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Whipple's disease is a rare, chronic, systemic infectious disorder with prominent intestinal manifestations. It presents with weight loss, arthralgia, diarrhea, and abdominal pain. There are different entities of infection or carriage, respectively, classical Whipple's disease, localized WD, and Isolated Neurological WD. The disease is commonly diagnosed by biopsy of lymph node or small-bowel. Histological detection within duodenal biopsies with "Periodic acid Schiff" (PAS) staining still is first choice for the diagnosis of classical Whipple's disease. PCR or immunohistochemistry can identify the agent more specifically, and DNA sequencing for Tropheryma whipplei on lymphocytes from blood and cerebrospinal fluid from PCR-positive specimens, is essential. Cell-mediated immunity in active and inactive Whipple's disease has subtle defects that might predispose some individuals to symptomatic infection with this bacillus. Successful treatment can be achieved in most of the cases by antimicrobial therapy. WD can be progressive lethal. Immune reconstitution inflammatory syndrome (IRIS) might complicate the course of treatment and in worst case end fatal., (Copyright © 2017. Published by Elsevier B.V.)

Whipple's disease is a rare infectious disease that can be fatal if left untreated. The disease is caused by infection with Tropheryma whipplei , a bacterium that may be more common than was initially assumed. Most patients present with nonspecific symptoms, and as routine cultivation of the bacterium is not feasible, it is difficult to diagnose this infection. On the other hand, due to the generic symptoms, infection with this bacterium is actually quite often in the differential diagnosis. The gold standard for diagnosis used to be periodic acid-Schiff (PAS) staining of duodenal biopsy specimens, but PAS staining has a poor specificity and sensitivity. The development of molecular techniques has resulted in more convenient methods for detecting T. whipplei infections, and this has greatly improved the diagnosis of this often missed infection. In addition, the molecular detection of T. whipplei has resulted in an increase in knowledge about its pathogenicity, and this review gives an overview of the new insights in epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of Tropheryma whipplei infections., (Copyright © 2017 American Society for Microbiology.)

Myorhythmia is defined as repetitive, rhythmic, slow (1-4 Hz) movement affecting chiefly cranial and limb muscles. When occurring in the limbs it may be oscillatory and jerky, whereas oculo-masticatory myorhythmia, typically associated with Whipple's disease, is a slow, repetitive, often asymmetrical, facial and ocular movement. Thus, myorhythmia overlaps phenomenologically with tremor and segmental myoclonus. Although often present at rest, it must be differentiated from parkinsonian or dystonic tremor. Recognition of this movement disorder is important because it is usually associated with lesions involving the brainstem, thalamus, or other diencephalic structures with potentially treatable etiologies. In addition to Whipple's disease, myorhythmia has been described in patients with cerebrovascular disease, listeria encephalitis, anti-N-methyl-d-aspartate receptor encephalitis, steroid-responsive encephalopathy associated with autoimmune thyroiditis, multiple sclerosis, and other disorders. In addition to our own experience, we have systematically reviewed the medical literature, focusing on the phenomenology, pathophysiology, and etiology of this poorly recognized movement disorder. In this review, we aim to highlight the clinical features that differentiate myorhythmia from other movement disorders. Treatment should be directed against the underlying etiology., (© 2014 International Parkinson and Movement Disorder Society.)

