Pain and hardening of the skin constricts shoulder movement
A 32-year-old man of Indian origin presented to the family medicine clinic with pain and swelling in both upper extremities of one-month duration. He described the pain as dull and aching in nature and confined to both upper arms and shoulders. Overhead movement at both shoulders was restricted beyond 90°.
The patient was currently taking OTC acetaminophen and ibuprofen for pain with minimal relief. He was alert but in distress from the pain. The physical examination of head, ear, eye, nose, and throat was normal, as was that of the lungs, heart, and abdomen. Musculoskeletal examination revealed swelling of the upper arms and hardening and tethering of skin to underlying tissue. Movements at both shoulders, particularly abduction and lateral rotation, were limited.
Laboratory studies revealed slightly increased C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and marked eosinophilia. Stool studies were negative for parasitic infections. The patient refused a recommendation for full-thickness skin-to-muscle biopsy.
The patient was treated empirically for possible eosinophilic fasciitis (EF) with prednisone for two months. Re-evaluation within two weeks demonstrated significant symptomatic improvement along with a decline in eosinophilia. Subsequent follow-up evaluation revealed complete resolution of symptoms and eosinophilia.
EF was first described by Shulman in 1974 as an inflammatory disease characterized by diffuse fasciitis and eosinophilia.1 It is an uncommon connective-tissue disorder that manifests primarily as sclerodermalike syndrome associated with symmetrical swelling, induration, and thickening of the skin and subcutaneous tissue of the proximal and distal extremities.
The incidence of this rare condition is not known, and there is no clear consensus about the demographics. The mean age of onset is between 30 and 50 years.2 However, the disease has been reported in children and elderly patients as well.3
EF has varying clinical presentations. Most patients typically present with swelling and induration of the arms and legs with skin thickening.4 The disease usually progresses from edema of the extremities to woody induration with skin tightness. Patients may also have joint pain with associated synovitis. Some patients have presented with progressive weakness, pain, and stiffness of both upper and lower extremities.2
The most common extracutaneous manifestation is the involvement of joints resulting in inflammatory arthritis, contracture, and carpal tunnel syndrome.5 Reactive lung disease, pleural effusions, and multiple myeloma have also been reported as extracutaneous manifestations of EF.6,7
Diagnosis of EF is often delayed due to overlapping features with other connective-tissue diseases (e.g., scleroderma, polymyositis, and hypereosinophilic syndrome). Confirmatory diagnosis is achieved by full-thickness skin-to-muscle biopsy,4 which shows inflammation and thickening of collagen bundles with infiltration of lymphocytes and plasma cells in superficial muscle fascia. Eosinophils are occasionally observed in biopsy but are not necessary to make the diagnosis. When used as a diagnostic tool, MRI shows fascia thickening and helps identify the suitable biopsy site, which facilitates accurate and timely diagnosis of EF.8
4. Laboratory analysis
Blood workup in patients with EF usually reveals peripheral eosinophilia (>7%), elevated ESR, and hypergammaglobulinemia. However, because of poor correlation between the degree of eosinophilia and disease severity, the laboratory analysis using this parameter is not a very accurate predictor for monitoring disease course and activity.2
Review of the literature suggests several etiologic factors contributing to the development of EF with no established consensus among these reports. The most frequently reported factors are physical exertion, trauma, ingestion of L-tryptophan, statins, arthropod bite, and borrelliosis.9-11
High-dose systemic corticosteroid therapy is the mainstay of treatment for EF.2 Other drugs, such as cyclosporine, hydroxychloroquine, cimetidine, azathioprine, and D-penicillamine, have been used to treat EF with varying success.12,13
Eosinophilic fasciitis is a rare form of sclerotic disease that has been considered a part scleroderma and systemic sclerosis. However, EF is not associated with Reynaud's phenomenon, and internal organs are not involved (as is commonly seen in sclerosis and scleroderma). Most patients present with painful swelling and indurations of skin, primarily involving proximal limb musculature. Joint contracture may occur as a sequel of indurations and sclerosis of the subcutaneous tissue. Lab analysis shows eosinophilia >7% in the differential blood cell count and elevated CRP and ESR. The cause of EF is not known, but strenuous exercise and ingestion of L-tryptophan have been considered as predisposing factors for the development of this disease. EF has also been associated with the use of simvastatin. While the identification of EF is made by clinical presentation, the final diagnosis is established by full-thickness skin-to-muscle biopsy.
