Whipple disease after bariatric surgery: from malabsorption to malnutrition status.

Introduction: Malabsorptive bariatric techniques are associated with nutritional deficiencies. However, when patients do not respond to supplemental intensive treatments they should be closely followed because they can hide other pathological conditions. We present the case of a 47-year-old man with morbid obesity (body mass index [BMI]: 48 kg/m2) who underwent bariatric surgery. In 2016, he presented severe pneumonia and hospitalization at the Intensive Unit Care was required. After this episode, his nutritional state impaired, presenting 6-7 diarrhea/steatorrhea events per-day and requiring several hospitalizations due to the persistence of severe hypoproteinemia. He was given parenteral high-protein associated with low-fat oral diet. He presented a temporary biochemical improvement, but the hypoproteinemia recurred. Finally, tests revealed the presence of Tropheryma whipplei as protein-losing enteropathy. Whipple's disease (WD) is a rare cause of diarrhea and malnutrition, and these symptoms can be confused with the postoperative status of malabsorptive bariatric techniques. WD requires early diagnosis with prolonged antibiotic treatment to avoid severe complications.

Introducción: Las técnicas bariátricas malabsortivas suelen asociarse a deficiencias nutricionales. Sin embargo, cuando los pacientes no responden a tratamientos intensivos suplementarios, deben valorarse otras condiciones patológicas. Presentamos el caso de un hombre de 47 años, obeso mórbido (índice de masa corporal [IMC]: 48 kg/m2) sometido a cirugía bariátrica, que dos años más tarde presentó neumonía severa, por lo que requirió ingreso en la Unidad de Cuidados Intensivos. Posteriormente, el estado nutricional se deterioró, presentando 6-7 episodios de diarrea-esteatorrea/día y requiriendo varias hospitalizaciones por hipoproteinemia severa. Recibió infusión parenteral rica en proteínas asociada con una dieta baja en grasas y presentó mejoría analítica temporal. Finalmente, las pruebas revelaron la presencia de Tropheryma whipplei, una bacteria que genera enteropatía pierde-proteínas. La enfermedad de Whipple (EW) es una causa poco común de diarrea y malnutrición. Estos síntomas pueden confundirse con el posoperatorio de técnicas bariátricas malabsortivas. La EW requiere un diagnóstico precoz con un tratamiento antibiótico prolongado para evitar complicaciones graves.

Myorhythmia: phenomenology, etiology, and treatment.

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.

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

BACKGROUND: Whipple's endocarditis is an uncommon disease, with approximately 100 cases reported to date. Case series suggest that Whipple's endocarditis usually presents without extracardiac manifestations of Whipple's disease. METHODS: We report 4 consecutive cases of Whipple's endocarditis associated with brain lesions. All patients fulfilled Duke Criteria for definite endocarditis. Whipple's disease was diagnosed through 16S rRNA polymerase chain reaction assays on valves excised from patients with culture-negative endocarditis (n=3) or through polymerase chain reaction and periodic acid staining-positive foamy macrophages on duodenal biopsy (n=1). RESULTS: All patients were male, aged 56 to 72 years. They presented with mitral (n=1), aortic (n=1), mitral and aortic (n=1), and tricuspid (n=1) endocarditis. Brain magnetic resonance imaging was performed because of mild-to-moderate cognitive disorders (n=3) or ataxia (n=1) and revealed multiple (n=3) or solitary (n=1) contrast-enhancing lesions. Cerebrospinal fluid studies revealed meningitis in 1 case. Polymerase chain reaction assays on cerebrospinal fluid were negative for all patients. All patients received intravenous ceftriaxone (2-4 weeks) associated with gentamicin (2 weeks), followed by 1 year of oral trimethoprim-sulfamethoxazole, with favorable outcomes. CONCLUSION: Whipple's associated central nervous system disease may be common but frequently undiagnosed, in patients with Whipple's endocarditis. Because treatment is different when neurologic disease is present (ie, trimethoprim-sulfamethoxazole vs doxycycline/hydroxychloroquine), clinicians should consider brain imaging in patients diagnosed with Whipple's endocarditis.

New insights into Whipple's disease - a rare intestinal inflammatory disorder.

Whipple's disease (WD) is a rare systemic infectious disorder caused by the actinomycete Tropheryma whipplei. This chronic disease, first described by Whipple as 'intestinal lipodystrophy', affects preferentially middle-aged white men who may present with weight loss, diarrhea, abdominal pain and arthralgia. Thus, it represents an important differential diagnosis of chronic diarrhea. A variety of other clinical patterns, such as involvement of the heart, lung, or central nervous system (CNS), are frequent. In addition, individuals with isolated heart valve involvement or asymptomatic carriers may be observed. The diagnosis often is established by small bowel biopsy, which is characterized by periodic acid-Schiff-positive inclusions representing the causative bacteria. T. whipplei can be detected by specific polymerase chain reaction, immunohistochemistry or electron microscopy and was cultured a few years ago. Several studies show that subtle defects of the cell-mediated immunity exist in active and inactive WD which may predispose individuals with a certain HLA type to a clinical manifestation of T. whipplei infection. As confirmed in a recent controlled trial, most patients respond well to a prolonged antibiotic treatment, but some patients with relapsing disease or CNS manifestation may have a poor prognosis. In the presentation, the relevance of WD in the differential diagnosis of chronic diarrhea and the new findings of this enigmatic rare disorder will be discussed.

