Bilateral Knee Arthritis Related to Immune CheckPoint Inhibitor Therapy in a Patient with Lung Adenocarcinoma

Summary: Background Immune checkpoint inhibitors (ICIs) like Pembrolizumab, used to treat non-small cell lung cancer, enhance the immune system's cancer-fighting ability. These ICIs, while transforming cancer treatment, may cause immune-related adverse events (irAEs) that can affect almost any organ system. Arthritis is the most common rheumatic irAE, but diagnosing it remains challenging due to varied clinical presentations and limited literature. This is a case of a patient on Pembrolizumab, who initially showed monoarthritis in the left knee, rapidly evolving into bilateral knee inflammatory arthritis. Case Presentation A 53-year-old man with metastatic lung adenocarcinoma and emphysema was hospitalized for acute onset severe left knee pain. He denied prior episodes of arthritis, recent illness or travel. His medications were pembrolizumab started 3.5 years ago and pemetrexed. On physical exam, he was afebrile with left knee swelling, redness, and warmth. Left knee arthrocentesis showed an inflammatory effusion with WBC 37,635 (69% neutrophils), no crystals and negative culture. Labs demonstrated peripheral WBC of 11.3 x 10^3 mcL, CRP 27.3 mg/dL, ESR 71, and uric acid 4 mg/dL. X-ray was normal other than effusion. Given his immunocompromised status and level of synovial fluid leukocytosis he was treated for presumptive septic arthritis. Despite initial improvement, he developed right knee synovitis on hospital day 7. Arthrocentesis showed WBC 29,932 (86% neutrophils), no crystals and negative culture. He had an ANA 1:80 fine granular pattern, RF of 17, negative anti-CCP antibodies and negative chlamydia and gonorrhea. Due to persistently negative cultures, development of R knee synovitis on antibiotics and negative crystal evaluation, a diagnosis of pembrolizumab associated arthritis was made. He was started on prednisone 20 mg daily with significant improvement and was discharged with a planned taper and appropriate follow up. Discussion Inflammatory arthritis (IA) linked to pembrolizumab presents variably, with symptom onset typically ranging from 1 to 10 months. Our patient developed IA acutely after 3 years, a previously unreported timeline. Information on synovial fluid analysis in these patients is extremely limited (WBC range: 7000-20000). Our case showed a striking leukocytosis of over 37,000, making ICI arthritis an important differential in patients on ICI with symptoms resembling septic arthritis but who are afebrile or have negative cultures. Minimizing unnecessary antibiotics is crucial as cancer patients may risk infection with resistant organisms. Inflammatory markers can vary and low titer ANA and RF may be present, as in our case. Treatment for ICI arthritis depends on severity and may include prednisone and disease-modifying antirheumatic agents (DMARDs) if steroids cannot be tapered. Conclusion Our case expands the understanding of ICI arthritis clinical presentation, and emphasizes the importance of reassessment in differential diagnosis for patients with atypical clinical courses.