A case of Tropheryma whipplei infective endocarditis of the aortic and mitral valves in association with psoriatic arthritis and lumbar discitis

Whipple's disease is a chronic condition that is characterized by diarrhea, weight loss and arthropathy, and caused by infection with the fastidious bacterium Tropheryma whipplei. Although once rare, Whipple's disease is being increasingly described owing mainly to advances in molecular genetics and an improved isolation of the organism. Whilst cardiac Whipple's disease occurs less commonly, especially in the absence of gastrointestinal symptoms, it has become apparent that some cases of culture-negative endocarditis may well be attributable to T. whipplei. The case is reported of a patient with Whipple's disease endocarditis in association with psoriatic arthritis and lumbar discitis.     

Immunosuppressive therapy in Whipple's disease patients is associated with the appearance of gastrointestinal manifestations

OBJECTIVES: Whipple's disease is a rare chronic disorder, which is caused by systemic infection with Tropheryma whipplei. The first symptom of Whipple's disease usually is a nondestructive polyarthritis resembling in many aspects seronegative rheumatoid arthritis. This polyarticular inflammatory arthropathy preceding the diagnosis of Whipple's disease for several years frequently is treated with nonsteroidal antiinflammatory drugs (NSAIDs) and with immunosuppressive therapy. There is evidence that altered immune functions play a role in the manifestation of the disease and that Whipple's disease is associated with opportunistic infections. We therefore asked whether immunosuppressive treatment for arthropathy may alter the course of Whipple's disease. PATIENTS AND METHODS: In a series of 27 patients with Whipple's disease clinical data were documented and the patients were followed for 3-4 yr. The patients were classified into three groups according to their medication: (i) patients with immunosuppressive therapy preceding the diagnosis, (ii) patients with NSAIDs before diagnosis, and (iii) patients without such therapies. RESULTS: Arthropathies occurred in the mean 8 yr before diagnosis and were the first symptom in 63% of the patients. Gastrointestinal involvement usually became evident later on and frequently led to the diagnosis of Whipple's disease. In patients with immunosuppressive treatment, diarrhea occurred in the median 4 months after the initiation of such therapy and diagnosis of Whipple's disease was made after another 2 months. In contrast, other medical treatments were not closely followed by the onset of diarrhea. CONCLUSIONS: These results indicate an association between immunosuppressive therapy and the onset of diarrhea in Whipple's disease and thus support the concept that immunologic factors play a role in disease pathogenesis. Further investigation on the interaction of the immune system and Tropheryma whipplei infection are required to understand the factors contributing to the clinical manifestation of this rare disorder and possibly to introduce preventive interventions.     

Sarcoidlike granulomas as an early manifestation of Whipple's disease

Whipple's disease is often accompanied by a long, preintestinal phase of vague symptoms, such as weight loss, fever, and migratory arthralgia, which may delay diagnosis and proper treatment. We report a patient who presented with sarcoidlike granulomas in the lung 1.5 yr before the development of gastrointestinal symptoms. He was treated with prednisone and his lung lesions improved dramatically. However, steroids could not be discontinued until the diagnosis of Whipple's disease was made and he was started on antibiotic treatment. Whipple's disease was diagnosed from a small intestinal biopsy specimen by electron microscopic demonstration of characteristic bacillary bodies. Liver biopsy specimens also demonstrated a few Kupffer cells containing degenerative bacillary bodies. Based on this case and other reported cases of Whipple's disease with sarcoidlike lesions in various organs, we suggest that sarcoidlike tissue reaction can be an early manifestation of Whipple's disease, recognition of which may have practical value in facilitating an early diagnosis and treatment.     

Whipple's endocarditis: review of the literature and comparisons with Q fever, Bartonella infection, and blood culture-positive endocarditis.

Whipple's disease is a systemic infection sometimes associated with cardiac manifestations. Recently, there has been an increase in the number of reported cases of Whipple's endocarditis. The purpose of our study was to describe this entity. Data from 35 well-described cases of Whipple's endocarditis were collected and compared with those of blood culture-positive endocarditis, Q fever endocarditis, and Bartonella endocarditis. Some patients with generalized Whipple's disease presented with cardiac involvement, among other symptoms. Others presented with a nonspecific, blood culture-negative endocarditis with no associated symptoms. In comparison with cases of endocarditis due to other causes, congestive heart failure, fever, and previous valvular disease were less frequently observed in the cases of Whipple's endocarditis. Without examination of the excised valves, the diagnosis of infective endocarditis could not have been confirmed in most cases. Treatment is not well established. Whipple's endocarditis is a specific entity involving minor inflammatory reactions and negative blood cultures, and its incidence is probably underestimated.     

