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Yu M, Wang W, Chen W, Ye K, Zhou Y, Vaishnani DK, Chen C, Jin X, Zhu X, Ma J, Qian F, Zhong X, Nie C. Diagnosis of Tropheryma whipplei pneumonia using targeted nanopore sequencing: a rare case report and literature review. Front Med (Lausanne) 2025; 12:1556735. [PMID: 40370737 PMCID: PMC12074902 DOI: 10.3389/fmed.2025.1556735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Accepted: 03/31/2025] [Indexed: 05/16/2025] Open
Abstract
Tropheryma whipplei (TW) pneumonia is a rare disease caused by Tropheryma whipplei infection. Due to the difficulty in obtaining pathogenetic evidence, the misdiagnosis rate is high, posing significant challenges for early diagnosis and treatment. Targeted sequencing technology based on nanopore sequencing technology (tNGS) allows for detecting rare pathogens that are difficult to identify using traditional methods, leading to improved detection rates for TW. This paper reports a case of pneumonia diagnosed as a TW infection through the use of tNGS on bronchoalveolar lavage fluid (BALF), with the patient showing improvement after treatment with sequential administration of meropenem followed by compounded sulfamethoxazole.
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Affiliation(s)
- Miao Yu
- Pulmonary and Critical Care Medicine, Hangzhou Linping District Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang, China
| | - Wenbin Wang
- Renji College, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Wei Chen
- Renji College, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Kexin Ye
- Renji College, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yuqing Zhou
- School of International Studies, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Deep K. Vaishnani
- School of International Studies, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Chen Chen
- Renji College, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xuancheng Jin
- School of the First Clinical Medical Sciences (School of Information and Engineering), Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiaojun Zhu
- Department of Pathology, Ruian People’s Hospital, Wenzhou, Zhejiang, China
| | - Jun Ma
- Department of Pathology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Fengfei Qian
- Pulmonary and Critical Care Medicine, Hangzhou Linping District Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang, China
| | - Xiaohua Zhong
- Pulmonary and Critical Care Medicine, Hangzhou Linping District Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang, China
| | - Chuanhua Nie
- Pulmonary and Critical Care Medicine, Hangzhou Linping District Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang, China
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Huo Y, Wu C, Ma D. Application of metagenomic next-generation sequencing in the diagnosis and treatment of acute pneumonia caused by Tropheryma whipplei. BMC Pulm Med 2025; 25:207. [PMID: 40307822 PMCID: PMC12042330 DOI: 10.1186/s12890-025-03657-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 04/09/2025] [Indexed: 05/02/2025] Open
Abstract
OBJECTIVE The treatment plan and process for acute pneumonia caused by Tropheryma whipplei have not been clearly defined. The study aimed to conduct a retrospective analysis of the treatment for patients with acute pneumonia, caused by Tropheryma whipplei, diagnosed through metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF). METHODS All patients underwent routine blood examinations and chest CT scans. Electronic fiberoptic bronchoscopy was performed to collect BALF samples from the lesion subsegments. The BALF samples were subjected to mNGS analysis. During hospitalization, all patients were treated with imipenem-cilastatin combined with compound sulfamethoxazole (SMZ-TMP) tablets for anti-infection, and they took SMZ-TMP orally for 3 months after discharge and followed up. RESULTS We identified 7 cases where Tropheryma whipplei was the primary pathogen, with 3 of these cases having it as the sole detected pathogen. The clinical manifestations of acute Tropheryma whipplei pneumonia are atypical. Chest CT scans revealed that 3 cases had exudative lesions in both lungs, 4 cases had unilateral pulmonary exudative lesions, 3 cases had bilateral pulmonary nodules, 2 cases had interstitial changes, and 3 cases had pleural effusion. Following treatment, all follow-up cases showed no recurrence. CONCLUSIONS The mNGS examination of bronchoalveolar lavage fluid can significantly improve the early diagnosis of acute pneumonia caused by Tropheryma whipplei. The treatment involving imipenem-cilastatin combined with SMZ-TMP, followed by oral SMZ-TMP for three months, is effective.
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Affiliation(s)
- Yinping Huo
- Department of Respiratory and Critical Care Medicine, Nanjing Pukou People's Hospital, No.166 Shanghe Street, Jiangpu Street, Pukou District, Nanjing, 211800, Jiangsu, China.
| | - Chao Wu
- Department of Respiratory and Critical Care Medicine, Nanjing Pukou People's Hospital, No.166 Shanghe Street, Jiangpu Street, Pukou District, Nanjing, 211800, Jiangsu, China
| | - Dawen Ma
- Department of Respiratory and Critical Care Medicine, Nanjing Pukou People's Hospital, No.166 Shanghe Street, Jiangpu Street, Pukou District, Nanjing, 211800, Jiangsu, China.
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Mansour MA, Malaeb RW, Elnemr IE, El-Salamoni MAF, Mostafa HN, Ahmadi Z. Central nervous system involvement in Whipple's disease: Report of a rare pathological entity and comparative review of treatment strategies and outcomes. Radiol Case Rep 2025; 20:1425-1430. [PMID: 39807114 PMCID: PMC11728665 DOI: 10.1016/j.radcr.2024.11.045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 11/06/2024] [Accepted: 11/17/2024] [Indexed: 01/16/2025] Open
Abstract
Whipple's disease, caused by the gram-positive actinomycete Tropheryma whipplei, is a rare chronic systemic illness with significant diagnostic and therapeutic challenges, particularly when the CNS is involved. This case report details a 46-year-old man presenting with a constellation of symptoms including fatigue, hypersomnia, weight loss, bifrontal headaches, abdominal pain, treatment-unresponsive diarrhea, and skin hyperpigmentation. Neurological examination revealed oculomasticatory myorhythmia, and imaging studies showed nodular enhancement of the hypothalamus and basal ganglia, along with retroperitoneal lymphadenopathy. Diagnosis was confirmed through duodenal biopsy with PAS staining and PCR analysis. The patient was successfully treated with a combination of intravenous ceftriaxone followed by oral doxycycline and hydroxychloroquine, resulting in significant symptom improvement and full recovery of neurological function. This case underscores the importance of early, aggressive treatment and provides a comprehensive review of the current literature on Whipple's disease with CNS involvement, including a comparison of treatment regimens and outcomes.
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Affiliation(s)
- Moustafa A. Mansour
- Department of Neurosurgery, Nasser Institute for Research and Treatment, Cairo, Egypt
- Department of Neurology and Neurosurgery, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Reem W. Malaeb
- Department of Health Professions, Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon
| | - Islam E. Elnemr
- Department of Neurosurgery, Nasser Institute for Research and Treatment, Cairo, Egypt
| | | | - Hamdi Nabawi Mostafa
- Department of Neurosurgery, Nasser Institute for Research and Treatment, Cairo, Egypt
- Department of Neurosurgery, Misr University for Science and Technology, Giza, Egypt
| | - Zarina Ahmadi
- Department of Infectious Diseases and Tropical Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
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Puéchal X. Whipple's disease: from in-vitro data to bedside practice via trial results. THE LANCET. INFECTIOUS DISEASES 2025:S1473-3099(25)00016-7. [PMID: 39978371 DOI: 10.1016/s1473-3099(25)00016-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 01/09/2025] [Indexed: 02/22/2025]
Affiliation(s)
- Xavier Puéchal
- National Referral Centre for Rare Systemic Autoimmune Diseases, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, University Paris Cité, Paris 75014, France.
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Moos V, Krüger J, Allers K, Moter A, Kikhney J, Kühl AA, Loddenkemper C, Stroux A, Schinnerling K, Schneider T. Oral treatment of Whipple's disease with doxycycline and hydroxychloroquine versus intravenous therapy with ceftriaxone followed by oral trimethoprim-sulfamethoxazole in Germany: a phase 2/3, prospective, open-label, randomised, controlled, non-inferiority trial. THE LANCET. INFECTIOUS DISEASES 2025:S1473-3099(24)00797-7. [PMID: 39978372 DOI: 10.1016/s1473-3099(24)00797-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 11/18/2024] [Accepted: 11/20/2024] [Indexed: 02/22/2025]
Abstract
BACKGROUND Previous studies have shown that intravenous ceftriaxone or meropenem for 14 days, followed by oral trimethoprim-sulfamethoxazole for 1 year, cures 98% of people with Whipple's disease. However, intravenous therapy requires hospitalisation and carries risks for treatment-associated complications. The aim of this study was to investigate whether oral-only treatment for Whipple's disease is non-inferior to intravenous therapy. METHODS This phase 2/3, prospective, open-label, randomised, controlled, non-inferiority trial enrolled individuals aged 18 years or older with confirmed Whipple's disease from across Germany who had received treatment for less than 1 month at Charité-Universitätsmedizin Berlin. Participants were randomly assigned (1:1) with block randomisation to receive either intravenous ceftriaxone (2 g once per day) for 14 days, followed by oral trimethoprim-sulfamethoxazole (960 mg twice per day) for 12 months, or oral doxycycline (100 mg twice per day) plus hydroxychloroquine (200 mg twice per day) for 12 months. Ten participants who had already received intravenous ceftriaxone were non-randomly assigned to the intravenous treatment group. Participants in the oral-only treatment group were PCR-positive for Tropheryma whipplei in cerebrospinal fluid received trimethoprim-sulfamethoxazole (960 mg five times per day) until clearance. The primary outcome was complete clinical remission without recurrence during the observation period of 24 months, assessed in the intention-to-treat (ITT) population. The prespecified non-inferiority margin was -18%. Safety was a secondary endpoint, assessed in the ITT population. The study was registered with the EU Clinical Trials Register, EudraCT 2008-003951-54, and is completed. FINDINGS Between May 26, 2010, and Oct 30, 2018, we screened 310 individuals and enrolled 64 participants in the study. After exclusion of four individuals whose diagnosis was not confirmed, 31 participants were assigned to the intravenous treatment group and 29 to the oral-only treatment group. By ITT, 25 (81%) of 31 participants in the intravenous treatment group and 28 (97%) of 29 participants in the oral-only treatment group had complete clinical remission without recurrence. The risk difference was 15·9 percentage points (95% CI -1·2 to 33·1), with the lower bound of the 95% CI above our non-inferiority margin of -18%. A post-hoc per-protocol analysis confirmed the non-inferiority of oral-only treatment. No participant relapsed, but two participants in the intravenous treatment group died from nosocomial infections. Serious adverse events occurred in 13 (42%) of 31 participants in the intravenous treatment group and eight (28%) of 29 participants in the oral-only treatment group, but this difference was not statistically significant (p=0·244). INTERPRETATION Oral-only treatment of Whipple's disease was safe and non-inferior to sequential intravenous-oral treatment. Oral treatment facilitates patient management and might reduce hospital-acquired treatment complications and costs. FUNDING German Research Foundation and the Robert Koch Institute. TRANSLATION For the German translation of the abstract see Supplementary Materials section.
