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We present the case of a 70-year-old woman with a history of seronegative arthritis, recurrent pleural effusion and weight loss. A prior lung biopsy had revealed non-caseating epithelioid cell granulomas without evidence for microbial organisms on special stains. Intestinal biopsy findings where suspicious for Whipple’s disease, which was confirmed by PCR testing, both on the intestinal and retrospectively on the lung tissue. Treatment with ceftriaxone resulted in clinical deterioration with fever, arthritis and recurrent pleuritis consistent with immune reconstitution inflammatory syndrome. Dose increase of glucocorticoids and therapy rotation to doxycycline and hydroxychloroquine resulted in rapid clinical improvement.

Resume Introduction L’expression clinique initiale de la maladie de Whipple (MW) peut mimer un rhumatisme inflammatoire chronique (RIC) et son diagnostic au cours d’un traitement par anti-TNF a ete rapporte dans la litterature depuis plusieurs annees, incluant des formes severes. L’impact de ce type de traitement sur le rapport hote-pathogene est fortement suspecte. La frequence du portage asymptomatique de Tropheryma whipplei dans la population generale complique le diagnostic positif d’une MW devant un RIC non classe. Observations Nous rapportons ici trois observations illustrant des situations redevables d’une recherche de T. whipplei au titre du diagnostic differentiel au cours de la prise en charge d’un rhumatisme inflammatoire. Conclusion L’evaluation clinique individuelle doit guider non seulement l’indication de la recherche de T. whipplei au cours d’un RIC, notamment en cas d’aggravation paradoxale sous traitement, de presentation ou d’evolution atypique, mais egalement l’interpretation des resultats de la biologie moleculaire et de l’anatomopathologie dont la rentabilite peut etre modifiee par les traitements immunomodulateurs. Une strategie de depistage systematique de T. whipplei avant traitement par anti-TNF parait deraisonnable.

Whipple’s disease is a rare chronic systemic infection caused by Tropheryma whipplei. The widespread infection by this rod is responsible for the protean clinical manifestations of the disease, although its classical form is notable for the prevalence of abdominal symptoms such as chronic diarrhea and abdominal pain. Whitish-yellow patches, suggestive of lymphangiectasia, are typically observed in the duodenum during upper endoscopy. The diagnosis of this condition is supported by the identification in duodenal biopsies of Periodic acid-Schiff staining within lamina propria macrophages. Nevertheless, a significant portion of patients do not have lesions within the range of conventional upper endoscopy. Therefore, other endoscopic procedures such as video capsule endoscopy and enteroscopy may be useful to detect more distal lesions. The authors describe a case where the combined used of both techniques allowed the unmasking of this disease.

Whipple’s disease is a rare and systemic infectious disease that classically presents with gastrointestinal symptoms. The epidemiology of cardiac involvement is unknown. However, with the advent of improved molecular techniques, it is increasingly recognized as a cause of culture-negative endocarditis. Monotherapy treatment with trimethoprim-sulfamethoxazole is associated with relapses, sometimes in organs different than those previously affected. We present the case of a man diagnosed with classic Whipple disease, initially treated with trimethoprim-sulfamethoxazole. Twenty-two years later, he is diagnosed with endocarditis by the same agent. Whipple’s disease, particularly Whipple’s endocarditis is an extremely difficult entity to diagnose and to treat. Indications for treatment remain controversial and are still based on clinical experience and case series. This particular patient, with a recurrence two decades after the initial episode, highlights the ineffectiveness of trimethoprim/sulfametoxazole for the treatment of Tropheryma whipplei infection, even when used for long periods. Furthermore, this case illustrates the diagnostic difficulty so often associated with endocarditis and the importance of interdisciplinarity when addressing this infection.

We report a 26-year-old man with left chest pain for 4 days. His chest CT showed a cavity in the left upper lung. Tuberculosis was suspected first, but metagenomics next generation sequencing (mNGS) in bronchoalveolar lavage fluid only detected Tropheryma whipplei. Tropheryma whipplei is the pathogen of Whipple’s disease. The most frequently involved organs are the eyes, heart, and central nervous system. Pulmonary parenchymal involvement is rare. To our knowledge, this is the first reported case of pulmonary cavity caused by Tropheryma whipplei. Nineteen cases of pulmonary parenchymal involvement were found by literature search. The most common respiratory symptom was cough, followed by dyspnea/breathlessness and chest pain. The most common finding in chest imaging was pulmonary nodules, followed by interstitial changes and patchy infiltration. Our case and literature review highlighted that Tropheryma whipplei infection should be considered in the differential diagnosis of pulmonary cavity, pulmonary nodules, interstitial changes, and patchy infiltration. mNGS is helpful to improve diagnosis rate.

Background Whipple’s disease (WD) is a rare, chronic, infection caused by gram-positive filamentous aerobic actinobacterium Tropheryma whipplei occurs classically in the gastrointestinal tract and shows histopathologically foamy macrophages with typical numerous PAS-positive, non-acid fast particles. Ocular WD in the form of uveitis may occur in the absence of systemic disease but has not been reported to present with scleral manifestation. We describe for the first time to the best of our knowledge 2 cases of scleral nodules with typical histopathological morphology of WD and without systemic involvement. Case presentation The first was a 53-year old diabetic male farmer who presented with 2 nontender right eye scleral nodules for 3 months, had a negative systemic workup, and surgical excision showed Periodic acid Schiff (PAS)-positive eosinophilic structures inside macrophages. Grocott’s methenamine silver (GMS) stain and acid-fast bacilli (AFB) stain of the tissue itself were negative. The second case was a 60-year old male who presented with an asymptomatic superior scleral nodule for 4 months, which showed similar appearance and negative GMS and AFB stains. Conclusion WD should be included in the differential diagnosis of scleral nodules even in the absence of systemic symptoms. Surgical excision without systemic treatment resulted in successful outcome without recurrence.

