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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two cases of Whipple's disease with secondary amyloidosis are described. One patient had a nephrotic syndrome, the other malabsorption. The chronic inflammatory stimulus of Whipple's disease is discussed as a trigger for the development of secondary amyloidosis. The clinical symptoms of seronegative arthritis, weight loss, chronic diarrhea, intermittent fever and lymphadenopathy may be the clue to the diagnosis of Whipple's disease. Peroral intestinal biopsy is the diagnostic procedure of choice. Adequate antibiotic treatment with a regimen of penicillin and trimethoprim-sulfamethoxazole is indicated and prevents the development of secondary amyloidosis.
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PMID:[Whipple's disease--a rare cause of secondary amyloidosis]. 751 14

Whipple's disease is a multisystemic disorder in which almost all organ systems can be invaded by rod-shaped bacteria. Without extended antimicrobial therapy, its course is lethal. Empirically, treatment consists of tetracyclines given for one to two years. Trimethoprim-sulfamethoxazole, a compound that crosses the blood-brain barrier, has been suggested as an alternative when patients were observed with progressive cerebral involvement. There has never been a formal evaluation of the selection of antibiotics for the treatment of Whipple's disease. In the present nonrandomized, partially retrospective study, we compared the result of two treatment regimens in 30 patients, all examined personally. Twenty-two patients were treated with tetracycline and eight patients with trimethoprim-sulfamethoxazole. In five patients, therapy with tetracycline was changed to another antimicrobial agent because of treatment failure or drug intolerance. The main treatment measure was disappearance of the clinical symptoms such as weight loss, arthritis, malabsorption, fever, edema, central nervous system manifestations, lymphadenopathy, and congestive heart failure. Drug intolerance requiring a change of medication was also considered a treatment failure. We found that trimethoprim-sulfamethoxazole induced complete clinical remission in 12 of 13 treatment cycles, tetracycline in 13 of 22 treatment cycles (P < 0.05; mean difference 33%; 95% confidence interval 8% to 58%). Trimethoprim-sulfamethoxazole was also more efficacious than tetracycline in the treatment of cerebral Whipple's disease. However, trimethoprim-sulfamethoxazole did not prevent cerebral manifestations in all cases. The only deaths due to Whipple's disease occurred in patients with cerebral involvement. It is concluded that treatment with trimethoprim-sulfamethoxazole was significantly superior to that with tetracycline in inducing clinical remission of Whipple's disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An evaluation of antimicrobial treatment for Whipple's Disease. Tetracycline versus trimethoprim-sulfamethoxazole. 751 38

Whipple's disease is a chronic systemic infectious disease caused by Tropheryma whippelii that typically involves the small intestine and causes malabsorption. Extraintestinal manifestations such as arthritis and fever are common and often exist prior to the onset of gastrointestinal symptoms. Involvement of the central nervous system can occur and lead to permanent sequelae. Weight loss, hyperpigmentation, and lymphadenopathy are frequent findings. The definitive diagnosis is made by biopsy of the small intestine mucosa which reveals infiltration of the lamina propria of the small intestine with periodic acid-Schiff positive macrophages. Treatment with trimethoprim combined with sulfamethoxazole for 1 year usually results in clinical remission and an excellent prognosis. Recent advances using molecular techniques to identify the uncultured bacillus of Whipple's disease should lead to a better understanding of the pathophysiology and allow for the development of a sensitive noninvasive diagnostic test.
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PMID:Whipple's disease. 758 31

Approximately 5% of all lymphomas are located in the gastrointestinal tract. These lesions may be secondary manifestations of systemic lymphomatous disease, but there are also primary lesions that are not associated with superficial lymph node enlargement mediastinal adenopathy, liver and spleen involvement or hematologic alterations. Primary lymphomas may arise in the stomach or intestine. Small intestinal lesions may or may not be preceded by other types of intestinal pathology, such as celiac or inflammatory disease. The former cases are characterized by persistent diarrhea, malabsorption and weight loss. Abdominal pain and later nausea and/or vomiting are the most common presenting symptoms of lesions that arise in an already diseased bowel, palpable abdominal masses are present in approximately one third of these cases. Gastric lymphomas often presents with non-specific symptoms: cramp-like epigastric pain, anorexia and weight loss.
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PMID:[Primary lymphomas of the gastrointestinal tract: clinical picture]. 853 64

A 22-year-old Libyan patient suffering from chronic diarrhea presented with an alpha-heavy chain paraprotein and a lympho-plasmacellular lymphoma infiltration of the duodenal mucosa. These findings supported the diagnosis of "immunoproliferative small intestinal disease" (IPSID). In this disease, that occurs almost solely in countries with low socioeconomic status, a diffuse infiltration of small intestinal mucosa by neoplastic lymphoid cells causes chronic malabsorption. About 65% of patients exhibit a paraprotein in serum, urine or jejunal juice that consists of the heavy chain of immunoglobulin A (alpha-heavy chain). In advanced stages, IPSID resembles histologically and clinically high grade lymphoma: some patients develop masses in the gut wall, an abdominal lymphadenopathy and involvement of other organs including bone marrow. The disease is believed to be triggered by a chronic infectious antigenic stimulus. Thus, in early stages in some patients cure may be achieved by antibiotic therapy alone. In advanced disease, chemotherapy including anthracyclins is necessary.
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PMID:[Libyan patient with chronic diarrhea]. 901 23

