Background/Purpose:

Inflammatory arthritis is a common, non-specific symptom of Whipple’s disease. Recovery of the organism by conventional culture is often unsuccessful. Synovial fluid polymerase chain reaction (PCR) testing for Tropheryma whippelii may increase the diagnostic yield; however the diagnostic specificity of this approach is unclear. A high rate of detection of T. whipplei PCR in saliva of healthy individuals has been reported. To date, there has been no study of the performance of PCR for T. whippelii in synovial fluid PCR.

Therefore, we aimed to summarize our experience with a T. whippelii synovial fluid PCR test in patients seen at a single referral center and clarify whether utilization of this test in patients with inflammatory arthritis would result in a high rate of false-positive results.

Methods:

DNA was extracted from synovial fluid using the automated MagNA Pure LC instrument. Real-time PCR with FRET probe detection, targeting the heat shock protein gene of T. whipplei, was performed on amplified DNA. The total number of patients who had synovial fluid PCR testing for T. whippelii between 01/01/2003-04/01/2015 was determined using the clinical microbiology database. A detailed chart review was performed for all patients with positive PCR results. All patients were followed up for a minimum of one year.

Results:

Over the past 12 years, 302 patients underwent synovial fluid PCR testing for T. whippelii at our institution. The PCR was positive in only 4 patients.  All PCR positive patients were middle-aged males who presented with chronic inflammatory arthritis and a variety of additional symptoms including fever, malaise, and peripheral edema and generalized weakness. They had been diagnosed and treated with various immunosuppressive drugs or antiinflammatories unsuccessfully. Small bowel biopsy to identify the organism was undertaken in 2 of the 4 patients with positive synovial fluid PCR. Tissue samples from these biopsies were negative for periodic acid Schiff stain (PAS) positive macrophages and by T. whippelii PCR.

All synovial fluid PCR positive patients (including the 2 with negative small bowel biopsies) were diagnosed with Whipple’s disease by their medical team and subsequently treated with antibiotics (ceftriaxone 2g IV q24 for 2-4 weeks followed by trimethoprim-sulfamethoxazole 160/800 mg 1 tablet twice daily for 1 year), resulting in complete resolution of symptoms in all patients. No recurrences occurred during the follow-up period of at least 1 year.

Conclusion:

Our experience suggests that T. whippelii synovial fluid PCR testing in patients with inflammatory arthritis is a highly specific test for Whipple’s disease. All patients who tested positive in our cohort had symptoms consistent with a diagnosis of Whipple’s disease, had previously been unsuccessfully treated with immunosuppressive therapies, and had a dramatic and complete improvement after starting antibiotic therapy. No recurrences/alternative diagnoses emerged during the follow-up period. Synovial fluid PCR testing for T. whippelii appears to be a valuable diagnostic test in patients with inflammatory arthritis and suspected Whipple’s disease even when the stain for PAS positive macrophages on small bowel biopsy is negative.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/whipples-disease-the-diagnostic-utility-of-synovial-fluid-tropheryma-whipplei-polymerase-chain-reaction/