Tropheryma whipplei is known as the bacterium that causes Whipple's disease, a rare systemic illness typically affecting gastrointestinal tract, joints, and central nervous system. In addition, T whipplei infection may present as an isolated endocarditis. Although previously regarded as a rare condition, T whipplei has been recognized as a major cause of culture-negative endocarditis when integrating specific molecular analysis of surgical material into the diagnostic algorithm. Here, we report the case of a 67-year-old man undergoing mitral valve replacement due to T whipplei endocarditis, and discuss diagnostic and therapeutic implications., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Acute whiplash is a heterogeneous disorder that becomes persistent in 40% to 60% of cases. Estimates of recovery have not changed in recent decades. This randomized, single-blind, controlled trial tested whether multidisciplinary individualized treatments for patients with acute whiplash (<4 weeks postinjury) could reduce the incidence of chronicity at 6 mo by 50% compared to usual care. Participants (n=101) were recruited from accident and emergency centres and the community. It was hypothesized that better recovery rates were achievable if the heterogeneity was recognised and patients received individualised interventions. Patients randomized to pragmatic intervention (n=49) could receive pharmaceutical management (ranging from simple medications to opioid analgesia), multimodal physiotherapy and psychology for post-traumatic stress according to their presentations. The treatment period was 10 wks with follow-up at 11 weeks and 6 and 12-months. The primary outcome was neck pain and disability (Neck Disability Index (NDI)). Analysis revealed no significant differences in frequency of recovery (NDI ≤ 8%) between pragmatic and usual care groups at 6 months (OR 95%, CI=0.55, 0.23-1.29), P=0.163) or 12 mo (OR 95%, CI=0.65, 0.28-1.47, P=0.297). There was no improvement in current nonrecovery rates at 6 mo (63.6%, pragmatic care; 48.8%, usual care), indicating no advantage of the early multiprofessional intervention. Baseline levels of pain and disability had a significant bearing on recovery both at 6 and 12 mo in both groups, suggesting that future research focus on finding early effective pain management, particularly for the subgroup of patients with initial high levels of pain and disability, towards improving recovery rates., (Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Background: Culture-negative endocarditis due to Tropheryma whipplei is a rare disease. Mostly the diagnosis is made by histologic examination of resected heart valve tissue., Case Presentation: In this case report, we described a patient with a classical Whipple's disease. Transesophageal echocardiography (TEE) showed a vegetation on noncoronary cusp of the aortic valve. Whipple's disease was confirmed by positive Tropheryma whipplei polymerase chain reaction (PCR) in EDTA blood and a duodenal biopsy with positive periodic acid-Schiff stain (PAS) macrophages., Conclusion: Due to timely diagnosis, our patient was treated with antibiotics without valve replacement.

Small intestinal diseases are a common, though often overlooked cause of diarrhoeal illness. Fully 1% of the Caucasian population are affected by coeliac disease and a substantial portion of children living in poverty in the developing world are affected by environmental enteropathy. These are but two examples of the many diseases that cause mucosal injury to the primary digestive and absorptive organ in our body. While diarrhoea may be a common, though not universally seen symptom of small bowel mucosal disease, the consequent malabsorption can lead to substantial malnutrition and nutrient deficiencies. The small intestine, unlike the colon, has been relatively inaccessible, and systematic evaluation is often necessary to identify and treat small intestinal mucosal diseases that lead to diarrhoea. Immunodeficiency states, including HIV enteropathy, adult autoimmune enteropathy, drug-associated enteropathy, and tropical sprue continue to occur and require specific therapy. All patients with severe diarrhoea or diarrhoea associated with features suggestive of malabsorption may have a disease of the small intestinal mucosa that requires careful evaluation and targeted management., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Although Whipple disease was described over a century ago, it remains challenging to recognize. To better understand the presentation of Whipple disease, we undertook a clinicopathologic study of our experience since implementation of the Whipple immunohistochemical stain. Twenty-three biopsy specimens from 15 patients were identified, and an association with immunomodulatory conditions was noted. Whipple disease involved the small intestine (19), brain (2), breast (1), and retroperitoneum (1). Whipple disease was suspected by 3 clinicians and by the majority of pathologists (9). Alternative clinical impressions included lymphoma, celiac disease, Crohn vasculitis, sepsis, an inflammatory process, liposarcoma, rheumatoid arthritis, seizure disorder, cerebrovascular accident, xanthoma, and central nervous system neoplasm. The nonspecific nature of the disease presentation likely contributed to the extended period between onset of symptoms and a definitive diagnosis, which ranged from at least 1 year to over 10 years. One patient died of unknown causes, and both patients with detailed follow-up had clinically persistent disease. We also describe Whipple disease with therapy effects, including partial and complete histologic treatment effects. Awareness of the unusual clinicopathologic presentations of Whipple disease is essential for timely diagnosis of this potentially lethal disease.

The diagnostic work-up in the case of a suspected cerebral involvement of Whipple's disease involves neuroimaging and analysis of cerebrospinal fluid (CSF) including polymerase chain reaction (PCR) assays for Tropheryma whipplei. As neurological findings may be complex and unspecific, extracerebral symptoms often lead to the suspicion of Whipple's disease. We report the cases of two patients in whom the suspected diagnosis of Whipple's disease could not be proved either by endoscopy or by the analysis of CSF. Only by means of a cerebral biopsy was the diagnosis assumed and specific therapy was initiated.

