scholarly journals Whipple's Disease and “Tropheryma whippelii”

2001 ◽  
Vol 14 (3) ◽  
pp. 561-583 ◽  
Author(s):  
Fabrizio Dutly ◽  
Martin Altwegg

SUMMARY Whipple's disease is a rare bacterial infection that may involve any organ system in the body. It occurs primarily in Caucasian males older than 40 years. The gastrointestinal tract is the most frequently involved organ, with manifestations such as abdominal pain, malabsorption syndrome with diarrhea, and weight loss. Other signs include low-grade fever, lymphadenopathy, skin hyperpigmentation, endocarditis, pleuritis, seronegative arthritis, uveitis, spondylodiscitis, and neurological manifestations, and these signs may occur in the absence of gastrointestinal manifestations. Due to the wide variability of manifestations, clinical diagnosis is very difficult and is often made only years or even decades after the initial symptoms have appeared. Trimethoprim-sulfamethoxazole for at least 1 year is usually considered adequate to eradicate the infection. The microbiological diagnosis of this insidious disease is rendered difficult by the virtual lack of culture and serodiagnostic methods. It is usually based on the demonstration of periodic acid-Schiff-positive particles in infected tissues and/or the presence of bacteria with an unusual trilaminar cell wall ultrastructure by electron microscopy. Recently, the Whipple bacteria have been characterized at the molecular level by amplification of their 16S rRNA gene(s). Phylogenetic analysis of these sequences revealed a new bacterial species related to the actinomycete branch which was named “Tropheryma whippelli.” Based on its unique 16S ribosomal DNA (rDNA) sequence, species-specific primers were selected for the detection of the organism in clinical specimens by PCR. This technique is currently used as one of the standard methods for establishing the diagnosis of Whipple's disease. Specific and broad-spectrum PCR amplifications mainly but not exclusively from extraintestinal specimens have significantly improved diagnosis, being more sensitive than histopathologic analysis. However, “T. whippelii” DNA has also been found in persons without clinical and histological evidence of Whipple's disease. It is unclear whether these patients are true asymptomatic carriers or whether differences in virulence exist among strains of “T. whippelii” that might account for the variable clinical manifestations. So far, six different “T. whippelii” subtypes have been found by analysis of their 16S-23S rDNA spacer region. Further studies of the pathogen “T. whippelii” as well as the host immune response are needed to fully understand this fascinating disease. The recent cultivation of the organisms is a promising major step in this direction.

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Jan Bureš ◽  
Marcela Kopáčová ◽  
Tomáš Douda ◽  
Jolana Bártová ◽  
Jan Tomš ◽  
...  

Whipple’s disease is a chronic infectious systemic disease caused by the bacteriumTropheryma whipplei. Nondeforming arthritis is frequently an initial complaint. Gastrointestinal and general symptoms include marked diarrhoea (with serious malabsorption), abdominal pain, prominent weight loss, and low-grade fever. Possible neurologic symptoms (up to 20%) might be associated with worse prognosis. Diagnosis is based on the clinical picture and small intestinal histology revealing foamy macrophages containing periodic-acid-Schiff- (PAS-) positive material. Long-term (up to one year) antibiotic therapy provides a favourable outcome in the vast majority of cases. This paper provides review of the literature and an analysis of our 5 patients recorded within a 20-year period at a tertiary gastroenterology centre. Patients were treated using i.v. penicillin G or amoxicillin-clavulanic acid + i.v. gentamicin for two weeks, followed by p.o. doxycycline (100 mg per day) plus p.o. salazopyrine (3 g per day) for 1 year. Full remission was achieved in all our patients.


2021 ◽  
Vol 84 (4) ◽  
pp. 665-667
Author(s):  
M Mascarenhas Saraiva ◽  
T Ribeiro ◽  
T Costa Pereira ◽  
P Andrade ◽  
H Cardoso ◽  
...  