Bone marrow involvement in Whipple's disease: rarely reported,but really rare?

Infection with Tropheryma whippelii, the causative agent of Whipple's disease, involves nearly every organ. Involvement of bone marrow may be an overlooked area of Whipple's disease. We report a case of lymphoma-like Whipple's disease with bone marrow involvement together with a brief review of the literature on this topic. Despite minimal documentation, bone marrow may be commonly involved in Whipple's disease and, although not specific, diastase-resistant periodic acid-Schiff (PAS)-positive macrophages in bone marrow may offer an important clue to diagnosis using PAS histology of upper endoscopic biopsies, polymerase chain reaction or electron microscopy.     

Whipple''s Disease

Whipple's disease in an 80-year old white man is described with endoscopic appearance, light and electron microscopic features and the treatment response. The subject is discussed in brief. This report of Whipple's disease is in the oldest patient recorded in the literature.     

Neurologic disease in patients with treated Whipple's disease.

Four patients with Whipple's disease which had responded to antibiotic therapy, later developed neurologic disease identical to that seen in patients with Whipple's disease who died without treatment. Dementia, myoclonus, ataxia, and supranuclear ophthalmoplegia were the main neurologic features. Restarting antibiotics has been followed by stabilization of disease in all four. Two have improved. In three, the previously diagnosed and treated Whipple's disease was not considered as a possible cause of the neurologic disease until the symptoms and signs were far advanced. It is advisable to periodically evaluate all patients with Whipple's disease, even after successful treatment. Signs of neurologic disease should be considered a possible recurrence of Whipple's disease and antibiotics restarted.     

REMISSION OF PSEUDO-SPONDYLITIS WITH TREATMENT OF WHIPPLE'S DISEASE

An HLA-B27 negative case of Whipple's Disease with ‘spondylitis’is reported in which antibiotic therapy gave sustained remissionof spondylitis as well as intestinal disease. KEY WORDS: Whipple's disease, Spondylitis, Antibiotic therapy     

Whipple''s Disease Can Mimic Chronic AIDS Enteropathy

Previous case reports have demonstrated that the intestinal pathology of Mycobacterium avium-intracellulare (MAI) infection in the acquired immune deficiency syndrome (AIDS) has a light microscopic appearance similar to Whipple's disease. This case report describes a 52-yr-old male patient with a clinical picture suggestive of AIDS, including diarrhea, weight loss, oral thrush, and intestinal cryptosporidiosis. The intestinal biopsy showed light microscopic features compatible with either MAI or Whipple's disease, but electron microscopy confirmed the presence of the Whipple bacillus. Markers of human immunodeficiency virus (HIV) infection were absent. Although immune abnormalities have been reported in Whipple's disease, this is the first report of opportunistic infections complicating this condition. A useful clinical pearl emerges from this and other cases: AIDS can mimic Whipple's disease; Whipple's disease can mimic AIDS.     

Should we systematically perform central nervous system imaging in patients with Whipple's endocarditis?

Background

Whipple's endocarditis is an uncommon disease, with approximately 100 cases reported to date. Case series suggest that Whipple's endocarditis usually presents without extracardiac manifestations of Whipple's disease.

Methods

We report 4 consecutive cases of Whipple's endocarditis associated with brain lesions. All patients fulfilled Duke Criteria for definite endocarditis. Whipple's disease was diagnosed through 16S rRNA polymerase chain reaction assays on valves excised from patients with culture-negative endocarditis (n = 3) or through polymerase chain reaction and periodic acid staining-positive foamy macrophages on duodenal biopsy (n = 1).

Results

All patients were male, aged 56 to 72 years. They presented with mitral (n = 1), aortic (n = 1), mitral and aortic (n = 1), and tricuspid (n = 1) endocarditis. Brain magnetic resonance imaging was performed because of mild-to-moderate cognitive disorders (n = 3) or ataxia (n = 1) and revealed multiple (n = 3) or solitary (n = 1) contrast-enhancing lesions. Cerebrospinal fluid studies revealed meningitis in 1 case. Polymerase chain reaction assays on cerebrospinal fluid were negative for all patients. All patients received intravenous ceftriaxone (2-4 weeks) associated with gentamicin (2 weeks), followed by 1 year of oral trimethoprim-sulfamethoxazole, with favorable outcomes.

