Severe pulmonary hypertension reversed by antibiotics in a patient with Whipple's disease

The case is described of a 58 year old man with systemic Whipple's disease with pericardial and pleural effusions and severe pulmonary hypertension. After three months of antibiotic treatment there was a complete resolution, not only of the symptoms known to be associated with Whipple's disease (diarrhoea, arthralgia, pericardial and pleural effusions), but also of pulmonary hypertension.     

Musculocutaneous nerve palsy following traumatic spinal cord injury

Whipple's disease is a multisystem bacterial disease usually characterized by malabsorption, diarrhea and polyarthritis. Ocular manifestations include uveitis, vitreitis, retinis, myositis, papilledema and optic atrophy. We report a case of a chronic bilateral vitreitis in a 63 year-old man who had been treated for a Whipple's disease with gastrointestinal involvement 30 years before. The jejunal biopsy was negative but the polymerase-chain-reaction (PCR) revealed the presence of Trophyrema Whippelii in the vitreous prelevement of both eye. This new, original strategy of PCR is specific and more sensitive than histological diagnosis.     

Whipple's syndrome (uveitis, B27-negative spondylarthropathy, meningitis, and lymphadenopathy) associated with Arthrobacter sp. infection

OBJECTIVE: To report an unusual case of Whipple's disease, including uveitis, seronegative spondylarthropathy, meningitis, and lymphadenopathy, associated with an Arthrobacter sp. infection. DESIGN: Interventional case report. PATIENT AND INTERVENTION: A 60-year-old white man presenting with severe chronic uveitis and systemic inflammatory manifestations was treated efficiently for Whipple's disease after histopathologic analysis of vitreous and inguinal adenopathy biopsy specimens. The authors performed a retrospective, laboratory-based evaluation of stored tissue specimens. MEASUREMENTS: Molecular analysis based on 16S ribosomal RNA gene amplification was applied to pretreatment biopsy specimens of inguinal lymph node to identify a causative bacterial agent. RESULTS: Tropheryma whippelii genome was not detected in these specimens. However, an amplification product was obtained after the first polymerase chain reaction run and subsequently was sequenced. It corresponded to an Arthrobacter sp., a gram-positive agent presenting diagnostic patterns and therapeutic management similar to those of Whipple's disease caused by T. whippelii. CONCLUSION: The absence of T. whippelii identification by molecular amplification during a clinically and histologically oriented Whipple's syndrome should not rule out the diagnosis. Arthrobacter infection may represent a new bacterial etiology of systemic inflammatory disorders involving the eye and associated with periodic acid-Schiff-positive inclusions.     

Spondylodiscitis caused by Tropheryma whippelii

We describe the first case of spondylodiscitis caused by Tropheryma whippelii in which this so far unculturable organism was shown to be present at the site of infection in a patient without significant gastrointestinal symptoms. The methods used included broad-range PCR amplification with universal primers complementary to constant sequences of the gene coding for 16S rRNA, direct sequencing of the amplified fragment, and comparison of the sequence determined with those deposited in sequence databases. In addition to demonstrating the presence of this organism in the affected vertebral body, we found in our patient that the specific PCR is more sensitive than histology for detecting Whipple's bacilli in bowel biopsy specimens. Because histology of small bowel biopsies from the duodenum were-in contrast to PCR from the same site-not diagnostic for Whipple's disease in our patient, we recommend PCR whenever Whipple's disease has to be excluded.     

Changing eating patterns of American children: a view from 1996

Whipple's disease (WD) is an uncommonly diagnosed infection caused by the recently characterized bacillus, Tropheryma whippelii. The association of WD with pericarditis and endocarditis is widely recognized, although less attention has been paid to the myocardium as a site of disease. Although the disease was uniformly fatal before antibiotic therapy, current treatment usually results in cure. We report two patients whose deaths were directly related to cardiac involvement by WD and whose underlying disease escaped diagnosis for years. The first, a 60-year-old white woman, suffered a cardiovascular collapse, and lymphocytic myocarditis was demonstrated at autopsy. The second, a 48-year-old black man, had a lengthy history of progressive cardiac failure that terminated in arrhythmia. Extensive myocardial fibrosis, with lymphocytic and granulomatous inflammation, was demonstrated at autopsy. The presence of T. whippelii was confirmed by electron microscopic examination in both cases and by polymerase chain reaction in one. Patients with WD might harbor an undiagnosed lymphocytic or granulomatous myocarditis, and this diagnosis should be considered in the evaluation of cardiac failure.     

