquisition, analysis, or interpretation of data: Wright, Mazori, Merola, Femia, Vleugels.

Drafting of the manuscript: Wright, Mazori, Femia.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Wright, Mazori.

Administrative, technical, or material support: Wright, Patel, Femia.

Study supervision: Wright, Merola, Femia, Vleugels.

Conflict of Interest Disclosures: Dr Merola is a consultant for Biogen IDEC, Amgen, Janssen, AbbVie, Eli Lilly, Momenta; licensed a questionnaire to AbbVie; is a speaker for AbbVie and Eli Lilly; and has received grants from Biogen IDEC. No other disclosures were reported.

Funding/Support: Dr Vleugels reported receiving a Medical Dermatology Career Development Award from the Dermatology Foundation. Dr Femia reported receiving funding from the Noah-Sadie K. Wachtel Foundation.

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Previous Presentations: This study was presented in part at the Medical Dermatology Society 2015 Annual Meeting; March 19, 2015; San Francisco, California; and at the Rheumatologic Dermatology Society 2014 Annual Meeting; November 15, 2014; Boston, Massachusetts.