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Affiliation(s)
- Verena Moos
- Department of Gastroenterology, Infectious Diseases, and Rheumatology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
| | - Justina Krüger
- Department of Gastroenterology, Infectious Diseases, and Rheumatology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Kristina Allers
- Department of Gastroenterology, Infectious Diseases, and Rheumatology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Annette Moter
- Department of Microbiology, Infectious Disease and Immunology, Biofilmcenter and National Consiliary Laboratory for Tropheryma whipplei, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Moter Diagnostics, Berlin, Germany
| | - Judith Kikhney
- Department of Microbiology, Infectious Disease and Immunology, Biofilmcenter and National Consiliary Laboratory for Tropheryma whipplei, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; MoKi Analytics, Berlin, Germany
| | - Anja A Kühl
- iPATH.Berlin, Core Unit Immunopathology for Experimental Models, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | | | - Andrea Stroux
- Institute for Biometrie and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Katina Schinnerling
- Department of Gastroenterology, Infectious Diseases, and Rheumatology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Universidad Andrés Bello, Faculty of Life Science, Santiago, Chile
| | - Thomas Schneider
- Department of Gastroenterology, Infectious Diseases, and Rheumatology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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Shan X, Li Z, Dong L. A case of pneumonia caused by infection with Tropheryma whipplei complicated by cryptococcus during treatment with a Janus kinase inhibitor: a case report. BMC Pulm Med 2024; 24:625. [PMID: 39707301 PMCID: PMC11662430 DOI: 10.1186/s12890-024-03401-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 11/18/2024] [Indexed: 12/23/2024] Open
Abstract
This report describes the case of a 41-year-old male patient complaining of a hacking cough. The patient was treated with a Janus kinase (JAK) inhibitor for psoriasis. Blood tests revealed mild lymphopenia and high levels of serum cryptococcal antigen. Chest computed tomography revealed infection in the lower lobe of the left lung. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid revealed Tropheryma whipplei. Tropheryma whipplei and Cryptococcus antimicrobial therapies were sequentially administered. During follow-up, the patient showed clinical and radiographic improvement. Tropheryma whipplei is an opportunistic Gram-positive rod-shaped bacterium belonging to the family Actinomycetes. Lung involvement is an unusual but classic manifestation of Whipple's disease. This is the first report of pneumonia caused by infection with Tropheryma whipplei complicated by Cryptococcus. To our knowledge, this is the first case report of Tropheryma whipplei infection following the use of JAK inhibitors. Clinicians should be aware of opportunistic infections that can occur during treatment with JAK inhibitors.
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Affiliation(s)
- Xiaoxi Shan
- Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, China
| | - Zhishu Li
- Department of Respiratory and Critical Care Medicine, Guangyuan Central Hospital, Guangyuan, China
| | - Lixia Dong
- Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, China.
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Moos V, von Lampe B, Schneider T. Massive Mesenteric Lymphadenopathy: An Unusual Outcome. Gastroenterology 2024; 166:e5-e9. [PMID: 38029847 DOI: 10.1053/j.gastro.2023.11.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 11/10/2023] [Accepted: 11/11/2023] [Indexed: 12/01/2023]
Affiliation(s)
- Verena Moos
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, CBF, Medical Department for Gastroenterology, Rheumatology and Infectious Diseases, Berlin, Germany.
| | - Bernd von Lampe
- Vivantes, Humboldt-Klinikum, Department of Gastroenterology and Hepatology, Berlin, Germany
| | - Thomas Schneider
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, CBF, Medical Department for Gastroenterology, Rheumatology and Infectious Diseases, Berlin, Germany
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Saffioti C, Nebiolo M, Caorsi R, Mesini A, Severino M, Brisca G, Castagnola E, Gattorno M. Whipple Disease Presenting as Isolated Transverse Myelitis with Permanent Neurological Damage in a Patient with Systemic Lupus Erythematosus: A Case Report of a Difficult Diagnosis with a Literature Review. Infect Dis Rep 2024; 16:269-280. [PMID: 38525769 PMCID: PMC10961757 DOI: 10.3390/idr16020022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 03/03/2024] [Accepted: 03/12/2024] [Indexed: 03/26/2024] Open
Abstract
We describe an atypical case of Whipple disease exclusively involving the spinal cord in an adolescent receiving immunosuppressive therapy for systemic lupus erythematosus. The diagnosis was particularly difficult since lupus and Whipple disease can present similar clinical features and the patient's prolonged contact with sewage was initially not mentioned. A literature review of the clinical, imaging, diagnostic, and therapeutic challenges of Whipple disease is also performed.
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Affiliation(s)
- Carolina Saffioti
- Pediatric Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy; (C.S.); (A.M.); (E.C.)
| | - Marta Nebiolo
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, 16132 Genoa, Italy;
| | - Roberta Caorsi
- Rheumatolgy and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy; (R.C.); (M.G.)
| | - Alessio Mesini
- Pediatric Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy; (C.S.); (A.M.); (E.C.)
| | | | - Giacomo Brisca
- Paediatric and Neonatal Intensive Care Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy
| | - Elio Castagnola
- Pediatric Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy; (C.S.); (A.M.); (E.C.)
| | - Marco Gattorno
- Rheumatolgy and Autoinflammatory Diseases Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy; (R.C.); (M.G.)
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Cappellini A, Minerba P, Maimaris S, Biagi F. Whipple's disease: A rare disease that can be spotted by many doctors. Eur J Intern Med 2024; 121:25-29. [PMID: 38105122 DOI: 10.1016/j.ejim.2023.12.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 12/05/2023] [Accepted: 12/10/2023] [Indexed: 12/19/2023]
Abstract
Whipple's disease, an extremely rare, chronic infection caused by Tropheryma whipplei, an actinobacterium ubiquitously present in the environment, is a multisystemic condition that can affect several organs. Therefore, Whipple's disease should always be considered by physicians working across various branches of medicine, including internal medicine, rheumatology, infectious diseases, gastroenterology, haematology, and neurology. Initially, Whipple's disease is challenging to diagnose due to both its rarity and non-specific clinical features, almost indistinguishable from rheumatological conditions. A few years later, the onset of gastrointestinal symptoms increases the specificity of its clinical picture and helps in reaching the correct diagnosis. Diagnosis is typically made by finding PAS-positive macrophages in the lamina propria at duodenal biopsy. PCR for Tropheryma whipplei is nowadays also increasingly available, and represents an undeniable help in diagnosing this condition. However, it may also be misleading as false positives can occur. If not promptly recognized and treated, central nervous system involvement may develop, which can be fatal. The therapeutic gold standard has not yet been fully established, particularly in cases of recurrent disease, neurological involvement, and an immune reconstitution inflammatory syndrome that may arise following the initiation of antibiotic therapy.
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Affiliation(s)
| | - Paolo Minerba
- Department of Internal Medicine and Therapeutics, University of Pavia, Italy
| | - Stiliano Maimaris
- Department of Internal Medicine and Therapeutics, University of Pavia, Italy
| | - Federico Biagi
- Department of Internal Medicine and Therapeutics, University of Pavia, Italy; Istituti Clinici Scientifici Maugeri IRCCS, Gastroenterology Unit of Pavia Institute, Italy.
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Shen Y, Cui SS, Teng XB, Han MF. Acute pneumonia due to Tropheryma whipplei diagnosed by metagenomic next-generation sequencing and pathology: A case report. Heliyon 2024; 10:e26747. [PMID: 38434082 PMCID: PMC10906431 DOI: 10.1016/j.heliyon.2024.e26747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 02/17/2024] [Accepted: 02/19/2024] [Indexed: 03/05/2024] Open
Abstract
Tropheryma whipplei (TW) is a rod-shaped, gram-positive bacterium that, when chronically infects humans, can lead to multi-system pathologies, including joint pain, abdominal pain with diarrhea and weight loss, myocarditis, pericarditis, and neurologic inflammation. Moreover, acute infections can lead to bronchopulmonary infections, bacteraemia, and acute diarrhea. However, fewer cases of acute pneumonia due to TW have been reported, and this diagnosis is not well founded. Herein, we report a case of acute pneumonia caused by a TW infection. The patient, a middle-aged man, underwent bronchoscopic alveolar lavage, and the metagenomic next-generation sequencing of the lavage fluid suggested TW infection. A lung puncture biopsy tissue specimen was also positive based on periodic acid-Schiff staining. After confirming the diagnosis, the patient was administered ceftriaxone for anti-infection treatment, improving clinical symptoms and lung imaging results. Therefore, in cases where conventional anti-infective treatment is ineffective for patients with acute pneumonia, we should consider the possibility of TW infection, conduct prompt pathogenetic examination, and provide timely treatment after diagnosis to improve overall patient prognosis.