Whipple’s disease is a rare infectious intestinal disease with lipid deposition and multiple macrophages that contain argyrophilic rod-shaped formations found in the intestines and lymph nodes. This disease is difficult to diagnose and it is only after several years of treatment of other diseases that the correct diagnosis is established. The advent of antibiotics has improved the disease outcome – tetracycline antibiotics are used in most cases.

Whipple's disease is caused by Tropheryma whipplei and is known to have protean clinical presentation which could be influenced by patient's immunologic and genetic features. In contemporary literature abundant amount of data could be found on extensive prevalence of infectious endocarditis caused by Tropheryma whipplei . This article presents history of a patient who was observed because of ischemic heart disease, angina pectoris, myocardial infarction, possible ischemic cardiomyopathy and in whom infectious endocarditis complicated by severe aortic regurgitation needing aortic valve replacement surgery was eventually diagnosed. Our patient did not meet Duke criteria, which is a sign of infectious endocarditis caused by Tropheryma whipplei , but a thorough analysis of the disease course, clinical features, heart ultrasound and clinical improvement on specific therapy against Tropheryma whipple i aroused our suspicion, and morphological and bacteriological analysis of the involved (excised) valve, confirmed the diagnosis of Whipple disease. The article presents differential diagnostic criteria of aortic insufficiency and possible causes of coronary insufficiency in the absence of marked coronary atherosclerosis.

International audience; Introduction Whipple's disease is a rare clinical entity that is usually fatal if left untreated.Tropheryma whippleiwas first cultured 20 years ago, and has led to the development of diagnostic tools that have greatly improved knowledge of the disease. T. whipplei is actually more common than initially described with the description of common asymptomatic carriage. Areas covered We reviewed current knowledge of microbiological diagnosis and summarized the diagnostic strategy ofT. whipplei infection. Articles were selected from Medline and Google scholar using the keywords `Tropheryma whipplei' OR `Whipple's disease' AND `diagnosis'. Expert opinion Definitive diagnosis of Whipple's disease is challenging and continues to be based on immunohistochemical analysis or PAS staining combined with positive qPCR on duodenal biopsy. Initially, screening forT. whipplei was recommended on stool and saliva which are associated with a high positive predictive value of Whipple's disease. However, given the presence of a large number of asymptomatic carriers, the specificity of a positive qPCR on these samples is likely to have decreased and their interests should be reevaluated. The development of new noninvasive tests may be useful for the diagnosis of Whipple's disease and qPCR performed on urine could be a promising alternative.

Whipple’s disease is one of the rare maladies in terms of spread but very fatal one as it is linked with many disorders (like Gastroenteritis, Endocarditis etc.). Also, current regimens include less effective drugs which require long duration follows up. This exploratory study was conducted to commence the investigation for crafting multi target epitope vaccine against its bacterial pathogen Tropheryma whipplei. The modern bioinformatics tools like VaxiJen, NETMHCII PAN 3.2, ALLERGEN-FP, PATCH-DOCK, TOXIC-PRED, MHCPRED and IEDB were deployed, which makes the study more intensive in analyzing proteome of T. whipplei as these methods are based on robust result generating statistical algorithms ANN, HMM, and ML. This Immuno-Informatics approach leads us in the prediction of two epitopes: VLMVSAFPL and IRYLAALHL interacting with 4 and 6 HLA DRB1 alleles of MHC Class II respectively. VLMVSAFPL epitope is a part of DNA-directed RNA polymerase subunit beta, and IRYLAALHL epitope is a part of membranous protein insertase YidC of this bacterium. Molecular-Docking and Molecular-Simulation analysis yields the perfect interaction based on Atomic contact energy, binding scores along with RMSD values (0 to 1.5 Ǻ) in selection zone. The IEDB (Immune epitope database) population coverage analysis exhibits satisfactory relevance with respect to world population.

BACKGROUND Whipple's disease is a very rare disease needing a long-term treatment. The most frequent symptoms are recurrent arthralgia or arthritis, chronic diarrhea, abdominal pain, and weight loss. OBJECTIVES In this article, we have highlighted the main clinical features and diagnostic procedures that lead to the diagnosis and comment on the clinical response, treatment, and the factors of relapse. METHODS Subjects were recruited from the Internal Medicine and Rheumatologic Departments of an University Hospital from November 1997 to January 2016. Overall, 12 subjects were finally diagnosed. RESULTS Mean age was 54.3 years (age range: 30-81), with more male patients (58.3%). Almost all patients had articular symptoms and impaired general condition (91.7%); and a majority had digestive symptoms (75%). Regardless of the symptoms, the most efficient diagnostic tools were the PCR screening on the gastrointestinal biopsies and saliva (83.3 and 72.7% positive results, respectively). More than half of the patients relapsed (55.6%). The relapsing patients were older [63.2 (44-81)] and mostly male with a majority (60%) of digestive symptoms and a delayed diagnosis. CONCLUSIONS In current practice, it is highly difficult to diagnose Whipple's disease. In order to decrease the delay between the first symptoms and the diagnosis, effective tools such as saliva and stools PCR should be used because higher delays of diagnosis lead to a higher number of relapses.