[Whipple's disease: current problems]. / A Whipple-kór aktuális kérdései.

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.

Exacerbation of Whipple's disease associated with infliximab treatment.

A 34-year-old man with chronic inflammatory joint disease and recurrent fever over 6 years was diagnosed as having Still's disease. Treatment with corticosteroids and azathioprine was ineffective. Therefore, infliximab/ methotrexate was started. The patient subsequently developed a wasting disease with rapid weight loss, erythema nodosum, diarrhoea, progressive lymph node enlargement, and a sigmoido-vesical fistula. Histological analysis of several enlarged lymph nodes, the margins of the fistula, and the small bowel established the diagnosis of Whipple's disease (WD). The presence of Tropheryma whipplei (Tw) DNA in the tissues was confirmed by polymerase chain reaction (PCR). Careful re-evaluation of biopsies taken from the ileum and the liver 2 years earlier, which at that time was not judged to be diagnostic for WD, retrospectively showed subtle histological signs of WD and were positive for Tw DNA. In summary, infliximab treatment seems to increase the risk of exacerbation of WD. WD should be carefully ruled out prior to application of tumour necrosis factor-alpha (TNF-alpha) blockade.

Monoclonal antibodies to immunodominant epitope of Tropheryma whipplei.

Recent isolation of Tropheryma whipplei (formerly Trophyrema whippelii), the agent of Whipple's disease, from the cardiac valve of a patient with Whipple's disease endocarditis now allows the detection of reactive epitopes that could be used in a serological assay. In order to propose an enzyme-linked immunosorbent assay (ELISA) that uses recombinant T. whipplei antigen, we first determined by Western blotting of human, mouse, and rabbit antisera that the common immunodominant epitope is an 84-kDa protein. We then produced 13 monoclonal antibodies (MAbs) against T. whipplei, 12 of which recognize this immunodominant epitope. These MAbs did not react with phylogenetically closely related bacteria or bacteria previously shown to be cross-reactive with T. whipplei, but they did react with two other strains of T. whipplei isolated, one from an ocular sample and the other from a duodenal biopsy specimen. By confocal microscopy, the MAbs allowed detection of T. whipplei within infected fibroblasts. The identification of the 84-kDa antigen with our MAbs will make it possible to develop a diagnostic antigen for use in a diagnostic ELISA for Whipple's disease.

[Whipple's disease as a complication of chronic lymphocytic leukemia treated with fludarabine]. / Choroba Whipple'a powiklaniem przewleklej bialaczki limfatycznej leczonej fludarabina.

The case of 53-year-old man who suffered from chronic lymphocytic leukemia since 1993 was presented. In the 6th year of treatment fludarabine was administered. Few days after administration of drug the patient developed watery diarrhoea not responding to treatment. We excluded both infectious etiological factors and infiltration of intestine in course of chronic lymphocytic leukemia. Histopathological examination with monoclonal antibodies and periodic acid-Schiff stain (PAS) revealed Whipple's disease as the reason of enteropathy. During 6 months diarrhoea caused extreme dyselectrolitemia, renal insufficiency and finally death of the patient.

Iron loading: a risk factor for Whipple's disease?

Because of impairment of microbial iron acquisition ability, some potential pathogens can cause disease only in iron loaded hosts. Tropheryma whippelii, the etiologic agent of Whipple's disease, is a possible example. Whipple's disease is non-contagious, occurs mainly in middle-aged white males, and displays many, but not all, of the complications of hereditary haemochromatosis. Tropheryma whippelii is a gastrointestinal commensal that causes disease in persons who have a Th1-Th2 imbalance. Host susceptibility may be exacerbated by iron loading. Consideration should be given to have patients evaluated for levels of interferon-gamma and interleukin-4 as well as for serum ferritin and transferrin iron saturation.

Detection of Tropheryma whippelii DNA (Whipple's disease) in faeces.

To date the diagnosis of Whipple's disease is based mainly on the histopathological analysis of duodenal biopsies since Tropheryma whippelii cannot be cultured in vitro. We investigated the possibility to diagnose Whipple's disease by detection of bacterial DNA in faces. Nested polymerase chain reaction with amplification of part of the 16S rRNA gene of this bacterium in DNA extracted from faeces of a patient with Whipple's disease was performed. Sequencing of the polymerase chain reaction product revealed the sequence of Tropheryma whippelii. We conclude that Whipple's disease will be able to be diagnosed non-invasively by DNA analysis from the faeces as soon as more specific sequences of this bacteria are known.

