Whipple's disease with normal duodenal histology diagnosed by ileal biopsy using balloon endoscopy

A 34 year-old previously healthy Japanese woman presented with a 4 year history of migratory arthralgia, chronic diarrhea, mild fever, and 10 kg weight loss. She was initially misdiagnosed with seronegative arthritis, followed by eosinophilic gastroenteritis. Oral prednisolone was found to be ineffective. Upper endoscopy revealed normal duodenal mucosa. Duodenal biopsy specimen indicated no abnormalities. However, balloon endoscopy revealed white shaggy villi in the ileum, and a biopsy specimen from which revealed diffuse infiltration of foamy macrophages in the lamina propria. These macrophages contained diastase-periodic acid-Schiff positive granules, consistent with Whipple's disease. Polymerase chain reaction analysis of DNA extracted from the ileum was compatible with Whipple's disease. In most previously reported cases of Whipple's disease, the duodenum was affected and duodenal biopsy specimens led to a diagnosis of Whipple's disease. Whipple's disease with normal duodenal histology is extremely rare and balloon endoscopy might be a useful diagnostic tool in such a case. The patient was treated with intravenous ceftriaxone and oral trimethoprim-sulfamethoxazole, and her symptoms improved one month after treatment. Balloon endoscopy performed 32 months later revealed complete improvement in lesions of the ileum.