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Whipple disease is a rare systemic illness associated with weight loss, diarrhea, and arthralgia. Asymptomatic carriage is common, but the disease can be complicated by cardiac involvement and may result in culture-negative endocarditis. Cardiac manifestations of the disease can lead to death. This report presents the case of a 66-year-old man with Whipple disease and biventricular heart failure with cardiogenic shock. Medical therapy followed by successful replacement of the aortic and mitral valves resulted in substantial improvement., (© 2024 The Authors. Published by The Texas Heart Institute®.)

A 60-year-old male patient presented with ischemic-embolic stroke. Transesophageal echocardiography revealed the cause to be aortic valve endocarditis with highly eccentric aortic valve regurgitation. The blood cultures taken several times remained sterile. The indication for surgical aortic valve replacement was made. Conventional microbiological work-up of the heart valve did not reveal any pathogens. The additional molecular genetic testing using eubacterial PCR ("polymerase chain reaction" [PCR]) finally demonstrated the presence of Tropheryma whipplei. A number of therapeutic options were available. The authors decided on intravenous antibiotic therapy with ceftriaxone for 14 days and follow-up therapy with oral trimethoprim/sulfamethoxazole for 1 year. The case illustrates the importance of additional molecular diagnostics beyond the conventional methods in blood culture-negative endocarditis to identify the pathogen and initiate appropriate therapy., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

A 63-year-old man was admitted to the hospital for nausea, vomiting, and right flank pain. He was found to have septic emboli in multiple organs secondary to aortic valve endocarditis. He was started on broad-spectrum antibiotics and underwent valve replacement. Blood cultures from admission were negative, but a blood polymerase chain reaction (PCR) test for fastidious difficult-to-culture pathogens showed a positive result for Tropheryma whipplei. Valve histopathological evaluation confirmed Tropheryma whipplei endocarditis. He was treated with intravenous penicillin followed by oral trimethoprim-sulfamethoxazole. A high index of suspicion for causes of culture-negative endocarditis needs to be maintained when blood cultures are negative despite clear evidence of endocarditis especially with large vegetation sizes and other complications such as septic emboli. Multiple imaging modalities are available to assist with diagnosis including transthoracic and transesophageal echocardiogram as well as cardiac computed tomography. A blood PCR test can identify the implicated pathogen in a more expeditious manner compared to valve histopathological evaluation. Treatment is complex and usually requires surgical intervention and prolonged antimicrobial therapy., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Whipple's disease is a multisystemic chronic infectious condition caused by Tropheryma whipplei ( T. whipplei ). Though characterised often by insidious weight loss, diarrhoea, and arthralgia, three other distinct manifestations can be observed, namely localised disease, acute infection and asymptomatic carriage. The diagnosis relies on histopathological examination of duodenal biopsies and polymerase chain reaction analysis of the 16S rRNA gene for T. whipplei. We report the case of a middle-aged man admitted for etiologic investigation of prolonged, migrating, and inflammatory arthralgias and subsequent development of gastrointestinal symptoms. Despite its reputation as a great mimicker of many different illnesses, the difficulty in diagnosis probably lies with its rarity rather than its masking., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: The authors report no conflicts of interest.

A 49-year-old female presented with a 5-month course of diarrhoea, nocturn abdominal pain, asthenia, and weight loss of 30% of her body mass in three months. The patient had also a four-year medical history of bilateral mechanic gonalgy and arthralgias of the metacarpophalangeal and interphalangeal joints, despite treatment with prednisolone. On examination the patient had hyperpigmentation of the face and thorax, low-grade fever, and a BMI of 15,8 Kg/m2. Diarrhoea was documented with watery stools seven times per day despite loperamide, brownish, with no visible blood or mucous. Since the upper GI endoscopy and colonoscopy had no macroscopic abnormalities, the patient underwent a capsule endoscopy, which revealed continuous mucosal lesion with lymphangiectasia, oedema, villous atrophy and areas of denudation with hematinic punctate from the duodenum to the ileum. Diagnosis of Whipple's Disease was made with typical histology findings in duodenum material and a positive PCR for Tropheryma whipplei.

