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Whipple's disease is a rare systemic disease of infectious etiology. Its clinical presentation is highly variable. The most common symptoms are diarrhea, weight loss, abdominal pain and joint manifestations. Non-digestive manifestations frequently precede digestive symptoms by several years. For all these reasons, diagnosis is difficult. Definitive diagnosis is established by the finding of PAS-positive macrophages in the lamina propria of the thin intestine. It is important to start appropriate antibiotic therapy early, as this improves the prognosis. We present the case of a male patient in whom the first manifestations of the disease were constipation and upper gastrointestinal hemorrhage, two forms of clinical presentation that have rarely been described in the literature on Whipple's disease.
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PMID:[Constipation and digestive bleeding as an atypical presentation of Whipple's disease]. 1198 1

Whipple's disease is a rare, without antibiotic treatment deadly systemic infectious disease caused by the ubiquitary Gram positive bacterium Tropheryma whipplei. The agent can be demonstrated by light and electron microscopy and by PCR in tissues and body fluids affected. Men are affected more often than women. Most patients lose weight, have diarrhea, abdominal pain and arthralgias. In 10-40% of cases involvement of the CNS, often asymptomatic, is observed. PAS-positive macrophages in the lamina propria of duodenal biopsies are typical but not pathognomonic of Whipple's disease. Nowadays, the infectious agent should also be demonstrated by PCR. Treatment, mostly as a sequential therapy, is with antibiotics that cross the blood-brain barrier and should last for at least 1 year in order to avoid relapses. Before ending therapy the absence of Tropheryma whipplei in duodenal tissue and cerebrospinal fluid must be confirmed.
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PMID:[Whipple disease--a rare systemic disease]. 1242 73

Whipple's disease, or intestinal lipodystrophy, is a systemic infectious disorder affecting mostly middle-aged white men. Patients present with weight loss, arthralgia, diarrhoea, and abdominal pain. The disease is commonly diagnosed by small-bowel biopsy; the appearance of the sample is characterised by inclusions in the lamina propria staining with periodic-acid-Schiff, which represent the causative bacteria. Tropheryma whipplei has been classified as an actinomycete and has been propagated in vitro, which allows the possibility of improving diagnostic strategies, for example through antibody-based detection of the bacillus on duodenal tissue or in circulating monocytes. Cell-mediated immunity in active and inactive Whipple's disease has subtle defects that might predispose some individuals to symptomatic infection with this bacillus, which probably occurs ubiquitously. Although most patients respond well to empirical antibiotic treatment, some with relapsing disease have a poor outlook. The recent findings and concerted research might allow development of new strategies for diagnosis, treatment, and monitoring of patients with Whipple's disease.
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PMID:Whipple's disease. 1254 51

Whipple's disease (WD) is a chronic systemic inflammatory disease of infectious origin caused by Tropheryma whipplei (TW). Abdominal pain and recurrent diarrhea are usually the main symptoms leading to the suspicion of a primary bowel disease. Systemic manifestations can mimic hematologic disorders. A 49-year-old man presented with fever, weight loss, long-standing arthralgia, and diarrhea. A duodenal biopsy was unremarkable. Bone marrow histology provided no evidence of a malignant hematological disorder but revealed noncaseating granulomas. TW was detected in the bone marrow trephine by polymerase chain reaction. This is the first report to describe TW-associated granulomatous myelitis as the initially recognized organ manifestation of WD, proven at the molecular level. This observation is relevant for the differential diagnosis of patients with systemic symptoms and granulomatous diseases affecting the bone marrow, emphasizing that WD should be considered in cases of unexplained granulomatous myelitis, even when small bowel biopsy specimens are negative.
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PMID:Primary diagnosis of Whipple's disease in bone marrow. 1511 37

