INTRODUCTION
In 1907, George H Whipple described a 36-year-old clinician with "gradual loss of weight and strength, stools consisting chiefly of neutral fat and fatty acids, indefinite abdominal signs, and a peculiar multiple arthritis" [1]. The patient died of this progressive illness; Whipple called it intestinal lipodystrophy since he observed accumulation of "large masses of neutral fats and fatty acids in the lymph spaces." It was renamed Whipple's disease in 1949 upon description of the sine qua non of this disorder, accumulation of macrophages in the lamina propria with intensely periodic acid-Schiff (PAS)-positive intracellular material [2]. An infectious etiology was suspected as early as Whipple's initial report; however, successful treatment with antibiotics was not reported until 1952 [3].Scientific understanding of the histology, immunology, and treatment of Whipple's disease has improved since the initial description, and the etiologic agent was identified in 1991. The cause is now known to be Tropheryma whipplei (from the Greek "trophe," nourishment, and "eryma," barrier, in reference to the nutrient malabsorption characteristic of the disease), a discovery made upon application of a new technique for identifying microbes based upon the DNA sequence encoding their 16S ribosomal RNA. T. whipplei is closely related to many other soil-borne actinomycetes [4,5].
This topic discusses the clinical manifestations, diagnosis, and treatment of Whipple’s disease. Discussion of the approach to chronic diarrhea and the evaluation of polyarticular pain in adults is found elsewhere. (See "Approach to the adult with chronic diarrhea in resource-abundant settings" and "Evaluation of the adult with polyarticular pain".)
MICROBIOLOGY
Whipple’s disease is caused by T. whipplei, a gram-positive bacillus related to Actinomycetes. Whipple suspected an infectious agent in 1907 when he noted the numerous "rod-shaped organisms" within the submucosa and macrophages of the index patient. Careful light and electron microscopy by numerous investigators between 1960 and 1992 subsequently identified a gram-positive, non-acid-fast, periodic acid-Schiff (PAS)-positive bacillus with a characteristic trilamellar plasma membrane surrounded by a cell wall.Application of polymerase chain reaction (PCR) allowed identification of a unique bacterial 16S ribosomal RNA in the intestinal and lymphatic tissue of 5 patients with Whipple's disease that was absent in 10 control patients [5]. Culture of the organism is extremely difficult. This had not been achieved until a 1997 report in which T. whipplei was propagated in cell culture; deactivation of peripheral blood monocytes with interleukin-4 was required for intracellular growth to occur [6]. Unfortunately, this culture technique could not be reproduced [7].