RARE DISEASE
Whipple disease
Whipple disease
Whipple disease
Synonyms: Intestinal lipodystrophy
Synonyms: Intestinal lipodystrophy
Synonyms: Intestinal lipodystrophy
Drug discovery
1
drug
With orphan designation
Overview
Whipple disease is a rare systemic infection caused by Tropheryma whipplei, a Gram-positive bacterium. It primarily affects the small intestine, causing malabsorption, with early symptoms including migratory arthritis and later progression to chronic diarrhea, weight loss, and abdominal pain. Extraintestinal manifestations (e.g., neurological, cardiac, ocular) may occur. Diagnosis relies on small-bowel biopsy demonstrating periodic acid-Schiff–positive macrophages and PCR confirmation. Treatment involves prolonged antibiotic regimens, typically starting with intravenous ceftriaxone followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) for 1–2 years [1][3][5][13].
Population
Demographics: Predominantly affects middle-aged and elderly Caucasians (male-to-female ratio ~8:1); incidence peaks >65 years [2][5][14].
Risk Factors: Linked to occupational soil exposure (e.g., farming); genetic susceptibility (HLA alleles DRB113/DQB106) [4][10].
Prevalence: ~9.8 cases per 1 million in the U.S., higher in non-Hispanic whites [2][6].
Burden
Mortality: Untreated disease is fatal; CNS involvement increases mortality risk (33% in severe cases) [12][16].
Morbidity: Chronic malnutrition, neurological deficits (e.g., dementia), endocarditis, and arthritis [1][5][6].
Healthcare Utilization: Prolonged hospitalizations (mean 7.4 days) and high treatment costs [6][13].
Therapies
First-line: IV ceftriaxone (2–4 weeks) followed by oral TMP-SMX (1–2 years); alternatives include doxycycline + hydroxychloroquine [3][8][13].
Relapse Prevention: Lifelong doxycycline prophylaxis considered in recurrent cases [3][14].
Monitoring: Regular clinical/PCR surveillance due to relapse risk (up to 40%) [9][13].
Categories: rare gastroenterological diseases, rare genetic diseases, rare immunological diseases, rare infectious diseases, rare neurological diseases
Research Papers
313 drug discovery papers about Whipple disease, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
313 drug discovery papers about Whipple disease, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-13 | Exploring treatment challenges in Whipple's disease: two case reports and review of the literature.
To review the literature concerning the antimicrobial treatment of Whipple's disease and to highlight consequences of diagnostic delay (including inappropriate use of immunosuppressants). This in the context of two illustrative case reports in which the standard treatment regimen of intravenous (IV) ceftriaxone for two weeks followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) was either ineffective or poorly tolerated. A narrative review of the literature on antimicrobial treatment and the interplay of Whipple's disease with immunosuppressants was conducted alongside the clinical case descriptions. A review of the literature identified two principal treatment strategies in use: the standard IV ceftriaxone/TMP-SMX regimen and the doxycycline/hydroxychloroquine oral-only combination. Debate regarding optimal approach is ongoing, however several studies report on the failure or relapse of the standard IV regimen. Diagnostic delay and inappropriate use of immunosuppressants can lead to severe complications. In patients with Whipple's disease who fail or cannot tolerate the standard IV regimen, combination of doxycycline and hydroxychloroquine represents a viable and effective alternative in patients without cerebral involvement. Clinical awareness of this condition and its treatment options is essential for a timely diagnosis and appropriate management.
2026-07-30 | Oral Doxycycline Plus Low-dose Hydroxychloroquine Following Intravenous Ceftriaxone may be Effective for Whipple's Disease in Japan : A Case Report and Literature Review.
A 52-year-old woman presented with weight loss and fever of unknown origin that had persisted for one year. She presented with multiple lymphadenopathies, primarily within the abdominal cavity, but no joint symptoms were observed. A second upper endoscopy revealed diffuse white shaggy villi in the duodenum and the ileum. A definitive diagnosis of Whipple's disease was made based on electron microscopy and polymerase chain reaction (PCR) of the biopsy specimen. Treatment was initiated with doxycycline plus low-dose hydroxychloroquine oral therapy, followed by ceftriaxone intravenous infusion. Ten months after treatment, the patient responded successfully with no side effects.
2026-05-14 | Whipple's Disease Complicated by Severe Pulmonary Hypertension and Right Ventricular Failure.