Whipple's disease: results of long-term follow-up

AIM: To analyze clinical, diagnostic and therapeutic aspects of Whipple's disease. MATERIALS AND METHODS: Diagnostic and therapeutic data are available for 7 patients registered in 1990-1997. The diagnosis was made using intestinoscope SIF-10L ("Olympus"). Biopsies were obtained from the jejunal, duodenal and gastric mucosa. The patients received tetracycline, erythromycin, biceptol, on demand--prednisolone. RESULTS: Whipple's disease was diagnosed 6 years on the average following the first clinical symptoms. In most patients the intestinal symptoms were preceded or accompanied by such extraintestinal symptoms as enlargement of the lymph nodes, lowering of hemoglobin, hypoproteinemia, ESR increase to 40-60 mm/h. To study biopsies from the distal duodenum is the only measure needed for diagnosis of Whipple's disease. In untreated patients PAS-positive macrophages are detectable also in gastric body mucosa. The immediate treatment outcome is favorable. The recurrence was observed only in one patient who had given up taking tetracycline. CONCLUSION: Long-term antibacterial therapy brings the recovery. Primary disorder of the cellular immunity responsible for the disease onset necessitates long-term follow-up of the patients. Control biopsy should be examined once a year.     

Abdominal lymphomas, convulsive seizure and coma: a case of successfully treated, advanced Whipple's disease with cerebral involvement

Whipple's disease is a rare, generalized inflammatory disorder due to the recently described bacterium Tropheryma whippelii. We report an unusual, successfully treated case of a 32-year-old woman, who presented with a 25 month history of large abdominal lymphomas, polyserositis and cachexia. The diagnosis of Whipple's disease was confirmed by duodenoscopy, lymph node and duodenal histology and polymerase chain reaction analysis of biopsy material and cerebrospinal fluid. A prolonged convulsive seizure with a subsequent 5 day period of coma were interpreted as signs of cerebral involvement. Under antibiotic treatment with trimethoprim-sulfamethoxazole (co-trimoxazole) the patient recovered completely, CT scans showed a complete regression of abdominal lymphomas. The therapy was continued over 18 months without the occurrence of a relapse.     

Severe chronic iron deficiency in a 17-year-old student

A 17 year old male suffered from iron deficiency of undetermined cause for 2 years. Iron substitution was able to correct it for short periods. With the exception of fatigue and recurring abdominal pain attributed to oral iron therapy no further symptoms were present. The physical status on admission was unremarkable. The laboratory detected intestinal disorders, an anemia of the chronic type without evidence for malignancy or renal failure suggested an inflammatory gastro-intestinal disorder. In spite of a twice negative noninvasive test for gluten-intolerance the clinician favored in his differential diagnosis non tropical sprue over inflammatory bowel disease (IBD, Crohn's disease, Whipple's disease). Histopathology of small bowel specimens did not indicate sprue. An ileo-colonoscopy revealed severe ulcerating ileitis and mild chronic colitis. The histologic specimen revealed a severe ileal inflammation with cosinophilia and the colon specimens epitheloid microgranuloma. These findings are highly compatible with the diagnosis of Crohn's disease. Iron deficiency anemia is common in Crohn's disease. In the current case it is due to disturbed iron uptake. Iron deficiency anemia as sole symptom of Crohn's disease is extremely rare.     

