Prevalence, characteristics, and clinical outcomes of Whipple disease in patients initially diagnosed with a rheumatic disease: a large nested case-control study in the Eastern Netherlands

Objectives: Whipple disease (WD) is a rare infectious disease with an estimated prevalence of 10 per million.As many patients with WD experience arthralgia or arthritis, they are often initially misdiagnosed with an inflammatory rheumatic disease (IRD).This study assesses the prevalence and determinants of new WD diagnoses in patients with IRD.Methods: A nested case-control study (Sint Maartenkliniek, East Netherlands) was conducted between 2012 and 2024, by comparing all WD cases initially diagnosed with IRD with a non-WD control group matched for duration of follow-up.Potential indicators (at presentation and during IRD follow-up) for WD were analysed using conditional logistic regression, and outcomes after treatment were assessed.Results: In 25,380 patients, the prevalence of WD was 1000 per million (25 cases).Male sex (odds ratio [OR], 16.3; 95% CI, 3.44-77.0),weight loss (OR, 44.7; 95% CI, 10.3-2081), polyarthritis (OR, 6.08; 95% CI, 1.64-22.5),symmetrical arthritis (OR, 11.7; 95% CI, 2.52-54.8),both small and large joint arthritis (OR, 13.6; 95% CI, 2.14-86.0),elevated C-reactive protein (OR, 10.4; 95% CI,3), and testing negative for rheumatoid factor and anticyclic citrullinated peptide (OR, 23.5; 95% CI, 2.02-273) were associated with having WD.After antibiotic treatment, 88% of WD cases achieved disease-modifying antirheumatic drug-free remission.Conclusions: The prevalence of WD was about 100-fold higher in patients with IRD than in the general population.WD cases are characterised by a specific profile of strongly associated characteristics at presentation, which can contribute to earlier diagnosis and treatment of WD.The excellent outcomes after WD treatment emphasise the initial misdiagnosis of IRD rather than comorbid infection.