Rheumatological features of Whipple disease

Abstract

Whipple disease (WD) is a rare infectious systemic disease. Rheumatologists are at the frontline of WD diagnosis due to the early rheumatological manifestations. An early diagnosis is crucial, as usual anti-rheumatic drugs, especially TNF inhibitors, may worsen the disease course. We conducted a retrospective multicentre national study from January 2010 to April 2020 to better characterize the rheumatological features of WD. Classic WD (CWD) was defined by positive periodic acid-Schiff (PAS) staining of a small-bowel biopsy sample, and non-CWD (NCWD) was defined by negative PAS staining of a small-bowel biopsy sample but at least one positive Tropheryma whipplei (TW) polymerase chain reaction (PCR) for a digestive or extradigestive specimen. Sixty-eight patients were enrolled, including 11 CWD patients. Twenty patients (30%) received TNF inhibitors during the WD course, with inefficacy or symptom worsening. More digestive symptoms and systemic biological features were observed in CWD patients than in NCWD patients, but both patient groups had similar outcomes, especially concerning the response to antibiotics and relapse rate. Stool and saliva TW PCR sensitivity were both 100% for CWD and 75% for NCWD and 89% and 60% for small-bowel biopsy sample PCR, respectively. WD encountered in rheumatology units has many presentations, which might result from different pathophysiologies that are dependent on host immunity. Given the heterogeneous presentations and the presence of chronic carriage, multiple TW PCR tests on samples from specific rheumatological sites when possible should be performed, but samples from nonspecific digestive and extradigestive sites also have great value.

Figure 1

Proposed overactive immune actors involved in Whipple disease pathophysiology. APC antigen presentation cell, DC dendritic cell, PNN neutrophils polynuclears, T Lymphocytes T, WD Whipple disease.

Figure 2

Proposed algorithm for Whipple disease in patients in whom rheumatism is suspected. CSF cerebro-spinal fluid, CWD classic Whipple disease, PAS periodic acid-Schiff, SB small bowel, WD Whipple disease. Cases of spondylodiscitis not considered in this algorithm. **Discuss CSF PCR in case of neurologic symptoms. *In case of chronic arthritis with negative synovial fluid PCR, discuss synovial biopsy. NB Data on cutaneous biopsy PCR were to scarce in our cohort integrate it on the algorithm.