Case Presentation: A 71-year-old male with a history of diabetes, hyperlipidemia, and stage II small cell bladder cancer on cycle 2 of cisplatin, etoposide, and atezolizumab that he received 1 week ago presented with neck stiffness, pain, fevers, and diffuse muscle aches to his PCP. Concerned about meningitis he was sent to the hospital. A lumbar puncture was performed which ruled out meningitis. The patient underwent a battery of tests including blood cultures, echocardiogram, lactic acid, CPK, chemistry panel, urinalysis, fungal markers, Lyme serology, autoimmune workup, and imaging of the chest, neck, and shoulder that was unrevealing. Statin medication was withheld for concerns of muscle injury. Specialties including Infectious Diseases, Rheumatology, Oncology, and Orthopedics were involved in the patient’s care. He was maintained on broad-spectrum antibiotics that were de-escalated on day 5. The patient was also given colchicine, topical NSAIDs, and muscle relaxants that provided minimal symptomatic relief. He continued to have fevers and now complained of pain in his knees, ankles, and elbows. Imaging of the knee showed some effusion that was aspirated. Synovial fluid analysis ruled out a septic joint and revealed calcium pyrophosphate crystals, consistent with acute pseudogout flare. The patient underwent a steroid injection which immensely helped with the pain. At this point, consideration was being given to systemic steroids. As all infectious etiology resulted negative patient was put on 1mg/kg steroids that significantly improved all of his muscle pain, joint pain, joint swelling, and fevers. His presentation, in the setting of recent anti-PD-L1 atezolizumab, was deemed consistent with an immune-related rheumatic adverse event. The patient continued steroids for 4-6 weeks and was back to his baseline health. The patient was taken off the atezolizumab and did not have any recurrence of rheumatic symptoms for the next 1 year.
Discussion: Despite unprecedented efficacy across multiple tumor types, immune checkpoint inhibitor therapy is associated with a unique and wide spectrum of immune‐related adverse events. While colitis, hepatitis, pneumonitis, and other IRAEs are well documented, IRAEs with rheumatic and musculoskeletal phenotypes are less well described. Rheumatic IRAEs have been infrequently reported in clinical trials and generally have been the subject of isolated case reports. Rheumatic and musculoskeletal IRAEs include inflammatory arthritis, arthralgia, myositis, polymyalgia-like syndrome, vasculitis, and sicca syndrome to potentially life‐threatening scleroderma. Atezolizumab can be used in the management of hepatocellular carcinoma, lung cancer, and melanoma in addition to urothelial cancer. It can cause pulmonary, GI, cardio, neurological, and dermatological toxicities which are well known in addition to rheumatic and musculoskeletal toxicity.
Conclusions: Admitting physicians along with sub-specialists including infectious diseases, oncologists, and rheumatologists need to be aware of the clinical presentation of serious but uncommon rheumatologic adverse effects associated with checkpoint inhibitors. Prompt diagnosis and management are critical to minimize serious complications and improve patient outcomes. Thus, the evaluation and treatment of rheumatic IRAEs require multidisciplinary cooperation among physicians.