Whipple's disease is a rare chronic infectious disorder first described in 1907 by G.H. Whipple. The disorder is caused by the newly identified bacterium Tropheryma whipplei and there is evidence that altered immune functions play a role in the manifestation of the disease. The organ systems mostly affected are the joints and the gut, and in the further course often also the heart, lung, brain, and eyes. The intestinal involvement occurs with abdominal pain and diarrhea, which leads to weight loss, malnutrition, and anemia. In some cases the infection spreads to the central nervous system, which may lead to loss of memory, confusion, or disturbances in gait. In the last few years, several steps towards an improved diagnosis of the disease and characterization of the causative bacterium have been made. While untreated disease may be lethal, treatment is often able to eradicate the organism. At present, therapy is based on observations in small patient groups and personal experience. There are different antibiotic therapy regimens often starting with intravenous application for 2 weeks followed by oral medication for 1 year. The first clinical therapy study is ongoing.
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PMID:Progress, problems, and perspectives in diagnosis and treatment of Whipple's disease. 1559 84

Whipple's disease is a rare chronic multi-systemic infectious disorder caused by the Gram-positive bacillus, Tropheryma whippelii. Infection may involve any organ in the body, and most commonly affects white men in the fourth to sixth decades of life. The most common presenting symptoms are gastrointestinal and include abdominal pain, diarrhoea, anorexia and associated weight loss. However, the variability in presentation is considerable and some patients may present with intermittent low-grade fever, neurological abnormalities (nystagmus, ophthalmoplegia, cranial nerve defects), migratory arthralgia, lymphadenopathy, or involvement of the cardiovascular system. In typical Whipple's disease, the most severe changes are seen in the proximal small intestine and biopsy reveals mucosal and lymph node infiltration with large, foamy histocytes, containing granules that stain positive with periodic acid-Schiff (PAS) reagent and represent intact or partially degraded bacteria. Extended antibiotic treatment (up to 1-year) is indicated. Life-long surveillance for recurrence is essential, once primary treatment has been completed. We report the case of a 58-year-old man who developed a rare infection with the actinobacterium, T. whippelii. The patient had suffered intermittent episodes of varying clinical symptoms associated with multiple hospital admissions and clinical diagnoses, spanning a period of 22 years. Historically, arthralgia was the primary manifestation in this patient and also was the chief complaint for which he was first hospitalized 22 years ago. At his most recent admission to our hospital department, his presenting symptoms were persistent fatigue, weight loss, arthralgia and diarrhoea. Thus, it is essential that clinicians retain a high index of suspicion for T. whippelii infection in patients who have a long-term history of arthritis, fever and diarrhoea.
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PMID:Whipple's disease: multiple hospital admissions of a man with diarrhoea, fever and arthralgia. 1603 47

Whipple's Disease is a rare multisystemic disease caused by Gram-positive bacillus, Tropheryma whippelii, family of Actinobacterias and group of Actinomycetes. Because the disease is rare and has different forms of presentation the diagnosis comes frequently late. The authors present the case of a white man, 50 years old, admitted with a clinical picture characterized by weight loss, abdominal pain, ascites, diarrhea. He suffered of arthralgias for four years. The diagnosis was made by biopsy of mesenteric adenopathies and liver, during the laparotomy. The biopsy specimens showed numerous aggregates of foamy macrophages containing granular periodic acid-shiff (PAS)--positive material, diastase resistant. Afterwards, the bacillus was identified by electronic microscopy. The patient was treated with trimethoprim-sulfamethoxazole. Symptoms disappeared and biological values returned to normal. The authors present the case and discuss auxiliary exams, differential diagnosis, follow-up, treatment and review the main characteristics of the disease.
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PMID:[Whipple's disease--a challenging diagnosis]. 1619 60