BACKGROUND Whipple disease (WD) is rare, with an incidence of only a few patients per million. It is caused by infection with the gram-positive bacterium Tropheryma whipplei, and presents with symptoms that include joint pain, fever, diarrhea, and weight loss. This report is of a 40-year-old man with a 7-year history of polyarthritis and a late diagnosis of Whipple disease. The atypical nature of his symptoms led to misdirection and misdiagnosis for years. CASE REPORT A middle-aged white man with seronegative migratory polyarticular arthritis underwent 7 years of treatment with steroids, disease-modifying anti-rheumatic drugs (DMARDs), and a TNF (tumor necrosis factor)-alpha inhibitor, all without any clinical improvement. Throughout this period, he had persistent loose stools and iron-deficiency anemia. Extensive diagnostic investigations for various possibilities yielded negative results. However, after 7 years, he began displaying clinical signs of malabsorption. This prompted further evaluation, including an upper-gastrointestinal endoscopy and biopsy, which revealed the presence of PAS (periodic acid-Schiff)-positive Treponema whipplei, which led to the diagnosis of WD. Following initiation of appropriate treatment, the patient experienced complete resolution of symptoms. Retrospectively, all the pieces of this puzzle fell into place, providing a comprehensive understanding of the prolonged medical challenge the patient faced. CONCLUSIONS This case illuminates the diagnostic challenge faced when dealing with migratory polyarticular inflammatory arthritis and fever. This report has highlighted that Whipple disease can be associated with multiple symptoms and signs, which can result in a delay in diagnosis. However, once the diagnosis is confirmed, antibiotic treatment is effective.