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Affiliation(s)
- Ya Shen
- Department of Respiratory and Critical Care Medicine, Fuyang Infectious Disease Clinical College of Anhui Medical University, Fuyang, Anhui, China
| | - Shun-Shun Cui
- Department of Respiratory and Critical Care Medicine, Fuyang People's Hospital, Fuyang, Anhui, China
| | - Xiao-Bao Teng
- Department of Respiratory and Critical Care Medicine, Fuyang Infectious Disease Clinical College of Anhui Medical University, Fuyang, Anhui, China
| | - Ming-Feng Han
- Department of Respiratory and Critical Care Medicine, Fuyang Infectious Disease Clinical College of Anhui Medical University, Fuyang, Anhui, China
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Arzivian A, Jones B, Joshua F, Paul M, Lynch T, Brown M, Gasiorowski R. Fever and Increased Gastrointestinal Uptake on Positron Emission Tomography after Anti-Tumour Necrosis Factor Therapy: A Case Report of Whipple's Disease. Case Rep Gastroenterol 2024; 18:221-230. [PMID: 38645407 PMCID: PMC11032180 DOI: 10.1159/000538462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 03/13/2024] [Indexed: 04/23/2024] Open
Abstract
Introduction Whipple's disease is a rare condition that can present with atypical and non-specific features requiring a high index of suspicion for diagnosis. Case Presentation We present a case of a man in his 40s with peripheral arthritis and bilateral sacro-ileitis for 4-5 years that was treated with an anti-tumour necrosis factor therapy, which led to worsening of his symptoms, elevation of the inflammatory markers, and the development of fever, night sweats, anorexia, and a significant weight loss. The patient had no abdominal pain, diarrhoea, or other gastrointestinal symptoms. An FDG-PET scan showed increased uptake in the stomach and caecum. Endoscopic examination showed inflammatory changes in the stomach and normal mucosa of the duodenum, jejunum, terminal ileum, caecum, and colon. Histopathology was inconclusive, but the diagnosis was confirmed with Tropheryma whipplei PCR testing. He had no neurological symptoms, but cerebrospinal fluid Tropheryma whipplei PCR was positive. He was treated with intravenous ceftriaxone 2 g daily for 4 weeks, followed by trimethoprim/sulfamethoxazole 160/800 mg twice daily for 1 year with close monitoring and follow-up. Conclusion This case presents an atypical and challenging presentation of Whipple's disease and the importance of proactive testing for neurological involvement.
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Affiliation(s)
- Arteen Arzivian
- Gastroenterology Department, Macquarie University Hospital, Sydney, NSW, Australia
| | - Brett Jones
- Gastroenterology Department, Macquarie University Hospital, Sydney, NSW, Australia
| | - Fredrick Joshua
- Rheumatology Department, Macquarie University Hospital, Sydney, NSW, Australia
| | - Miriam Paul
- Douglass Hanly Moir Pathology, Macquarie Park, Sydney, NSW, Australia
| | - Thomas Lynch
- Douglass Hanly Moir Pathology, Macquarie Park, Sydney, NSW, Australia
| | - Martin Brown
- Cardiology Department, Macquarie University Hospital, Sydney, NSW, Australia
| | - Robin Gasiorowski
- Haematology Department, Macquarie University Hospital, Sydney, NSW, Australia
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Tjandra DP, Brett A, Murugasu A. Use of bevacizumab in a patient with Whipple's disease: managing diagnostic uncertainty. BMJ Case Rep 2023; 16:e256460. [PMID: 37879715 PMCID: PMC10603426 DOI: 10.1136/bcr-2023-256460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2023] Open
Abstract
A man in his 30s with intellectual disability presented with 1 month of diarrhoea, weight loss and dyspnoea. Investigations were hampered due to significant anxiety. Laboratory tests detected microcytic anaemia and hypoalbuminaemia. CT demonstrated a fat-containing infiltrate in the mediastinum, mesentery and axillae, and pulmonary ground-glass infiltrates. Biopsy of the axilla showed cystic lymphatic malformations involving adipose tissue and lymph nodes, leading to a provisional diagnosis of generalised lymphatic anomaly. Over the subsequent 4 months, the patient's respiratory status deteriorated, leading to type 1 respiratory failure necessitating intubation. After multidisciplinary discussion, a decision was made to trial bevacizumab, an anti-VEGF agent, with subsequent improvement in respiratory status. While intubated, gastroscopy was performed; duodenal biopsies revealed pathognomonic changes of Whipple's disease, confirmed on PCR of duodenal and axillae biopsies. This was deemed the most likely unifying diagnosis; antibiotic treatment was commenced, bevacizumab was ceased, and the patient has remained well after 18 months.
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Affiliation(s)
- Douglas Peter Tjandra
- Department of Gastroenterology, The Royal Melbourne Hospital City Campus, Parkville, Victoria, Australia
| | - Andrew Brett
- Department of Gastroenterology, The Royal Melbourne Hospital City Campus, Parkville, Victoria, Australia
| | - Anand Murugasu
- Department of Gastroenterology, The Royal Melbourne Hospital City Campus, Parkville, Victoria, Australia
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Song X, Duan R, Duan L, Wei L. Current knowledge of the immune reconstitution inflammatory syndrome in Whipple disease: a review. Front Immunol 2023; 14:1265414. [PMID: 37901208 PMCID: PMC10611461 DOI: 10.3389/fimmu.2023.1265414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Accepted: 09/25/2023] [Indexed: 10/31/2023] Open
Abstract
Immune reconstitution inflammatory syndrome (IRIS) is characterized by exaggerated and dysregulated inflammatory responses that occur as a result of reconstitution of adaptive or innate immunity. A wide range of microorganisms have been found to be associated with IRIS, such as human immunodeficiency virus (HIV), Mycobacterium and actinobacteria. Whipple disease (WD) is an infectious disorder caused by the Gram-positive bacterium Tropheryma whipplei (T. whipplei) and IRIS also serves as a complication during its treament. Although many of these pathological mechanisms are shared with related inflammatory disorders, IRIS in WD exhibits distinct features and is poorly described in the medical literature. Novel investigations of the intestinal mucosal immune system have provided new insights into the pathogenesis of IRIS, elucidating the interplay between systemic and local immune responses. These insights may be used to identify monitoring tools for disease prevention and to develop treatment strategies. Therefore, this review synthesizes these new concepts in WD IRIS to approach the feasibility of manipulating host immunity and immune reconstitution of inflammatory syndromes from a newer, more comprehensive perspective and study hypothetical options for the management of WD IRIS.
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Affiliation(s)
| | | | | | - Lijuan Wei
- Department of Gastroenterology and Digestive Endoscopy Center, The Second Hospital of Jilin University, Chang Chun, Jilin, China
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14
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Chen Q, Niu YL, Zhang T. Diagnosis and treatment of Whipple disease after kidney transplantation: A case report. World J Clin Cases 2023; 11:6019-6024. [PMID: 37727483 PMCID: PMC10506035 DOI: 10.12998/wjcc.v11.i25.6019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 07/20/2023] [Accepted: 08/01/2023] [Indexed: 09/01/2023] Open
Abstract
BACKGROUND Kidney transplantation is the standard treatment for end-stage renal disease. Particularly, rare and specific pathogenic infections which are asymptomatic are often difficult to diagnose, causing delayed and ineffective treatment and thus seriously affecting prognosis. Tropheryma whipplei (T. whipplei) is a Gram-positive actinomycete widely found in soil, sewage, and other external environments and is present in the population as an asymptomatic pathogen. There is relatively little documented research on T. whipplei in renal transplant patients, and there are no uniform criteria for treating this group of post-transplant patients. This article describes the treatment of a 42-year-old individual with post-transplant T. whipplei infection following kidney transplantation. CASE SUMMARY To analyze clinical features of Whipple's disease and summarize its diagnosis and treatment effects after renal transplantation. Clinical data of a Whipple's disease patient treated in the affiliated hospital of Guizhou Medical University were collected and assessed retrospectively. The treatment outcomes and clinical experience were then summarized via literature review. The patient was admitted to the hospital due to recurrent diarrhea for 1 mo, shortness of breath, and 1 wk of fever, after 3 years of renal transplantation. The symptoms of the digestive and respiratory systems were not significantly improved after adjusting immunosuppressive regimen and anti-diarrheal, empirical antibiotic treatments. Bronchoscopic alveolar fluid was collected for meta-genomic next-generation sequencing (mNGS). The deoxyribonucleic acid sequence of Tropheryma whipplei was detected, and Whipple's disease was diagnosed. Meropenem, ceftriaxone, and other symptomatic treatments were given, and water-electrolyte balance was maintained. Symptoms resolved quickly, and the patient was discharged after 20 d of hospitalization. The compound sulfamethoxazole tablet was continued for 3 mo after discharge. No diarrhea, fever, and other symptoms occurred during the 6-month follow-up. CONCLUSION Whipple's disease is rare, with no specific symptoms, which makes diagnosis difficult. Polymerase chain reaction or mNGS should be immediately performed when the disease is suspected to confirm the diagnosis.
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Affiliation(s)
- Qian Chen
- Department of Organ Transplantation, Affiliated Hospital of Guizhou Medical University, Guiyang 550000, Guizhou Province, China
| | - Yu-Lin Niu
- Department of Organ Transplantation, Affiliated Hospital of Guizhou Medical University, Guiyang 550000, Guizhou Province, China
| | - Tao Zhang
- Department of Organ Transplantation, Affiliated Hospital of Guizhou Medical University, Guiyang 550000, Guizhou Province, China
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15
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Menier CA, Rheaume P, Bernatchez J. Two consecutive cases of mycotic aneurysms resulting from Whipple disease. J Vasc Surg Cases Innov Tech 2023; 9:101182. [PMID: 37388672 PMCID: PMC10300405 DOI: 10.1016/j.jvscit.2023.101182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 03/28/2023] [Indexed: 07/01/2023] Open
Abstract
Whipple disease is a rare multisystemic infectious process caused by Tropheryma whipplei. Classical clinical manifestations include chronic diarrhea, malabsorption, weight loss, and arthralgias. Cases of endocarditis and isolated involvement of the central nervous system have also been reported. Isolated vascular complications are not common with this disease. Vascular manifestations are mainly described as systemic embolization from underlying endocarditis. We report two consecutive cases of mycotic pseudoaneurysms resulting from Whipple disease treated with successful vascular reconstruction using autologous vein grafting.