Introduction: Whipple’s disease is a rare, chronic, systemic disease caused by the actinomycete Tropheryma whipplei. Clinical manifestations vary widely depending on the affected system, the most common being the digestive tract. Case Presentation: The authors report the case of a 52-year-old man with malabsorption syndrome, diarrhea, marked weight loss, melanoderma, and visual and proprioception disorders. Periodic acid-Schiff staining of a proximal small bowel biopsy and peripheral-blood PCR identification of T. whipplei confirmed the disease. The patient was initially treated with intravenous ceftriaxone, followed by oral trimethoprim/sulfamethoxazole with significant clinical improvement. Conclusions: This case is reported due to its rarity and the diagnostic challenge it presents. Although uncommon, Whipple’s disease should be considered as a differential diagnosis of malabsorption syndrome due to its systemic impact and possible treatment with targeted antibiotic therapy.

Background Whipple’s disease is a clinically relevant multi-system disorder that is often undiagnosed given its elusive nature. We present an atypical case of Whipple’s disease involving pan-valvular endocarditis and constrictive pericarditis, requiring cardiac intervention. A literature review was also performed assessing the prevalence of atypical cases of Whipple’s disease. Case presentation A previously healthy 56-year-old male presented with a four-year history of congestive heart failure with weight loss and fatigue. Notably, he had absent gastrointestinal symptoms. He went on to develop pan-valvular endocarditis and constrictive pericarditis requiring urgent cardiac surgery. A clinical diagnosis of Whipple’s disease was suspected, prompting duodenal biopsy sampling which was unremarkable, Subsequently, Tropheryma whipplei was identified by 16S rDNA PCR on the cardiac valvular tissue. He underwent prolonged antibiotic therapy with recovery of symptoms. Conclusions Our study reports the first known case of Whipple’s disease involving pan-valvular endocarditis and constrictive pericarditis. A literature review also highlights this presentation of atypical Whipple’s with limited gastrointestinal manifestations. Duodenal involvement was limited and the gold standard of biopsy was not contributory. We also highlight the Canadian epidemiology of the disease from 2012 to 2016 with an approximate 4% prevalence rate amongst submitted samples. Routine investigations for Whipple’s disease, including duodenal biopsy, in this case may have missed the diagnosis. A high degree of suspicion was critical for diagnosis of unusual manifestations of Whipple’s disease.

Introduction Whipple's disease (WD) is a rare multi-systemic disorder caused by actinomycetes, Tropheryma Whipplei (T. Whipplei). It presents with weight loss, arthralgia and diarrhea and may involve the heart, lung or central nervous system. The use of immunosuppressive medications or underlying immunodeficiency states are associated risk factors. Six cases in transplant recipients have so far been reported worldwide. We describe our experience of Whipple's disease in renal transplant recipients. Methods All renal transplant recipients who presented with diarrhea and were diagnosed with Whipple's disease on duodenal biopsy from 2016 till 2019 were included. Their data regarding duration since transplantation, immunosuppressive therapy, symptoms, treatment response and outcome was analyzed. Results Seven cases were diagnosed as Whipple's disease based on duodenal biopsy, with histological findings of Periodic acid Schiff positive granules in macrophages. All were male. The most common symptoms were chronic diarrhea and weight loss. Average time since transplantation was 4.8 years. All patients were on azathioprine and everolimus. Clinical relapse or adverse effects was seen in 5 of 7 patients treated with doxycycline and hydroxychloroquine which was discontinued. Trimethoprim/sulphamethoxazole for one year, with initial intravenous ceftriaxone in 2 patients, resulted in complete remission in all patients at a follow-up period averaging 1.5 years. Conclusion Whipple's diseases in renal transplant recipients most commonly presents as an intestinal disorder. Treatment of one year with Trimethoprim/sulphamethoxazole has good response with complete remission at 1.5 years of follow up. This article is protected by copyright. All rights reserved.

Introduction: Whipple’s disease (WD) is a rare multivisceral disorder with few descriptions of pulmonary hypertension (PH) Aims and objectives: To describe the association between PH and WD (PH-WD). Methods: We report the characteristics and outcomes of two patients with PH-WD hospitalized in the French PH reference center. Results: PH-WD was diagnosed in two men (54 and 59-yo) hospitalized for right heart failure. Both reported a deterioration in general state over the previous year, associated with diarrhea and mood change (patient 1) and a seronegative polyarthritis and purpura (patient 2). Initial right heart catheterization (RHC) confirmed severe precapillary PH in patient 1: mean pulmonary artery pressure 40 mmHg, cardiac index 2 L/min/m2, pulmonary artery wedge pressure13 mmHg, pulmonary vascular resistance 8 WU. The second patient presented with advanced right heart failure, high echocardiographic probability of PH and no evidence of left heart disease. Both patients were treated with intravenous dobutamine and large spectrum antibiotics. The diagnosis of WD was established by duodenal biopsies and positive T. whipplei PCR in the saliva (patient 1) and in the blood and stools (patient 2). The first patient rapidly improved and experienced complete recovery after one year of treatment associating bosentan, tadalafil, doxycycline and hydroxychloroquine. The second patient rapidly deteriorated and died 24h after his admission because of end-stage right heart failure. Conclusions: WD is a rare cause of severe but potentially reversible PH. Due to poor awareness, delayed diagnosis may lead to death due to end-stage right heart failure.

