Published online Dec 26, 2014. doi: 10.4330/wjc.v6.i12.1278
Revised: September 2, 2014
Accepted: November 17, 2014
Published online: December 26, 2014
Processing time: 46 Days and 19.8 Hours
AIM: To test whether treatment with tumor necrosis factor inhibitors (TNFI) is associated with complications of Tropheryma whipplei (T. whipplei) infection.
METHODS: Because unexplained arthritis is often the first Whipple’s disease (WD) symptom, patients may undergo treatment with TNFI before diagnosis. This may influence the course of infection with T. whipplei, which causes WD, because host immune defects contribute to the pathogenesis of WD. A literature search and cross referencing identified 19 reports of TNFI treatment prior to WD diagnosis. This case-control study compared clinical data in patients receiving TNFI therapy (group I, n = 41) with patients not receiving TNFI therapy (group II, n = 61). Patients from large reviews served as controls (group III, n = 1059).
RESULTS: The rate of endocarditis in patient group I was significantly higher than in patient group II (12.2% in group I vs 1.6% in group II, P < 0.05), and group III (12.2% in group I vs 0.16% in group III, P < 0.01). Other, severe systemic or local WD complications such as pericarditis, fever or specific organ manifestations were increased also in group I as compared to the other patient groups. However, diarrhea and weight loss were somewhat less frequent in patient group I. WD is typically diagnosed with duodenal biopsy and periodic acid Schiff (PAS) staining. PAS-stain as standard diagnostic test had a very high percentage of false negative results (diagnostic failure in 63.6% of cases) in group I. Polymerase chain reaction (PCR) for T. whipplei was more accurate than PAS-stainings (diagnostic accuracy, rate of true positive tests 90.9% for PCR vs 36.4% for PAS, P < 0.01).
CONCLUSION: TNFI trigger severe WD complications, particularly endocarditis, and lead to false-negative PAS-tests. In case of TNFI treatment failure, infection with T. whipplei should be considered.
Core tip: Arthritis frequently is the first symptom of Whipple’s disease (WD). Therefore, many patients are treated with anti-inflammatory drugs or tumor necrosis alpha inhibitors (TNFI) before diagnosis. As host immune defects contribute to the pathogenesis of WD, immunosuppressive therapy may deteriorate the course of Tropheryma whipplei (T. whipplei) infection. In this study, it is shown that treatment with TNFI is associated with severe complications of T. whipplei infection, particularly with endocarditis. TNFI therapy may lead to false negative periodic acid-Schiff-tests and thereby hinder the diagnosis of WD. T. whipplei infection should be considered in case of TNFI treatment failure.