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Affiliation(s)
| | | | - Julien Bernatchez
- Correspondence: Julien Bernatchez, MD, MMSc, Division of Vascular Surgery, CHU de Quebec, Hopital St-Francois D'Assise, Universite Laval, 10 rue de l’Espinay, Quebec City, QC G1L 3L5, Canada
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16
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Weber M, Dancygier H, Blasberg T, Wedi E. [Co-occurrence of Whipple's disease and hyperparathyroidism - coincidence or causal relationship?]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1214-1220. [PMID: 37309099 DOI: 10.1055/a-1984-0403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
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.
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Affiliation(s)
- Marie Weber
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie und Interventionelle Endoskopie, Sana Klinikum Offenbach GmbH, Offenbach, Germany
| | | | - Tobias Blasberg
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie und Interventionelle Endoskopie, Sana Klinikum Offenbach GmbH, Offenbach, Germany
| | - Edris Wedi
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie und Interventionelle Endoskopie, Sana Klinikum Offenbach GmbH, Offenbach, Germany
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17
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Naser JA, Fogwe D, Ho M, Corsini Campioli C, Shah A. Hiding in Plain Sight. N Engl J Med 2022; 387:2075-2081. [PMID: 36449424 DOI: 10.1056/nejmcps2205021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Affiliation(s)
- Jwan A Naser
- From the Division of General Internal Medicine, Department of Internal Medicine (J.A.N., D.F., M.H.), and the Division of Public Health, Infectious Diseases, and Occupational Medicine (C.C.C., A.S.), Mayo Clinic, Rochester, MN
| | - Delvise Fogwe
- From the Division of General Internal Medicine, Department of Internal Medicine (J.A.N., D.F., M.H.), and the Division of Public Health, Infectious Diseases, and Occupational Medicine (C.C.C., A.S.), Mayo Clinic, Rochester, MN
| | - Matthew Ho
- From the Division of General Internal Medicine, Department of Internal Medicine (J.A.N., D.F., M.H.), and the Division of Public Health, Infectious Diseases, and Occupational Medicine (C.C.C., A.S.), Mayo Clinic, Rochester, MN
| | - Cristina Corsini Campioli
- From the Division of General Internal Medicine, Department of Internal Medicine (J.A.N., D.F., M.H.), and the Division of Public Health, Infectious Diseases, and Occupational Medicine (C.C.C., A.S.), Mayo Clinic, Rochester, MN
| | - Aditya Shah
- From the Division of General Internal Medicine, Department of Internal Medicine (J.A.N., D.F., M.H.), and the Division of Public Health, Infectious Diseases, and Occupational Medicine (C.C.C., A.S.), Mayo Clinic, Rochester, MN
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18
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Barbero-Aznarez P, Perez-Tanoira R, Aguirre-Mollehuanca D, Trascasa-Caño A, Fortes-Alen J, Manzarbeitia-Arrambari F, Castillo-Alvarez J, Montoya-Bordon J, Petkova-Saiz E, Prieto-Perez L. Isolated central nervous system Whipple disease. Surg Neurol Int 2022; 13:477. [DOI: 10.25259/sni_591_2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 09/19/2022] [Indexed: 11/04/2022] Open
Abstract
Background:
Whipple disease (WD) is an infection caused by Tropheryma whipplei, which might present in three different forms: classical, localized, and isolated in the central nervous system (CNS).
Methods:
We report the result of a systematic review of the literature on WD unusually presenting with exclusively neurological symptoms, including two previously unpublished cases. A description of two cases with isolated CNS WD was performed, as well as a literature search in Cochrane, Scielo, and PubMed.
Results:
Two male adult patients presented with exclusively neurological symptomatology. Both magnetic resonance imaging (MRI) showed an intracranial mass suggestive of brain tumor. The histopathological examination was consistent with WD, with no systemic involvement. In the review of the literature, 35 cases of isolated CNS WD were retrieved. The median age at diagnosis was 43.5 (IQR 31.5–51.5). In 13 patients, the MRI showed a brain mass consistent with a brain tumor. The most common finding in the biopsy was the periodic-acid Schiff-stained foamy macrophages. Only five cases presented the pathognomonic sign of oculomasticatory myorhythmia. Thirteen cases had an adverse outcome that resulted in death during follow-up, whereas another 13 improved. The other nine patients remained stable or presented moderate improvement.
Conclusion:
Isolated CNS WD is a rare disease that should be considered among the differential diagnosis of CNS mass lesions. Brain biopsy is necessary to establish the diagnosis. It is stressed in the literature that an extended antibiotic course is required to prevent relapses and to control the disease.
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Affiliation(s)
- Pablo Barbero-Aznarez
- Department of Neurosurgery, Instituto Clavel, San Francisco De Asis University Hospital, Madrid, Spain
| | - Ramon Perez-Tanoira
- Department of Microbiology, Principe de Asturias University Hospital, Madrid, Spain
| | | | | | - Jose Fortes-Alen
- Department of Pathology, Fundacion Jimenez Diaz University Hospital, Madrid, Spain
| | | | | | | | | | - Laura Prieto-Perez
- Internal Medicine, Fundacion Jimenez Diaz University Hospital, Madrid, Spain
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19
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Stezin A, Pal PK. Treatable Ataxias: How to Find the Needle in the Haystack? J Mov Disord 2022; 15:206-226. [PMID: 36065614 DOI: 10.14802/jmd.22069] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 07/05/2022] [Indexed: 11/24/2022] Open
Abstract
Treatable ataxias are a group of ataxic disorders with specific treatments. These disorders include genetic and metabolic disorders, immune-mediated ataxic disorders, and ataxic disorders associated with infectious and parainfectious etiology, vascular causes, toxins and chemicals, and endocrinopathies. This review provides a comprehensive overview of different treatable ataxias. The major metabolic and genetic treatable ataxic disorders include ataxia with vitamin E deficiency, abetalipoproteinemia, cerebrotendinous xanthomatosis, Niemann-Pick disease type C, autosomal recessive cerebellar ataxia due to coenzyme Q10 deficiency, glucose transporter type 1 deficiency, and episodic ataxia type 2. The treatment of these disorders includes the replacement of deficient cofactors and vitamins, dietary modifications, and other specific treatments. Treatable ataxias with immune-mediated etiologies include gluten ataxia, anti-glutamic acid decarboxylase antibody-associated ataxia, steroid-responsive encephalopathy associated with autoimmune thyroiditis, Miller-Fisher syndrome, multiple sclerosis, and paraneoplastic cerebellar degeneration. Although dietary modification with a gluten-free diet is adequate in gluten ataxia, other autoimmune ataxias are managed by short-course steroids, plasma exchange, or immunomodulation. For autoimmune ataxias secondary to malignancy, treatment of tumor can reduce ataxic symptoms. Chronic alcohol consumption, antiepileptics, anticancer drugs, exposure to insecticides, heavy metals, and recreational drugs are potentially avoidable and treatable causes of ataxia. Infective and parainfectious causes of cerebellar ataxias include acute cerebellitis, postinfectious ataxia, Whipple's disease, meningoencephalitis, and progressive multifocal leukoencephalopathy. These disorders are treated with steroids and antibiotics. Recognizing treatable disorders is of paramount importance when dealing with ataxias given that early treatment can prevent permanent neurological sequelae.
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Affiliation(s)
- Albert Stezin
- Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India.,Centre for Brain Research, Indian Institute of Science, Bengaluru, India
| | - Pramod Kumar Pal
- Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India
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20
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Clarke MCC, Price RN. Delayed Diagnosis of Whipple’s Disease Complicated by Jarisch–Herxheimer Reaction to Ceftriaxone Treatment: A Case Report and Literature Review. Trop Med Infect Dis 2022; 7:tropicalmed7030040. [PMID: 35324587 PMCID: PMC8954982 DOI: 10.3390/tropicalmed7030040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/28/2022] [Accepted: 03/01/2022] [Indexed: 01/25/2023] Open
Abstract
Whipple’s disease is a rare chronic infection caused by the actinomycete Tropheryma whipplei. Patients commonly present with gastrointestinal symptoms. We present a case of classic Whipple’s disease complicated by a probable Jarisch–Herxheimer reaction following the initiation of ceftriaxone treatment.
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Affiliation(s)
- Marcus C C Clarke
- Division of Medicine, Royal Darwin Hospital, 105 Rocklands Dr, Tiwi, NT 0810, Australia
| | - Ric N Price
- Division of Medicine, Royal Darwin Hospital, 105 Rocklands Dr, Tiwi, NT 0810, Australia
- Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Ellengowan Dr, Casuarina, NT 0810, Australia
- Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 2JD, UK
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21
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Challenging case of Whipple's disease: The contribution of radiology. Radiol Case Rep 2022; 17:1008-1012. [PMID: 35111275 PMCID: PMC8790621 DOI: 10.1016/j.radcr.2021.12.063] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 12/27/2021] [Accepted: 12/30/2021] [Indexed: 12/17/2022] Open
Abstract
Whipple's disease is a rare chronic infectious disease, caused by Tropheryma whipplei. The disease can be challenging to diagnose due to the variable clinical manifestations and the nonspecific laboratory and imaging findings. We report the case of a 75-year-old man, complaining of weight loss and arthralgias with an insidious onset. A thoracic, abdominal and pelvic CT was performed, demonstrating features suggestive of Whipple's disease. Although not specific, the imaging findings of fatty attenuation mesenteric and retroperitoneal enlarged lymph nodes are a common finding in Whipple's disease. Esophagogastroduodenoscopy with duodenal biopsy confirmed the diagnosis through PCR analysis.
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22
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Bulut K, Markova A, Canbay AE, Schmidt WE, Kahraman A. Whipple's disease - a rare and challenging complication in a patient with Crohn's disease. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:598-601. [PMID: 35176806 DOI: 10.1055/a-1747-3666] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
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.