Whipple’s disease is a rare chronic systemic infection caused by Tropheryma whipplei. The widespread infection by this rod is responsible for the protean clinical manifestations of the disease, although its classical form is notable for the prevalence of abdominal symptoms such as chronic diarrhea and abdominal pain. Whitish-yellow patches, suggestive of lymphangiectasia, are typically observed in the duodenum during upper endoscopy. The diagnosis of this condition is supported by the identification in duodenal biopsies of Periodic acid-Schiff staining within lamina propria macrophages. Nevertheless, a significant portion of patients do not have lesions within the range of conventional upper endoscopy. Therefore, other endoscopic procedures such as video capsule endoscopy and enteroscopy may be useful to detect more distal lesions. The authors describe a case where the combined used of both techniques allowed the unmasking of this disease.


2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Sabah Sid’Amar ◽  
Giacomo Puppa

Whipple’s disease is a rare chronic systemic bacterial infectious disease which can affect multiple organs, with a wide clinical spectrum encompassing many symptoms presenting in various forms and combinations. In the cases where the gastrointestinal tract is implicated, the more frequent localizations involve the small bowel, especially the duodenum. A case of a 67-year-old man who underwent clinical investigation after presenting with a progressive weight loss and showing a hypercapting right paracoeliac adenopathy at PET-CT scan is reported herein. A gastroscopy and a colonoscopy were done. The biopsies of the endoscopically normal ileal mucosa encompassed some submucosal Peyer’s patches. Histological examination of this lymphoid tissue revealed several foamy macrophages which turned out positive on periodic acid-Schiff special staining. Polymerase chain reaction of the microdissected lymph follicles allowed for confirming Whipple’s disease diagnosis. A targeted antibiotic treatment administrated to the patient led to a rapid clinical improvement. This finding of a previously unreported localization of infected macrophages in Whipple’s disease suggests that sampling the organized mucosal-submucosal lymphoid tissue may increase the diagnostic yield in endoscopic biopsies.


2015 ◽  
Vol 33 (2) ◽  
pp. 190-199 ◽  
Author(s):  
Thomas Marth

Background: The actinobacterium Tropheryma whipplei was detected 20 years ago by molecular techniques, and following its culture has been characterized as the cause of a systemic infection known as Whipple's disease (WD). T. whipplei occurs in the environment, is prevalent only in humans, is believed to be transmitted via oral routes and to be host dependent. Key Messages: The classical form of T. whipplei infection, i.e. classical WD (CWD), is rare. It is well defined as slowly progressing chronic infection with arthralgia, diarrhea and weight loss, mostly in middle-aged men. However, current research revealed a much broader spectrum of clinical features associated with T. whipplei infection. Thus, T. whipplei may cause acute and transient infections (observed primarily in children) and the bacterium, which is found in soil and water, occurs in asymptomatic carriers as well as in CWD patients in clinical remission. In addition, T. whipplei affects isolated and localized body compartments such as heart valves or the central nervous system. Subtle immune defects and HLA associations have been described. New findings indicate that the progression of asymptomatic T. whipplei infection to clinical WD may be associated with medical immunosuppression and with immunomodulatory conditions. This explains that there is a discrepancy between the widespread occurrence of T. whipplei and the rareness of WD, and that T. whipplei infection triggered by immunosuppression presents with protean clinical manifestations. Conclusions: This review highlights recent findings and the clinical spectrum of infection with T. whipplei and WD, focusing specifically on the role of host immunity and immunosuppression. Current concepts of the pathogenesis, diagnosis and therapy are discussed.


2015 ◽  
Vol 25 (2) ◽  
Author(s):  
Henrique Carvalho Rocha ◽  
Wóquiton Rodrigues Marques Martins ◽  
Marcos Roberto de Carvalho ◽  
Lígia Menezes do Amaral

2004 ◽  
Vol 48 (3) ◽  
pp. 747-752 ◽  
Author(s):  
Areen Boulos ◽  
Jean-Marc Rolain ◽  
Didier Raoult

