Whipple’s disease: imaging contribution for a challenging case

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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Tropheryma whipplei, Immunosuppression and Whipple's Disease: From a Low-Pathogenic, Environmental Infectious Organism to a Rare, Multifaceted Inflammatory Complex

Digestive Diseases ◽

10.1159/000369538 ◽

2015 ◽

Vol 33 (2) ◽

pp. 190-199 ◽

Cited By ~ 10

Author(s):

Thomas Marth

Keyword(s):

Heart Valves ◽

Clinical Manifestations ◽

Systemic Infection ◽

Tropheryma Whipplei ◽

Molecular Techniques ◽

Whipple’S Disease ◽

Whipple's Disease ◽

New Findings ◽

The Central Nervous System ◽

Body Compartments

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.

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Antibiotic Susceptibility of Tropheryma whipplei in MRC5 Cells

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.3.747-752.2004 ◽

2004 ◽

Vol 48 (3) ◽

pp. 747-752 ◽

Cited By ~ 87

Author(s):

Areen Boulos ◽

Jean-Marc Rolain ◽

Didier Raoult

Keyword(s):

Clinical Manifestations ◽

Extensive Study ◽

Tropheryma Whipplei ◽

Whipple’S Disease ◽

Chronic Infections ◽

Pcr Assay ◽

Whipple's Disease ◽

Reference Treatment ◽

Clinical Observations ◽

Reference Strains

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.

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Monoclonal Antibodies to Immunodominant Epitope of Tropheryma whipplei

Clinical and Vaccine Immunology ◽

10.1128/cdli.9.1.156-159.2002 ◽

2002 ◽

Vol 9 (1) ◽

pp. 156-159 ◽

Cited By ~ 2

Author(s):

Zhongxing Liang ◽

Bernard La Scola ◽

Didier Raoult

Keyword(s):

Monoclonal Antibodies ◽

Biopsy Specimen ◽

Tropheryma Whipplei ◽

Duodenal Biopsy ◽

The Other ◽

Enzyme Linked Immunosorbent Assay ◽

Whipple’S Disease ◽

Immunodominant Epitope ◽

Whipple's Disease ◽

The Common

ABSTRACT Recent isolation of Tropheryma whipplei (formerly Trophyrema whippelii), the agent of Whipple’s disease, from the cardiac valve of a patient with Whipple’s disease endocarditis now allows the detection of reactive epitopes that could be used in a serological assay. In order to propose an enzyme-linked immunosorbent assay (ELISA) that uses recombinant T. whipplei antigen, we first determined by Western blotting of human, mouse, and rabbit antisera that the common immunodominant epitope is an 84-kDa protein. We then produced 13 monoclonal antibodies (MAbs) against T. whipplei, 12 of which recognize this immunodominant epitope. These MAbs did not react with phylogenetically closely related bacteria or bacteria previously shown to be cross-reactive with T. whipplei, but they did react with two other strains of T. whipplei isolated, one from an ocular sample and the other from a duodenal biopsy specimen. By confocal microscopy, the MAbs allowed detection of T. whipplei within infected fibroblasts. The identification of the 84-kDa antigen with our MAbs will make it possible to develop a diagnostic antigen for use in a diagnostic ELISA for Whipple’s disease.

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Tropheryma whipplei Detection by Nanopore Sequencing in Patients With Interstitial Lung Disease

Frontiers in Microbiology ◽

10.3389/fmicb.2021.760696 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yifan Guo ◽

Lijuan Li ◽

Zhenzhong Li ◽

Lingxiao Sun ◽

Hui Wang

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Quantitative Polymerase Chain Reaction ◽

