Customize your JAMA Network experience by selecting one or more topics from the list below.
Eosinophilic fasciitis (EF) is a disorder in which the subcutaneous tissues become indurated and then sclerotic leading to myalgia, arthralgia, and occasionally contractures and disability. High-dose systemic steroids are first-line therapy; however, steroid-sparing agents are often used owing to disease progression or to avoid the adverse effects of long-term corticosteroid use. We describe a case of EF with rapid response to sirolimus.
Report of a Case
A man in his 30s had a 6-month history of arthralgia involving his shoulders, hands, knees, ankles, and feet, which made it difficult for him to stand or walk for long periods. He complained of swelling and “skin tightness” of his arms, lower legs, and hands. On examination, he had woody induration of his distal extremities creating both peau d’orange surface change and linear depressions along the veins of his right forearm consistent with a groove sign. His fingers were held in a slight flexion contracture at the proximal interphalangeal joints (Figure, A).
A, Induration and skin tightness causes discomfort and inability to make a fist. B, Much improved finger mobility allows the patient to make a fist after 2 months of sirolimus therapy.
Laboratory tests revealed a transient eosinophilia (total eosinophil count, 600/μL), polyclonal hypergammaglobulinemia, a mildly elevated erythrocyte sedimentation rate (22 mm/h), and negative results for antinuclear antibodies and anti-U1RNP and anti-Scl-70 antibodies. He lacked features of systemic sclerosis, including Raynaud phenomenon, sclerodactyly, or nail fold capillary changes. An incisional biopsy of his calf extending into the deep subcutaneous fat, but not including fascia, revealed thickening of the subcutaneous septae with edema and a lymphoplasmacytic infiltrate with eosinophils. The histopathologic findings was most compatible with a deep sclerosing process such as morphea profunda or EF. Given his cutaneous findings and histopathologic deep sclerosis, he was diagnosed with EF.
The patient was treated with physical therapy, low-dose prednisone, and methotrexate, 25 mg/wk, for 4 months without an improvement in induration or pain. His prednisone dose ranged between 5 and 20 mg/d for 7 months (the patient had concerns about the adverse effects of high-dose steroids). Given the progressive sclerosis, methotrexate treatment was stopped; prednisone regimen was continued at 5 mg/d; and sirolimus therapy was started at 2 mg/d. Within 6 weeks, there was a reduction of pain and skin thickening (Figure, B). Nine months into therapy, the patient remained on the regimen of sirolimus, 2 mg/d, and prednisone, 5 mg/d. He experienced occasional hand arthralgia but regained the ability to walk long distances, exercise in the gym, and make a fist. The sirolimus regimen will be tapered once his clinical symptoms have completely resolved.
Mechanistic target of rapamycin (mTOR) is a cell-signaling serine–threonine kinase that exists as 2 distinct complexes, mTORC1 and mTORC2. Sirolimus predominately inhibits mTORC1 and is commonly used to prevent graft rejection in transplant patients. Sirolimus has been shown to decrease the development of fibrosis in transplanted donor organs in both animal models and clinical studies.1 The mTOR complexes are one of the downstream signals of transforming growth factor (TGF)-β, a key regulator of fibrosis, and inhibition of mTOR is believed to decrease fibroblast function, collagen deposition, and epithelial to mesenchymal transition, a process important in generating fibroblasts and myofibroblasts.2 Sirolimus has led to improvement in cases of nephrogenic systemic fibrosis and modest improvement in systemic sclerosis.3,4 Recently, a dual inhibitor of mTOR complexes 1 and 2 has been shown to reverse TGF-β–induced fibrosis by dermal fibroblasts.5
Eosinophilic fasciitis is a sclerosing disorder for which both high-dose corticosteroids and methotrexate treatments are frequently used, but a complete response is seen in only two-thirds of cases.6
Based on this case report, sirolimus holds potential as an alternative therapy for EF. Further research on mTOR and the development of newer mTOR inhibitors could provide future therapies for other difficult-to-treat sclerosing skin disorders.
Corresponding Author: Jenny E. Murase, MD, Department of Dermatology, Palo Alto Foundation Medical Group, 701 E El Camino Real (31-104), Mountain View, CA 94040 (email@example.com).
Published Online: March 2, 2016. doi:10.1001/jamadermatol.2016.0048.
Conflict of Interest Disclosures: None reported.
Oza VS, Walsh R, North J, Berger TG, Murase JE. Treatment of Eosinophilic Fasciitis With Sirolimus. JAMA Dermatol. 2016;152(4):488–490. doi:10.1001/jamadermatol.2016.0048
Coronavirus Resource Center