A 60-year-old gentleman presented with chronic diarrhoea and weight loss. Following an array of investigations, primarily targeting a possible malignancy, gastritis and duodenitis were observed on endoscopy. Gastric and duodenal biopsies showed aggregates of PAS positive macrophages in the lamina propria. Polymerase chain reaction confirmed the presence of Whipple's disease (WD). WD is a rare multisystemic granulomatous infectious disorder, affecting many organ systems but predominantly the gastrointestinal system. WD has a two stage process. The prodromal stage is dominated by arthralgia and arthritis, followed by a latency period, from one to ten years and then by a later steady-state stage which is characterized by the involved organ systems. WD can be fatal if left untreated, however a strict antibiotic regime may eradicate the causative organism, Tropheryma whipplei. We report a rare case of WD diagnosed on a gastric biopsy with an agglomeration of misleading signs and symptoms which demonstrate the mimicry of this potential infectious disease.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that can affect major organs possibly leading to life-threatening complications and appears with heterogeneous clinical picture. SLE could present with broad spectrum of clinical and laboratory features that can resemble those of other diseases, such as hemopoietic malignancies, infections, or immune-mediated disorders. Its complexity and protean features overlap with many other diseases, hindering the differential diagnosis. Rarely, true overlap with other diseases may occur. Herein, we report a case series of two patients affected by infectious diseases, namely visceral leishmaniasis and Whipple’s disease (WD), intertwined with clinical or serological features of SLE. In both cases, several confounding factors have led to a delay in the diagnosis. Moreover, we first describe the persistent elevation of autoantibodies and a monoclonal gammopathy in a patient with WD. Awareness of unusual presentations of infections or other rare disorders, which may be encountered in clinical practice when taking care of SLE patients, is essential for timely diagnosis and treatment of potentially lethal diseases.

Whipple's disease is a rare, multisystem infection caused by the Gram-positive Tropheryma whippelii organism. In addition to neurological and rheumatological manifestations, this disease can result in significant gastrointestinal symptoms such as malabsorption, diarrhea, and weight loss. Given the diagnostic challenge and rare occurrence, a high index of suspicion is critical to prevent morbidity and mortality from this otherwise highly infectious disease transmitted via the fecal-oral route. We present a very rare but near-fatal case of hypovolemic shock secondary to protein-losing enteropathy and gastrointestinal bleeding from small bowel T. whippelii infection. Furthermore, the epidemiology, clinical presentation, diagnosis, and management of Whipple's disease is reviewed.

Objective: Whipple’s disease is a very rare systemic infectious disease with an annual incidence of 3 in one million, which may be fatal if not diagnosed and treated appropriately. Clinical Presentation and Intervention: Herein we describe a 49-year-old patient admitted to the hospital with symptoms of severe malabsorption and diagnosed with Whipple’s disease. The diagnosis was based on the histopathological findings of small intestine biopsies and PCR analysis. Conclusion: Whipple’s disease should be kept in mind while dealing with patients with severe malabsorption, even in the absence of accompanying features of the disease.

Der Morbus Whipple (MW) ist eine seltene chronische Multiorganerkrankung, welche durch Tropheryma whipplei (TW), ein ubiquitar vorkommendes Bakterium, ausgelost werden kann. TW kann in den betroffenen Geweben durch einen histologischen Nachweis von PAS(„periodic acid-Schiff reaction“)-positiven Makrophagen und in der Polymerasekettenreaktion (PCR) nachgewiesen werden. Klinisch gepragt wird der MW haufig durch eine gastrointestinale Klinik (Diarrhoe, kolikartige Bauchschmerzen, Gewichtsverlust). Arthritiden werden haufig beobachtet, sodass eine initiale Fehldiagnose einer seronegativen rheumatoiden Arthritis mit konsekutiver immunsuppressiver Therapie nicht selten ist. Der MW kann sich unterschiedlich manifestieren und mit einer Beteiligung weiterer Organsysteme einhergehen (z. B. kardiale oder neurologische Beteiligung), was den klinischen Verdacht bzw. die Diagnosestellung erschwert. Die hier beschriebenen 3 Falle mit unterschiedlicher fuhrender Symptomatik (initiale Fehldiagnose einer seronegativen rheumatoiden Arthritis, Spondylarthritis und eines Morbus Still) illustrieren den Facettenreichtum des MW und sollen demonstrieren, dass die dem Bereich der Gastroenterologie zugeordnete und v. a. mit gastrointestinaler (GI) Symptomatik assoziierte Erkrankung auch ohne diese Beschwerden auftreten kann. Bei klinischem Verdacht sollte der Erregernachweis aus dem jeweils symptomatischen Organ angestrebt werden. Die 01/2015 publizierte Deutsche S2k-Leitlinie zu gastrointestinalen Infektionen und MW fasst den aktuellen Kenntnisstand zum MW zusammen. Als Primartherapie kommen liquorgangige Antibiotika zum Einsatz, typischerweise Ceftriaxon, gefolgt von einer mehrmonatigen Cotrimoxazol-Therapie.

