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Whipple disease (WD) is an infection caused by the bacterium Tropheryma whipplei (TW). Few cases have been reported in the USA. To report on the demographics, clinical manifestations, diagnostic findings, treatment, and outcomes of TW infection. Cases of TW infection diagnosed from 1995 to 2010 were identified in three US referral centers and from 1995 to 2015 in one. Definite classic WD was defined by positive periodic acid-Schiff (PAS) staining and probable WD by specific positive TW polymerase chain reaction (PCR) of intestinal specimens. Localized infections were defined by a positive TW PCR result from samples of other tissues/body fluids. Among the 33 cases of TW infections, 27 (82%) were male. Median age at diagnosis was 53 years (range 11–75). Diagnosis was supported by a positive TW PCR in 29 (88%) and/or a positive PAS in 16 (48%) patients. Classic WD was the most frequent presentation (n = 18, 55%), with 14 definite and 4 probable cases. Localized infections (n = 15, 45%) affected the central nervous system (n = 7), joints (n = 4), heart (n = 2), eye (n = 1), and skeletal muscle (n = 1). Blood PCR was negative in 9 of 17 (53%) cases at diagnosis. Ceftriaxone intravenously followed by trimethoprim and sulfamethoxazole orally was the most common regimen (n = 23, 70%). Antibiotic therapy resulted in clinical response in 24 (73%). TW infection can present as intestinal or localized disease. Negative small bowel PAS and PCR do not exclude the diagnosis of TW infection, and blood PCR is insensitive for active infection.

Whipple's disease is a chronic inflammatory systemic disorder in which all organs can be invaded by the rod-shaped bacterium Tropheryma whipplei. It is a rare disease and frequently misdiagnosed, though there is no valid estimate of its actual incidence and prevalence. Only about 1,000-1,500 cases have been reported. The clinical course of untreated Whipple's disease can include three stages: (1) a non-specific prodromal stage which includes migratory polyarthralgias; (2) a classic abdominal manifestation which involves weight loss, weakness, chronic diarrhea, and abdominal pain; and (3) a generalized stage characterized by steatorhea, cachexia, lymphadenopathy, hyper-pigmentation, and cardiovascular, pulmonary, and neurological dysfunction. The authors describe a case of a 39-year-old male patient with about a year's history of generalized adenopathy, inappetence, weight loss, progressive weakness, subfebrilities, and convulsive abdominal pain. Following primary exclusion of a tumor disease, a lymph node biopsy demonstrated a typical picture of a granulomatous inflammation-Whipple's lymphadenitis with partial exemption of the Gram reaction, and stain features corresponding to T. whipplei, which is regarded as the etiological agent causing this disorder. Further tests confirmed the generalized form of the disorder, affecting the lymphatic tissues, gastrointestinal system, respiratory system, and nervous system, with sensory and motor polyneuropathy. HLA-B27 antigen, which is frequent among those with Whipple's disease, was also present. Following treatment for three months with antibiotics a significant reduction of the changes typical of Whipple's disease was found upon follow-up biopsy, hence we assume the applied therapy was successful. In our case study we emphasize the atypical course of the disease with dominant generalized lymphadenopathy and only mild gastrointestinal symptoms.

Whipple's disease is a multisystemic disorder in which almost all organ systems can be invaded by rod-shaped bacteria. Without extended antimicrobial therapy, its course is lethal. Empirically, treatment consists of tetracyclines given for one to two years. Trimethoprim-sulfamethoxazole, a compound that crosses the blood-brain barrier, has been suggested as an alternative when patients were observed with progressive cerebral involvement. There has never been a formal evaluation of the selection of antibiotics for the treatment of Whipple's disease. In the present nonrandomized, partially retrospective study, we compared the result of two treatment regimens in 30 patients, all examined personally. Twenty-two patients were treated with tetracycline and eight patients with trimethoprim-sulfamethoxazole. In five patients, therapy with tetracycline was changed to another antimicrobial agent because of treatment failure or drug intolerance. The main treatment measure was disappearance of the clinical symptoms such as weight loss, arthritis, malabsorption, fever, edema, central nervous system manifestations, lymphadenopathy, and congestive heart failure. Drug intolerance requiring a change of medication was also considered a treatment failure. We found that trimethoprim-sulfamethoxazole induced complete clinical remission in 12 of 13 treatment cycles, tetracycline in 13 of 22 treatment cycles (P