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Affiliation(s)
- Kerem Bulut
- Clinic for Internal Medicine and Gastroenterology, St. Clemens-Hospital Geldern, Germany
| | - Antoaneta Markova
- Department of Gastroenterology and Hepatology, University Clinic of Essen, Germany
| | - Ali E Canbay
- Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Germany
| | - Wolfgang E Schmidt
- Department of Internal Medicine, St. Josef Hospital, Ruhr-University Bochum, Germany
| | - Alisan Kahraman
- Gastroenterology and Hepatology, Max Grundig Clinic, Bühl/Baden, Bühl, Germany.,Department of Gastroenterology and Hepatology, University Clinic of Essen, Germany
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23
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Nasim A, Dodani SK, Badlani S, Babar ZU, Shakil S, Mubarak M, Luck N, Aziz T. Whipple's disease in renal transplant recipients: Management experience of seven cases from Pakistan. Transpl Infect Dis 2021; 24:e13769. [PMID: 34837443 DOI: 10.1111/tid.13769] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 10/23/2021] [Accepted: 11/10/2021] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Whipple's disease (WD) is a rare multi-systemic disorder caused by actinomycetes, Tropheryma 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 WD in renal transplant recipients. METHODS All renal transplant recipients who presented with diarrhea and were diagnosed with WD on duodenal biopsy from 2016 till 2019 were included. Their data regarding duration since transplantation, immunosuppressive therapy, symptoms, treatment response, and outcome were analyzed. RESULTS Seven cases were diagnosed as WD based on duodenal biopsy, with histological findings of periodic acid Schiff-positive granules in macrophages. All were males. 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 five of seven patients treated with doxycycline and hydroxychloroquine which was discontinued. Trimethoprim/sulfamethoxazole for 1 year, with initial intravenous ceftriaxone in two patients, resulted in complete remission in all patients at a follow-up period averaging 1.5 years. CONCLUSION WDs in renal transplant recipients most commonly presents as an intestinal disorder. Treatment of 1 year with trimethoprim/sulfamethoxazole has good response with complete remission at 1.5 years of follow up.
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Affiliation(s)
- Asma Nasim
- Sindh Institute of Urology and Transplantation, Chand Bibi Road, Karachi, Pakistan
| | - Sunil Kumar Dodani
- Sindh Institute of Urology and Transplantation, Chand Bibi Road, Karachi, Pakistan
| | - Sanjay Badlani
- Sindh Institute of Urology and Transplantation, Chand Bibi Road, Karachi, Pakistan
| | - Zaheer Udin Babar
- Sindh Institute of Urology and Transplantation, Chand Bibi Road, Karachi, Pakistan
| | - Shaheera Shakil
- Sindh Institute of Urology and Transplantation, Chand Bibi Road, Karachi, Pakistan
| | - Mohammad Mubarak
- Sindh Institute of Urology and Transplantation, Chand Bibi Road, Karachi, Pakistan
| | - Nasir Luck
- Sindh Institute of Urology and Transplantation, Chand Bibi Road, Karachi, Pakistan
| | - Tahir Aziz
- Sindh Institute of Urology and Transplantation, Chand Bibi Road, Karachi, Pakistan
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24
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Leyens J, Bender TTA, Mücke M, Stieber C, Kravchenko D, Dernbach C, Seidel MF. The combined prevalence of classified rare rheumatic diseases is almost double that of ankylosing spondylitis. Orphanet J Rare Dis 2021; 16:326. [PMID: 34294115 PMCID: PMC8296612 DOI: 10.1186/s13023-021-01945-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 07/02/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Rare diseases (RDs) affect less than 5/10,000 people in Europe and fewer than 200,000 individuals in the United States. In rheumatology, RDs are heterogeneous and lack systemic classification. Clinical courses involve a variety of diverse symptoms, and patients may be misdiagnosed and not receive appropriate treatment. The objective of this study was to identify and classify some of the most important RDs in rheumatology. We also attempted to determine their combined prevalence to more precisely define this area of rheumatology and increase awareness of RDs in healthcare systems. We conducted a comprehensive literature search and analyzed each disease for the specified criteria, such as clinical symptoms, treatment regimens, prognoses, and point prevalences. If no epidemiological data were available, we estimated the prevalence as 1/1,000,000. The total point prevalence for all RDs in rheumatology was estimated as the sum of the individually determined prevalences. RESULTS A total of 76 syndromes and diseases were identified, including vasculitis/vasculopathy (n = 15), arthritis/arthropathy (n = 11), autoinflammatory syndromes (n = 11), myositis (n = 9), bone disorders (n = 11), connective tissue diseases (n = 8), overgrowth syndromes (n = 3), and others (n = 8). Out of the 76 diseases, 61 (80%) are classified as chronic, with a remitting-relapsing course in 27 cases (35%) upon adequate treatment. Another 34 (45%) diseases were predominantly progressive and difficult to control. Corticosteroids are a therapeutic option in 49 (64%) syndromes. Mortality is variable and could not be determined precisely. Epidemiological studies and prevalence data were available for 33 syndromes and diseases. For an additional eight diseases, only incidence data were accessible. The summed prevalence of all RDs was 28.8/10,000. CONCLUSIONS RDs in rheumatology are frequently chronic, progressive, and present variable symptoms. Treatment options are often restricted to corticosteroids, presumably because of the scarcity of randomized controlled trials. The estimated combined prevalence is significant and almost double that of ankylosing spondylitis (18/10,000). Thus, healthcare systems should assign RDs similar importance as any other common disease in rheumatology.
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Affiliation(s)
- Judith Leyens
- Center for Rare Diseases Bonn (ZSEB), University Hospital, Bonn, Germany
- Department of Neonatology and Pediatric Care, Children's University Hospital, Bonn, Germany
| | - Tim Th A Bender
- Center for Rare Diseases Bonn (ZSEB), University Hospital, Bonn, Germany
- Institute of Human Genetics, University Hospital, Bonn, Germany
| | - Martin Mücke
- Center for Rare Diseases Bonn (ZSEB), University Hospital, Bonn, Germany
| | - Christiane Stieber
- Institute of General Practice and Family Medicine, University Hospital, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Dmitrij Kravchenko
- Center for Rare Diseases Bonn (ZSEB), University Hospital, Bonn, Germany
- Department of Radiology, University Hospital, Bonn, Germany
| | - Christian Dernbach
- Division of Medical Psychology and Department of Psychiatry, University Hospital, Bonn, Germany
| | - Matthias F Seidel
- Department of Rheumatology, Spitalzentrum-Centre hospitalier, Biel-Bienne, Switzerland.
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25
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Zhu B, Tang J, Fang R, Fei X, Wang Q, Wang W, Wu X, Liu C, Wang Q. Pulmonary coinfection of Mycobacterium tuberculosis and Tropheryma whipplei: a case report. J Med Case Rep 2021; 15:359. [PMID: 34243811 PMCID: PMC8269402 DOI: 10.1186/s13256-021-02899-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Accepted: 05/10/2021] [Indexed: 12/18/2022] Open
Abstract
Background We diagnosed a clinical case of pulmonary infection involving Mycobacterium tuberculosis and Tropheryma whipplei in a patient with acute respiratory distress syndrome. The diagnosis was assisted by metagenomic next-generation sequencing of bronchoalveolar lavage fluid. Case presentation A 44-year-old Han Chinese inmate was transferred to the emergency department because of dry cough, chest tightness, and shortness of breath. The patient’s body temperature rose to 39.3 °C following empirical cephalosporin treatment for 1 week. The blood CD4+/CD8+ ratio was 0.7, suggesting immunodeficiency. Routine microbiological tests were performed, and tuberculosis interferon gamma release assays were positive. Mycobacterium tuberculosis polymerase chain reaction was also positive. Chest computed tomography scan revealed miliary nodules and ground-glass opacifications, which were in accordance with tuberculosis. To fully examine the etiology, we performed routine laboratory tests and metagenomic sequencing, the results of which indicated the presence of Mycobacterium tuberculosis and Tropheryma whipplei. We administered anti-tuberculosis regimen in combination with trimethoprim/sulfamethoxazole. The patient recovered, with chest computed tomography scan showing absorption of lesions. Conclusions Compared with traditional diagnostic methods such as culture and serology, metagenomic next-generation sequencing has the advantage of detecting a wide array of microorganisms in a single test and therefore can be used for clinical diagnosis of rare pathogens and microbial coinfections. It is particularly useful for immunocompromised patients as they are more prone to infection by opportunistic microorganisms.
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Affiliation(s)
- Binghua Zhu
- Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, China
| | - Jing Tang
- Shanghai Guanghua Hosptial of Integrated Traditional Chinese and Western Medicine, Shanghai, 200052, China
| | - Rong Fang
- Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, China
| | - Xuejie Fei
- Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, China
| | - Qing Wang
- Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, China
| | - Wenqing Wang
- Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, China
| | - Xueqin Wu
- Hangzhou Matridx Biotechnology Co., Ltd, Bd 5, 208 Zhenzhong Road, Hangzhou, 311113, Zhejiang, China
| | - Chao Liu
- Hangzhou Matridx Biotechnology Co., Ltd, Bd 5, 208 Zhenzhong Road, Hangzhou, 311113, Zhejiang, China.
| | - Qian Wang
- Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, China.
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Kobayashi T, Amram AL, Gehrs K, Diekema D, Barker J. A 52-Year-Old Man With Uveitis and Altered Mental Status. Clin Infect Dis 2021; 72:873-875. [PMID: 33667312 DOI: 10.1093/cid/ciaa051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Takaaki Kobayashi
- Division of Infectious Diseases, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
| | - Alec L Amram
- Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, USA
| | - Karen Gehrs
- Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, USA
| | - Daniel Diekema
- Division of Infectious Diseases, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
| | - Jason Barker
- Division of Infectious Diseases, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
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27
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Melas N, Amin R, Gyllemark P, Younes AH, Almer S. Whipple's disease: the great masquerader-a high level of suspicion is the key to diagnosis. BMC Gastroenterol 2021; 21:128. [PMID: 33743602 PMCID: PMC7980341 DOI: 10.1186/s12876-021-01664-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 02/12/2021] [Indexed: 12/18/2022] Open
Abstract
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.
