We undertook a computer-aided search of PubMed, which identified 1216 publications on Whipple's disease (1140 on Whipple disease). In addition, mostly overlapping, we found 1139 references on intestinal lipodystrophy (111 on Intestinale Lipodystrophie) and six on Morbus Whipple. We had in-depth discussions with participants at the nine partner institutes in the European project on Whipple's disease. Finally, we took into account several doctoral theses, several general and specialist book
SeminarWhipple's disease
Section snippets
Bacteriology
The cause of Whipple's disease remained obscure for years. In his initial description, Whipple reported that silver-stained rod-shaped microorganisms were visible in the vacuole of macrophages, but he did not link this observation with a possible causative agent.1 Later staining procedures with periodic-acid-Schiff (PAS) showed abnormal material.2, 3 In 1960 and 1961, observations of bacteria-like bodies were made by transmission electron microscopy, and a bacterial cause was strongly suspected.
Epidemiology and pathogenesis
Whipple's disease is rare, and no valid estimate of the incidence is available. The disorder has been described most frequently in white people and in mid-Europe (of 696 cases, 55% were reported from Europe and 38% from North America).40 Only a few cases have been reported in Hispanic, black, Indian, or Asian populations. Many of the published cases come from rural regions, and farmers are frequently among the documented occupations.40, 41 The disease sometimes occurs in local clusters.42, 43,
Clinical features and diagnosis
Whipple's disease has traditionally been regarded as a gastrointestinal disease, but in most cases, the disease begins insidiously with arthropathy. In one large series,63, 75 arthropathy was the first symptom in 63% of patients, preceding the diagnosis of Whipple's disease by a mean of 8 years. Arthropathy, in many cases associated with HLA-B27 positivity, consists of chronic, migratory, non-destructive, and seronegative joint disease, mainly in the peripheral joints.40, 43 The sacroiliac
Histopathological and laboratory diagnosis
The first diagnostic method is the histological appearance. When the disease is suspected, duodenal-biopsy specimens should be obtained. Depending on the clinical manifestations, other samples should be tested, such as cerebrospinal fluid (CSF), cardiac-valve tissue, lymph nodes, and synovial tissue.46, 94 The infiltration of the bowel wall is associated with a widening and flattening of the villi and with dilated lacteals containing yellow lipid deposits, the result of blockade of the villous
Treatment and prognosis
Untreated Whipple's disease can be fatal. However, in many patients with the disease, antibiotic therapy leads to rapid improvement in clinical status and to lasting remission11, 40, 109, 110, 111 Diarrhoea and fever can resolve as quickly as within 1 week of the start of therapy, and arthropathy and other symptoms improve in many cases after a few weeks. Clinical improvement is generally accompanied by a normalisation of laboratory findings and gradual reconstitution of the villous
Future perspectives
The reservoir of T whipplei should be identified beyond doubt. At present, environment waste is suspected to be contaminated, and the atypical geographical distribution can be explained by unknown environmental factors. The true prevalence of the infection by T whipplei may differ from that of recognised Whipple's disease. Benign forms and atypical manifestations without PAS-positive foamy macrophages could exist. The complete clinical range, including infectious endocarditis, might differ from
Search strategy and selection criteria
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Whipple's disease: light and electron microscope correlation of jejunal mucosal histology with antibiotic treatment and clinical status
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Concurrent Whipple's disease and Giardia lamblia infection in a patient presenting with weight loss
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Lymphocytes in Whipple's disease
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Persistent reduction of complement receptor 3 alpha-chain expressing mononuclear blood cells and transient inhibitory serum factors in Whipple's disease
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Immunological defect in Whipple's disease
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Invasion and destruction of mucosal plasma cells by Tropheryma whippelii
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Defects of monocyte interleukin-12 production and humoral immunity in Whipple's disease
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Dysregulated peripheral and mucosal Th1/Th2 response in Whipple's disease
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A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues
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Tinctorial demonstration of a glycoprotein in Whipple's disease
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Ultrastructural abnormalities in Whipple's disease
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Ultrastructure of bacilli and bacillary origin of the macrophagic inclusions in Whipple's disease
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Whipple's disease: observation on systemic involvement, II gross and histological observations
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Whipple's disease: a review of the literature and report of 15 patients
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Description of Tropheryma whipplei gen nov, sp nov, the Whipple's disease bacillus
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Whipple's disease: immunological and histochemical studies of eight cases
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Deactivation of macrophages with interleukin-4 is the key to the isolation of Tropheryma whippelii
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Cultivation of the bacillus of Whipple's disease
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The survival of Tropheryma whipplei, the agent of Whipple's disease, requires phagosome acidification
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Phagolysosomal alkalinization and the bactericidal effect of antibiotics
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A guinea pig model for Q fever endocarditis
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Identification of the uncultured bacillus of Whipple's disease
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Improving the sensivity of progressive multiple sequence alignment through sequence weighting, position specific gap panlties and weight matrix choice
Nucl Acids Res
PHYLIP-Phylogeny Inference Package (version 3.2)
Cladistics
A simple method for estimating evolutionary rate of base subsitutions through comparative studies of nucleotide sequences
J Mol Evol
Reassessment of the phylogenetic position of the bacterium associated with Whipple's disease and determination of the 16S–23S ribosomal intergenic spacer sequence
Int J Syst Bacteriol
Homogeneity of 16S-23S ribosomal intergenic spacer regions of Tropheryma whippelii in Swiss patients with Whipple's disease
J Clin Microbiol
Evaluation of a specific nested PCR targeting domain III of the 23S rRNA gene of “Tropheryma whippelii” and proposal of a classification system for its molecular variants
J Clin Microbiol
Detection of three different types of 'Tropheryma whippelii' directly from clinical specimens by sequencing, single-strand conformation polymorphism (SSCP) analysis and type-specific PCR of their 16S-23S ribosomal intergenic spacer region
Int J Syst Bacteriol
Whipple's disease
Clin Diagn Lab Immunol
Environmental occurrence of the Whipple's disease bacterium (Tropheryma whippelii)
Appl Environ Microbiol
Detection of Tropheryma whippelii (Whipple's disease) in faeces
Ital J Gastroenterol Hepatol
Tropheryma whippelii DNA in saliva of patients without Whipple's disease
Infection
Tropheryma whippelii DNA is rare in the intestinal mucosa of patients without other evidence of Whipple disease
Ann Intern Med
Whipple's disease
Cited by (230)
Whipple's disease and Tropheryma whipplei infections: from bench to bedside
2022, The Lancet Infectious DiseasesCitation Excerpt :Its prevalence is estimated at 1·1 cases per one million people, with an annual incidence between one and six cases per ten million people worldwide.31 Classical Whipple's disease generally manifests as intermittent arthralgia, arthritis, or other joint problem accompanied by chronic digestive trouble (diarrhoea and abdominal pain)32,33 and mainly affects middle-aged White males (mean age at the time of diagnosis is 55 years, 85% of cases are males), although, the prevalence of female cases has increased in the past 30 years.12,34,35 In 80% to 90% of classical Whipple's disease cases, seronegative arthritis and arthralgia are the main clinical manifestations.7,12,36
Tropheryma whipplei agent of self-limiting infections and whipple’s disease
2019, Gastrointestinal Diseases and Their Associated InfectionsInfections of the Gastrointestinal Tract
2018, Diagnostic Pathology of Infectious DiseaseCase report: A systemic lupus erythematosus patient with Tropheryma whipplei infection
2024, International Journal of Rheumatic DiseasesOphthalmic manifestations of Whipple's disease
2024, Current Opinion in Ophthalmology