ABSTRACT Whipple's disease is considered a rare chronic disease with a broad spectrum of clinical manifestations. Several antibiotics have been used for the treatment of this disease, and the current reference treatment was determined empirically on the basis of only a few clinical observations. Patients should be treated for months, and many relapse after antibiotic withdrawal. We report here the first extensive study on the susceptibilities of three reference strains of Tropheryma whipplei to antibiotic in cell culture by using a real-time PCR assay as previously described. We found that doxycycline, macrolides, ketolides, aminoglygosides, penicillin, rifampin, teicoplanin, chloramphenicol, and trimethoprim-sulfamethoxazole were active, with MICs ranging from 0.25 to 2 μg/ml. Vancomycin was somewhat active at an MIC of 10 μg/ml. We found heterogeneity in the susceptibility to imipenem, with one strain being susceptible and the two other strains being resistant. Cephalosporins, colimycine, aztreonam, and fluoroquinolones were not active. We also demonstrated that a combination of doxycycline and hydroxychloroquine was bactericidal. This combination has been shown to be active in the treatment of patients suffering from chronic infections with Coxiella burnetii, a bacterium that is also found intracellularly in acidic vacuoles. We believe, then, that this combination therapy should be further evaluated in clinical trials for the treatment of Whipple's disease.


2020 ◽  
pp. 2909-2911
Author(s):  
Florence Fenollar ◽  
Didier Raoult

Whipple’s disease is an uncommon infection caused by the actinomycete Tropheryma whipplei, most commonly diagnosed when overt small intestinal disease leads to malabsorption, but with protean other clinical manifestations (e.g. systemic, neurological, or cardiological). Diagnosis usually depends upon demonstration of classical histological features in the small intestine, and positive identification of T. whipplei DNA by polymerase chain reaction. Treatment is with antibiotics, initially doxycycline and hydroxychloroquine followed by long-term therapy with doxycycline. Clinical improvement occurs within a few weeks, but prolonged treatment for at least a year is recommended. Relapse can occur, even after many years, especially when progressive central nervous system disease occurs in the absence of other systemic manifestations.


Author(s):  
Maria de Lourdes de Abreu FERRARI ◽  
Eduardo Garcia VILELA ◽  
Luciana Costa FARIA ◽  
Claudia Alves COUTO ◽  
Célio Jefferson SALGADO ◽  
...  

Whipple's disease (WD) is a rare systemic disease of infectious etiology which involves the small intestine but can virtually affect any organ. We present here five cases (four males and one female) ranging in age from 20 to 59 years. All patients had intestinal involvement associated or not with clinical manifestations linked to this organ. Vegetation in the tricuspid valve was observed in one patient, suggesting endocarditis caused by Tropheryma whippelii, with disappearance of the echocardiographic alterations after treatment. In one of the male patients the initial clinical manifestation was serologically negative spondylitis, with no diarrhea occurring at any time during follow-up. Ocular involvement associated with intestinal malabsorption and significant weight loss were observed in one case. In the other two cases, diarrhea was the major clinical manifestation. All patients were diagnosed by histological examination of the jejunal mucosa and, when indicated, of extraintestinal tissues by light and electron microscopy. After antibiotic treatment, full remission of symptoms occurred in all cases. A control examination of the intestinal mucosa performed after twelve months of treatment with sulfamethoxazole-trimethoprim revealed the disappearance of T. whippelii in four patients. The remaining patient was lost to follow-up.


2020 ◽  
Vol 13 (2) ◽  
pp. e233071
Author(s):  
Ana Aguiar Ferreira ◽  
Paula Gomes ◽  
Luís Curvo-Semedo ◽  
Paulo Donato

Whipple’s disease is a rare and difficult-to-diagnose infectious disease, related to infection by gram-positive bacillum Tropheryma whipplei. Clinical manifestations are very variable, but the classic form usually begins with recurring arthritis, followed several years later by non-specific abdominal symptoms, leading to late diagnosis. We present the case of a 52-year-old man who was admitted in the emergency department with an insidious clinical picture characterised by weight loss, abdominal pain, diarrhoea and arthralgias. An abdominal ultrasound was performed, showing findings suggestive of Whipple’s disease, which, in conjunction with the clinical and laboratory findings, allowed the diagnosis to be correctly addressed. Upper endoscopy with duodenal biopsy revealed findings compatible with Whipple’s disease, and the diagnosis was also confirmed through PCR techniques of blood. The patient was given antibiotic therapy, with rapid and substantial clinical improvement.


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