PO:10:155 | Etanercept-induced lupus in a patient with rheumatoid arthritis: diagnostic challenges and multidisciplinary therapeutic approach

Camilla Riboldi^1|2, Claudia Iannone^1|2, Maria Gerosa^1|2, Roberto Felice Caporali^1|2 | ¹ASST G. Pini-CTO, U.O.C. di Clinica Reumatologica, Milano; ²Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Italy

Background. To present a case of anti-TNFα drug-induced lupus (DIL) in a patient with rheumatoid arthritis (RA) and progressive respiratory complications.

Materials and Methods: Review of clinical records and multidisciplinary follow-up. Results: A 60-year-old female smoker with a history of GERD, bronchial asthma, and OSAS was diagnosed with RA in 2022 due to polyarthritis (ANA 1:320, low-titer RF, negative ACPA). After failure of methotrexate, abatacept and tocilizumab, etanercept was initiated. In April 2024, purpuric lesions appeared on the upper back and chest, associated with resting dyspnea and a right-sided pleural effusion on chest X-ray, initially treated as parapneumonic. In May 2024, the patient was hospitalized for a widespread maculopapular rash and active arthritis (SDAI 39.3). Laboratory tests showed elevated ESR and CRP, ANA 1:1280, positive anti-dsDNA, anti-histone, and anti-nucleosome antibodies. ENA, ANCA and antiphospholipid antibodies were negative. Skin biopsy was consistent with a drug-induced toxic-allergic rash. Chest CT revealed post-inflammatory bibasal atelectasis. A diagnosis of etanercept-induced DIL was made based on clinical and serological criteria. The biologic was discontinued and steroid therapy, azithromycin, and antihistamines were started, with subsequent cutaneous improvement. However, dyspnea persisted with bilateral pleural effusion and severe mixed ventilatory syndrome requiring nocturnal CPAP. In September 2024, due to anti-dsDNA normalization and ongoing arthritis (with previous methotrexate failure), filgotinib 200 mg/day was started, achieving good cutaneous and joint response (SDAI 12.1 at 3 months). In December 2024, the patient was rehospitalized for acute type I respiratory failure due to worsening bilateral pleural effusion, treated with oxygen therapy, nebulization bronchodilator therapy and levofloxacin. In March 2025, due to residual debilitating dyspnea, medical cannabis was initiated.

Discussion. Anti-TNFα DIL occurs in 0.1–0.5% of treated patients, more frequently in elderly women. Clinical features are variable: cutaneous involvement is present in up to 80% of cases. Diagnostic criteria include drug exposure, compatible clinical manifestations, positive ANA/anti-dsDNA, and improvement after discontinuation. The recurrent, antibiotic-resistant nature of pleural effusions suggests possible immune-mediated etiology. Early recognition is crucial to prevent systemic progression. Filgotinib has shown efficacy in controlling both articular and cutaneous disease activity, representing a valuable therapeutic alternative. The use of medical cannabis for refractory dyspnea highlights the importance of personalized, symptom-oriented approaches.

Conclusions. This case illustrates the complex management of RA complicated by etanercept-induced DIL. Persistent respiratory manifestations, steroid-related complications, and intolerance to conventional DMARDs require a multidisciplinary, patient-tailored approach, emphasizing early DIL recognition and the selection of safe and effective alternative therapies.