Azacitidine Beyond the Bone Marrow: An Unexpected Journey Into Azacitidine-Induced Arthropathy

Azacitidine, a DNA hypomethylating agent, is a cornerstone in the treatment of myelodysplastic syndromes and acute myeloid leukemia (AML) in patients unfit for intensive chemotherapy. While its adverse effect profile is well-documented, musculoskeletal complications such as inflammatory arthropathy are exceedingly rare and underrecognized. We report a 61-year-old male with AML, chronic kidney disease, and hypertension, who developed seronegative inflammatory arthropathy during the sixth and seventh cycles of intravenous chemotherapy. The patient presented with bilateral shoulder joint pain, marked morning stiffness, and a restricted range of motion, particularly affecting the left side. Inflammatory markers were elevated, while autoimmune serologies, including rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), antinuclear antibodies (ANA), and human leukocyte antigen B27 (HLA-B27), were negative. The clinical and temporal profile, along with symptom resolution following intra-articular corticosteroid administration and gabapentin therapy, supported a diagnosis of azacitidine-induced arthropathy. The Naranjo Adverse Drug Reaction Probability Score was 9, indicating a definite causal relationship. This case underscores a rare but important immune-mediated adverse effect of azacitidine: seronegative inflammatory arthropathy. As the use of hypomethylating agents expands, awareness of such atypical complications is critical. Early recognition can prevent diagnostic delays, reduce unnecessary investigations, and allow appropriate therapeutic intervention without compromising oncologic care. Further research is needed to elucidate underlying mechanisms and identify at-risk populations.