Whipple’s disease (WD) is an uncommon cause of seronegative arthritis. WD is known for its gastrointestinal symptoms of diarrhea, weight loss, and abdominal pain. However, arthritis may precede gastrointestinal symptoms by 6 to 7 years. We describe a case of an 85-year-old Caucasian male with multiple joint complaints, not responsive to traditional treatments for conditions such as rheumatoid arthritis and osteoarthritis. We suggest that WD be considered for seronegative arthritis especially affecting large joints.

Whipple’s disease is a bacterial infection caused by Tropheryma whipplei and is known to cause perplexing clinical presentations, making its diagnosis challenging. The beginning by the involvement of the gastrointestinal tract, Whipple's disease can slowly progress to affect almost any organ system and lead to chronic multi-system inflammatory disease. Hereby, we present a middle age man who initially manifested with shortness of breath and chronic weight loss. He subsequently developed pleuro-pericardial effusion, ascites, mesenteric lymphadenopathy, possible myocarditis, and severe osteopenia with multiple vertebral fractures during his illness. Esophagogastroduodenoscopy with the biopsy and subsequent molecular confirmation of disease led to the confirmation of WD. Therapeutic management included two separate antibiotic regimens in an attempt to address the refractory course of WD in this patient.

Background/Aims A 45-year-old male patient presented in 2015 with a six-month history of relapsing and remitting polyarthralgia. Hand X-rays appeared normal. Serology showed mildly elevated inflammatory markers. Autoimmune profile including anti-CCP antibody, rheumatoid factor and ANA was negative. His initial diagnosis was palindromic rheumatism. He was under watchful waiting in rheumatology clinic having declined a trial of hydroxychloroquine, when in 2018 he developed severe epigastric pain. Over the subsequent 18 months he was noted to have dramatic weight loss, fatigue and drenching night sweats. Methods Investigations showed microcytic anaemia with elevated inflammatory markers (Hb 98 g/L, CRP 161 mg/L, ESR 68 mm/hr). Serum ACE, bone profile, thyroid function and urate levels were normal. Chest X-ray was unremarkable. HIV and hepatitis screening was negative. Endoscopy with jejunal biopsy was performed, with mild gastritis only on histopathology and normal D2 biopsies. He was found to be H pylori positive, and notably felt his B-symptoms much improved with triple antibiotic and PPI eradication therapy. CT abdomen demonstrated widespread mesenteric lymphadenopathy. Para-aortic lymph node biopsy showed non-necrotising granulomata suggestive of either sarcoidosis or an infective etiology such as tuberculosis (TB). Given the clinical picture, the patient was commenced on high dose oral prednisolone and methotrexate for suspected sarcoidosis. Results The patient made some clinical improvement, particularly with regards to arthralgia, however his B-symptoms returned with any reduction in steroid dose. Serology showed worsening anaemia with iron and folate deficiency, and increasing inflammatory markers. We therefore decided to perform a PET CT and refer to Haematology for consideration of a lymphoproliferative disease. PET CT demonstrated lymphadenopathy without avid uptake. A second lymph node biopsy was performed which showed florid histiocytic infiltration within which there were numerous PAS positive particles consistent with Whipple's disease. This was confirmed as tropheryma whipplei on PCR. Whipple's disease is a rare systemic infectious disease causing arthralgia, diarrhoea, abdominal pain and weight loss. Treatment consists of antibiotic therapy. On further questioning, the patient had grown up on a farm. There is a known association with Whipple's disease in the agricultural community as it is a soil-borne organism. Conclusion Our patient has made an excellent recovery. He remains under the care of our rheumatology team and the London School of Tropical Medicine and Hygiene. Treatment plan is 12 months of combined therapy with doxycycline and hydroxychloroquine. He underwent a lumbar puncture to rule out meningeal Whipple disease. We have also commenced sulfasalazine for persistent arthritis, which we feel could be a reactive phenomenon. Our key learning points from this case were to use a stepwise approach to diagnosis, involve relevant specialty teams and that it in complex cases it is useful to go back to the history. Disclosure F. Baldeweg: None. A. Nuttall: None. D. Arul: None. A. Childerhouse: None.

Introduction Whipple's disease is a rare chronic infectious disease caused by Tropheryma whipplei. The infection mainly affects the small intestine of middle-aged patients, approximately three times more often in males than in females causing malabsorption and excessive weight loss but other organs may be affected as well. Case report We describe a case of a 42-year-old woman with a history of chronic diarrhea and weight loss evolving for at least the last 6 years. The diagnosis of Whipple's disease was confirmed by histopathological examination of duodenal biopsy samples with Periodic acid-Schiff positive macrophages and by polymerase chain reaction technique detecting the DNA of Tropheryma whipplei. The patient was commenced on several antimicrobials including beta-lactams and co-trimoxazole but she did not improve. Finally, after-long lasting i.v. tigecycline 100 mg BID she was commenced on p.o. doxycycline along with hydroxychloroquine 200 mg TID for one year and after by p.o. doxycycline alone. Discussion The intriguing thing with this case was not only the natural resistance to co-trimoxazole but that the infection was controlled empirically with long-lasting i.v. tigecycline since several failed attempts to discontinue i.v. treatment followed. This might be due to erratic absorption of oral drugs due to gut inflammation. Conclusions To our knowledge, this is the first case of Whipple's disease successfully treated with long-lasting induction parenteral tigecycline followed by p.o. doxycycline along with hydroxychloroquine for one year and after by p.o. doxycycline alone.

