Whipple's disease diagnosis following the use of TNF-α blockade

A 46-year-old man with inflammatory back pain and large and small joint arthritis was diagnosed with AS 10 years following symptom onset. Physical examination showed decreased vertebral range of motion. Laboratories revealed ESR of 40 mm/h, RF negative, ANA negative with positive HLA-B27. Plain radiographs demonstrated sacroiliac pseudo-widening. Anti-inflammatories, MTX (25 mg s.c. weekly) and prednisone (7.5–10 mg daily) were initiated. Five months later, infliximab (5 mg/kg increased to 10 mg/kg every 6 weeks) was added for inflammatory back pain with improvement.

After 2 years of infliximab, the patient developed fevers and migratory arthritis precipitating hospitalization. Abnormal laboratories included white blood cell (WBC) count 36 k/mm³, haemoglobin (Hgb) 11.6 g/dl and ESR 58 mm/h. Evaluation including WBC scan, histoplasma antigen, brucella serology, routine and lysis centrifugation blood cultures, hepatitis and HIV serology, and bone marrow biopsy were negative. Symptoms resolved with cessation of infliximab and MTX. Three months later, re-challenge with adalimumab and MTX for recurrent inflammatory symptoms resulted in fevers, migratory arthritis and new weight loss with diarrhoea. Endoscopy with duodenal biopsy showed altered architecture and intracellular bacilli on periodic acid-Schiff stain (Fig. 1). Trophyrema whipplei was detected from blood and duodenal tissue by PCR. Intravenous ceftriaxone (2 g daily for 2 weeks) was commenced followed by trimethoprim-sulphamethoxazole with improved symptoms.

Fig. 1.

Detection of Whipple's disease. (A) Duodenal mucosa showing loss of normal villous architecture with foamy macrophages filling and expanding the lamina propria (haematoxylin and eosin stain, objective magnification 10×). (B) Intense periodic acid–schiff staining of bacilli demonstrated within the macrophages of the lamina propria (objective magnification 10×).

Trophyrema whipplei is a ubiquitous organism, rarely associated with multisystemic and relapsing disease. The organism may be detectable by PAS staining of involved organ tissue or with 16S rRNA gene identification [1]. Arthropathies associated with T. whipplei may precede diagnosis and exhibit axial and peripheral involvement, with symptom exacerbation following TNF-α inhibitors [1, 2]. Our case illustrates the consideration of alternative aetiologies in patients with articular symptoms, most importantly following clinical deterioration on immunomodulatory agents like TNF-α inhibitors.

Disclosure statement: The authors have declared no conflicts of interest.