Whipple's disease is a rare, chronic systemic infection caused by Tropheryma whipplei that commonly presents with gastrointestinal manifestations but may involve multiple extraintestinal organs. Cardiac involvement, particularly culture-negative endocarditis, is described; however, pulmonary complications such as pulmonary hypertension (PH) are uncommon. We report a case of Whipple's disease presenting with severe pre-capillary pulmonary hypertension and right ventricular (RV) failure with reversibility following antimicrobial therapy. A 62-year-old woman with seropositive rheumatoid arthritis on adalimumab, presented with one month of profuse watery diarrhoea, abdominal pain, dizziness and weakness. Imaging revealed diffuse mesenteric and para-aortic lymphadenopathy. Upper endoscopy demonstrated oedematous whitish granular villi in the duodenum, and biopsies showed periodic acid-Schiff-positive, acid-fast bacillus-negative foamy macrophages diagnostic of Whipple's disease. Transthoracic echocardiography revealed RV dilation and dysfunction with pulmonary hypertension, which was confirmed on right heart catheterisation as severe pre-capillary PH with elevated pulmonary vascular resistance and normal wedge pressure. The patient developed RV-predominant cardiogenic shock requiring inotropic and vasopressor support. Following initiation of intravenous ceftriaxone her haemodynamics improved rapidly, with normalisation of cardiac output and marked reduction in pulmonary pressures on repeat catheterisation. Gastrointestinal symptoms resolved, immunosuppressive therapy was discontinued, and she was discharged on prolonged antimicrobial therapy. This case underscores PH as a rare but potentially reversible manifestation of Whipple's disease. Recognition of this entity is critical, as PH-specific vasodilator therapy alone is often ineffective, whereas early targeted antimicrobial treatment can result in rapid and profound clinical and haemodynamic recovery, even in cases presenting with severe RV failure. Whipple's disease should be considered in the differential diagnosis of otherwise unexplained pre-capillary pulmonary hypertension, particularly when accompanied by chronic diarrhoea, arthralgia or systemic features.Unlike idiopathic pulmonary arterial hypertension, Whipple's disease-associated pulmonary hypertension is often driven by a reversible inflammatory process and may present with severe right ventricular failure and haemodynamic compromise.Recognition of this rare entity is critical, as pulmonary hypertension-specific vasodilator therapy alone is frequently insufficient, whereas timely initiation of targeted antimicrobial treatment can result in rapid and profound clinical and haemodynamic recovery.
2026-04-15 | Pulmonary infection caused by Tropheryma whipplei in a child before hematopoietic stem cell transplantation: a case report.
Tropheryma whipplei (TW) triggers Whipple's disease (WD), a rare, chronic multisystemic infection with heterogeneous clinical presentations that can be easily overlooked, particularly Whipple's pneumonia. The advent of metagenomic next-generation sequencing (mNGS) technology applied to bronchoalveolar lavage fluid (BALF) analysis has enabled the identification of an increasing number of patients with acute pneumonia due to TW. Most reports describe symptomatic middle-aged males with cough, while asymptomatic pediatric cases remain exceptionally rare. Without adequate antibiotic therapy, WD is invariably fatal, especially in patients undergoing hematopoietic stem cell transplantation (HSCT). There is no established consensus on the optimal treatment regimen or duration, particularly for pediatric patients. An 8-year-old boy with primary immunodeficiency due to a genetic mutation presented without respiratory symptoms. Yet, high-resolution computed tomography (HRCT) revealed nodular lesions. Initially misdiagnosed as a fungal infection, subsequent mNGS analysis of BALF identified TW as the sole pathogen, leading to a diagnosis of TW-associated pneumonia. Following a combined anti-infective therapy regimen, the patient successfully underwent the myeloablative conditioning (MAC) regimen. Neutrophil and platelet engraftment occurred promptly, with no severe transplant-related complications. This retrospective analysis describes a clinical scenario involving a pediatric patient who exhibited no respiratory symptoms prior to transplantation but showed characteristic nodular lesions on imaging studies, ultimately confirming acute pneumonia caused by TW. Under a combination anti-infection regimen consisting of intravenous ceftriaxone, oral doxycycline, and oral hydroxychloroquine, the child tolerated the MAC regimen well. Neutrophil and platelet engraftment proceeded without delay, and follow-up imaging confirmed complete resolution of the pulmonary lesions.
2026-04-14 | Whipple's disease with multiple serous effusions as the clinical manifestation: a case report and literature review.