Conclusion

Whipple's associated central nervous system disease may be common but frequently undiagnosed, in patients with Whipple's endocarditis. Because treatment is different when neurologic disease is present (ie, trimethoprim-sulfamethoxazole vs doxycycline/hydroxychloroquine), clinicians should consider brain imaging in patients diagnosed with Whipple's endocarditis.     

Giardia lamblia Infestation Reveals Underlying Whipple''s Disease in a Patient with Longstanding Constipation

Whipple's disease is an uncommon disorder, generally associated with gastrointestinal symptoms; of these, diarrhea is a common feature. We report a case of Whipple's disease associated with chronic constipation which was not diagnosed until after Giardia lamblia infestation had caused diarrhea. To the best of our knowledge this association has not previously been reported. The clinical, laboratory, endoscopic, and manometric aspects are described and discussed.     

Thrombocytosis in Whipple's disease

Three men with Whipple's disease had platelet counts of 729,000-1,142,000 per mm3, which fell to normal as their illness responded to antibiotic therapy. Reports on Whipple's disease and hospital charts from the largest published series reveal thrombocytosis in 11 of the 24 patients whose counts were recorded. The prevalence of anemia, marrow infiltration, and classic manifestations of Whipple's disease did not differ between patients with and without thrombocytosis. The thrombocytosis of Whipple's disease is similar to that of celiac sprue, Crohn's disease, and ulcerative colitis.     

Tropheryma whippelii as a cause of afebrile culture-negative endocarditis: the evolving spectrum of Whipple's disease

With the advent of molecular diagnostics culture-negative endocarditis caused by the organism Tropheryma whippelii is an increasingly described entity. We describe two patients with afebrile, culture-negative endocarditis caused by T. whippelii who had neither the gastrointestinal nor arthritic manifestations of Whipple's disease. Whipple's disease is a systemic illness caused by the organism Tropheryma whippelii and is typically characterized by diarrhea, weight loss, and arthropathy [Clin. Microbiol. Rev. 2001;14:561-583; Medicine (Baltimore) 1997;76:170-184]. Whipple's endocarditis is relatively common in autopsy studies [Can. J. Cardiol. 1996;12:831-834] but has rarely been diagnosed before death. With the advent of molecular diagnostic tools such as the polymerase chain reaction (PCR), Tropheryma whippelii as a cause of culture-negative endocarditis has become increasingly recognized [Clin. Infect. Dis. 2001;33:1309-1316; Ann. Intern. Med. 1999;131:112-116; Infection 2001;29:44-47; Ann. Intern. Med. 2000;132:595]. With this increased recognition has come the realization that Whipple's endocarditis can occur without other common manifestations of Whipple's disease [Ann. Intern. Med. 1999;131:112-116; Infection 2001;29:44-47; Ann. Intern. Med. 2000;132:595]. We report here two cases of Whipple's endocarditis without discrete febrile illness, gastrointestinal manifestations, or arthritic manifestations, diagnosed by PCR of resected valvular material.     

Whipple's disease: easily diagnosed, if considered

Patients present with arthralgia, abdominal pain, diarrhoea and weight loss. The disease is commonly diagnosed by histological examination of small bowel biopsies, especially after staining with periodic acid-Schiff. Because of the rarity of the disease, its diagnosis is not often considered. Therefore the necessary investigations might be omitted. This case report might serve as a reminder for internists or gastroenterologists to consider Whipple's disease in patients with abdominal, articular or other symptoms after having excluded common differentials. We also review the current literature on Whipple's disease. Whipple's disease is an infectious disorder caused by Tropheryma whipplei.     

Whipple's disease of the lung.

Described here is a unique case of Whipple's disease in a 54 year old man with chronic severe cough and gastrointestinal symptoms in whom the initial diagnosis of Whipple's disease was made by lung biopsy. This is, to our knowledge, the first reported case in which the bacilliform structures of Whipple's disease have been demonstrated in tissues from other than the gastrointestinal tract of lymph nodes. Subsequently, a peroral biopsy of the small intestine was performed and revealed identical and pathognomonic features of Whipple's disease. The pulmonary roentgenologic findings are described and the histologic differential diagnosis of histiocytic infiltrates in the lung, which may be histologically similar to Whipple's disease, are briefly reviewed.     