A 69-year-old woman developed non-convulsive status epilepticus during inpatient investigation for abdominal pain. Initial detailed investigations did not identify the cause of seizures, but a jejunal biopsy and PCR testing in various fluids led to the diagnosis of Whipple's disease with neurological involvement. The seizures were controlled but she subsequently had moderate cognitive impairment. Whipple's disease is an important diagnosis, being treatable with antibiotics. Testing for Whipple's disease is not part of the recommended workup in for status epilepticus, but this case highlights the importance of considering this condition., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Whipple's Disease (WD) is a rare disease caused by the infection of Tropheryma whipplei. It can lead to immunosuppression and a multitude of effects on different organ systems, resulting in a constellation of seemingly unrelated findings. Although treatment may appear straightforward, T. whipplei can be difficult to eradicate. We present the case of a 36-year-old male with months of progressively worsening watery diarrhea, migratory arthralgias, and weight loss. He had undergone an extensive evaluation for rheumatologic, oncologic, and infectious disorders without positive findings. Esophagogastroduodenoscopy and colonoscopy revealed esophageal candidiasis, Helicobacter pylori infection, and foamy macrophages in the lamina propria of the duodenum and ileum with positive polymerase chain reaction for T. whipplei. There were no other risk factors for esophageal candidiasis. He received treatment for his esophageal candidiasis and H. pylori infection and was treated for WD with ceftriaxone for 2 weeks, followed by hydroxychloroquine and doxycycline for 1 year. Symptoms resolved after 3 months of therapy. One year later, repeat bidirectional endoscopy was performed. Biopsies were negative for T. whipplei, although there were persistent foamy macrophages. There have been previously reported cases of patients with WD with concomitant esophageal candidiasis, and this association implies a likely state of relative immunosuppression associated with WD, which is thought to be the result of impaired T helper cell 1 activity. This impairment likely contributes to the high rate of relapse. Having a low threshold for repeat evaluation is advisable for recurrent symptoms, but long-term surveillance strategies are not clearly defined., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objectives: Whipple's disease (WD) is a rare and potentially fatal infectious disease caused by Tropheryma whipplei. It is characterized by a long prodromal phase that mimics a rheumatological disease, often leading to immunosuppressant treatment. Immune reconstitution inflammatory syndrome (IRIS) is currently the most important complication of WD, requiring prompt recognition and treatment as it can be fatal. However, epidemiological data on IRIS are scarce. We aimed to identify the clinical and laboratory predictors of IRIS at WD diagnosis and to evaluate whether the prevalence of IRIS has changed over time., Methods: Forty-five patients with WD (mean age 52 ± 11 years; 10 females) were followed up between January 2000 and December 2021. Clinical and laboratory data at WD diagnosis were retrospectively collected and compared among patients who developed IRIS and those who did not., Results: Erythrocyte sedimentation rate (ESR; 33.4 ± 11.8 mm/h vs 67.1 ± 26.3 mm/h, P < 0.01), platelet (PLT; 234 × 10 9 /L vs 363 × 10 9 /L, P < 0.01), and body mass index (22.0 ± 2.0 kg/m 2 vs 19.8 ± 3.0 kg/m 2 , P = 0.04) differed significantly between patients who subsequently developed IRIS and those who did not. ROC analysis identified ESR ≤46 mm/h (AUROC 0.88, 95% CI 0.72-1.00) and PLT ≤ 327 × 10 9 /L (AUROC 0.85, 95% CI 0.70-1.00) as optimal cut-off values to discriminate WD patients at a high risk of developing IRIS. Prevalence of IRIS remained stable (22.2%) over time., Conclusions: Low ESR and PLT count at diagnosis help identify WD patients at high risk of developing IRIS. Instead, a greater inflammatory response suggests a lower risk of IRIS. Prevalence of IRIS did not change over two decades., (© 2023 The Authors. Journal of Digestive Diseases published by Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Whipple's disease is a rare infectious disease with multiple clinical manifestations. The disease is named after George Hoyt Whipple, who first recorded the illness in 1907 after conducting the autopsy of a 36-year-old man with weight loss, diarrhea, and arthritis. Under the microscope, Whipple discovered a rod-shaped bacterium in the patient's intestinal wall, which was not confirmed as a new bacterial species until 1992, when it was named Tropheryma whipplei.Recurrence of Whipple's disease can occur years after an initial diagnosis and often manifests with extraintestinal symptoms such as arthritides or skin efflorescences, years before a gastrointestinal complaint. However, the simultaneous occurrence of primary hyperparathyroidism in the present case is a hitherto unknown clinical picture and opens up new questions and perspectives in the context of diagnostics and therapy., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Whipple's disease is an uncommon chronic systemic disease caused by Tropheryma whippelii . The most characteristic findings of late Whipple's disease include diarrhoea, abdominal pain, weight loss, and arthralgias, however, other clinical findings can occur, including lymphadenopathy, fever, neurologic manifestations, myocarditis and endocarditis. The aim of the present study was to systematically review all cases of Whipple's disease-associated infective endocarditis (IE) in the literature. A systematic review of PubMed, Scopus, and Cochrane Library (all published studies up to 28 May 2022) for studies providing data on epidemiology, clinical characteristics as well as data on treatment and outcomes of Whipple's disease-associated IE was performed. A total of 72 studies, containing data for 127 patients, were included. A prosthetic valve was present in 8% of patients. The aortic valve was the most commonly involved intracardiac site followed by the mitral valve. Heart failure, embolic phenomena, and fever were the most common clinical presentations, however, fever occurred in less than 30% of patients. Sepsis was rarely noted. The diagnosis was most commonly performed through pathology through positive PCR or histology in cardiac valves in 88.2% of patients. Trimethoprim with sulfamethoxazole were the most commonly used antimicrobials followed by cephalosporins and tetracyclines. Surgery was performed in 84.3% of patients. Mortality was 9.4%. A multivariate logistic regression analysis model identified presentation with sepsis or development of a paravalvular abscess to be independently associated with increased mortality, while treatment with the combination of trimethoprim with sulfamethoxazole was independently associated with reduced mortality.

