Trial of Mepolizumab in Refractory Eosinophilic Fasciitis

Summary: Background: Eosinophilic fasciitis is a rare sclerodermatiform disorder characterized by the accumulation of white blood cells in the fascia leading to inflammation of this area (2). This phenomenon mostly affects the arms and legs, causing the skin to eventually swell, thicken and harden. Eosinophilic fasciitis is a condition with varying clinical manifestations that may present with overlapping features of other disorders. Due to this variability, the diagnosis may be delayed (4). The first-line treatment for this disease continues to be systemic corticosteroids, though refractory cases do not have an accepted treatment at this time (6). While the precise etiology of this ailment is unknown, an elevated level of interleukin-5 (IL-5) has been suggested as playing a part in the pathogenesis. Mepolizumab is an IL-5 antagonist monoclonal antibody (IgG1 kappa) approved for the treatment of eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. Case: A 58-year-old Caucasian female with a past medical history of psoriatic arthritis (PSA) and type 2 diabetes mellitus initially presented to the outpatient clinic with worsening psoriasis. She also noted a lesion along her xiphoid process which she described as a pulling and tightening of the skin, associated with burning and itching (Figure 1A), which was present prior to starting treatment for PSA. She underwent a biopsy of the lesion that was significant for morphea, and she was subsequently started on methotrexate. Despite treatment, she complained of worsening skin thickening with widespread erythema and pain along her chest, upper back, arms and legs (Figure 1B-F). The patient did not exhibit systemic features of systemic sclerosis, raising concern for a mimicking process that was further explored (Table 1A). Laboratory results revealed significant peripheral eosinophilia (Table 1B). During her follow-up visit at the outpatient clinic, the skin lesions were noted to be prominent on her extremities. The exam findings coupled with the laboratory results of persistent eosinophilia raised suspicion for eosinophilic fasciitis, and the patient was subsequently started on methylprednisolone. She underwent punch biopsies of the skin lesions which confirmed eosinophilic fasciitis (Table 1C). She was transitioned to a methylprednisolone taper and was started on dupilumab. Despite these treatments her eosinophilic fasciitis persisted, which became concerning for a refractory case. She was then transitioned to mepolizumab. Once she began mepolizumab she reported more mobility of her extremities and improvement in the thickness of her skin. On physical exam it was also evident the patient had less edema and better range of motion. Discussion: Refractory cases of eosinophilic fasciitis have only been seen in some case reports and are fairly rare. Early diagnosis and treatment are important in the prognosis of this disease and response to treatment, which is often delayed due to suspicion of other common disease processes that are worked up first. The exact mechanisms of the pathogenesis that cause eosinophilic fasciitis remain uncertain. Nevertheless, extensive extracellular matrix formation and autoimmune dysfunction are believed to be crucial pathogenic processes (1). It is also essential to note that morphea appearing together with eosinophilic fasciitis is atypical and may be a sign of poor prognosis and resistance to treatment (3), which was seen with this patient who also exhibited biopsy-proven morphea. While corticosteroids and steroid-sparing agents are the recommended therapy, there are no guidelines or approved therapies in the cases of refractory disease (6). In a retrospective medical record analysis of patients with eosinophilic disorders who received off-label anti-IL-5 or anti-IL-5 receptor treatment, the patient with eosinophilic fasciitis had resolution of limb edema and discomfort (7). We chose mepolizumab because IL-5 comprises a fundamental role in eosinophilia and in innate and acquired immune responses. IL-5 has been acknowledged as the major maturation and differentiation factor for eosinophils in humans (5). Thus, advances in medications targeting IL-5 and its receptor through humanized monoclonal antibodies have stemmed from further understanding the mechanisms by which IL-5 affects the development and activation of eosinophils. Conclusion: Usage of medications targeting IL-5 and its receptor should be further explored and may be successful in treating various rare eosinophil-mediated disorders.