ABSTRACT
Pembrolizumab, a programmed cell death protein 1 (PD1) inhibitor, has been known to be associated with several adverse reactions, including immune related adverse events. In less than one percent of patients, PD1 inhibitors have been linked to the development of connective tissue disease. Patients with previously known connective tissue disease are hypothesized to be at increased risk of flares in as many as 40% of cases. A 70-year-old man with a past medical history significant for rheumatoid arthritis in remission and stage IV lung adenocarcinoma presented to the dermatology clinic after one cycle of nivolumab and eight cycles of pembrolizumab exhibiting worsening, painful bilateral lower extremity ulcers for approximately one month. On the lower legs, three large black retiform eschars and bullous purpuric plaques were observed. Vasculitis is a rare complication of PD1 inhibitor therapy, with the majority of cases reported in literature either medium vessel or large vessel vasculitis. Only glucocorticoids have proven effective for PD1-induced vasculitis and these patients generally require multi-specialty management.
Subject(s)
Adenocarcinoma of Lung/drug therapy , Antibodies, Monoclonal, Humanized/adverse effects , Immune Checkpoint Inhibitors/adverse effects , Leg Ulcer/chemically induced , Lung Neoplasms/drug therapy , Rheumatoid Vasculitis/chemically induced , Adenocarcinoma of Lung/complications , Adenocarcinoma of Lung/secondary , Aged , Arthritis, Rheumatoid/complications , Deprescriptions , Glucocorticoids/therapeutic use , Heart Failure/chemically induced , Humans , Leg Ulcer/drug therapy , Leg Ulcer/pathology , Lung Diseases, Interstitial/chemically induced , Lung Neoplasms/complications , Lung Neoplasms/pathology , Male , Nivolumab/adverse effects , Rheumatoid Vasculitis/drug therapy , Rheumatoid Vasculitis/pathologyABSTRACT
Rheumatoid vasculitis is a rare etiology for pulmonary hypertension (PH) in patients with connective tissue disease. We encountered a case of acute PH crisis in a case with rheumatoid vasculitis eight months after undergoing adalimumab reduction. Since no repetition of arthralgia occurred after the adalimumab reduction, we decided to not increase the dose of adalimumab. However, hemodynamic collapse thereafter developed and even though steroid pulse therapy was administered, the patient nevertheless died. The autopsy showed clusters of acute and chronic inflammation around the remodeled pulmonary arteries along with micro-thrombi in the vessel lumen. We should consider the possibility of critical worsening of PH as a phenotype of vasculitis related to immunosuppressive therapy reduction.