We report a case of a 45-year-old man who complained of progressive vision loss in his right eye. Visual acuity was 20/300 in the right eye and 20/25 in the left eye. Bilateral uveitis intermedia R>L was diagnosed and treated with systemic and local steroids. An internal checkup was also done, and duodenal biopsy identified Whipple's disease. Despite specific antibiotic therapy, the patient's follow-up examination showed increased inflammatory activity R>L and bilateral cataracta complicata. Cataract surgery and pars plana vitrectomy with removal of epiretinal membranes were done. Histologic analysis of the vitreous and epiretinal membranes showed periodic acid-Schiff-positive macrophages, pathognomonic for Whipple's disease. Whipple's disease is a rare but severe disease with multiple manifestations and should be considered a differential diagnosis in uveitis.

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.

Purpose of Review: The availability of and advantages in molecular technology and immunology have led to an improved understanding of the etiology and pathogenesis of Whipple disease. As this rare infection represents a model disease reflecting the input of novel findings into clinical medicine and therapy, this review intends to highlight newer findings and put them in context., Recent Findings: Sequencing of 16S rRNA allowed the phylogeny of the bacterium to be determined. The culture and subsequent genome analysis have led to improved diagnosis and monitoring of the disease, for example by PCR or immunohistochemistry. New experimental approaches hint of defects in T-cell and macrophage immunity in patients. Antibiotic therapy will soon be based on data from the first prospective therapy study., Summary: Within a few years the findings from molecular genetics and immunology as well as concerted research activities from the European Consortium on Whipple Disease which established a data and material bank could be translated into clinical medicine. Thus, for patients with Whipple disease an improved basis for diagnosis and therapy have been achieved.

A 30-year-old Chinese male with a history of diarrhea and arthralgia presented for evaluation of progressive dementia, epilepsy, and increased intracranial pressure. Imaging of the brain showed progressive cortical and subcortical lesions with hemorrhage involving the bilateral temporal and occipital lobes, the posterior parietal lobes, and the left frontal lobe. "Foamy" periodic acid-Schiff (PAS)-positive macrophages were demonstrated on brain biopsy. The patient showed clinical improvement following treatment with chloromycetin and sulfadiazine for 2 months. This constitutes the first reported case of cerebral Whipple's disease with diffuse cortical lesions with hemorrhage reported in a Chinese individual. Further, this case points out the significance of early recognition and treatment of cerebral Whipple's disease, especially in those cases with unusual manifestations.

Whipple's disease is a rare multisystemic infectious disease of bacterial origin characterized by variable clinical manifestations, and an insidious and chronic relapsing course. Untreated disease can be even fatal. The presence of the characteristic (though not specific) triad of weight loss, chronic diarrhea and arthralgias may raise its suspicion. When chronic intermittent fever and lymphadenopathy are associated, the suspicion is substantial. Recognition of the causative agent, Tropheryma whippelii with unique characteristics was essential. Despite the presumed ubiquitous presence of the bacteria the disease probably occurs only in cases of immunological host susceptibility. Presence of the bacteria living and multiplying especially in macrophages has suggested alterations of the mononuclear-phagocytic system. (Whipple's disease is commonly mentioned as a macrophage disorder.) Clinical manifestations are quite diverse. While it has traditionally been regarded as a gastrointestinal disease, currently is considered to be a systemic disorder. In cases of suspected infection the approach of first choice is upper gastrointestinal endoscopy. Small, whitish-yellow diffusely distributed plaques alternating with an erythematous, erosive, friable mucosa in the postbulbar region of the duodenum or in the jejunum can appear. Histological samples indicate tissue infiltration of macrophages with intracellular bacterial invasion. The hallmark of Whipple's disease is the presence of PAS positive macrophages in the lamina propria of duodenal biopsy specimens, still the diagnosis needs to be confirmed with the detection of bacteria by PCR. The selection of antibiotics and duration of treatment still remains largely empiric.

Reversible dementia is rare and accounts for approximately 1.5% of all dementias. Systematic ancillary investigations aimed at detecting an infectious disease, an endocrine aetiology or a vitamin deficiency are rarely contributive, but remain relevant since reversible dementia may, very rarely, mimic Alzheimer-type dementia. Aetiological investigations are much better selected and contributory when they rely on a precise analysis of the clinical picture (past medical history, age of the patient, cognitive, psychiatric and behavioural symptoms, type of onset, and associated signs) and of cerebral imaging. Discovering a reversible cause of dementia does not always mean that the patient will completely recover; thus it is more appropriate to use the term "potentially reversible dementia". Finally, when the patient does not recover from dementia, systematic ancillary investigations can identify and treat concomitant reversible conditions, which in nearly 25% of dementia cases contribute to worsening the condition.