In our patient, typical symmetrical sclerosis and indurations of both upper arms and eosinophilia >7% was found. High doses of prednisone (2mg/kg/day) resulted in dramatic clinical improvement within three weeks, which is in agreement with previous studies.2,14
Studies have also shown a favorable outcome using the combination of corticosteroid-hydroxychloroquine.2 Because EF has been regarded as a variant of morphea, phototherapy utilizing UVA plus psoralen (PUVA) has also been used as treatment.15 However, the exact mechanism of action of PUVA and long-term safety in patients with EF is not known. Individuals with EF have also been reported to respond well to methotrexate, cimetidine, penicillamine, and cyclosporine.12,13 Penicillamine and cyclosporine are especially useful when corticosteroids are less effective or contraindicated. The current consensus suggests that early therapy with systemic corticosteroids may be associated with a good outcome in EF patients.
Dr. Shailendra Saxena is assistant professor, department of family medicine, Creighton University Medical Center (CUMC), Omaha, Neb. Dr. Phulwani is a first-year resident in the department of surgery at CUMC. Dr. Shikhar Saxena is a first-year cardiology fellow at the University of Nebraska Medical Center in Omaha. Dr. Khatri isa family physician in Omaha. Dr. Rafiq is assistant professor, department of family medicine, CUMC.
1. Shulman LE. Diffuse fasciitis with eosinophilia: a new syndrome? Trans Assoc Am Physicians. 1975;88:70-86.
2. Lakhanpal S, Ginsburg WW, Michet CJ, et al. Eosinophilic fasciitis: clinical spectrum and therapeutic response in 52 cases. Semin Arthritis Rheum. 1988;17:221-231.
3. Antic M, Lautenschlager S, Itin PH. Eosinophilic fasciitis 30 years after - what do we really know? Report of 11 patients and review of the literature. Dermatology. 2006;213:93-101.
4. Bischoff L, Derk CT. Eosinophilic fasciitis: Demographics, disease pattern and response to treatment: report of 12 cases and review of the literature. Int J Dermatol. 2008;47:29-35.
5. Yamanishi Y, Ishioka S, Yamakido M. Complete remission of relapsing eosinophilic fasciitis associated with bronchial asthma following regular steroid inhalation. Rheumatology (Oxford). 2000;39:339-340. Available at rheumatology.oxfordjournals.org/cgi/content/full/39/3/339.
6. Khanna D, Verity A, Grossman JM. Eosinophilic fasciitis with multiple myeloma: A new haematological association. Ann Rheum Dis. 2002;61:1111-1112. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC1753970/.
7. Minciullo PL, Morabito F, Mandaglio R, et al. Eosinophilic fasciitis associated with autoimmune phenomena after bone marrow transplantation: report of two cases. Clin Rheumatol. 2006;25:80-82.
8. Baumann F, Bruhlmann P, Andreisek G, et al. MRI for diagnosis and monitoring of patients with eosinophilic fasciitis. AJR Am J Roentgenol. 2005;184:169-174. Available at www.ajronline.org/cgi/content/full/184/1/169.
9. Blauvelt A, Falanga V. Idiopathic and L-tryptophan-associated eosinophilic fasciitis before and after L-tryptophan contamination. Arch Dermatol. 1991;127:1159-1166.
10. Hamilton ME. Eosinophilic fasciitis associated with L-tryptophan ingestion. Ann Rheum Dis. 1991;50:55-56. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC1004327/.
11. Choquet-Kastylevsky G, Kanitakis J, Dumas V, et al. Eosinophilic fasciitis and simvastatin. Arch Intern Med. 2001;161:1456-1457.
12. Bukiej A, Dropinski J, Dyduch G, Szczeklik A. Eosinophilic fasciitis successfully treated with cyclosporine. Clin Rheumatol. 2005;24:634-636.
13. Herson S, Brechignac S, Godeau P. Cimetidine in eosinophilic fasciitis. Ann Intern Med. 1990;113:412-413.
14. Britt WJ, Duray PH, Dahl MV, Goltz RW. Diffuse fasciitis with eosinophilia: a steroid-responsive variant of scleroderma. J Pediatr. 1980;97:432-434.
15. Schiener R, Behrens-Williams SC, Gottlober P, et al. Eosinophilic fasciitis treated with psoralen-ultraviolet A bath photochemotherapy. Br J Dermatol. 2000;142:804-807.
All electronic documents accessed August 15, 2010.