To describe posterior ocular involvement features of Whipple's disease (WD) in a patient with no gastrointestinal symptoms.Retrospective case report.A 53-year-old man with a 2-year history of seronegative arthritis presented with bilateral intraocular inflammation, optic disc edema, and cystoid macular edema (CME) in the left eye. A diagnosis of noninfectious uveitis was made and oral prednisolone was started. Despite initial improvement, after 6 weeks, CME was found in both eyes. Because of the initial response, the anti-tumor necrosis factor agent Adalimumab was started. Twelve weeks after initiation of adalimumab, fundus examination revealed widespread dot-blot retinal hemorrhages and multifocal chorioretinal lesions at the posterior pole and mid-periphery. The chorioretinal lesions appeared as hyperreflective drusen-like deposits located in the sub-retinal pigment epithelium (RPE) space on the tomographic scan. WD was considered and confirmed by polymerase chain reaction test and duodenal biopsy.Posterior ocular involvement in WD may present with a wide clinical spectrum including intraocular inflammation and unique features of sub-RPE deposits, widespread retinal hemorrhages, and optic disc edema.

Whipple’s disease is a rare, chronic, systemic disorder caused by Tropheryma whipplei infection. The most common symptoms are weight loss, arthralgia, diarrhea and abdominal pain. Other organ involvement can also occur in the patients. Joint manifestations may mimic rheumatoid arthritis or spondyloarthritis. Arthalgia, arthritis, spondylodiscitis, bursitis and/or tenosynovitis are seen in the majority of the patients. This explains why some of the symptoms are misdiagnosed as those of rheumatic diseases. Understanding of Whipple’s disease is important for differential diagnostics of several rheumatic symptoms.

Whipple’s disease (WD) is a rare infection due to Tropheryma whipplei. Following in-vitro cultivation of T. whipplei, an indirect-immunofluorescence serological assay (IFA) was developed. We tested the hypothesis that this assay could be used to either identify WD patients, or rule out WD, in patients in whom the diagnosis is being considered, based on the antibody titers of their IgM and IgG antibody responses. In this small study fourteen WD patients and 22 healthy volunteers’ sera were obtained from across Australia. All specimens were coded and de-identified before testing. A patient with an IgG antibody titer of ≤1:16 may have WD [sensitivity 57% (8/14) and specificity close to 100% (22/22)]. High IgM antibody titers (≥1:256) were more common in WD patients [sensitivity 50% (7/14) and specificity 86% (19/22)] than in controls. The area under Receiver-Operator-Characteristic curve for IgG in the IFA assay was 0.84 (95% CI 0.69-1.00). At an IgG antibody titer of ≤1:16 the Youden’s index was 0.57. WD patients’ under-produce IgG antibody to T.whipplei but are more likely to over-produce IgM antibodies. This screening IFA serological assay may be clinically useful in detecting those with a possible diagnosis of WD. Patients with an IgG antibody titer of ≤1:16 and an IgM antibody titer of ≥1:256 may have WD and should proceed to a tissue biopsy and PCR for confirmation. Further validation of this assay, by increasing the sample size, by testing it in patients with non-WD disease and trialing in other countries should be undertaken.

Background Whipple's disease is a chronic infectious disease that primarily affects the small intestine, but several organs can simultaneously be involved. The disease is caused by a gram-positive bacterium called Tropheryma whipplei. The disease is difficult to suspect because it is rare with unspecific and long-term symptoms; it can be lethal if not properly treated. Case presentation We here present three patients who presented with a plethora of symptoms, mainly long-standing seronegative arthritis and gastrointestinal symptoms in the form of diarrhea with blood, weight loss, fever, and lymphadenopathy. They were after extensive investigations diagnosed with Whipple's disease, in two of them as long as 8 years after the first occurrence of joint manifestations. The diagnosis was made by PCR targeting the T. whipplei 16S rRNA gene from small bowel specimen in all three patients, and, besides from histopathologic findings from the duodenum and distal ileum in one and mesenteric lymph nodes in another patient. Conclusions This report aims to raise awareness of a very rare disease that presents with a combination of symptoms mimicking other and significantly more common diseases.

Maria Juliana da Silva Almeida , Patrícia Milani de Moraes , Renata Vaz de Oliveira , Taísa Morete da Silva

Whipple’s Disease (WD) was first described by George H. Whipple in 1907. Classic Whipple disease (CWD) is a systemic chronic infection by Tropheryma whipplei (T. whipplei) that can involve various organ systems such as gastrointestinal tract, joints, and central nervous system (CNS). Central nervous system Whipple’s disease (CNS- WD) can be a part of the classical WD, a recurrent phenomenon or an isolated disease. It encompasses a wide array of clinical manifestations depending on the anatomic region affected by the pathological process. Diagnosis is made by polymerase chain reaction testing. It is vital to implement an aggressive mode of treatment to reduce the chances of complications like cognitive impairment, or disease recurrence, even many years later.