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Affiliation(s)
- Nikolaos Melas
- Department of Gastroenterology and Emergency Care, Gävle Hospital, Gävle, Sweden
| | - Rasjan Amin
- Department of Anesthesiology and Intensive Care Unit, S:T Göran Hospital, Stockholm, Sweden
| | - Paula Gyllemark
- Department of Infectious Diseases, Region Jönköping County, Jönköping, Sweden.,Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Amil Haji Younes
- Department of Gastroenterology and Emergency Care, Gävle Hospital, Gävle, Sweden
| | - Sven Almer
- Department of Medicine, Karolinska Institutet, Solna, Sweden. .,Division of Gastroenterology, Karolinska University Hospital, Stockholm, Sweden.
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28
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Feurle GE, Moos V, Stroux A, Gehrmann-Sommer N, Poddubnyy D, Fiehn C, Schneider T. Differential diagnostic value of rheumatic symptoms in patients with Whipple's disease. Sci Rep 2021; 11:5980. [PMID: 33727566 PMCID: PMC7966399 DOI: 10.1038/s41598-021-85217-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 02/15/2021] [Indexed: 12/17/2022] Open
Abstract
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.
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Affiliation(s)
- Gerhard E Feurle
- DRK Krankenhaus Neuwied, Eduard Moerikestrasse 12, 56567, Neuwied, Germany.
| | - Verena Moos
- Medizinische Klinik I für Gastroenterologie, Infektiologie und Rheumatologie, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Andrea Stroux
- Institut für Biometrie und Klinische Epidemiologie, Charité-Universitätsmedizin Berlin, Berlin Institute of Health, Berlin, Germany
| | - Nadine Gehrmann-Sommer
- Medizinische Klinik I für Gastroenterologie, Infektiologie und Rheumatologie, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Denis Poddubnyy
- Medizinische Klinik I für Gastroenterologie, Infektiologie und Rheumatologie, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Christoph Fiehn
- Praxis für Rheumatologie, Klinische Immunologie, Medical Center, Baden-Baden, Germany
| | - Thomas Schneider
- Medizinische Klinik I für Gastroenterologie, Infektiologie und Rheumatologie, Charité-Universitätsmedizin Berlin, Berlin, Germany
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29
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Camboulive A, Jutant EM, Savale L, Jaïs X, Sitbon O, Mussini C, Bénichou J, Lagier JC, Humbert M, Montani D. Reversible pulmonary hypertension associated with multivisceral Whipple's disease. Eur Respir J 2020; 57:13993003.03132-2020. [PMID: 33093116 DOI: 10.1183/13993003.03132-2020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 10/06/2020] [Indexed: 11/05/2022]
Affiliation(s)
- Alice Camboulive
- Assistance Publique - Hôpitaux de Paris (AP-HP), Dept of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France.,INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies", Hôpital Marie Lannelongue, Le Plessis-Robinson, France.,Contributed equally
| | - Etienne-Marie Jutant
- Assistance Publique - Hôpitaux de Paris (AP-HP), Dept of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France.,INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies", Hôpital Marie Lannelongue, Le Plessis-Robinson, France.,Contributed equally
| | - Laurent Savale
- Assistance Publique - Hôpitaux de Paris (AP-HP), Dept of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France.,INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies", Hôpital Marie Lannelongue, Le Plessis-Robinson, France
| | - Xavier Jaïs
- Assistance Publique - Hôpitaux de Paris (AP-HP), Dept of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France.,INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies", Hôpital Marie Lannelongue, Le Plessis-Robinson, France
| | - Olivier Sitbon
- Assistance Publique - Hôpitaux de Paris (AP-HP), Dept of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France.,INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies", Hôpital Marie Lannelongue, Le Plessis-Robinson, France
| | - Charlotte Mussini
- AP-HP, Service d'Anatomie et de Cytologie Pathologiques, Hôpital de Bicêtre, Le Kremlin Bicêtre, France.,Hôpitaux Universitaires Paris-Saclay, Le Kremlin-Bicêtre, France
| | - Jérémie Bénichou
- Hôpitaux Universitaires Paris-Saclay, Le Kremlin-Bicêtre, France.,AP-HP, Service d'ophtalmologie, Hôpital de Bicêtre, Le Kremlin Bicêtre, France
| | - Jean-Christophe Lagier
- Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Marc Humbert
- Assistance Publique - Hôpitaux de Paris (AP-HP), Dept of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France.,INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies", Hôpital Marie Lannelongue, Le Plessis-Robinson, France
| | - David Montani
- Assistance Publique - Hôpitaux de Paris (AP-HP), Dept of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France .,Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France.,INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies", Hôpital Marie Lannelongue, Le Plessis-Robinson, France
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30
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Yetmar Z, Cano Cevallos E, Mahmood M. Abdominal Pain, Fevers, and Intestinal Lymphangiectasia. Clin Infect Dis 2020; 69:2035-2036. [PMID: 31724060 DOI: 10.1093/cid/ciz041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Zachary Yetmar
- Department of Internal Medicine, and, Rochester, Minnesota
| | | | - Maryam Mahmood
- Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota
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31
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Sampaio F, Moreira J, Jordão S, Vieira B, Pereira S, Carvalho R. Whipple's disease orbitopathy: case report and review of literature. Orbit 2020; 41:112-117. [PMID: 32912014 DOI: 10.1080/01676830.2020.1820044] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
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.
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Affiliation(s)
- Filipa Sampaio
- Ophthalmology Department, Hospital Pedro Hispano, Unidade Local de Saúde de Matosinhos, Matosinhos, Portugal
| | - Jorge Moreira
- Ophthalmology Department, Hospital Pedro Hispano, Unidade Local de Saúde de Matosinhos, Matosinhos, Portugal
| | - Sofia Jordão
- Infectious Diseases Department, Hospital Pedro Hispano, Unidade Local de Saúde de Matosinhos, Matosinhos, Portugal
| | - Bruna Vieira
- Ophthalmology Department, Hospital Pedro Hispano, Unidade Local de Saúde de Matosinhos, Matosinhos, Portugal
| | - Sara Pereira
- Ophthalmology Department, Hospital Pedro Hispano, Unidade Local de Saúde de Matosinhos, Matosinhos, Portugal
| | - Rui Carvalho
- Ophthalmology Department, Hospital Pedro Hispano, Unidade Local de Saúde de Matosinhos, Matosinhos, Portugal
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32
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Schiepatti A, Nicolardi ML, Marone P, Biagi F. Long-term morbidity and mortality in Whipple's disease: a single-center experience over 20 years. Future Microbiol 2020; 15:847-854. [PMID: 32662657 DOI: 10.2217/fmb-2019-0315] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
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.
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Affiliation(s)
- Annalisa Schiepatti
- Istituti Clinici Scientifici Maugeri IRCCS, Gastroenterology Unit of Pavia Institute, University of Pavia, Pavia 27100, Italy
| | - Maria Luisa Nicolardi
- Istituti Clinici Scientifici Maugeri IRCCS, Gastroenterology Unit of Pavia Institute, University of Pavia, Pavia 27100, Italy
| | - Piero Marone
- Department of Microbiology & Virology, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy
| | - Federico Biagi
- Istituti Clinici Scientifici Maugeri IRCCS, Gastroenterology Unit of Pavia Institute, University of Pavia, Pavia 27100, Italy
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33
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Affiliation(s)
- Camila D Odio
- From the Department of Medicine (C.D.O., C.R.O., J.J.), Section of Hematology (A.I.L.), and the Department of Pathology, Section of Digestive Diseases (D.J.), Yale School of Medicine, New Haven, CT
| | - Corey R O'Brien
- From the Department of Medicine (C.D.O., C.R.O., J.J.), Section of Hematology (A.I.L.), and the Department of Pathology, Section of Digestive Diseases (D.J.), Yale School of Medicine, New Haven, CT
| | - Jeremy Jacox
- From the Department of Medicine (C.D.O., C.R.O., J.J.), Section of Hematology (A.I.L.), and the Department of Pathology, Section of Digestive Diseases (D.J.), Yale School of Medicine, New Haven, CT
| | - Dhanpat Jain
- From the Department of Medicine (C.D.O., C.R.O., J.J.), Section of Hematology (A.I.L.), and the Department of Pathology, Section of Digestive Diseases (D.J.), Yale School of Medicine, New Haven, CT
| | - Alfred I Lee
- From the Department of Medicine (C.D.O., C.R.O., J.J.), Section of Hematology (A.I.L.), and the Department of Pathology, Section of Digestive Diseases (D.J.), Yale School of Medicine, New Haven, CT
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34
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Moter A, Janneck M, Wolters M, Iking-Konert C, Wiessner A, Loddenkemper C, Hartleben B, Lütgehetmann M, Schmidt J, Langbehn U, Janssen S, Geelhaar-Karsch A, Schneider T, Moos V, Rohde H, Kikhney J, Wiech T. Potential Role for Urine Polymerase Chain Reaction in the Diagnosis of Whipple's Disease. Clin Infect Dis 2020; 68:1089-1097. [PMID: 30351371 PMCID: PMC6424077 DOI: 10.1093/cid/ciy664] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Accepted: 08/07/2018] [Indexed: 02/06/2023] Open
Abstract
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.
