Disseminated tuberculosis associated with fingolimod treatment in a patient with multiple sclerosis.

Fingolimod is a sphingosine-1-phosphate receptor modulator approved as a disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (MS). A woman in her 30s was treated with fingolimod for relapsing-remitting MS. After 7 years of treatment, she presented with non-productive cough, night sweats, breathlessness and unintentional weight loss. She had a negative interferon-gamma release assay (IGRA). A high-resolution CT thorax showed innumerable miliary opacities in both lungs. Bronchoalveolar lavage was positive for Mycobacterium tuberculosis complex PCR. An MRI head showed multiple small punctate contrast-enhancing lesions most typical for tuberculomas. We describe the first reported case of disseminated tuberculosis (TB) associated with fingolimod treatment. Patients who are receiving DMT must be closely observed for the development of opportunistic infections, and IGRA results should be interpreted with caution. Screening for latent TB prior to commencing fingolimod should be considered on an individual basis. The management of TB in MS patients on DMT requires an interdisciplinary approach.

Systematic review and meta-analysis of prevalence of undiagnosed major cardiac comorbidities in COPD.

Background: It is often stated that heart disease is underdiagnosed in COPD. Evidence for this statement comes from primary studies, but these have not been synthesised to provide a robust estimate of the burden of undiagnosed heart disease. Methods: A systematic review of studies using active diagnostic techniques to establish the prevalence of undiagnosed major cardiac comorbidities in patients with COPD was carried out. MEDLINE, Embase, Scopus and Web of Science were searched for terms relating to heart failure (specifically, left ventricular systolic dysfunction (LVSD), coronary artery disease (CAD) and atrial fibrillation), relevant diagnostic techniques and COPD. Studies published since 1980, reporting diagnosis rates using recognised diagnostic criteria in representative COPD populations not known to have heart disease were included. Studies were classified by condition diagnosed, diagnostic threshold used and whether participants had stable or exacerbated COPD. Random-effects meta-analysis of prevalence was conducted where appropriate. Results: In general, prevalence estimates for undiagnosed cardiac comorbidities in COPD had broad confidence intervals, with significant study heterogeneity. Most notably, a prevalence of undiagnosed LVSD of 15.8% (11.1-21.1%) was obtained when defined as left ventricular ejection fraction <50%. Undiagnosed CAD was found in 2.3-18.0% of COPD patients and atrial fibrillation in 1.4% (0.3-3.5%). Conclusion: Further studies using recent diagnostic advances, and investigating therapeutic interventions for patients with COPD and heart disease are needed.