Background and Study Aims: Endoscopic retrograde cholangiopancreatography (ERCP) is an established modality for evaluation and treatment of pancreaticobiliary disorders. However, it is technically more challenging in patients with post-surgical anatomy. The success rate of ERCP in patients with prior pancreaticoduodenectomy (Whipple resection) is unknown. We assessed the technical success and safety of ERCP in this patient population., Patients and Methods: Post pancreaticoduodenectomy patients who had undergone ERCP between January 2002 and May 2005 were identified through a computerized medical index system. ERCP was considered successful if the duct of clinical interest had been cannulated and endoscopic therapy had been performed when indicated., Results: ERCP was attempted 88 times in 51 patients with prior pancreaticoduodenectomy, including 37 procedures for pancreatic indications, 44 for biliary obstruction, and 7 for both biliary and pancreatic indications. The overall technical success rate of ERCP based on the intention behind the procedure was 51 % (45 of the 88 procedures). Success was significantly more likely for biliary indications (37/44, 84 %) than for pancreatic indications (3/37, 8 %) ( P < or = .001). Complications occurred in 2 % of the procedures and included one self- contained perforation treated medically and one Mallory-Weiss tear., Conclusions: When performed by experienced endoscopists, ERCP in patients with prior pancreaticoduodenectomy is safe, with a high success rate for biliary indications and a low success rate for pancreatic duct indications. Better methods of achieving pancreatic duct cannulation after pancreaticoduodenectomy are needed.

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.

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.

Whipple disease is a rare infection caused by the bacterium Tropheryma whippelii. Patients usually present with gastrointestinal symptoms or migratory arthralgias. Although symptomatic central nervous system (CNS) involvement frequently occurs, Whipple disease confined to the CNS is rare. The authors present the case of a 40-year-old man who was surgically treated for a symptomatic left frontal tumor that had the neuroimaging features of a low-grade glioma (LGG). A histopathological investigation revealed a perivascular accentuated inflammation with macrophages harboring PAS-positive diastase-resistant rods, which are distinctive features of cerebral Whipple disease. The patient received cotrimoxazole for 1 year postoperatively and recovered well. This case is exceptional because it represents an isolated cerebral manifestation of Whipple disease that presented as a solitary frontal tumor, thus raising the differential diagnosis of LGG. A review of diagnostic and therapeutic options in suspected cases is presented.

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 disease is an uncommon chronic bacterial infection due to Tropheryma whipplei. Clinical manifestations are protean (joint pain, fever, weight loss, abdominal pain, lymphadenopathies), and the diagnosis is often delayed. Although previously considered a late manifestation of Whipple disease, neurological involvement is now frequently the initial clinical manifestation and represents the greatest risk for long-term disability. All patients should be treated and monitored as if they had central nervous system disease even if they are asymptomatic. Neurological manifestations include dementia (56 percent), abnormalities of eye movements (33p. cent), involuntary movements (28 percent), seizures, hypothalamic dysfunction, myelopathy, ataxia and psychiatric manifestations. Uveitis, retinitis, optic neuritis and papilloedema may be found. 80 percent of the reported cases of neuro-Whipple had associated systemic symptoms or signs but many patients are presenting without concurrent intestinal manifestation. Thus, the disease may remain undiagnosed or misdiagnosed, as rheumatoid arthritis or sarcoidosis. Traditionally, the diagnostic procedure of choice is biopsy of the duodenal mucosa by demonstrating PAS-positive foamy macrophages. However, not all cases have small bowel infiltration and tissue obtained from sites clinically affected may be helpful. CT and MR images of the central nervous system are normal or not specific: atrophic changes, mass lesions, focal abnormalities and hydrocephalus. The application of a PCR assay against Tropheryma whipplei has transformed the diagnosis. Positive results have been obtained from several tissues and from CSF and PCR is more sensitive than other techniques. All patients must be treated with antibiotics which cross the blood-brain barrier. Most agree that initial treatment with a combination of parenteral penicillin and streptomycin for at least 14 days is appropriate, thereafter cotrimoxazole orally 3 times a day for at least one and probably for two years. Third generation cephalosporins, rifampicin and chloramphenicol have been used successfully. PCR is recognized to be a useful tool for monitoring progress but it is sometimes difficult to reverse established neurological defects.

