Differential diagnostic value of rheumatic symptoms in patients with Whipple's disease.

Most patients with Whipple's disease have rheumatic symptoms. The aim of our prospective, questionnaire-based, non-interventional clinical study was to assess whether these symptoms are useful in guiding the differential diagnosis to the rheumatic disorders. Forty patients with Whipple's disease, followed by 20 patients for validation and 30 patients with rheumatoid-, 21 with psoriatic-, 15 with palindromic- and 25 with axial spondyloarthritis were recruited for the present investigation. Patients with Whipple's disease and patients with rheumatic disorders were asked to record rheumatic symptoms on pseudonymized questionnaires. The data obtained were subjected to multiple logistic regression analysis. Episodic pain with rapid onset, springing from joint to joint was most common in patients with palindromic arthritis and second most common and somewhat less conspicuous in Whipple's disease. Continuous pain in the same joints predominated in patients with rheumatoid-, psoriatic-, and axial spondyloarthritis. Multiple logistic equations resulted in a predicted probability for the diagnosis of Whipple's disease of 43.4 ± 0.19% (M ± SD) versus a significantly lower probability of 23.8 ± 0.19% (M ± SD) in the aggregate of patients with rheumatic disorders. Mean area under the curve (AUC) ± SD was 0.781 ± 0.044, 95% CI 0.695-0.867, asymptotic significance p < 0.001. The logistic equations predicted probability for the diagnosis of Whipple's disease in the initial series of 40 patients of 43.4 ± 0.19% was not significantly different in the subsequent 20 patients of 38.2 ± 0.28% (M ± SD) (p = 0.376). The data may be useful in a predictive algorithm for diagnosing Whipple's disease. The project is registered as clinical study DRK S0001566.

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.

Whipple disease after bariatric surgery: from malabsorption to malnutrition status / La enfermedad de Whipple después de cirugía bariátrica: de la malabsorción a la malnutrición

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

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.

Chorioretinitis and vitreitis due to Tropheryma whipplei after transplantation: case report and review.

Whipple's disease is a very rare chronic multisystemic bacterial disease characterized by diarrhea, malabsorption, fever, and polyarthritis. Ocular manifestations occur very rarely. Previous reports have suggested that the use of immunosuppressive drugs appears to accelerate or exacerbate the clinical course of Whipple's disease; however, the illness has yet to be reported in the setting of transplantation. Herein, we describe what we believe is the first reported case of Whipple's disease after transplantation. The patient is a 51-year-old woman who developed progressive visual floaters and blurring of vision 30 years after living-related kidney transplantation for an autosomal-dominant polycystic kidney disease. Her allograft was functioning well on maintenance immunosuppressive therapy with azathioprine and prednisone when she developed visual abnormalities. Transient weight loss, gastrointestinal symptoms, and migratory polyarthralgia predated the onset of ocular disease by several years. The diagnosis of Whipple's bilateral vitreitis and chorioretinitis was confirmed by polymerase chain reaction analysis demonstrating Tropheryma whipplei nucleic acid in vitreous fluid and peripheral blood sample as well as by demonstration of the bacilli by cytopathology. Intraocular vancomycin, intravenous ceftriaxone, and prolonged course of oral trimethoprim-sulfamethoxazole therapy led to clinical improvement and recovery of visual acuity.

A systematic literature review of psychological factors and the development of late whiplash syndrome.

This systematic literature review aims to assess the prognostic value of psychological factors in the development of late whiplash syndrome (LWS). We included prospective cohort studies that provided a baseline measure of at least one psychological variable and used outcome measures relating to LWS (i.e. pain or disability persisting 6 months post injury). A search of electronic databases (Pubmed, Medline, Cinahl, Embase and Psychinfo) up to August 2006 was done using a predetermined search strategy. Methodological quality was assessed independently by two assessors. Data extraction were carried out using a standardised data extraction form. Twenty-five articles representing data from 17 cohorts were included. Fourteen articles were rated as low quality with 11 rated as adequate quality. Meta-analysis was not undertaken due to the heterogeneity of prognostic factors, outcome measures and methods used. Results were tabulated and predefined criterion applied to rate the overall strength of evidence for associations between psychological factors and LWS. Data on 21 possible psychological risk factors were included. The majority of findings were inconclusive. Limited evidence was found to support an association between lower self-efficacy and greater post-traumatic stress with the development of LWS. No association was found between the development of LWS and personality traits, general psychological distress, wellbeing, social support, life control and psychosocial work factors. The lack of conclusive findings and poor methodological quality of the studies reviewed highlights the need for better quality research. Self-efficacy and post-traumatic distress may be associated with the development of LWS but this needs further investigation.

[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.

Enfermedad de Whipple. Dos nuevos casos de una enfermedad infradiagnosticada / Whipple´s disease. Two new cases of an underdiagnosed disease

La enfermedad de Whipple, también conocida como lipodistrofia intestinal, es un proceso infeccioso, multisistémico y poco frecuente, causado por la bacteria Tropheryma whippelii. El diagnóstico precoz es fundamental porque esta enfermedad es potencialmente letal, pero responde espectacularmente al tratamiento antibiótico. El diagnóstico se confirma con la reacción en cadena de la polimerasa (PCR) que también es útil para monitorizar la respuesta al tratamiento. Actualmente el tratamiento recomendado consiste en la administración de cotrimoxazol oral dos veces al día durante un año. Cuando hay afectación del SNC se aconseja iniciar el tratamiento con la administración intramuscular de 1 gramo de estreptomicina asociado a 1,2 MU de bencil penicilina (penicilina G) de forma diaria durante 14 días

Whipple’s disease is a rare systemic infectious disease caused by the bacterium Tropheryma whippelii. Early diagnosis is essential. Whipple’s disease is potentially fatal but responds dramatically to antibiotic treatment. The diagnosis is confirmed by means of polymerase chain reaction (PCR) technology. This analysis may be useful for monitoring the efficacy of therapy. The recommended treatment al present is administration of cotrimoxazole twice daily for one year. When CNS involvement occurs, it is recommended initial treatment with daily parenteral administration of streptomycin 1 g and 1,2 million units of benzyl penicillin (Penicillin G) over a period of 14 days

Can Whipple's disease be transmitted by gastroscopes?

OBJECTIVE: To determine whether disinfection protocols currently used for gastroscopes are effective against cultures of Tropheryma whipplei. DESIGN: The bactericidal activity of 2% glutaraldehyde and two peracetic acids on the Twist-Marseille strain of T. whipplei grown in cell monolayers was determined. PATIENTS: Two patients who were diagnosed as having Whipple's disease 3 years after they had had intestinal biopsies. RESULTS: The disinfectants reduced bacteria by approximately 2 log to 3 log10 after 5 to 60 minutes of contact. CONCLUSION: The bactericidal activity of a disinfectant is usually considered significant if it causes a 5 log10 or greater reduction in viable bacterial titers. Disinfecting gastroscopes with 2% glutaraldehyde or peracetic acids for 20 minutes may be insufficient to prevent transmission of T. whipplei on the instruments or stop false-positive results on polymerase chain reaction.

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.