A 51-year-old man presented with watery diarrhea and 7-kg weight loss for six months. As computed tomography scans showed multiple mesenteric and retroperitoneal lymphadenopathy, 18F-fluoro-deoxyglucose positron emission tomography was performed, showing marked accumulation in the jejunum. Enteroscopy disclosed diffuse yellow-white swollen villi in the jejunum and biopsies revealed clubbed villi with marked periodic acid-Schiff-positive foamy macrophages. The electron microscopic examination showed numerous extracellular bacilli and bacillary forms of degradation in the macrophages. 16S rRNA PCR revealed Tropheryma whipplei in the mucosal specimens, making the diagnosis of Whipple’s disease. Therapy with ceftriaxone followed by long-term trimethoprim-sulfamethoxazole was effective. Whipple's disease is briefly discussed.

A 59-year-old female patient was diagnosed with Whipple's disease (WD) after several months of constitutional complaints and adenopathies that were initially misinterpreted as sarcoidosis. Initial treatment included doxycycline, hydroxychloroquine and prednisolone, which was suspended due to long-term clinical stability. Four months after prednisolone suspension, the patient presented with right periorbital oedema and erythema. Ophthalmological examination revealed restricted eye movements. A computed tomography (CT) scan demonstrated signs of myositis. The patient was treated with anti-inflammatory and antibiotic drugs, that induced remission of the orbitopathy. During the following two years, she presented three relapses, affecting both the right or the left eyes. The last episode was also associated with systemic corticosteroid tapering. Orbitopathy is a rare form of WD presentation and the diagnosis of this condition may be challenging. As the clinical spectrum may range from an incidentaloma to a severe compressive neuropathy, proper recognition and management of WD orbitopathy is essential.

Background: Little is known about long-term morbidity and mortality in Whipple’s disease (WD). Aim: To describe morbidity and mortality in patients with WD on a long-term follow-up. Materials & methods: Comorbidities, mortality and causes of death were retrospectively registered. Results: A total of 35 patients with WD (9F, 54 ± 11 years) were followed-up for a median of 104 months. Nine patients developed ten complications; three patients died. A total of 31 severe comorbidities apparently unrelated to WD were found in 20 patients: preneoplastic/neoplastic disorders in seven, thromboembolic and cardiovascular events in seven, pneumonia in four, candidiasis in ten patients. Conclusion: WD is frequently complicated by potentially life-threatening infectious, neoplastic and thromboembolic disorders, thus highlighting the need for a life-long multidisciplinary follow-up.

We report a case of an elderly Caucasian male with past medical history of dextrocardia with situs inversus totalis, polymyalgia rheumatica, history of cryptogenic stroke, and severe mitral regurgitation with mitral valve prolapse, who presented with acute heart failure symptoms, including severe dyspnea on exertion and worsening lower extremity edema in the setting of immunosuppression with steroids for a year-old diagnosis of polymyalgia rheumatica. One month prior to this presentation, the patient suffered a transient ischemic attack and during the workup, his transthoracic echocardiography showed myxomatous degeneration of posterior mitral leaflet, partially flail, with severe mitral regurgitation, which required mitral valve replacement. Genome sequencing of mitral valve anterior leaflet pathology detected Tropheryma whipplei as a causal agent of culture-negative endocarditis. The patient was treated with 6 weeks of ceftriaxone and ampicillin–sulbactam and further continued trimethoprim–sulfamethoxazole for 1 year. He continued antibiotic treatment with resolution of shortness of breath along with arthralgia.

Background Whipple’s disease (WD) is a rare multisystem infectious disorder that is caused by the actinomycete Tropheryma whipplei. It presents with joint pain followed by abdominal pain, diarrhea, malabsorption and finally failure to thrive. Diagnosis requires tissue sampling and histology with periodic acid-Schiff [PAS] staining. Thrombocytopenia associated with endocarditis associated with WD has been reported twice. Case presentation A 56 year old Caucasian male presented with years of steroid treated joint pain and recent onset diarrhea, weight loss and abdominal pain. Ultimately he was found to have a platelet count of 4000 with concomitant endocarditis and embolic stroke. Small bowel biopsy confirmed the diagnosis of WD approximately 1 year after his first visit. His platelets improved with antibiotic treatment but he eventually expired 16 months after his initial consult and 5 months after his definitive diagnosis. Conclusion WD can remain undiagnosed and untreated until late in the course of the illness. A high index of suspicion is recognized as necessary for early diagnosis to begin treatment. Critical thrombocytopenia associated with endocarditis is a rare and potentially poor prognostic sign in late stage Whipple’s disease.

International audience; Joint complaints, most commonly intermittent arthritis, are the initial manifestation in about three-fourths of Whipple's disease cases. We herein report on two cases wherein Whipple's disease manifested itself as chronic bursitis and tenosynovitis at several sites. A 42 year-old man had bilateral olecranon bursitis, a right patellar bursitis and an extensor tenosynovitis on the left wrist and a 54 year-old man had extensor tenosynovitis at both wrists and a bilateral tenosynovitis of the extensors at both ankle. Methotrexate in both patients and etanercept in one of them were not effective. Polymerase chain reaction testing revealed Tropheryma whipplei on feces, bursitis and articular fluid samples. Duodenal biopsy proved to be normal. Doxycycline and hydroxychloroquine were rapidly effective. Chronic bursitis and tenosynovitis must be added to the list of rheumatologic manifestations that may evoke the diagnosis of Whipple disease.