George Hoyot Whipple (1878-1976) was awarded the Nobel Prize in Physiology and Medicine in 1934, along with Minot and Murphy for their studies in pernicious anemia. Whipple's name has been given to the bacterial disease which he describes in 1907 that we know today as Whipple's disease or intestinal lipodystrophy. He gave the name of thalasemia to the Mediterranean anemia of Cooley, and made diverse contributions to hematology and general pathology. He worked with William Welch in the Department of Pathology at Johns Hopkins Hospital and later became director of the University of Rochester. He died in 1976 at the age of 98.

Whipple's disease is a multisystemic infection that affects middle-aged white men. It typically presents with fever, polyarthritis, diarrhea, steatorrhea, and weight loss. Many other systems can be involved, however, including the central nervous system, heart, lymphatics, lungs, bone marrow, and skin. Recent work has demonstrated the causative organism to be a complex bacteria, Tropheryma whipplei. The diagnosis is established most securely by periodic acid-Schiff staining of foamy monocyte-macrophages in biopsy tissue and body fluids, by electron microscopy, which reveals bacilli within membrane-bound vesicles, and by molecular amplification techniques using polymerase chain reaction of tissues and body fluids. The differential diagnosis includes chronic multisystemic infections and granulomatous disorders, because Whipple's disease is a fascinating blend of both. The condition can resemble sarcoidosis and mycobacterial disease and fungal, protozoal, and bacillary infections. Earlier diagnosis leads to earlier treatment and hopefully the prevention of chronic disabling complications and needless mortality from this once uniformly fatal condition.

Whipple's disease is a rare, chronic, and systemic infectious disease caused by the ubiquitously occurring bacterium Tropheryma whippelii. For two reasons, the disease represents a good example for documenting the input of modern molecular-based techniques into pathogenetic, diagnostic, and therapeutic concepts in clinical medicine. First, the unidentified and uncultivable causative organism has been characterized by novel molecular-genetic techniques. Second, in contrast to other chronic inflammatory disorders, clinical manifestations of T. whippelii infection seem to be based on reduced T-cell helper type 1 (TH1) activity. These findings have led to an improved pathophysiologic understanding of the disease and to new aspects in treatment strategies that are discussed in this paper.

Whipple's disease (WD) is a rare systemic disease of infectious etiology which involves the small intestine but can virtually affect any organ. We present here five cases (four males and one female) ranging in age from 20 to 59 years. All patients had intestinal involvement associated or not with clinical manifestations linked to this organ. Vegetation in the tricuspid valve was observed in one patient, suggesting endocarditis caused by Tropheryma whippelii, with disappearance of the echocardiographic alterations after treatment. In one of the male patients the initial clinical manifestation was serologically negative spondylitis, with no diarrhea occurring at any time during follow-up. Ocular involvement associated with intestinal malabsorption and significant weight loss were observed in one case. In the other two cases, diarrhea was the major clinical manifestation. All patients were diagnosed by histological examination of the jejunal mucosa and, when indicated, of extraintestinal tissues by light and electron microscopy. After antibiotic treatment, full remission of symptoms occurred in all cases. A control examination of the intestinal mucosa performed after twelve months of treatment with sulfamethoxazole-trimethoprim revealed the disappearance of T. whippelii in four patients. The remaining patient was lost to follow-up.

During the past 10 years considerable progress and increase of knowledge on small intestinal diseases has been achieved. This short review will cover some selected small bowel diseases including coeliac disease, Whipple's disease, rare congenital enteropathies, non-steroidal anti-inflammatory drug enteropathy and autoimmune enteropathy.

The authors describe a case of Whipple's disease diagnosed early during gastroduodenofibroscopy from a bioptioc specimen of the prepyloric gastric mucosa, and treated in time. The disease was complicated by superinfection with Salmonella enteritidis. In the clinical picture digestive symptoms predominated, loose stools, malabsorption, loss of body weight, anaemia, skin pigmentation. After antibiotic and later chemotherapeutic treatment clinical symptoms receded and the histological finding in bioptic specimens from the stomach was normal.

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.

Due to the systemic nature of Whipple's disease, its clinical presentation may be highly variable. The diagnosis may, therefore, be unduly delayed. Untreated, Whipple's disease is still potentially lethal. Although it traditionally presents with signs and symptoms of small intestine involvement, such as diarrhea and malabsorption, Whipple's disease can involve many other organs. Typically, the diagnosis is established by biopsy of the small intestine. The authors describe a case of Whipple's disease in order to stress the importance of bearing this polymorphic disease in mind, with special emphasis on its possible lethal outcome in spite of therapy.