Whipple's disease, caused by Tropheryma whipplei, is a rare multisystem infectious disorder with diverse clinical manifestations. Typical symptoms include arthralgia, nausea, vomiting, diarrhoea, and weight loss, while nonspecific features such as fever, anaemia, and lymphadenopathy may also occur. Presentations with multiple serous effusions are exceedingly rare. Diagnosis remains particularly challenging in resource-limited regions because of nonspecific symptoms and limited access to advanced diagnostic techniques. A 34-year-old male presented with fever, vomiting, diarrhoea, mild dry cough, and anorexia. Whole-body computed tomography revealed systemic inflammatory changes that mimicked vasculitis, including multiple serous effusions (pleural, peritoneal, pericardial, and pelvic) and omental thickening. Initial anti-infective therapy failed. Serological tests, pleural fluid analysis, and thoracoscopic pleural biopsy excluded systemic vasculitis and pleural malignancy. Given the diagnostic uncertainty, subsequently 18F-fluorodeoxyglucose positron emission tomography demonstrated diffuse peritoneal thickening accompanied by hypermetabolism, which prompted a biopsy. Definitive diagnosis was achieved via laparoscopic omental biopsy with histopathology, periodic acid-Schiff staining, and polymerase chain reaction. Despite receiving targeted antibiotic therapy for T. whipplei, the patient showed suboptimal clinical improvement. We speculated that the recurrence of the patient's condition was more likely attributable to immune reconstitution inflammatory syndrome. Combination therapy with doxycycline, hydroxychloroquine, and short-term glucocorticoids induced sustained remission. After more than 2 years of targeted anti-T. whipplei therapy, the patient demonstrated a favourable recovery. Multiple serous effusions are uncommon clinical manifestations of Whipple's disease. Early identification of T. whipplei infection and timely targeted therapy are critical for improving patient prognosis.
antibodies
2026-04-12 | Whipple's disease in rheumatology: insights from a Portuguese multicenter series.
Whipple's disease (WD) is a rare chronic infection caused by Tropheryma whipplei, often presenting initially with musculoskeletal (MSK) manifestations that precede gastrointestinal (GI) or systemic symptoms by years. Its protean features and response to immunosuppression make it a diagnostic challenge in rheumatology. We conducted a national, multicenter, retrospective study of WD cases initially assessed for suspected rheumatic disease in Portuguese Rheumatology departments. Diagnosis was confirmed by duodenal histopathology and/or polymerase chain reaction (PCR) detection of T. whipplei. Demographic, clinical, laboratory, and therapeutic data were analyzed descriptively. Seven patients were identified (71.4% male; mean age 59.9 ± 8.2 years). The median diagnostic delay from MSK symptom onset was 4 years. MSK presentations included migratory arthritis/arthralgia (n=4), polymyalgia rheumatica-like symptoms (n=1), asymmetric sacroiliitis (n=1), and rheumatoid arthritis mimics (n=2). GI symptoms occurred in 57.1% and systemic manifestations in 85.7%, all with weight loss. One patient had central nervous system involvement. All showed anemia and elevated inflammatory markers. The median interval between MSK and extra-articular symptoms was 2.6 years. Five patients received immunosuppressive therapy; notably, earlier systemic/GI involvement occurred in those without such exposure, while the only patient treated with biologics did not develop extra-articular symptoms. WD may mimic diverse rheumatic diseases, causing diagnostic delay. A high index of suspicion is warranted in patients with refractory rheumatic symptoms, anemia, and weight loss. The observed variability in systemic progression highlights a potentially complex relationship between immunosuppression and host immune response to T. whipplei, warranting further investigation.
2026-01-03 | When it's not RA: unmasking Whipple's disease in seronegative, difficult-to-treat rheumatoid arthritis.
Whipple's disease (WD) is a rare systemic infection caused by Tropheryma whipplei, often misdiagnosed as seronegative rheumatoid arthritis (RA) due to overlapping clinical features. Delayed diagnosis may lead to multisystem complications, particularly in patients treated with immunosuppressive or biologic therapies. We describe two cases of WD initially misdiagnosed as refractory seronegative rheumatoid arthritis. Both patients were middle-aged men with persistently elevated inflammatory markers and poor responses to multiple biologic treatments. One developed constrictive pericarditis-the first reported to be successfully treated with anakinra-while the other presented with immune reconstitution inflammatory syndrome (IRIS)-related myositis, representing the first reported IRIS myositis in WD. A literature review of 215 cases of WD misdiagnosed as RA or RA-like arthritis (including the two current cases) revealed that 77% were male, and most were seronegative. Among 139 patients with serologic data, 13.6% were RF-positive; of 132 with ACPA results, only 3.7% were positive. Erosive disease was reported in 33%. The median diagnostic delay was 7 years (range: 3-35 years). Gastrointestinal and constitutional symptoms were the most frequent triggers for reevaluation. Non-invasive PCR testing (saliva, stool) has emerged as a sensitive and practical diagnostic approach, particularly in localized or rheumatology-predominant presentations. WD remains underrecognized in rheumatology practice. Early consideration in patients with refractory seronegative arthritis-especially middle-aged men with persistent inflammation-may prevent unnecessary immunosuppression and life-threatening complications. Based on accumulated evidence, we propose a pragmatic, tiered diagnostic algorithm to guide screening and confirmation of WD in rheumatologic settings, emphasizing the integration of noninvasive PCR-based testing to improve diagnostic yield and reduce delays. Key Points • Whipple's disease should be considered in inflammatory arthritis that is refractory to treatment and often seronegative with elevated CRP despite multiple immunosuppressive therapies. • Structured screening strategies may be warranted in rheumatology settings for patients meeting "high-risk criteria". Further studies are needed to assess the utility and cost-effectiveness of such approaches. • Saliva and stool PCR testing demonstrate high negative predictive value in the literature and are proposed as suitable non-invasive tools for initial screening. • Immune reconstitution inflammatory syndrome (IRIS) is a potentially serious complication following antimicrobial therapy for Whipple's disease, especially in patients previously treated with immunosuppressive agents. Early recognition is critical for appropriate management.