Prolonged p53 protein accumulation in trichothiodystrophy fibroblasts dependent on unrepaired pyrimidine dimers on the transcribed strands of cellular genes

The 16S ribosomal RNA (rRNA) gene of the phylogenetic subdivision containing gram-positive bacteria with a high G + C content was detected specifically in clinical specimens from patients suspected of having Whipple's disease. The primary structure of 16S rDNA amplified from clinical samples was determined by cloning and sequencing. Two sorts of sequences were identified: one corresponded exactly to the rRNA sequence of Tropheryma whippelii (GenBank accession no. M87484) while the other was related to that of members of the genus Corynebacterium. No sequence related to Mycobacterium spp. or Rhodococcus equi was observed. Exhaustive examination of negative specimens with broad-range eubacterial primers detected one sequence related to Enterobacteriaceae and another related to Enterococcus spp. To speed identification of T. whippelii, a nested amplification method was devised. A first amplification specific for the gram-positive bacteria subdivision was performed, followed by a second amplification with T. whippelii-specific primers. The amplified T. whippelii product was checked by digestion with AvaII, StuI, and PstI endonucleases. These techniques were applied to DNA extracted from seven intestinal biopsy samples, two cerebrospinal fluid samples and one articular fluid from patients suspected of having Whipple's disease. T. whippelii 16S rDNA was found in two of the biopsy samples, one of the cerebrospinal fluid samples and in the articular fluid.     

Changes in the duodenal mucosa in Whipple's disease

A case of Whipple's disease is described in a male patient of 43 who has been previously examined in different hospitals for six years. The diagnosis was established after surgery and histological examination of the duodenum biopsy. Infiltration of the tunica propria of the duodenum with PAS-positive macrophages was observed. Therapy with rondomycin in combination with GUMET-P produced a response but the recurrence took place after therapy. A new operation was followed by peritonitis and pneumonia which terminated in the patient's death.     

Liver transplantation for metastatic neuroendocrine carcinoma: an analysis of 103 patients

BACKGROUND: Patients with neuroendocrine carcinoma often present with liver metastases not amenable to hepatic resection. For them, liver transplantation has been considered a viable treatment option, especially if hormonal symptoms and pain cannot be controlled medically. Still, little is known regarding potential prognostic factors and long-term survival after liver transplantation for neuroendocrine tumors. METHODS: A search of English, French, and German literature identified patients with liver transplantation for extensive metastases from neuroendocrine carcinoma for whom follow-up data were available. RESULTS: Overall, 2-year and 5-year survival for all 103 patients was 60% and 47%, respectively, but recurrence-free 5-year survival did not exceed 24%. Univariate analysis identified age less than 50 years, primary tumor location in lung or bowel, and pretransplant somatostatin therapy as favorable prognostic factors, whereas extended operations combining liver transplantation with upper abdominal exenteration or Whipple's procedure were associated with poor prognosis. Multivariate analysis identified age greater than 50 years (P<0.03) and transplantation combined with upper abdominal exenteration or Whipple's operation (P<0.001) as adverse prognostic factors. CONCLUSIONS: Liver transplantation may be justified in selected patients to provide immediate relief of otherwise intractable pain or hormone-related symptoms. Transplantation with curative intent appears worthwhile in young patients with only hepatic disease. In older patients with extrahepatic disease requiring extended operations, long-term results are discouraging, and the small benefit achieved by liver transplantation must be weighed against medical treatment options and the natural course of often slowly progressing disease.     

Whipple's disease - current status of diagnostics and therapy

Whipple's disease is a multisystemic infectious disease whose pathogen, a gram-unstable actinomycete, has been characterized in the meantime by molecular-biological techniques (polymerase chain reaction). This infectious disease which was firstly described in 1907 by G.H. Whipple as intestinal lipodystrophy appears rarely and sporadically and can affect nearly every organ, in the course of which the small intestine is also concerned in the majority of patients. The symptoms and signs are polymorphous and depend on organic involvement and stage. This leads to significant difficulties concerning differential diagnosis and to a delay in diagnosis. Misjudging the syndromes provokes invalidism and death whereas correct therapy leads to a cure in most of the cases.     