Periodic Acid ◽

Tropheryma Whipplei ◽

Whipple’S Disease ◽

Nanopore Sequencing ◽

Whipple's Disease ◽

Periodic Acid Schiff ◽

Laboratory Findings

Tropheryma whipplei is a bacterium associated with Whipple’s disease, which commonly manifests as weight loss, arthralgia, and diarrhea. The most frequently involved organs comprise the heart and eyes, in addition to the central nervous system. Few studies have explored the relationship between T. whipplei and pneumonia. Herein, we report three patients with interstitial lung disease (ILD) of unknown cause, whose bronchoalveolar lavage fluid (BALF) were evaluated via Nanopore sequencing. In our in-house BALF Nanopore platform, human DNA was removed with saponin, to improve the reads ratio of microorganisms/host. T. whipplei was the sole or most abundant pathogen in all the patients, comprising 1,385, 826, and 285 reads. The positive result was confirmed via quantitative polymerase chain reaction (PCR) with two pairs of primers (cycle threshold value: 33.26/36.29; 31.68/32.01; 28.82/28.80) and Sanger sequencing. To our knowledge, this is the first report of T. whipplei detection using Nanopore-based sequencing. The turnaround time was approximately 6–8 h in clinical laboratories, including less than 1 h for analysis. In conclusion, the results of this study confirm that Nanopore sequencing can rapidly detect rare pathogens, to improve clinical diagnosis. In addition, diagnosis of Whipple’s disease should be combined other laboratory findings, such as periodic acid-Schiff (PAS) staining, and considered a possibility in middle-aged men presenting with ILD and a clinical history of unexplained arthralgia and/or fever.

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Role of enteroscopy in the diagnosis of whipple’s disease

Acta Gastro Enterologica Belgica ◽

10.51821/84.4.020 ◽

2021 ◽

Vol 84 (4) ◽

pp. 665-667

Author(s):

M Mascarenhas Saraiva ◽

T Ribeiro ◽

T Costa Pereira ◽

P Andrade ◽

H Cardoso ◽

...

Keyword(s):

Periodic Acid ◽

Clinical Manifestations ◽

Systemic Infection ◽

Whipple’S Disease ◽

Upper Endoscopy ◽

Whipple's Disease ◽

Periodic Acid Schiff ◽

Abdominal Symptoms ◽

Duodenal Biopsies

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.

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Tropheryma whipplei, the Whipple's disease bacillus, induces macrophage apoptosis through the extrinsic pathway

Cell Death and Disease ◽

10.1038/cddis.2010.11 ◽

2010 ◽

Vol 1 (4) ◽

pp. e34-e34 ◽

Cited By ~ 21

Author(s):

L Gorvel ◽

K Al Moussawi ◽

E Ghigo ◽

C Capo ◽

J-L Mege ◽

...

Keyword(s):

Tropheryma Whipplei ◽

Whipple’S Disease ◽

Extrinsic Pathway ◽

Whipple's Disease ◽

Macrophage Apoptosis

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Whipple's Disease and “Tropheryma whippelii”

Clinical Microbiology Reviews ◽

10.1128/cmr.14.3.561-583.2001 ◽

2001 ◽

Vol 14 (3) ◽

pp. 561-583 ◽

Cited By ~ 157

Author(s):

Fabrizio Dutly ◽

Martin Altwegg

Keyword(s):

Bacterial Species ◽

Periodic Acid ◽

Clinical Manifestations ◽

The Body ◽

Rrna Gene ◽

Low Grade ◽

Whipple’S Disease ◽

Major Step ◽

Whipple's Disease ◽

Initial Symptoms

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.

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Tropheryma whippleiCrystalline Keratopathy: Report of a Case and Updated Review of the Literature

Case Reports in Ophthalmological Medicine ◽

10.1155/2012/707898 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Scott D. Schoenberger ◽

Sumeer Thinda ◽

Stephen J. Kim

Keyword(s):

Signs And Symptoms ◽

Tropheryma Whipplei ◽

Extensive Literature ◽

Whipple’S Disease ◽

Whipple's Disease ◽

Case Presentation ◽

Search Terms ◽

Crystalline Keratopathy ◽

Extensive Literature Search ◽

English Articles

Purpose. To report a case ofTropheryma whippleiinfection with crystalline keratopathy and review the recent literature on the presentation, diagnosis, and management of Whipple's disease.Methods. Detailed case presentation and extensive literature search of Pubmed for all years through February 2012 using the following search terms:Whipple's disease, Tropheryma whipplei, corneal deposits, crystalline keratopathy, and uveitis. Relevant articles were retrieved and analyzed. English abstracts were used for non-English articles. Cross-referencing was employed and reference lists from selected articles were used to identify additional pertinent articles.Results. Diagnosis of Whipple's disease remains challenging and untreated infection can result in mortality. Ocular signs and symptoms are usually nonspecific, but several independent cases have reported the presence of intraocular crystals or crystalline-like deposits.Conclusions. The presence of intraocular crystals or crystalline-like deposits may be an identifying feature of ocular Whipple’s disease.

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