Enfermedad de Whipple: caso clínico y revisión bibliográfica / Whipple's disease: case report and bibliographic review

Se presenta un caso de enfermedad de Whipple confirmado, en una mujer de 61 años, por estudio histológico de biopsias escalonadas de duodeno y yeyuno.Se señala la etiología bacteriana y el carácter sistémico de la afección, que es producida por la Tropheryma whippelii, que es un bacilo Gram positivo con forma de hoz. Se describe el cuadro clínico que es esencialmente polimorfo pero dentro del cual destacan la diarrea crónica de tipo alto, con caracteres de síndrome de malabsorción y marcado compromiso progresivo del estado general; las artralgias y poliartritis y la fiebre. La enfermedad responde favorablemente a diversos antibióticos que deben administrarse en forma prolongada para intentar reducir las recurrencias que son muy frecuentes y que comprometen muchas veces al sistema nervioso central

Doença de Whipple / Whipple's Disease

A Doença de Whipple é uma doença bacteriana sistêmica rara, com maior incidência entre a quarta e sexta décadas, no sexo masculino e na raça caucasiana. Cursa com infiltraçäo por macrófagos com grânulo PAS positivos nos órgäos e tecidos afetados. O microrganismo responsável é o bacilo gram-positivo intracelular Tropheryma whippelli. Relata-se o caso de paciente masculino, 53 anos, branco, quadro clínico compatível com doença má-absortiva, cujo diagnóstico foi realizado através da esôfago-gastroduodenoscopia com presença de papilite e duodenite serveras, onde a biópisa evidenciou os grânulos PAS positivos infiltrando a lâmina própria do intestino delgado. Após 3 meses de tratamento com sulfametoxazol e trimetroprim, apresenta-se assintomático e com ganho ponderal satisfatório. Como os sintomas da DW säo inespecíficos é importante a realizaçäo de diagnóstico diferencial com outras doenças má-absortivas(doença celíaca, doença de Crohn, linfoma intra-abdominal, SIDA)

Whipple's disease.

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.

Whipple's disease, familial Mediterranean fever, adult-onset Still's disease, and enteropathic arthritis.

Whipple's disease is a rare multisystem disorder of infectious etiology. Efforts to culture the responsible organism have been unsuccessful. Nucleotide sequencing and amplification of bacterial 16S ribosomal DNA revealed the organism to be most similar to bacteria of the Rhodococcus, Streptomyces, and Arthrobacter genera. Several clinical studies of the long-term use of colchicine for the treatment of familial Mediterranean fever demonstrate its utility for symptom control and prevention of complications by amyloidosis in both adults and children. Normal growth, development, and subsequent fertility were seen in children treated with colchicine. Adult-onset Still's disease has previously been thought to have a generally good outcome, although some patients develop chronic arthritis and disability. No markers have been available for prognosis. A study of 62 patients revealed the presence of polyarthritis, root joint involvement, and rash at initial presentation to be associated with a poorer outcome. Enteropathic arthritis may be seen as a complication of both Crohn's disease and ulcerative colitis. The onset of peripheral arthritis coincides with or follows the onset of bowel symptoms in most cases, whereas spondylitis may precede the onset of inflammatory bowel disease by years. HLA-B27 is present in 50% to 75% of cases of spondylitis. No HLA association with inflammatory bowel disease or peripheral arthritis has been consistently found.

[Histopathology and ultrastructure of opportunistic infections of the digestive tract in acquired immunodeficiency syndrome]. / Histopathologie et ultrastructure des infections opportunistes du tube digestif au cours du syndrome d'immunodéficience acquis.

Light and electron microscopy studies of digestive tract biopsy specimens from AIDS patients are very useful for the detection of opportunistic pathogens which may be located in: the lumen (bacteria, Candida albicans, Giardia lamblia), enterocyte brush border (Cryptosporidium sp), enterocyte cytoplasm (Enterocytozoon bieneusi), enterocyte nuclei (cytomegalovirus), or cytoplasm of lamina propria macrophages (Mycobacterium avium intracellulare). These studies may also be useful to detect combinations of morbid conditions and to evaluate the effectiveness (if any) of therapeutic agents.

Whipple's disease: pathogenetic considerations.

A typical case of Whipple's disease was manifested by malabsorption and nondeforming peripheral arthritis for five years. A definite diagnosis was made by duodenal mucosal biopsy which revealed the characteristic histologic features by light microscopy, intracellular and extracellular Whipple's bacilli by electron microscopy, and a typical immune cross-reactivity pattern by immunofluorescence technique. Whipple's bacilli apparently elicit no effective humoral and cellular immune response; macrophages thus play the key role in its pathogenesis. Antibiotic treatment resulted in a dramatic relief of symptoms and rapid restoration of body weight. We stress that in patients with nondeforming peripheral arthritis associated with malabsorption syndrome, Whipple's disease, despite its rarity, should be included in the differential diagnosis.