Comparative effects of enteric-coated pancreatin microsphere therapy after conventional and pylorus-preserving pancreatoduodenectomy

BACKGROUND: A comparative study was performed between patients with exocrine pancreatic insufficiency after conventional pancreatoduodenectomy (Whipple's procedure) and pylorus-preserving pancreatoduodenectomy (PPPD). In these patients the pharmacodynamics of 2-mm enteric-coated pancreatin microspheres (ECPMs) and their gastric transit time in relation to that of a solid meal were investigated. The efficacy of ECPM preparations may differ after Whipple's procedure compared with PPPD, because the latter procedure does not include gastrectomy. METHODS: Gastric transit was assessed by double-isotope scintigraphy. A pancake meal was labelled with 99mTc. ECPMs were cold-labelled with 170Er and neutron activated shortly before ingestion to enable imaging with a gamma camera. Intraluminal pancreatic enzyme activity was assessed during a 6-h period with two indirect tests: the cholesteryl [14C]octanoate breath test and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid-p-aminosalicylic acid (NBT-PABA-PAS) test. RESULTS: In patients who had Whipple's procedure, the gastric transit time of ECPMs and of the pancake meal was not significantly different. The outcome of the indirect pancreatic function tests during enzyme supplementation was comparable, and not significantly different, from that in healthy volunteers. In patients who had PPPD, however, the gastric transit time of microspheres was greatly delayed compared with that of the pancake meal (P < 0.05). Improvement in the outcome of the indirect pancreatic function tests during enzyme supplementation was much less and remained well below that of healthy volunteers (P < 0.05). CONCLUSION: In cases of exocrine pancreatic insufficiency after Whipple's procedure, 2-mm ECPM treatment adequately restores pancreatic enzyme activity. Following PPPD, however, ECPM treatment is often ineffective because the microspheres are retained in the stomach. In these patients, use of conventional powdered pancreatin enzyme preparations may improve the efficacy of treatment.     

The prevalence of Chlamydia pneumoniae in atherosclerotic and nonatherosclerotic blood vessels of patients attending for redo and first time coronary artery bypass graft surgery

The current genetic strategies used to identify Tropheryma whippelii, the putative agent of Whipple's disease, are based on PCR-mediated amplification of a part of its 16S rRNA gene (16S rDNA). Because there is very little intraspecies variation in these molecules, they are not suitable as targets for epidemiologic investigations. However, the intergenic spacer region between the 16S and 23S rDNAs is usually much more variable and has repeatedly been used for epidemiologic purposes. We have therefore amplified the spacer region of T. whippelii directly from clinical specimens from nine independent Swiss patients with Whipple's disease by PCR with primers complementary to the 3' and 5' ends of the 16S and 23S rDNAs, respectively. The amplicons were directly sequenced and the sequences were compared to the T. whippelii reference sequence in GenBank/EMBL (accession no. X99636). Complete sequence homogeneity was found between the samples from our nine patients; the spacer sequence was also identical to the reference sequence. However, the sequences corresponding to the 3' and 5' ends of the 16S and the 23S rDNAs of T. whippelii, respectively, differed from the respective sequences in GenBank/EMBL. The same sequence found in our patients was then found in a sample from the German patient from which the published sequence had been derived. We conclude that the 16S-23S rDNA spacer region seems to be very conserved in T. whippelii and that the respective reference entry in public databases should be revised.     

Inflammatory amyloidosis

Inflammatory amyloidosis consists of AA protein. In developed countries, its predominant causes are chronic inflammatory rheumatism (rheumatoid arthritis, chronic juvenile arthritis, spondylarthropathy, etc.). More rare are other chronic inflammatory disorders (Crohn's disease, ulcerative colitis, Whipple's disease, etc.), hemopathies and neoplasia. In developing countries, infectious causes are the most common (tuberculosis, leprosy, chronic bacterial suppuration). Other infectious diseases complicated with amyloidosis are less common (bronchial dilatation, mucoyiscidosis, heroin injection-related skin suppuration). In chronic infection, amyloidosis is observed a mean of 10 years after the beginning of the triggering disorder and is mainly localised in the kidney, the liver and the gastrointestinal tract. The course is most often slow and prolonged survival has been reported.     