Background: Whipple's disease is a chronic infection due to Tropheryma whipplei, commonly reported in the Caucasian but not in the Chinese population., Case Presentation: A 52-year-old female with good past health, was diagnosed with Whipple's disease, presenting with constipation, unintentional weight gain, and fleeting polyarthralgia. Investigations prior to admission showed raised CA125 and computed tomography of the abdomen showed multiple retroperitoneal mesenteric lymphadenopathies. Extensive investigations performed on secondary causes of weight gain were unrevealing. Subsequent PET-CT scan revealed generalized lymphadenopathy involving the left deep cervical, supraclavicular, and retroperitoneal mesenteric area. Excisional biopsy of the left supraclavicular lymph node was performed, with histology showing infiltrations of Periodic acid-Schiff positive foamy macrophages. T. whipplei DNA was detected in her serum, saliva, stool, and lymph node by PCR targeting the 16S ribosomal RNA gene. She was started on intravenous ceftriaxone, and then stepped down to oral antibiotics for a total of 44 months. The recurrence of fever after 12 days of ceftriaxone raised the suspicion of Immune Reconstitution Inflammatory Syndrome (IRIS). Serial imaging showed a gradual reduction in the size of retroperitoneal lymphadenopathies. Literature review on Whipple's disease in the Chinese population identified 13 reports of detectable T. whipplei DNA in clinical specimens. The majority of the cases were pneumonia, followed by culture-negative endocarditis, encephalitis, and skin and soft tissue infection. However, most patients with pneumonia were diagnosed based on next generation sequencing alone, with the resolution of pulmonary infiltrates without adequate duration of antibiotics, suggesting the possibility of colonization instead of infection. The recommendation of long-term doxycycline suppression after treatment may be supported by the slow response of retroperitoneal lymphadenopathies to antibiotics in our patient., Conclusions: Unintentional weight gain and constipation could be atypical presentations of Whipple's disease. It is a rare disease in the Chinese population despite the advancement of molecular techniques in the diagnosis of infections. A prolonged course of antibiotics may be required due to slow clinical response as documented by serial imaging in our case. The possibility of IRIS should be considered in patients with breakthrough fever during treatment of Whipple's disease., (© 2023. The Author(s).)

Introduction: Whipple's disease is a rare systemic infection due to an impaired immunological response against T. whipplei in genetically predisposed individuals. Since we previously noted development of H. pylori related complications in some patients with Whipple's disease, our aim was to study the prevalence of H. pylori infection and H. pylori related disorders in Whipple's disease., Methods: Whipple's disease patients diagnosed from Jan-2002 to Dec-2021 and two controls per patient, matched for age, gender, ethnicity and year of H. pylori testing were enrolled., Results: 34 patients with Whipple's disease and 68 controls were enrolled. H. pylori infection (13/34 vs 8/68, p<0.01), H. pylori-related gastritis (p<0.01) and gastric atrophy (p = 0.01) were significantly more common in patients with Whipple's disease than controls. H. pylori infection and Whipple's disease were diagnosed synchronously in 6/13 patients, and during follow-up in the remaining 7. Interestingly, these last 7 patients were all on trimethoprim-sulfamethoxazole long-term therapy. Two patients developed H. pylori-related gastric malignancies during follow-up. No patients on doxycycline developed H. pylori infection., Conclusions: H. pylori infection and related disorders are common in patients with Whipple's disease and should always be excluded both at time of diagnosis and during follow-up. These findings should be taken into account when selecting antibiotics for Whipple's disease long-term prophylaxis., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Whipple's disease is a chronic multisystemic infectious disease that rarely presents as culture-negative endocarditis. Most patients reported with Tropheryma whipplei endocarditis involve a native valve and few describe prosthetic valve disease., Case Presentation: A patient with chronic polyarthritis and previous mitral valve replacement developed decompensated heart failure without fever. Transesophageal echocardiography revealed a prosthetic mitral valve vegetation and he underwent prosthetic mitral valve replacement. Blood and prosthetic mitral valve cultures were unrevealing. Broad-range polymerase chain reaction (PCR) of the extracted valve and subsequent Periodic-acid-Schiff (PAS) staining established the diagnosis of T. whipplei prosthetic valve endocarditis., Conclusion: Whipple's disease may present as culture-negative infective endocarditis and affect prosthetic valves. Histopathology with PAS staining and broad-range PCR of excised valves are essential for the diagnosis. Greater clinical awareness and implementation of these diagnostic procedures should result in an increased reported incidence of this rare disease., (© 2023. The Author(s).)