Whipple’s Disease, a rare diagnosis caused by the slow-growing bacterium Tropheryma whipplei, most often presents with the classically described signs of malabsorption due to gastrointestinal colonization. However, it can also have signs and symptoms that clinically overlap with rheumatic diseases, potentially resulting in misdiagnosis. Furthermore, treatment with modern potent biologic immunosuppressive agents and classic disease modifying anti-rheumatic drugs (DMARDs) can lead to serious exacerbation of undiagnosed infections. We present the case of a middle-aged woman with long term complaints of arthalgias, who was diagnosed with seronegative rheumatoid arthritis and subsequently treated for almost 7 years with such immunosuppressive therapies. The patient’s disease course included chronic diarrhea that abruptly intensified and culminated in fatal hypovolemic shock/sepsis. A diagnosis of WD was made by autopsy examination, wherein several organ systems were found to be heavily involved by Tropheryma whipplei organisms, and their identification was confirmed with histochemical and molecular evaluation. Notably, most bacterial organisms were located deeply in the submucosa/muscularis of affected organs, a practical reminder to practicing pathologists that challenges the classic histopathologic description of Whipple disease as an infiltration of predominantly lamina propria, and the potential for sampling bias in typically superficial endoscopic biopsies during routine procedures.

Prior studies on the epidemiology of Whipple’s disease are limited by small sample size and case series design. We sought to characterize the epidemiology of Whipple’s disease in the USA utilizing a large population-based database. We queried a commercial database (Explorys Inc, Cleveland, OH), an aggregate of electronic health record data from 26 major integrated healthcare systems in the USA. We identified a cohort of patients with a diagnosis of Whipple’s disease based on systemized nomenclature of medical terminology (SNOMED CT) codes. We calculated the overall and age-, race-, ethnicity, and gender-based prevalence of Whipple’s disease and prevalence of associated diagnoses using univariate analysis. A total of 35,838,070 individuals were active in the database between November 2012 and November 2017. Of these, 350 individuals had a SNOMED CT diagnosis of Whipple’s disease, with an overall prevalence of 9.8 cases per 1 million. There was no difference in prevalence based on sex. However, prevalence of Whipple’s disease was higher in Caucasians, non-Hispanics, and individuals > 65 years old. Individuals with a diagnosis of Whipple’s disease were more likely to have associated diagnoses/findings of arthritis, CNS disease, endocarditis, diabetes, malignancy, dementia, vitamin D deficiency, iron deficiency, chemotherapy, weight loss, abdominal pain, and lymphadenopathy. To our knowledge, this is the largest study to date examining the epidemiology of Whipple’s disease. In this large population-based study, the overall prevalence of Whipple’s disease in the USA is 9.8 cases per 1 million people. It affects men and women at similar rates and is more common in Caucasians, non-Hispanics, and people > 65 years old.

Background Whipple’s disease (WD) is a rare infection with Tropheryma whipplei that is fatal if untreated. Diagnosis is challenging and currently based on invasive sampling. In a case of WD diagnosed from a kidney biopsy, we observed morphologically-intact bacteria within the glomerular capsular space and tubular lumens. This raised the questions of whether renal filtration of bacteria is common in WD and whether polymerase chain reaction (PCR) testing of urine might serve as a diagnostic test for WD. Methods We prospectively investigated urine samples of 12 newly-diagnosed and 31 treated WD patients by PCR. As controls, we investigated samples from 110 healthy volunteers and patients with excluded WD or acute gastroenteritis. Results Out of 12 urine samples from independent, therapy-naive WD patients, 9 were positive for T. whipplei PCR. In 3 patients, fluorescence in situ hybridization visualized T. whipplei in urine. All control samples were negative, including those of 11 healthy carriers with T. whipplei–positive stool samples. In our study, the detection of T. whipplei in the urine of untreated patients correlated in all cases with WD. Conclusions T. whipplei is detectable by PCR in the urine of the majority of therapy-naive WD patients. With a low prevalence but far-reaching consequences upon diagnosis, invasive sampling for WD is mandatory and must be based on a strong suspicion. Urine testing could prevent patients from being undiagnosed for years. Urine may serve as a novel, easy-to-obtain specimen for guiding the initial diagnosis of WD, in particular in patients with extra-intestinal WD., We found that in the majority of therapy-naive Whipple’s disease patients, Tropheryma whipplei is detectable in urine samples by polymerase chain reaction; therefore, urine may serve as a novel, easy-to-obtain diagnostic specimen for the initial diagnosis of Whipple’s disease.

Whipple's disease, affecting the CNS, can cause a wide variety of symptoms. Movement disorders are very prevalent, and some are pathognomonic of the disease. This systematic review analyzed all published cases of movement disorders because of CNS Whipple's disease, providing detailed information on clinical and associated features. We have also attempted to address sources of confusion in the literature, particularly related to differing uses of the terminology of movement disorder. This comprehensive overview of Whipple's disease-induced movement disorders aims to aid neurologists in recognizing this very rare disorder and successfully reaching a laboratory-confirmed diagnosis in order to initiate appropriate therapy. © 2018 International Parkinson and Movement Disorder Society.

Joint Bone Spine - In Press.Proof corrected by the author Available online since vendredi 17 janvier 2020