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The diagnosis of Whipple's disease in the absence of intestinal involvement is difficult and often overlooked. We describe five patients aged 8-71 years with normal jejunal biopsies and disparate clinical features, previously unrecognized in Whipple's; all were investigated at a single institution over a period of 18 months. Routine histological examination for periodic acid-Schiff (PAS) positive macrophages and polymerase chain reaction (PCR) analysis for Tropheryma whippelii was performed on the small intestine in all patients. PCR analysis was also performed on various tissues including peripheral blood, lymph node, muscle, synovium and spleen in individual patients. Patients 1, 2, 4 and 5 had unusual presenting features not previously associated with Whipple's: intractable immune thrombocytopenic purpura (ITP), juvenile chronic arthritis, isolated muscle weakness and quadriparesis, respectively. Patient 3 presented with pyrexia of unknown origin. All patients had histologically normal small-bowel biopsies with no evidence of PAS positive macrophages. PCR for T. whippelii was positive in all patients in one or more tissues: peripheral blood, intestine, muscle, lymph node and synovium. PAS-positive macrophages were found in 4/5 patients in various sites: lymph node, muscle, spinal cord. Whipple's disease presents with protean clinical features and should be considered in granulomatous disorders of unknown aetiology even in the absence of gastrointestinal involvement.

Whipple's disease without malabsorption: new atypical features