A rheumatology clinic is updating its patient safety protocols to ensure appropriate baseline screening and long-term monitoring for patients on immunomodulatory therapies. Match each pharmacologic agent commonly used in the management of rheumatologic diseases to its most characteristic severe adverse effect.
- MethotrexateHepatotoxicity, stomatitis, and macrocytic anemia
- HydroxychloroquineBulls-eye retinopathy and visual field defects
- CyclophosphamideHemorrhagic cystitis and bladder carcinoma
- AdalimumabReactivation of latent tuberculosis
Answer
Methotrexate matches with hepatotoxicity, stomatitis, and macrocytic anemia. Hydroxychloroquine matches with bulls-eye retinopathy. Cyclophosphamide matches with hemorrhagic cystitis. Adalimumab matches with reactivation of latent tuberculosis.
Each immunosuppressive agent has a highly stereotyped toxicity profile. Methotrexate is a folate pathway inhibitor, leading to myelosuppression (macrocytic anemia), mucosal damage (stomatitis), and liver damage (hepatotoxicity). Hydroxychloroquine is generally well-tolerated but binds to melanin in the retina, potentially causing irreversible macular damage (bulls-eye retinopathy). Cyclophosphamide is an alkylating agent whose breakdown product, acrolein, is directly toxic to the bladder epithelium, leading to hemorrhagic cystitis and an increased risk of bladder cancer (preventable with hydration and mesna). Adalimumab inhibits TNF-alpha, a cytokine essential for the formation and maintenance of granulomas; consequently, patients are at high risk for reactivation of latent tuberculosis and must be screened prior to initiation.
Step-by-Step Solution
Key Concept
Adverse effect profiles and required monitoring for disease-modifying antirheumatic drugs (DMARDs) and biologic agents.