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Affiliation(s)
- Annette Moter
- Biofilmcenter and German Consiliary Laboratory for Tropheryma whipplei, German Heart Center Berlin.,Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin
| | - Matthias Janneck
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg
| | - Manuel Wolters
- Institute of Medical Microbiology, Virology and Hygiene, University Hospital Hamburg-Eppendorf
| | | | - Alexandra Wiessner
- Biofilmcenter and German Consiliary Laboratory for Tropheryma whipplei, German Heart Center Berlin.,Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin
| | | | - Björn Hartleben
- Institute of Pathology, Nephropathology Section, University Hospital Hamburg-Eppendorf
| | - Marc Lütgehetmann
- Institute of Medical Microbiology, Virology and Hygiene, University Hospital Hamburg-Eppendorf
| | - Julia Schmidt
- Biofilmcenter and German Consiliary Laboratory for Tropheryma whipplei, German Heart Center Berlin.,Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin
| | - Ulrike Langbehn
- Institute of Pathology, Nephropathology Section, University Hospital Hamburg-Eppendorf
| | - Sabrina Janssen
- Medical Department I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Germany
| | - Anika Geelhaar-Karsch
- Medical Department I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Germany
| | - Thomas Schneider
- Medical Department I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Germany
| | - Verena Moos
- Medical Department I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Germany
| | - Holger Rohde
- Institute of Medical Microbiology, Virology and Hygiene, University Hospital Hamburg-Eppendorf
| | - Judith Kikhney
- Biofilmcenter and German Consiliary Laboratory for Tropheryma whipplei, German Heart Center Berlin.,Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin
| | - Thorsten Wiech
- Institute of Pathology, Nephropathology Section, University Hospital Hamburg-Eppendorf
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35
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Whipple's disease: diagnosis and predictive factors of relapse. Eur J Gastroenterol Hepatol 2020; 32:325-328. [PMID: 31764405 DOI: 10.1097/meg.0000000000001611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
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.
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36
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Aguiar Ferreira A, Gomes P, Curvo-Semedo L, Donato P. Whipple's disease: imaging contribution for a challenging case. BMJ Case Rep 2020; 13:13/2/e233071. [PMID: 32047086 DOI: 10.1136/bcr-2019-233071] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Whipple's disease is a rare and difficult-to-diagnose infectious disease, related to infection by gram-positive bacillum Tropheryma whipplei Clinical manifestations are very variable, but the classic form usually begins with recurring arthritis, followed several years later by non-specific abdominal symptoms, leading to late diagnosis. We present the case of a 52-year-old man who was admitted in the emergency department with an insidious clinical picture characterised by weight loss, abdominal pain, diarrhoea and arthralgias. An abdominal ultrasound was performed, showing findings suggestive of Whipple's disease, which, in conjunction with the clinical and laboratory findings, allowed the diagnosis to be correctly addressed. Upper endoscopy with duodenal biopsy revealed findings compatible with Whipple's disease, and the diagnosis was also confirmed through PCR techniques of blood. The patient was given antibiotic therapy, with rapid and substantial clinical improvement.
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Affiliation(s)
| | - Paula Gomes
- Medical Imaging, Coimbra University Hospital Centre, Coimbra, Portugal
| | - Luís Curvo-Semedo
- Medical Imaging, Coimbra University Hospital Centre, Coimbra, Portugal.,Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Paulo Donato
- Medical Imaging, Coimbra University Hospital Centre, Coimbra, Portugal.,Faculty of Medicine, University of Coimbra, Coimbra, Portugal
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37
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Kloek AT, Piet JR, Adriani KS. Pearls & Oy-sters: A rare presentation of Whipple disease: Still waters run deep. Neurology 2020; 94:e758-e761. [PMID: 32015179 DOI: 10.1212/wnl.0000000000008976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Affiliation(s)
- Anne T Kloek
- From the Department of Neurology (A.T.K.), Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam; Department of Neurology (J.R.P., K.S.A.), OLVG Hospital, Amsterdam; Department of Neurology (J.R.P., K.S.A.), Zaans Medisch Centrum, Zaandam; and Department of Viroscience (K.S.A.), Erasmus MC, Rotterdam, the Netherlands.
| | - Jurgen R Piet
- From the Department of Neurology (A.T.K.), Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam; Department of Neurology (J.R.P., K.S.A.), OLVG Hospital, Amsterdam; Department of Neurology (J.R.P., K.S.A.), Zaans Medisch Centrum, Zaandam; and Department of Viroscience (K.S.A.), Erasmus MC, Rotterdam, the Netherlands
| | - Kirsten S Adriani
- From the Department of Neurology (A.T.K.), Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam; Department of Neurology (J.R.P., K.S.A.), OLVG Hospital, Amsterdam; Department of Neurology (J.R.P., K.S.A.), Zaans Medisch Centrum, Zaandam; and Department of Viroscience (K.S.A.), Erasmus MC, Rotterdam, the Netherlands
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38
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Tropheryma whipplei endocarditis presenting as chronic valvular disease: A case report and review of literature. HUMAN PATHOLOGY: CASE REPORTS 2019. [DOI: 10.1016/j.ehpc.2019.200321] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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39
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Paymard M, Sukumaran V, Senanayake S, Watson A, Das C, Abhayaratna WP. Tropheryma Whipplei Endocarditis: Case Report and Literature Review. Heart Views 2019; 19:150-151. [PMID: 31057709 PMCID: PMC6487297 DOI: 10.4103/heartviews.heartviews_112_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
We describe a young man who initially presented with stroke and febrile illness. He was eventually diagnosed with Tropheryma whipplei endocarditis. This is a very rare condition and to the best of our knowledge, this is the first documented case of T. whipplei endocarditis in Australia and New Zealand regions. This report aims to increase awareness of clinicians of this very rare but potentially treatable condition. It is reasonable to exclude T. whipplei endocarditis when dealing with high-risk patients who are suspected for “culture-negative” endocarditis.
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Affiliation(s)
- Mohammad Paymard
- Department of Cardiology, The Canberra Hospital, Canberra, Australian Capital Territory, Australia.,College of Medicine, Biology and Environment, Australian National University, Canberra, Australian Capital Territory, Australia
| | - Vichitra Sukumaran
- Department of Infectious Diseases, The Canberra Hospital, Canberra, Australian Capital Territory, Australia
| | - Sanjaya Senanayake
- Department of Infectious Diseases, The Canberra Hospital, Canberra, Australian Capital Territory, Australia.,College of Medicine, Biology and Environment, Australian National University, Canberra, Australian Capital Territory, Australia
| | - Ashley Watson
- Department of Infectious Diseases, The Canberra Hospital, Canberra, Australian Capital Territory, Australia.,College of Medicine, Biology and Environment, Australian National University, Canberra, Australian Capital Territory, Australia
| | - Chandi Das
- Department of Neurology, The Canberra Hospital, Canberra, Australian Capital Territory, Australia
| | - Walter P Abhayaratna
- Department of Cardiology, The Canberra Hospital, Canberra, Australian Capital Territory, Australia.,College of Medicine, Biology and Environment, Australian National University, Canberra, Australian Capital Territory, Australia
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Abstract
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.
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Abstract
BACKGROUND Whipple disease (WD) is an infection caused by the bacterium Tropheryma whipplei (TW). Few cases have been reported in the USA. AIMS To report on the demographics, clinical manifestations, diagnostic findings, treatment, and outcomes of TW infection. METHODS Cases of TW infection diagnosed from 1995 to 2010 were identified in three US referral centers and from 1995 to 2015 in one. Definite classic WD was defined by positive periodic acid-Schiff (PAS) staining and probable WD by specific positive TW polymerase chain reaction (PCR) of intestinal specimens. Localized infections were defined by a positive TW PCR result from samples of other tissues/body fluids. RESULTS Among the 33 cases of TW infections, 27 (82%) were male. Median age at diagnosis was 53 years (range 11-75). Diagnosis was supported by a positive TW PCR in 29 (88%) and/or a positive PAS in 16 (48%) patients. Classic WD was the most frequent presentation (n = 18, 55%), with 14 definite and 4 probable cases. Localized infections (n = 15, 45%) affected the central nervous system (n = 7), joints (n = 4), heart (n = 2), eye (n = 1), and skeletal muscle (n = 1). Blood PCR was negative in 9 of 17 (53%) cases at diagnosis. Ceftriaxone intravenously followed by trimethoprim and sulfamethoxazole orally was the most common regimen (n = 23, 70%). Antibiotic therapy resulted in clinical response in 24 (73%). CONCLUSIONS TW infection can present as intestinal or localized disease. Negative small bowel PAS and PCR do not exclude the diagnosis of TW infection, and blood PCR is insensitive for active infection.
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Affiliation(s)
- Joesph Sellin
- Professor Emeritus, Division of Gastroenterology, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Ian L P Beales
- Department of Gastroenterology, Norfolk and Norwich University Hospital, Norwich, NR4 7UY, UK.
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43
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Sluszniak M, Tarner IH, Thiele A, Schmeiser T. [The rich diversity of Whipple's disease]. Z Rheumatol 2018; 78:55-65. [PMID: 30552512 DOI: 10.1007/s00393-018-0573-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Whipple's disease (WD) is a rare, chronic multiorgan disease which can caused by Tropheryma whipplei, a ubiquitous gram positive bacterium. Detection of T. whipplei is mostly performed histologically using periodic acid-Schiff (PAS) staining in affected tissues to visualize characteristic PAS-positive macrophages and by the polymerase chain reaction (PCR). Clinically, WD is often characterized by gastrointestinal symptoms (diarrhea, colic-like abdominal pain and weight loss). Arthritis is a common presentation of WS, often leading to a misdiagnosis of seronegative rheumatoid arthritis and as a consequence to immunosuppressive therapy. The clinical presentation of WD is highly polymorphic affecting different organ systems (e. g. cardiac or neurological manifestation) and making an appropriate clinical diagnosis and even the diagnostic process itself difficult. This article reports on three cases presenting with completely different leading symptoms (initially misdiagnosed as seronegative rheumatoid arthritis, spondyloarthritis and adult onset of Still's disease, respectively) that illustrate the rich diversity of WD. The cases were chosen to draw attention to the fact that although WD is mainly associated with the field of gastroenterology and gastrointestinal (GI) involvement is common, it may appear without GI symptoms. In cases of a clinical suspicion of WD, diagnostic efforts should be made to detect the bacterium in the affected organ. The German S2k guidelines on GI infections and WD published in January 2015 summarized the current state of the art for WD. The currently recommended primary treatment is antibiotics that can infiltrate the cerebrospinal fluid, e. g. ceftriaxone, followed by cotrimoxazole, which should be maintained over several months.