Background: Whipple's disease is known to cause multiple varied systemic symptoms, and is a well-documented cause of culture-negative endocarditis. Endocarditis secondary to Whipple disease, however, has rarely been known to present primarily as a cause of acute limb ischemia. We describe such a case here., Case Presentation: A previously healthy 40 year old man presented to the emergency department with acute-onset right arm paresthesias. On exam, he was found to be tachycardic with a VI/VI systolic ejection murmur. He was diagnosed with critical limb ischemia and severe aortic regurgitation, and echocardiography showed a large mass on his bicuspid aortic valve. Thrombectomy was performed urgently, with aortic valve repair the following day. As blood cultures and valvular tissue culture remained unrevealing, the patient remained on empiric vancomycin and ceftriaxone for culture-negative endocarditis. 16 s rRNA nucleic acid amplification testing (NAAT) of his formalin-fixed, paraffin-embedded valvular tissue detected T. whipplei, after which the patient was transitioned to ceftriaxone and trimethoprim-sulfamethoxazole for a year of therapy. He continues to do clinically well., Conclusions: We report an unusual presentation of Whipple endocarditis as an acute upper limb ischemia, absent other classic symptoms of Whipple's disease, and with diagnosis made by 16 s rRNA NAAT of valvular tissue in the setting of culture-negative endocarditis., (© 2023. The Author(s).)

Background: In 15-25% of patients with rheumatoid arthritis, the presence of pathognomonic autoantibodies (anti-citrullinated protein (aCCP) or rheumafactor (RF) is lacking. In these cases of seronegative rheumatoid arthritis, diagnosis is based on clinical presentation. However, some of the patients with seronegative rheumatoid arthritis are misdiagnosed., Case Description: Here we discuss a case of a 64 year old female, with a diagnoses of seronegative rheumatoid arthritis for 18 years. Although extensively treated with immunosuppressive medication, she did not reach remission. After second opinion in our hospital we diagnosed Whipple's disease., Conclusion: This case report illustrates the importance of a broad differential diagnosis of seronegative arthritis as well as the importance of re-assessment of patients diagnosed with seronegative rheumatoid arthritis, who do not reach remission upon immunosuppressive treatment.

Background: In 15-25% of patients with rheumatoid arthritis, the presence of pathognomonic autoantibodies (anti-citrullinated protein (aCCP) or rheumafactor (RF) is lacking. In these cases of seronegative rheumatoid arthritis, diagnosis is based on clinical presentation. However, some of the patients with seronegative rheumatoid arthritis are misdiagnosed., Case Description: Here we discuss a case of a 64 year old female, with a diagnoses of seronegative rheumatoid arthritis for 18 years. Although extensively treated with immunosuppressive medication, she did not reach remission. After second opinion in our hospital we diagnosed Whipple's disease., Conclusion: This case report illustrates the importance of a broad differential diagnosis of seronegative arthritis as well as the importance of re-assessment of patients diagnosed with seronegative rheumatoid arthritis, who do not reach remission upon immunosuppressive treatment.

Purpose: To describe posterior ocular involvement features of Whipple's disease (WD) in a patient with no gastrointestinal symptoms., Methods: Retrospective case report., Observation: 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., Conclusion: 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.