PCR analysis of T. whippelii DNA in a case of Whipple's disease: effect of antibiotics and correlation with histology

A 58-yr-old man developed severe weight loss, arthralgias, and diarrhea. Endoscopic examination of the stomach and duodenum revealed thickened folds of duodenal mucosa. Biopsy of the gastric mucosa was negative, whereas duodenal biopsy revealed blunted epithelial villi and PAS-positive foamy macrophages within the lamina propria. Bacilli typical of those associated with Whipple's disease were found by electron microscopy. The diagnosis was confirmed by polymerase chain reaction (PCR) assay, which detected a portion of the 16S ribosomal RNA gene sequence corresponding to the Whipple bacillus (Tropheryma whippelii) in duodenum, stomach, and liver biopsies before therapy. T. whippelii DNA was eliminated from all tissues tested within 3 months of starting antibiotic treatment, but the histological improvement lagged behind the clinical and molecular evidence of improvement.     

Adenocarcinoma of the duodenal bulb. A clinical case report

A rare case of adenocarcinoma of the duodenal bulb, arising from adenoma and submitted to Whipple's procedure is presented. A diagnostic delay of about 3 months, according to literature is observed. This delay is generally due to the low incidence of the illness, aspecific symptoms and frequent endoscopic and radiologic false negative, most of all in lesions of the third and fourth duodenal portions. Diagnostic tools for these duodenal tumors are endoscopy and upper gastrointestinal barium studies (UGI). CT is useful to determine preoperatively the stage of the illness and can occasionally show the primary duodenal lesion, as in this case. Surgical approach is still controversial, except in lesions of the second duodenal portion, where Whipple operation is the procedure of choice, if the tumor is resectable, of course. In the other duodenal portions some authors suggest segmental duodenal resections instead of Whipple's procedure.     

Budget development and implementation for the APN in independent practice

Whipple's disease (WD) is a rare systemic disease caused by infection with the recently identified actinomycetes, Tropheryma whippelii. The disorder affects mostly middle-aged men, and the major clinical features are weight loss, arthropathy, and diarrhea; other symptoms, caused by systemic infection, are not infrequent. The diagnosis is usually established by duodenal biopsy, which shows the pathognomonic periodic acid Schiff-positive infiltrates in the lamina propria. In addition, RT-polymerase chain reaction of tissue specimens can be used to verify the presence of T whippelii. In most cases, patients can be successfully treated by prolonged administration of antimicrobials, such as trimethoprim-sulfamethoxazole. The unusual chronic-relapsing course of the disease, the predisposition of middle-aged, HLA-B27-positive men for WD, and other characteristics of the disease imply that host factors are involved in the etiopathogenesis of WD. Indeed, it has been shown that patients with WD have suppressed delayed-type hypersensitivity responses in vivo and decreased in vitro T-cell responses, eg, to phytohemagglutinin and concanavalin A. In addition, serum-suppressor factors and shifts in T-cell subpopulations have been found. Perhaps most importantly, WD macrophages have a decreased ability to degrade intracellular microorganisms and patients have reduced numbers of circulating cells expressing CD11b, a cell adhesion and complement receptor molecule on macrophages involved in the activation of intracellular killing of pathogens. Most of those immunologic alterations also occur in patients with longstanding clinical remission, suggesting that this subtle host-defense defect plays an important role in disease pathogenesis.     

Carcinoid tumor in the retroperitoneal space

Authors present a rare case of the pancreatic carcinoid. Diagnosis was based on clinical examination, ultrasonography, CT, and histopathological evaluation. The patient was operated on twice: (Whipple's procedure with the right hemicolectomy and then Roux-Y anastomosis). During follow-up the liver metastases appeared. The patient was treated with chemotherapy. She died 19 month after operation because of neoplastic dissemination.