P104 Disseminated tuberculosis in a patient on tumor necrosis factor (TNF)-α inhibitor treatment for ankylosing spondylitis: a case report

Abstract Introduction Tumor necrosis factor (TNF) plays a pivotal role in the inflammatory cascades of ankylosing spondylitis (AS), driving immune activation and chronic inflammation in the spine and sacroiliac joints. TNF-α inhibitors—adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab—are recommended for severe, treatment-resistant AS. Adalimumab, a monoclonal anti-TNF-α antibody, has been linked to a higher tuberculosis (TB) risk than etanercept, with literature suggesting a three- to fourfold increase. We present a rare case of aggressive disseminated TB in an AS patient treated with adalimumab, resulting in fatality, highlighting the importance of rigorous screening and monitoring in high-risk populations receiving anti-TNF-α therapy. Case description A 40-year-old white British male with a history of psoriasis was diagnosed with ankylosing spondylitis (AS) in his early 20s and treated with NSAIDs for 13 years, with inadequate symptom control. In 2015, following a lapse in follow-up, he re-presented with a BASDAI score of 8. Prior to initiating anti-TNF-α therapy, screening—including chest X-ray and viral hepatitis tests—revealed no abnormalities. Golimumab was commenced, leading to symptomatic improvement. After two years, side effects prompted a switch to adalimumab, with stable disease control. In January 2024, the patient presented with respiratory distress, fever, night sweats, abdominal distension, and weight loss. Chest X-ray revealed diffuse nodular opacities; sputum culture confirmed miliary TB. CT imaging showed bilateral pulmonary nodules, splenomegaly with low-density foci, and chronic sacroiliac joint fusion. Anti-TB therapy was started, and adalimumab was discontinued. One week post-discharge, liver enzymes were significantly elevated (ALT 235 IU/L, ALP 843 IU/L), necessitating cessation of TB treatment. In March, he was readmitted with worsening symptoms. Imaging revealed progressive miliary TB, bilateral effusions, mediastinal lymphadenopathy, pulmonary embolism, and small bowel obstruction. The liver appeared normal, but inflammation persisted, with elevated CRP and liver dysfunction. While on the ward, he developed a large left-sided pneumothorax requiring emergency chest drain insertion. He deteriorated rapidly, was intubated, and transferred to ICU. Despite initiation of rifampicin, levofloxacin, isoniazid, and ethambutol, his condition progressed to multiorgan failure, and he died later that month. This case highlights a rare but devastating instance of rapidly progressive disseminated TB following anti-TNF-α therapy. Despite appropriate screening and initial TB exclusion, fulminant disease developed, underscoring the need for ongoing vigilance in high-risk patients. Discussion The pleiotropic cytokine TNF-α plays a significant role in the pathophysiology of AS, inflammatory bowel disease, rheumatoid arthritis, and other immune-mediated or inflammation-related conditions. Evidence suggests individuals receiving TNF-α antagonists have an elevated risk of developing TB. Prior to initiating anti-TNF-α treatment, all patients should follow British Society for Rheumatology (BSR) guidelines. Tuberculin tests are generally not recommended for most rheumatology patients. Instead, TB risk should be assessed through clinical history, examination, chest X-ray, and, if necessary, an algorithm weighing chemoprophylaxis risk against TB. Resource implications of increased TB specialist consultations must be considered. However, it might be worth considering interferon-gamma release assay or tuberculin tests before initiating anti-TNF therapy in the future. In this case, due to inadequate response to NSAIDs for AS, anti-TNF-α therapy was started per BSR guidelines, which required pre-treatment screening, including hepatitis screening and chest X-ray. Given the patient’s diagnosis, absence of recent TB exposure, travel history, or contact with TB cases, and White-British ethnicity, latent TB testing via IGRA or Mantoux was not justified. The decision was based on clinical history and normal chest X-ray findings. The UK’s cultural diversity includes migrants from TB-endemic countries. Migrants arriving via formal visa routes undergo chest X-ray screening, but unofficial arrivals do not, increasing TB risk. The majority of active TB cases in England occur in people born outside the UK, posing transmission risks, especially to immunocompromised patients on drugs like adalimumab and infliximab. Immunocompromised status may cause false-negative TB screening results, highlighting the need to consider chemoprophylaxis for high-risk patients. In this case, anti-TB medications were halted for five weeks due to abnormal liver function. Treatment resumed after biochemical markers normalized, with second-line fluoroquinolones added to reduce drug resistance risk. Balancing adverse effects against treatment benefits is vital to avoid resistance and prolonged therapy. Key learning points • Comprehensive latent TB screening must be performed before starting anti-TNF therapy, even in patients with no traditional risk factors. • TNF-α inhibitors carry a real risk of rapid disseminated TB reactivation, which can be fatal. • This case highlights the danger of relying solely on chest X-ray and history, reinforcing the urgent need to strengthen screening protocols.