Background & Aims: Classical Whipple's disease (CWD) affects the gastrointestinal tract and causes chronic diarrhea, malabsorption, and barrier dysfunction with microbial translocation (MT). Immune reconstitution inflammatory syndrome (IRIS) is a serious complication during antimicrobial treatment of CWD. The pathomechanisms of IRIS have not been identified and mucosal barrier integrity has not been studied in patients with IRIS CWD., Methods: In 96 CWD patients (n = 23 IRIS, n = 73 non-IRIS) and 30 control subjects, we analysed duodenal morphology by histology, measured serum markers of MT, and proinflammatory cytokines in biopsy supernatants, and correlated microbial translocation with T cell reconstitution and activation., Results: Before treatment, duodenal specimens from patients who later developed IRIS exhibited a more pronounced morphological transformation that suggested a disturbed barrier integrity when compared with the non-IRIS group. Villous atrophy was mediated by increased apoptosis of epithelial cells, which was insufficiently counterbalanced by regenerative proliferation of crypt cells. Pretreatment deficiencies in the mucosal secretion of proinflammatory cytokines and chemokines (e.g., IL-6, CCL2) in these patients markedly resolved after therapy induction. High serum levels of lipopolysaccharides (LPS), soluble CD14 (sCD14), and LPS-binding protein (LBP) combined with low endotoxin core antibody (EndoCAb) titres suggested systemic MT in CWD patients developing IRIS. CD4 + T cell count and activation in IRIS CWD patients correlated positively with sCD14 levels and negatively with EndoCAb titres. Furthermore, the degree of intestinal barrier dysfunction and MT was predictive for the onset of IRIS., Conclusion: Prolonged MT across a dysfunctional intestinal mucosal barrier due to severe tissue damage favors dysbalanced immune reconstitution and systemic immune activation in IRIS CWD. Therefore, the monitoring of inflammatory and MT markers in CWD patients might be helpful in identifying patients who are at risk of developing IRIS. Therapeutic strategies to reconstitute the mucosal barrier and control inflammation could assist in the prevention of IRIS., (© 2022 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Introduction: Whipple's disease (WD) is a rare and infectious condition leading to multi-organ impairment caused by Tropheryma whipplei (TW), a ubiquitously occurring bacterium. TW can be detected in tissues by histological detection of PAS ("periodic acid-ship reaction")-positive macrophages and by polymerase-chain-reaction (PCR). Clinically, WD is often characterized by diarrhea, abdominal pain, and weight loss. These symptoms are also typical for a flare in Crohn's disease (CD) and, therefore, can lead to fatal misdiagnosis and wrong treatment by using biologics (e.g., anti-TNF-α)., Case Report: We here report a young male patient with pre-existing CD. The patient's symptoms were misinterpreted as a flare of CD and illustrate the multifaceted nature of WD. After intensifying immunosuppressive therapy, the patient developed therapy-refractory diarrhea with several opportunistic infections with a final, fatal outcome., Conclusion: Patients with inflammatory bowel disease (IBD) are not only at risk from infectious complications known with clostridium difficile or cytomegalovirus (CMV); infection with WD should also be ruled out by endoscopy and biopsy before the escalation of the immunosuppressive regime., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Whipple's disease (WD) is a rare infectious disease with a wide clinical spectrum. Associated thrombotic manifestations are not well described in WD, only related to 'stroke-like syndrome'. We present a case of a 39-year-old man with a 1-year history of self-limited episodes of fever, associated with generalised adenopathies and recurrent superficial and deep venous thrombosis events, which have resorted four times despite the anticoagulant treatment. Finally, the patient is diagnosed with WD. Following treatment the patient improved in his general condition, and no more episodes of fever neither thrombosis appeared during a follow-up of more than 3 years., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Whipple's disease (WD) is a systemic, chronic, relapsing disease caused by Tropheryma whipplei, which can mimic signs and symptoms of various clinical entities. Typical manifestations are represented by gastrointestinal and systemic symptoms, among which neurological ones are frequent. We present the case of a patient with WD and rapidly progressive cognitive impairment and a review of literature aimed to report epidemiological, clinical, neuroimaging, and laboratory findings of cognitive impairment associated with WD., Methods: A systematic review of medical literature published until November 22, 2020, was performed. Full-text, peer-reviewed case reports and series in English language presenting patients with WD and cognitive impairment were included. Data concerning demographic, clinical, neuroimaging, and laboratory characteristics were collected and synthesized qualitatively., Results: The patient was a 54-year-old male who developed rapidly progressive dementia, fluctuating arousal disturbances, and supranuclear ophthalmoparesis associated with chronic diarrhea and fever spikes. T. whipplei was detected in the cerebrospinal fluid, and appropriate antimicrobial therapy was given with progressive clinical benefit. The systematic review of 114 case reports/series identified 147 patients with WD and cognitive impairment; this latter was rarely isolated. Neurological symptoms associated with cognitive decline were psychiatric disturbances, supranuclear ophthalmoplegia, hypothalamic involvement, and consciousness disorders. Brain imaging and cerebrospinal fluid findings were heterogeneous and nonspecific., Conclusions: Cognitive impairment represents one of the most common neurological features associated with WD. The clinical suspicion of this disease in patients with rapidly progressive dementia is crucial to guide diagnostic strategies and proper antimicrobial therapy, which may revert the clinical deterioration., (© 2022. Fondazione Società Italiana di Neurologia.)