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Affiliation(s)
- M Sluszniak
- Klinik für Rheumatologie, Immunologie und Osteologie, Krankenhaus St. Josef Wuppertal, Bergstr. 6-12, 42105, Wuppertal, Deutschland.
| | - I H Tarner
- Abt. für Rheumatologie, Klinische Immunologie, Osteologie und Physikalische Medizin, Kerckhoff-Klinik GmbH Bad Nauheim, Bad Nauheim, Deutschland.,Lehrstuhl für Innere Medizin mit Schwerpunkt Rheumatologie, Justus-Liebig-Universität Gießen, Gießen, Deutschland
| | - A Thiele
- Klinik für Rheumatologie, Immunologie und Osteologie, Krankenhaus St. Josef Wuppertal, Bergstr. 6-12, 42105, Wuppertal, Deutschland
| | - T Schmeiser
- Klinik für Rheumatologie, Immunologie und Osteologie, Krankenhaus St. Josef Wuppertal, Bergstr. 6-12, 42105, Wuppertal, Deutschland
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44
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Lopes A, Santos AF, Alvarenga MJ, Mello E Silva A. Whipple's disease: a rare case of malabsorption. BMJ Case Rep 2018; 2018:bcr-2017-222955. [PMID: 29507019 DOI: 10.1136/bcr-2017-222955] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Whipple's disease is a chronic, rare, multisystemic, infectious entity, described for the first time in 1907. Its aetiological agent is the Gram-negative rod, Tropheryma whipplei, which was isolated for the first time in 2001 from a cardiac valve of a patient with endocarditis. We present the case of a 71-year-old man, who came into the emergency room complaining of anorexia, weakness, abdominal pain and diarrhoea with haematochezia and presented disseminated palpable purpuric lesions, predominantly in the lower limbs. The upper endoscopy showed a duodenal vasculitis and the biopsy of that location revealed aspects suggestive of Whipple's disease. We started him on antibiotics according to the recent orientations with progressive clinical and analytical improvement, although he developed an immune reconstitution syndrome, which lasted for 2 weeks.
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Affiliation(s)
- Ana Lopes
- Department of Medicina Interna, Hospital Egas Moniz, Lisbon, Portugal
| | - Ana Filipa Santos
- Department of Pneumologia, Hospital Egas Moniz, CHLO, Lisboa, Portugal
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Epple HJ, Friebel J, Moos V, Troeger H, Krug SM, Allers K, Schinnerling K, Fromm A, Siegmund B, Fromm M, Schulzke JD, Schneider T. Architectural and functional alterations of the small intestinal mucosa in classical Whipple's disease. Mucosal Immunol 2017; 10:1542-1552. [PMID: 28176790 DOI: 10.1038/mi.2017.6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Accepted: 01/10/2017] [Indexed: 02/04/2023]
Abstract
Classical Whipple's disease (CWD) affects the gastrointestinal tract and rather elicits regulatory than inflammatory immune reactions. Mechanisms of malabsorption, diarrhea, and systemic immune activation are unknown. We here analyzed mucosal architecture, barrier function, and immune activation as potential diarrheal trigger in specimens from 52 CWD patients. Our data demonstrate villus atrophy and crypt hyperplasia associated with epithelial apoptosis and reduced alkaline phosphatase expression in the duodenum of CWD patients. Electrophysiological and flux experiments revealed increased duodenal permeability to small solutes and macromolecules. Duodenal architecture and permeability ameliorated upon antibiotic treatment. Structural correlates for these alterations were concordant changes of membranous claudin-1, claudin-2, claudin-3, and tricellulin expression. Tumor necrosis factor-α and interleukin-13 were identified as probable mediators of epithelial apoptosis, and altered tight junction expression. Increased serum markers of microbial translocation and their decline following treatment corroborated the biological significance of the mucosal barrier defect. Hence, mucosal immune responses in CWD elicit barrier dysfunction. Diarrhea is caused by loss of absorptive capacity and leak flux of ions and water. Downregulation of tricellulin causes increased permeability to macromolecules and subsequent microbial translocation contributes to systemic inflammation. Thus, therapeutic strategies to reconstitute the mucosal barrier and control inflammation could assist symptomatic control of CWD.
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Affiliation(s)
- H-J Epple
- Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - J Friebel
- Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - V Moos
- Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - H Troeger
- Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - S M Krug
- Institute of Clinical Physiology/Nutritional Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - K Allers
- Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - K Schinnerling
- Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - A Fromm
- Institute of Clinical Physiology/Nutritional Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - B Siegmund
- Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - M Fromm
- Institute of Clinical Physiology/Nutritional Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - J D Schulzke
- Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.,Institute of Clinical Physiology/Nutritional Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - T Schneider
- Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
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Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections. Clin Microbiol Rev 2017; 30:529-555. [PMID: 28298472 DOI: 10.1128/cmr.00033-16] [Citation(s) in RCA: 97] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Whipple's disease is a rare infectious disease that can be fatal if left untreated. The disease is caused by infection with Tropheryma whipplei, a bacterium that may be more common than was initially assumed. Most patients present with nonspecific symptoms, and as routine cultivation of the bacterium is not feasible, it is difficult to diagnose this infection. On the other hand, due to the generic symptoms, infection with this bacterium is actually quite often in the differential diagnosis. The gold standard for diagnosis used to be periodic acid-Schiff (PAS) staining of duodenal biopsy specimens, but PAS staining has a poor specificity and sensitivity. The development of molecular techniques has resulted in more convenient methods for detecting T. whipplei infections, and this has greatly improved the diagnosis of this often missed infection. In addition, the molecular detection of T. whipplei has resulted in an increase in knowledge about its pathogenicity, and this review gives an overview of the new insights in epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of Tropheryma whipplei infections.
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Seddon O, Hettiarachchi I. Whipple's endocarditis presenting as ulnar artery aneurysm; if you don't look, you won't find. BMJ Case Rep 2017; 2017:bcr-2017-221327. [PMID: 28928251 DOI: 10.1136/bcr-2017-221327] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
A 54-year-old female patient presented to her local district general hospital with a painful, swollen left arm. Imaging revealed an ulnar artery aneurysm. The aetiology was embolic, with an echocardiogram revealing vegetations on the aortic valve. The patient was treated empirically for 6 weeks with amoxicillin and gentamicin for endocarditis. Eight months later, she had an elective aortic valve replacement for symptomatic aortic regurgitation. The valve was culture negative but analysis by 16S rDNA PCR was positive for Tropheryma whipplei In retrospect, the ulnar artery aneurysm and a history of arthralgia were attributed to an underlying diagnosis of Whipple's endocarditis. She continues on antibiotic treatment with resolution of her arthralgia and no clinical signs of infection. Once thought to be rare entity, molecular assays have revolutionised the diagnosis of Whipple's endocarditis, but this case highlights the difficulties and pitfalls in diagnosis.
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Affiliation(s)
- Owen Seddon
- Department of Public Health Wales, University Hospital of Wales, Cardiff, UK
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Chizinga M, Schiliro D, Mullin B, Barrie RL. Mesenteric lymphadenitis as a presenting feature of Whipple's disease. IDCases 2017; 9:50-52. [PMID: 28660130 PMCID: PMC5479967 DOI: 10.1016/j.idcr.2017.06.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 06/10/2017] [Accepted: 06/10/2017] [Indexed: 11/25/2022] Open
Abstract
Detecting Whipple’s disease, a “great imitator”, requires a high index of suspicion so that antimicrobial treatment can be initiated in a timely manner; a missed diagnosis can be fatal. Although an uncommon cause, Whipple’s disease must be considered in adults with mesenteric lymphadenitis. We report the case of a 39-year-old African American man who presented with chronic joint pain, chronic weight loss, and acute onset epigastric pain. Contrast-enhanced computed tomography of the abdomen and pelvis showed extensive mesenteric lymphadenopathy. A diagnosis of Whipple’s disease was made based upon demonstration of PAS-positive macrophages in the mesenteric lymph node and duodenal biopsies. Antimicrobial therapy resulted in weight gain and resolution of abdominal pain and arthralgia at six months follow-up. Whipple’s disease can be fatal without antibacterial therapy and it always needs to be considered in individuals presenting with any combination of abdominal pain, weight loss, and diarrhea in the background of nonspecific arthritis or arthralgia. Whipple’s disease must also be considered in adults presenting with mesenteric lymphadenitis. Review of CT scans may be helpful, as Whipple’s disease characteristically causes low attenuation mesenteric lymphadenopathy.
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Affiliation(s)
- Mwelwa Chizinga
- Yale University, School of Medicine, Yale-Waterbury Residency Program (Department of Internal Medicine), United States
| | - Danise Schiliro
- Yale University, School of Medicine, Yale-Waterbury Residency Program (Department of Internal Medicine), United States
| | - Brett Mullin
- Yale University, School of Medicine, Yale-Waterbury Residency Program (Department of Internal Medicine), United States
| | - Rashida La Barrie
- Yale University, School of Medicine, Yale-Waterbury Residency Program (Department of Internal Medicine), United States
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Chen GJ, Chen CY, Pan SC, Yang CY, Hsueh PR, Chang SC. A rarely considered diagnosis of unknown fever, disseminated lymphadenopathy and chronic peritonitis in Taiwan: Whipple's disease. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2017; 50:401-402. [PMID: 28655572 DOI: 10.1016/j.jmii.2016.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 10/05/2016] [Accepted: 10/18/2016] [Indexed: 11/27/2022]
Affiliation(s)
- Guan-Jhou Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, 100
| | - Chien-Yuan Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, 100
| | - Sung-Ching Pan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, 100.
| | - Ching-Yao Yang
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, 100
| | - Po-Ren Hsueh
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, 100; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan, 100
| | - Shan-Chwen Chang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, 100; College of Medicine, National Taiwan University, Taipei, Taiwan, 100
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50
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Whipple's disease. J Neurol Sci 2017; 377:197-206. [DOI: 10.1016/j.jns.2017.01.048] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Revised: 12/16/2016] [Accepted: 01/15/2017] [Indexed: 11/24/2022]
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