Hydrogen breath tests (H2 BT) have been used extensively to investigate intestinal dissacharidase deficiencies. A potentially useful test for assessing intestinal absorptive function, the H2 BT withd-xylose (H2 BT-d-xylose), has received scant attention. We report here the results of our investigation of this test in 45 patients. Fifteen patients had proved malabsorption that was due to nontropical sprue in nine, and to lymphoma, Whipple's disease, or giardiasis in the remainder. Nine patients had small-bowel bacterial overgrowth secondary to either postsurgical sequelae or intestinal dysmotility. Twenty-one patients with irritable bowel syndrome and 21 healthy individuals served as control groups. All participants ingested 25 g ofd-xylose, and alveolar breath samples were obtained thereafter at 30 min intervals for 5 hr. Breath H2 was measured by chromatography. Basal H2 production, peak change (Δ) and area under the curve (AUC) were calculated. Simultaneously, 5-hr urinary excretion ofd-xylose was measured by colorimetry and served as the reference test. In healthy individuals,d-xylose ingestion increased H2 production (Δ=5.8±1.4 ppm,P

There is controversy as to the role of immune deficiency, if any, in Whipple's disease. This report summarizes published data in regard to immune function in this disease. Thirty-two publications during the past ten years offer varying amounts of immunological data in 61 patients — 50 males, 6 females, and 5 patients in whom the sex was not reported. There is no evidence for humoral immune deficiency in these patients. Secretory immunoglobulins are within normal limits. Intestinal mucosal plasma cells are decreased before treatment, but are normal after treatment. There are no abnormal deposits of complement or immunoglobulins within the intestinal mucosa. There is no evidence for autoantibody production. These patients invariably have lymphocytopenia prior to treatment and have a decreased percentage of T cells both before and after treatment. There is decreased responsiveness of lymphocytes to the mitogens PHA and Con A, before and after treatment. The cutaneous response to antigens is clearly diminished before treatment, improves somewhat after treatment, but is still significantly less than that seen in normal controls. There may be an increased association with HLA B27, which suggests that an abnormality in the cellular immune system promotes susceptibility to the Whipple bacillus.

Intraepithelial lymphocytes (IEL) of the intestinal mucosa of normal man and of patients with Whipple's disease were studied by light microscopy of 1-micron-thick sections, and by electron microscopy of thin sections. IEL in normal human intestine tend to be elongated in outline, have few cytoplasmic organelles, have compact nuclei, and are unattached to epithelial cells. IEL in Whipple's disease are more likely to be activated in appearance, ie, to be larger and to contain more cytoplasmic organelles than IEL of normal intestine. The number of IEL/100 intestinal epithelial cells is similar in normal man and in patients with Whipple's disease. Other intraepithelial (IE) cells found in normal intestine include eosinophils and mast cells, and we note for the first time the presence of IE macrophages. There are no "globule leukocytes" in the intestine of normal man or of patients with Whipple's disease. Other IE cells found in the intestine in Whipple's disease include eosinophils, polymorphonuclear (PMN) leukocytes, and macrophages in untreated disease and intraepithelial macrophages in treated disease. These IE cells may be involved in the acute and chronic immune responses of the intestine.

At endoscopy, a 30-year-old man with acquired immune deficiency syndrome (AIDS), Kaposi's sarcoma, diarrhea, and unexplained malabsorption showed erythematous macular duodenal lesions consistent with Whipple's disease by histology and electron microscopy. Symptoms did not respond to tetracycline. Subsequent cultures revealed systemic Mycobacterium avium (M. avium) infection. Tissue from this patient, from patients with Whipple's disease and from a macaque with M. avium were compared. All contained PAS-positive macrophages but M. avium could be distinguished by positive acid-fast stains and a difference in pattern of indirect immunofluorescence staining with bacterial typing antisera. PAS-positive macrophages in the intestinal lamina propria are no longer pathognomonic of Whipple's disease. Ultrastructural and histological similarities between Whipple's disease and M. avium infection suggest that both are manifestations of immune deficits limiting macrophage destruction of particular bacteria after phagocytosis. M. avium must be considered in the differential diagnosis of diarrhea in patients with AIDS and other immunosuppressed conditions.

We describe a patient with Whipple's disease without apparent intestinal involvement at initial presentation. Electron microscopy demonstrated the typical bacilli in PAS-negative lymph node and muscle biopsy specimens.

Histological review of a liver biopsy from a patient with known Whipple's disease revealed a prominence of Kupffer cells containing PAS-positive granules. Electron microscopy revealed rod-shaped organisms in the Kupffer cells but the presence of these structures were not associated with overt liver injury. This is thought to be the first reported demonstration of these bacillary bodies in this location.