The disease is named after George H. Whipple who, in 1907, was the first to describe an intestinal "lipodystrophy". Although Whipple's disease is generally recognized as a multisystem chronic granulomatous disease, primarily involving the digestive system, it can also appear as a primary neurological disorder in rare cases. Most often it is manifested with loss of weight, diarrhea, malabsorption, abdominal pain, lymphadenopathy, cardiopathy, hyperpigmentation and hypotension. The presence of periodic acid-Schiff (PAS)-positive macrophages in biopsy specimens (not only jejunal) and demonstration of "Whipple's bacilli" visible by electron microscopy, are diagnostic signs of active Whipple's disease. Whipple's disease confined to the CNS is rare. It is rarely found in the differential diagnosis of patients with progressive neurological deterioration. The most common neurological picture includes progressive dementia, external ophalmoplegia, myoclonus, seizures, ataxia, hypothalamic dysfunction (sleep disorders, hyperphagia, polydipsia) and meningitis. Oculofacial-skeletal myorhythmia as a movement disorder, associated with Whipple's disease, is reported. Fulminant course of cerebral Whipple's disease is unusual and unfavourable. The confusing and nonspecific clinical appearance is typical for primary CNS involvement. It has recently been suggested that CNS involvement occurs in all cases, although only 10-20% of patients may show it. The CNS is the most common site of disease relapse. The CT scans and MRI of the brain are often normal, but may show cortical/subcortical atrophy, hydrocephalus, focal or intracerebral mass lesions. The cerebrospinal fluid can sometimes contain PAS-positive macrophages. Brain biopsy is suggested as a diagnostic method in cases of high suspicion of CNS Whipple's disease. However, the lesions are frequently inaccessible and false negative. Without extended antibiotic therapy, the course of Whipple's disease is lethal. Now, the prognosis is good, although the optimal antimicrobial regimen is not clearly established. Initial parenteral therapy (tetracycline, penicilline, streptomycine, chloramphenicol, ampicilline) and peroral long-term treatment with trimetoprime-sulphametoxasole, are recommended. As CNS relapse of Whipple's disease may occur after several years, long-term treatment should include antibiotics that are able to cross the blood-brain barrier. The CNS relapse, in contrast to the systemic ones, is resistant to the treatment. Appropriate therapy instituted earlier in the course of the disease is associated with a better neurological outcome. Early recognition can be critical in Whipple's disease because of irreversible neurological sequelae seen later in the course of this potentially treatable condition. In cases with high clinical suspicion in which Whipple's disease cannot be diagnosed with procedures such as jejunal biopsy, antibiotic therapy is recommended. Recovery of an established neurological deficit may rarely occur. Longterm follow-up studies would help to identify the optimal antibiotic regimen and duration of treatment.
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PMID:[Neurologic disorders in Whipple's disease]. 910 28

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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PMID:Whipple's disease and "Tropheryma whippelii". 1143 14

Whipple disease is a rare infectious disorder with multiorgan manifestations and a widely varied clinical presentation. Involvement of the small intestine with resultant malabsorption is a classic finding, although extraintestinal manifestations such as fever and arthralgias may precede gastrointestinal symptoms by many years. We describe a 63-year-old man in whom Whipple disease was diagnosed 22 years after his initial presentation (36 years after symptom onset) with lymphadenopathy, when a biopsy yielded nonnecrotizing granulomas. His recent symptoms included persistent fatigue, weight loss, fever, and arthralgias. Endoscopic biopsy specimens from the distal duodenum showed features consistent with Whipple disease, and Tropheryma whippelii DNA was detected in both the small bowel biopsy specimen and the blood specimen by polymerase chain reaction and DNA probe hybridization. His symptoms resolved with long-term co-trimoxazole therapy. We discuss the protean manifestations of Whipple disease, the difficulties in clinical diagnosis, and the recent advances in the molecular diagnosis of this disorder.
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PMID:Successful treatment of Whipple disease diagnosed 36 years after symptom onset. 1160 93

