Eosinophilic Fasciitis Following Checkpoint Inhibitor Therapy: Four Cases and a Review of Literature

Abstract

Background. Checkpoint inhibitor therapy is widely known to cause a number of immune-related adverse events. One rare adverse effect that is emerging is eosinophilic fasciitis, a fibrosing disorder causing inflammatory infiltration of subcutaneous fascia. It is characterized clinically by edema and subsequent induration and tightening of the skin and subcutaneous tissues. The condition is rare, yet at our institutions we have seen four cases in the past 3 years. We describe our 4 cases and review 11 other cases reported in the literature. Case Presentation. We present four cases of eosinophilic fasciitis following treatment with programmed cell death protein 1 or programmed cell death-ligand 1 blockade. All patients had extremity involvement with characteristic skin changes ranging from peripheral edema to induration, tightening, and joint limitation. The patients had varying degrees of peripheral eosinophilia. In two of our patients, the diagnosis was made by full-thickness skin biopsy showing lymphocytic infiltration of the subcutaneous fascia, with CD4+ T cells predominating in one case and CD8+ T cells in the other. In the other two cases, the diagnosis was made on the basis of characteristic imaging findings in the context of clinical features consistent with the diagnosis. All four patients were treated with glucocorticoids with varying degrees of success; immunotherapy had to be discontinued in all four. Patients with advanced melanoma who experienced this adverse effect had either a partial response or a complete response to therapy. Conclusion. Eosinophilic fasciitis can occur as a result of checkpoint inhibitor therapy. Although a tissue diagnosis is the gold standard, imaging studies may facilitate the diagnosis in the presence of consistent clinical features, but a degree of suspicion is key to recognizing the condition early. Therapy requires a collaborative approach by oncology, rheumatology, and dermatology; physical therapy is an important adjunct in treatment. For advanced melanoma, it may be a good prognostic indicator. The Oncologist 2020;25:140-149 Implications for Practice: It is important for clinicians to recognize that eosinophilic fasciitis is a potential immune-related adverse event (irAE) as a consequence of immune checkpoint inhibitor therapy. The presentation is quite stereotypical; the diagnosis can be made by imaging in the absence of a full-thickness skin biopsy. Early intervention is important to limit morbidity. This irAE may be a good prognostic sign among patients with melanoma.

Eosinophilic fasciitis induced by nivolumab therapy managed without treatment interruption or systemic immunosuppression

“…In a recent literature review, the authors found 15 cases of fasciitis from immunotherapy, with 9 fulfilling the proposed diagnostic criteria for EF. 5 To our knowledge, there are 10 reported cases of EF from ICI therapy in the literature. 4 , 5 , 6 , 7 , 8 , 9 , 10 Among these 10 cases, the median age was 55 years (range, 43-77), 5 were females, median onset was 11 months (3-22) after initiation of ICI therapy, and 8 of 9 (89%) had peripheral eosinophilia.…”

“…All had discontinuation of their respective ICIs due to new-onset EF, and 9 of 10 (90%) were started on systemic immunosuppressive therapy, including prednisone (regimens ranging from 40-80 mg daily), infliximab (3 mg/kg), mycophenolate mofetil (3 g/d), solumedrol (24 mg 6-day taper), or methotrexate (20 mg/wk). 5 …”

“… 3 More recently, there are reports of EF in patients on anti–programmed death-1 or anti–programmed death ligand-1 therapy, usually requiring treatment interruption and systemic immunosuppression. 4 , 5 , 6 , 7 , 8 , 9 , 10 We present a case of new-onset EF during nivolumab therapy managed without treatment interruption or systemic immunosuppression.…”

Skin puckering and edema during durvalumab therapy

“… 1 It has been recently recognized as an immune-related adverse event secondary to programmed cell death 1 and programmed death-ligand 1 inhibitors. 3 In addition to the classic cutaneous findings, between 10% and 40% of patients may experience concurrent inflammatory arthritis. 1 Eosinophilia myalgia syndrome—Incorrect.…”

“…In the setting of immune checkpoint inhibitor therapy, eosinophilic fasciitis is a novel immune-related adverse event that can result in significant morbidity, including joint contracture. 3 Prompt treatment with systemic corticosteroids may reduce the severity. Other choices include corticosteroid-sparing agents, which may be effective upon improvement of initial symptoms.…”