Whipple disease is a rare, multiorgan disease with prominent intestinal manifestations. We report a retrospective clinical study of 52 patients recruited in various parts of France from 1967 to 1994. Seventy-three percent of the patients were male. Clinical manifestations preceding the diagnosis were articular for 35 patients (67%), digestive for 8 patients (15%), general for 7 patients (14%), and neurologic for 2 patients (4%). At a later stage of the disease, 44 patients (85%) presented diarrhea, weight loss, and malabsorption, while 8 patients (15%) did not show any gastrointestinal symptom throughout the development of the disease. Forty-three patients (83%) presented arthralgia or arthritis, and 11 (21%) had prominent neurologic symptoms. In addition, cardiovascular symptoms were present in 9 patients (17%); mucocutaneous symptoms, in 9 patients (17%); pleuropulmonary symptoms, in 7 patients (13%); and ophthalmologic symptoms, in 5 patients (10%). All patients but 1 were given a positive diagnosis on histopathologic criteria: jejunal biopsy for 46 patients (90%), lymph node biopsy for 3 patients (6%), brain biopsy for 1 patient (2%), postmortem jejunal and cerebral biopsy for 1 patient (2%). With treatment, the disease evolved favorably in 47 patients (90%), while 5 patients (10%) had unfavorable outcomes (2 deaths from neurologic involvement, 1 patient with chronic dementia, and 2 patients with digestive symptoms insensitive to antimicrobial therapy). Of the 41 patients initially treated successfully and whose treatment has been completed, clinical evolution after discontinuation of treatment was favorable in 34 cases (83%). Clinical relapses occurred in 7 patients. No relapse was observed after treatment by trimethoprim-sulfamethoxazole, alone or following a combination of penicillin and streptomycin, or after the combination of penicillin and streptomycin, whatever the oral follow-up treatment prescribed. The evolution of patients showing a relapse was favorable in all cases after reintroduction of antibiotic therapy. These results are discussed in the light of previously published series and case reports of Whipple disease. The diagnosis of the disease remains difficult at an early phase or when digestive symptoms are absent. It is noteworthy that proximal enteroscopy is sometimes misleading, considered normal on macroscopic examination and nonspecific on pathologic grounds. A normal erythrocyte sedimentation rate represents another pitfall. Histopathology is the key for positive and differential diagnosis, and may require multiple and repeated biopsies. Findings from molecular biology confirm the central role of an uncultured Gram-positive bacillus which was named in 1992 Tropheryma whippelii. A recent report suggests that polymerase chain reaction (PCR) analysis of peripheral blood might allow the diagnosis of Whipple disease in some cases. However, immunologic or cellular parameters such as macrophagic function may play an important, although not clearly elucidated, role in the pathogeny of the disease. Trimethoprim-sulfamethoxazole should be considered the antimicrobial agent of choice in the treatment of Whipple disease, minimizing the risk of cerebral involvement and relapses.

Whipple's disease is a chronic systemic syndrome which typically involves small intestinal mucosa. There is no doubt today about its bacterial etiology and its good response to antibiotic therapy. A peculiar case is reported, in which the failure of a protracted corticosteroidal treatment is demonstrated and a particularly prompt endoscopic healing after therapy with cotrimoxazole is obtained. The value of duodenal biopsy in course of upper gastrointestinal endoscopy in comparison with classic intraluminal jejunal biopsy is confirmed for the diagnosis of Whipple's disease.

Multimodality and differentiated treatment of small-intestinal diseases is to combine methods of etiological action with pathogenetic treatment of the main clinical syndromes: chronic diarrhea, malabsorption syndrome, hypercatabolic exudative enteropathy. Each nosological form should be treated specifically. Pathogenetic treatment involves diet therapy, chemotherapeutic correction of metabolic processes (vitamin administration, recovery of normal protein and lipid metabolism, water and electrolyte balance, anemia), management of chronic diarrhea. Treatment regimens are specified for gluten enteropathies, total variable immunodeficiency, Whipple disease, small-intestinal diverticulosis, Crohn's disease, amyloidoses, intestinal lymphoma and retroperitoneal lymph nodes. Clinical experience justifies the above methods as highly effective.

We report a case of late CNS relapse of Whipple disease without articular or digestive signs. Magnetic resonance (MR) imaging of the brain clearly showed the disappearance of the normal low intensity signal of the aqueduct of Sylvius and the presence of high intensity signals in the frontal white matter and in the caudate nucleus. This case suggests that MR imaging of the brain is the procedure of choice for identifying cerebral involvement in Whipple disease.