Whipple's disease (WD) is a chronic debilitating disease caused by the bacillus Tropheryma whippleii. WD classically presents with the main clinical symptoms of polyarthralgias, chronic diarrhea, weight loss, and abdominal pain. Given its systemic involvement, it is common for WD to present with a multitude of other clinical scenarios--sometimes with predominant neurologic, cardiac, and dermatologic manifestations. WD can occur at any age, but it generally occurs during the fifth decade and predominantly in men. The diagnosis of WD is established by demonstrating the organism on biopsies from the involved system, by histology, electron microscopy, polymerase chain reaction, and more recently, by culture of bacteria. The histologic features include a coarse granular cytoplasm and foamy macrophages that stain strongly with the period-acid Schiff reagent. Current therapy includes an initial 2-week course of intravenous cephalosporins followed by 1-year oral trimethoprim-sulfamethoxazole.
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PMID:Whipple's Disease. 1652 45

Whipple's disease (WD) is a rare chronic infectious disorder caused by the rod- shaped bacterium Tropheryma whipplei. The disorder is characterized clinically by arthralgia, abdominal pain, diarrhea, malabsorbtion and progressive weight loss. Other important sites of infection include the heart (resulting in the clinical picture of endocarditis and heart failure) and the central nervous system (CNS) (manifestations include confusion, memory loss, focal cranial nerve signs, nystagmus and ophtalmoplegia). The bacterium is presumed to be ubiquitously present. A defect in cellular immune response may predispose patients for an infection with T. whipplei and this might explain the rarity of the disorder despite the ubiquitous bacterial presence. The presumed immunological defect is likely to be quite specific for T. whipplei, since patients are not generally affected by other infections. Decreased production of Interleukin(IL)-12, IL-2 and Interferon (IFN)-g accompanied by an increased secretion of IL-4 are the main features of this defective immunological response. The finding of periodic acid-Schiff (PAS)-positive macrophages in the lamina propria of tissue samples obtained by duodenal biopsy usually establishes the diagnosis. The PAS-positive inclusions represent the remnants of the bacteria. Attempts to isolate the causative agent were unsuccessful for nearby 100 years after the first recognition of the disease. In the year 2000, the bacterium was finally successfully grown on a human fibroblast cell line. Untreated WD patients suffer from a chronic progressive disorder which possibly leads to death. Most patients show a fast clinical improvement to antibiotic therapy, but clinical relapses are described frequently. There is a number of patients, unable to eradicate the bacterium even after several antibiotic treatments and patients with CNS disease, in both of whom alternative therapy strategies are necessary.
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PMID:Current concepts of immunopathogenesis, diagnosis and therapy in Whipple's disease. 1707 38

There is dispute about the cause of Beethoven's death; alcoholic cirrhosis, syphilis, infectious hepatitis, lead poisoning, sarcoidosis and Whipple's disease have all been proposed. In this article all primary source documents related to Beethoven's terminal illness and death are reviewed. The documents include his letters, the report of his physician Andreas Wawruch, his Conversation Books, the autopsy report, and a new toxicological report of his hair. His terminal illness was characterised by jaundice, ascites, ankle oedema and abdominal pain. The autopsy data indicate that Beethoven had cirrhosis of the liver, and probably also renal papillary necrosis, pancreatitis and possibly diabetes mellitus. His lifestyle for at least the final decade of his life indicated that he overindulged in alcohol in the form of wine. Alcohol was by far the most common cause of cirrhosis at that period. Toxicological analysis of his hair showed that the level of lead was elevated. During the eighteenth and early nineteenth centuries, lead was added illegally to inexpensive wines to sweeten and refresh them. These findings strongly suggest that liver failure secondary to alcoholic cirrhosis, associated with terminal spontaneous bacterial peritonitis, was the cause of death. This was complicated in the end stages by renal failure. If the presence of endogenous lead was verified by analysis of Beethoven's skeletal remains, it would suggest that the lead was derived from wine that he drank. Lead poisoning may account for some of his end-of-life symptoms. There is little clinical or autopsy evidence that Beethoven suffered from syphilis.
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PMID:Beethoven's terminal illness and death. 1721 30


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