Whipple disease is rare, potentionally life-threatening disease with broad scale of possible symptoms and therefore wide differential diagnosis. Localized forms as well as systemic manifestations are possible. Etiological agent is bacteria Tropheryma whipplei. The most common manifestations include arthralgias, fever, diarrhea, abdominal pain, malabsorption syndrome and weight loss. In my article I present literature review and a case report of the pacient with relatively typical course of the disease.

Introduction: Whipple's disease (WD) can mimic chronic inflammatory rheumatism leading to incorrect prescription of tumor necrosis factor inhibitors (TNFI). Several complicated cases of WD have been reported during TNFI treatment which is strongly suspected to modify the host-pathogen relationship. Tropheryma whipplei asymptomatic carriage is high in the general population, making the diagnosis of WD more difficult face to unexplained arthritis., Observations: We report three observations that illustrate situations for which the detection of T. whipplei might be valuable to investigate the differential diagnosis of inflammatory rheumatism., Conclusion: The decision to check for T. whipplei infection should rely on individual clinical assessment. It should be considered in the absence of clinical response or in case of worsening of an inflammatory rheumatism under TNFI treatment, especially in front of atypical features. A systematic screening for T. whipplei before anti-TNF treatment seems unjustified since asymptomatic carriers are frequent., (Copyright © 2021 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Abstract: Whipple disease (WD) is a rare bacterial infectious disease that is classically characterized by years of arthralgia, followed by malabsorption, diarrhea, and weight loss. However, WD may manifest in virtually any organ system, and patients with WD rarely develop subcutaneous erythema nodosum-like lesions. We report a case of a 51-year-old man diagnosed with WD who subsequently developed widely distributed erythematous subcutaneous nodules after 5 months of antibiotic therapy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Tropheryma whipplei is a bacterium that causes a rare infection called Whipple's disease and can cause devastating effects if left untreated. It is important to recognize that patients with this infection may present with atypical symptoms and are often apyrexial with normal inflammatory markers. Moreover, routine blood cultures often do not isolate these bacteria in conventional growth media. Therefore, it requires a high level of clinical suspicion to make this diagnosis. Here, we present two cases of Tropheryma whipplei aortic valve endocarditis, with atypical presentation and similar unusual but striking echocardiographic images., (© 2021 Wiley Periodicals LLC.)

Whipple's disease is a chronic mutisystem disease caused by the bacteria Tropherima whipplei. Approximately 1200 cases have been described in the literature. The worldwide incidence is estimated at 9.8 cases per million people. Data from South America and Europe show that it affects middle-aged males. It is believed that host immunological factors rather than agent genotypic traits influence the course of the infection. Since the clinical characteristics are usually nonspecific and the wide spectrum of manifestations in individual organs may be underestimated, the diagnosis remains challenging. We present a case with multisystem compromise confirmed by histopathology. We consider its publication important given the few cases documented in South America and the relevance of bearing in mind the importance of an early diagnosis for a prompt treatment that improves the prognosis of this rare disease.

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.

Introduction: Many clinical manifestations can be related to Tropheryma whipplei infection., Case Report: We report a Tropheryma whipplei limbic encephalitis developed as a relapse of classical Whipple's disease., Discussion: This case is to the best of our knowledge the first proof of the effective brain-blood barrier crossing of both doxycycline and hydroxychloroquine as demonstrated by direct concentration monitoring on brain biopsy.