Because of the wide variations in the clinical presentation of celiac disease and because treatment exists that is effective in most cases, screening of the general population for celiac disease has been considered. There is still no evidence that patients who have symptom-free celiac disease are at increased risk of small intestinal lymphoma or other complications. Prevention of osteoporosis seems to be the strongest indicator for widespread screening today [22]. The major cause of failure to respond to a gluten-free diet is continuing ingestion of gluten, but other underlying diseases must be considered. Many different drugs (eg, anti-tumor necrosis factor [TNF]-alpha) have been used in patients who have RCD [23]. Steroid treatment has been reported to be effective even in patients who have underlying early EATL. Histologic recovery in patients who have celiac disease usually takes several months but can take up to 1 year, even if the patient remains on a strict gluten-free diet. Some patients report celiac-related symptoms for months after a single gluten intake. The definitions for RCD in literature vary. The authors consider the definition give by Daum and colleagues [24] suitable. They defined true RCD as villous atrophy with crypt hyperplasia and increased IELs persisting for more than 12 months in spite of a strict gluten-free diet. If a patient is not responding well to a gluten-free diet, three considerations are necessary: (1) the initial diagnosis of celiac disease must be reassessed;(2) the patient should be sent to a dietician to check for errors in diet or compliance problems, because problems with the gluten-free diet are the most important cause for persisting symptoms; (3) other reasons for persisting symptoms (eg, pancreatic insufficiency, irritable bowel syndrome, bacterial overgrowth, lymphocytic colitis, collagenous colitis, ulcerative jejunitis, protein-losing enteropathy,T-cell lymphoma, fructose intolerance, cavitating lymphadenopathy, and tropical sprue) should be considered. Other causes for villous atrophy are Crohn's disease, collagenous sprue, and autoimmune enteropathy. Abdulkarim and colleagues [25] examined 55 patients who had a diagnosis of nonresponsive celiac disease. He found that 6 did not have celiac disease, and25 still had some gluten ingestion.Tursi and colleagues [26] reported 15 patients who had celiac disease with persisting symptoms. Because histology improved in all patients after several months, RCD was excluded. Of the 15 patients, 10 had small intestinal bacterial overgrowth, 2 showed lactose malabsorption causing the described symptoms, 1 had mistakenly taken an antibiotic containing gluten, and 1 patient each had Giardia lamblia and Ascaris lumbricoides. Thus, other entities must be considered in patients who have celiac disease and ongoing symptoms. In a follow-up clinical trial, 158 patients who had celiac disease underwent follow-up small intestine biopsies within 2 years after starting a gluten-free diet. Eleven patients (7.0%) with persisting (partial) villous atrophy were considered to have RCD; 5 of them developed EATL [27].RCD type I is characterized by normal expression of T-cell antigens and polyclonal TCR gene rearrangement.RCD type II is characterized by an abnormal IEL phenotype with the expression of intracytoplasmic CD3e, surface CD103, and the lack of classic surface T-cell markers such as CD8, CD4, and TCR-alpha/beta. This clonal IEL population can be considered crypt IEL [24]. RCD II has a poor prognosis, which is a problem for therapy. Clonal TCR gene rearrangements and loss of T-cell antigens such as CD8 and TCR-beta in IELs may indicate the development of an EATL in patients who have RCD. The markers for an overt EATL are a positive stool blood test, increased lactate dehydrogenase, or beta2-microglobulin [24]. If an overt lymphoma is suspected, upper and lower endoscopy, an ear, nose, and throat work-up, CT scan, capsule endoscopy, and possibly double-balloon enteroscopy should be performed. Most reports of the difficulties in treating patients who have true RCE are casereports. Turner and colleagues [28] reported on an induction of remission by useof the anti-TNF-alpha antibody infliximab and maintenance with prednisoloneand azathioprine. Olaussen and colleagues [29] and Mandal and colleagues [30]tried a nonimmunogenic elemental diet. Gillet and colleagues [31] reported successful treatment of a patient who hadRCD using anti-TNF-alpha antibodies (infliximab) for induction and azathioprinefor maintenance. Maurino and colleagues [32] studied seven consecutive patients diagnosed ashaving refractory sprue and no response to oral or parenteral steroids. Aftertreatment with azathioprine (2 mg/kg/d) and oral prednisone (1 mg/kg/d), fivepatients had a complete clinical remission. Two patients who did not respond totreatment at any time died. Goerres and colleagues [33] described 18 patients who had RCD, 10 of whomhad type I RCD, and 8 of whom had type II RCD. Treatment consisted ofazathioprine combined with prednisone for 1 year. Consistent with reports byother investigators, the response rates in the two groups differed. Eight of the10 patients who had type I RCD had a histologic response. Seven of the eightpatients who had type II RCD died, and six of the eight developed a lymphoma. At present there is no effective treatment for type II RCD.Fig. 3 presents a proposed algorithm for monitoring patients who have ce-liac disease.
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PMID:Monitoring nonresponsive patients who have celiac disease. 1687 29

Whipple's disease of the brain is one of the most challenging neurological diagnoses. "Is it Whipple's disease?" is a frequent question, but rarely is the answer yes. The neurological manifestations do not help to distinguish primary from secondary Whipple's disease of the brain, and although MR brain scanning with gadolinium is mandatory, it can be normal and any abnormalities are non-specific. There must be a comprehensive search for multisystem involvement such as raised inflammatory markers, lymphadenopathy or malabsorption; biopsy of lymph node or duodenum may be necessary. PCR and DNA sequencing for Tropheryma whipplei on lymphocytes from blood and cerebrospinal fluid is essential. Treatment is as difficult as the diagnosis-there are no randomised controlled trials.
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PMID:Diagnosis and management of Whipple's disease of the brain. 1879 86


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