Endoscopic and pathological aspect of small bowel and colonic involvement in Whipple's disease: a case report

We describe a case of Whipple's disease confirmed by clinical, histological, bacteriological and molecular criteria. The duodenal involvement was associated with the presence of an endoscopic and histological enterocolitis. Final diagnosis of small bowel and colonic involvement by Whipple's disease was confirmed by histology and molecular biology. We review the literature on extra duodenal involvement. We underline the fact that enterocolitis in Whipple's disease is non-specific. We also discuss the other causes of intestinal mucosal infiltration by macrophages.     

Localization of Tropheryma whippelii rRNA in tissues from patients with Whipple's disease

Whipple's disease is caused by a cultivation-resistant bacterium, Tropheryma whippelii. Ultrastructural studies of intestinal biopsy specimens from patients with Whipple's disease have shown that intracellular and extracellular bacteria are present, but the preferred site of growth is unknown. Tissue sections from 8 patients with Whipple's disease and from 19 healthy control subjects were analyzed by use of fluorescence in situ hybridization and laser scanning confocal microscopy, to determine the location of rRNA that would indicate the presence of metabolically active bacteria. T. whippelii rRNA was most prevalent near the tips of intestinal villi, in the lamina propria, just basal to epithelial cells. Most of the bacterial rRNA signal appeared to be located between cells and did not colocalize with the human intracellular protein vimentin. The location of bacterial rRNA in tissues from patients with Whipple's disease provides evidence that bacteria are growing outside cells and suggests that T. whippelii is not an obligate intracellular pathogen.     

Fission of Whipple's disease rod bodies

Summary A duodenal biopsy from an untreated patient with Whipple's disease was studied by light and electron microscopy. The specimen contained innumerable instances of binary fission of the rod-shaped bodies characteristic of the disease. The findings add further support for a bacterial concept of Whipple's disease.     

Diagnostic application of a polymerase chain reaction assay for the Whipple's disease bacterium to intestinal biopsies

BACKGROUND & AIMS: The uncultured Whipple's disease bacterium (Tropheryma whippelii) was characterized in 1991-1992 by polymerase chain reaction (PCR) and sequencing of the bacterial 16S ribosomal RNA gene. The aim of this study was to develop a PCR assay for diagnostic purposes. METHODS: Modified primers for PCR and a specific probe for hybridization were designed. The specificity of this PCR assay was tested using 37 bacterial control strains and intestinal biopsy samples from 16 patients without Whipple's disease. The sensitivity was tested in 88 intestinal biopsy samples from 35 patients with Whipple's disease. RESULTS: PCR and hybridization were negative in all 37 bacterial controls and in all 16 patients without Whipple's disease. Before therapy, DNA of T. whippelii was detected in all 30 patients with Whipple's disease from whom formalin-fixed biopsy material was available, whereas Bouin-fixed material was negative. During and after treatment, PCR was negative in 23 of the 24 patients who were followed up. Generally, conversion to negative occurred within 1 year. Despite negative intestinal PCR, symptomatic cerebral Whipple's disease appeared in 3 patients. CONCLUSIONS: This PCR assay is specific and sensitive and is applicable as a diagnostic test. However, PCR from intestinal biopsy samples seems less helpful for monitoring the effect of treatment. (Gastroenterology 1996 Jun;110(6):1735-43)     

Whipple's disease: a curable encephalitis

Introduction

Whipple's disease is a rare systemic infectious disorder. It may present with a wide range of clinical manifestations and therefore its diagnosis may be challenging.

Case report

We report a 45-year-old man who presented with acute encephalitis related to Whipple's disease. Despite the negativity of the polymerase chain reaction (PCR) test in cerebrospinal fluid, diagnosis was obtained by histopathology, PCR tests and immunohistochemistry in multiple samples. The outcome with antibiotherapy was considered as “spectacular”.

Conclusion

Whipple's disease is a rare cause of encephalitis. Its diagnosis needs the confrontation of histology and PCR tests in multiple samples. The outcome with an adapted antibiotherapy may be very successful.