Erythema nodosum‐like panniculitis mimicking disease recurrence: A novel toxicity from immune checkpoint blockade therapy—Report of 2 patients

Abstract

Immunotherapies targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have showed substantial therapeutic benefit in patients with clinically advanced solid malignancies. However, autoimmune toxicities are common and often significant adverse events with these agents. While rash and pruritus remain the most common cutaneous complications in treated patients, novel dermatologic toxicities related to immune checkpoint blockade continue to emerge as the number of patients exposed to immunotherapy increases. Here, we describe 2 patients treated with combination immunotherapy with ipilimumab and nivolumab who developed painful subcutaneous nodules. Although the findings were clinically concerning for disease recurrence, histopathologic examination of biopsies from the lesions revealed a subcutaneous mixed septal and lobular erythema nodosum-like panniculitis. Notably, neither patient received immunosuppressive therapy for these lesions, which subsequently remained stable, and both patients' cancer remained controlled. These cases show that the dermatologic toxicity profile of immune checkpoint blockade is diverse and continues to expand, and illustrates that recognition of such toxicities is critical to optimal patient management.

Panniculitis in a patient with pathologic complete response to talimogene laherparepvec treatment for recurrent, in‐transit melanoma

“…A subset of cases manifests with a concomitant dermal sarcoid‐like granulomatous process . Even more relevant to the current report are three cases of subcutaneous panniculitis with a granulomatous component in patients treated with ICIs . Two presented with painful, subcutaneous erythema nodosum‐like nodules during combined immunotherapy with ipilimumab and nivolumab for treatment of metastatic clear cell ovarian carcinoma and melanoma, respectively.…”

“…[27][28][29] Even more relevant to the current report are three cases of subcutaneous panniculitis with a granulomatous component in patients treated with ICIs. 1 Two presented with painful, subcutaneous erythema nodosum-like nodules during combined immunotherapy with ipilimumab and nivolumab for treatment of metastatic clear cell ovarian carcinoma and melanoma, respectively. The third case involved a patient treated with pembrolizumab for metastatic melanoma who developed lobular panniculitis with a sarcoid-like granulomatous component.…”

“…Immunotherapies have an increasingly important role in the treatment of advanced melanoma and other malignancies. In addition to systemic immune checkpoint inhibitor (ICI) therapies, such as anti‐cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA4), anti‐programmed cell death 1 (PD‐1), and anti‐programmed cell death ligand 1 (PD‐L1) antibodies, locally delivered immunotherapies have shown promise. Talimogene laherparepvec (T‐VEC), a novel intralesional oncolytic viral therapy, is Food and Drug Administration (FDA) approved for the treatment of unresectable cutaneous, subcutaneous, and nodal melanoma .…”

Oral immune‐related adverse events associated with PD‐1 inhibitor therapy: A case series

“…They are thought to develop due to a loss of tolerance to self‐antigens which may consequently lead to organ toxicities (Brahmer et al, ; Chen & Han, ; Topalian et al, ). While all organs may be affected, more commonly reported irAEs include dermatological (lichenoid eruptions, vitiligo), gastrointestinal (diarrhea, hepatitis), endocrine (thyroiditis), pulmonary (pneumonitis), and renal (nephritis) (Belli et al, ; De Velasco et al, ; Hofmann et al, ; Michot et al, ; Ohtsuka, Miura, Mori, Ishikawa, & Yamamoto, ; Tetzlaff et al, ). When sufficiently severe, irAEs may require dose modification or suspension of treatment, which may lead to unfavorable outcomes and a negative impact on survival (Rapoport et al, ; Wang et al, ).…”

Gene expression profiling of lichenoid dermatitis immune‐related adverse event from immune checkpoint inhibitors reveals increased CD14+ and CD16+ monocytes driving an innate immune response

“…Inflammatory‐related cutaneous irAEs of any grade may occur in up to ~40‐50% of patients treated with CPI therapy . A spectrum of inflammatory‐related cutaneous irAEs have been reported, including lichenoid dermatitis (LD), bullous pemphigoid, granulomatous/sarcoid‐like lesions, psoriasiform reactions, and infrequently, Stevens‐Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) . Although some cutaneous irAEs can be managed with topical steroids, others are sufficiently severe to warrant systemic anti‐inflammatory medication or cessation of CPIs altogether—both of which present important challenges to effective clinical management.…”