2023-10-30 | Use of bevacizumab in a patient with Whipple's disease: managing diagnostic uncertainty.
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.
2018-05-29 | Architectural and functional alterations of the small intestinal mucosa in classical Whipple's disease.
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.
2015-07-09 | Nearly Fatal Case of Whipple's Disease in a Patient Mistakenly on Anti-TNF Therapy.
Whipple's disease is a rare cause of chronic diarrhea and abdominal pain that may be confused with inflammatory bowel disease. We report a Whipple's case misdiagnosed as Crohn's disease in which treatment with anti-tumor necrosis factor (anti-TNF) therapy led to nearly fatal progression. Lymph node tissue obtained during laparotomy for suspected bowel necrosis stained dramatically with periodic acid-Schiff (PAS), and electron microscopy showed a bacterium consistent with Trophyrema whipplei. The patient made a remarkable recovery complicated only by cholestatic hepatitis, which was likely a treatment-associated inflammatory response. This case serves as a reminder that all granulomatous infections should be considered prior to initiation of anti-TNF therapies.
vaccines
2024-10-26 | Pangenome analysis of five representative Tropheryma whipplei strains following multiepitope-based vaccine design via immunoinformatic approaches.
Whipple disease caused by Tropheryma whipplei a gram-positive bacterium is a systemic disorder that impacts not only the gastrointestinal tract but also the vascular system, joints, central nervous system, and cardiovascular system. Due to the lack of an approved vaccine, this study aimed to utilize immunoinformatic approaches to design multiepitope -based vaccine by utilizing the proteomes of five representative T. whipplei strains. The genomes initially comprised a total of 4,844 proteins ranging from 956 to 1012 proteins per strain. We collected 829 nonredundant lists of core proteins, that were shared among all the strains. Following subtractive proteomics, one extracellular protein, WP_033800108.1, a WhiB family transcriptional regulator, was selected for the chimeric-based multiepitope vaccine. Five immunodominant epitopes were retrieved from the WhiB family transcriptional regulator protein, indicating MHC-I and MHC-II with a global population coverage of 70.61%. The strong binding affinity, high solubility, nontoxicity, nonallergenic properties and high antigenicity scores make the selected epitopes more appropriate. Integration of the epitopes into a chimeric vaccine was carried out by applying appropriate adjuvant molecules and linkers, leading to the vaccine construct having enhanced immunogenicity and successfully eliciting both innate and adaptive immune responses. Moreover, the abilityof the vaccine to bind TLR4, a core innate immune receptor, was confirmed. Molecular dynamics simulations have also revealed the promising potential stability of the designed vaccine at 400 ns. In summary, we have designed a potential vaccine construct that has the ability not only to induce targeted immunogenicity for one strain but also for global T. whipplei strains. This study proposes a potential universal vaccine, reducing Whipple's disease risk and laying the groundwork for future research on multi-strain pathogens.
2020-05-18 | In-Silico Proteomic Exploratory Quest: Crafting T-Cell Epitope Vaccine Against Whipple’s Disease
Whipple's disease is one of the rare maladies in terms of spread but very fatal one as it is linked with many disorders (like Gastroenteritis, Endocarditis etc.). Also, current regimens include less effective drugs which require long duration follows up. This exploratory study was conducted to commence the investigation for crafting multi target epitope vaccine against its bacterial pathogen Tropheryma whipplei. The modern bioinformatics tools like VaxiJen, NETMHCII PAN 3.2, ALLERGEN-FP, PATCH-DOCK, TOXIC-PRED, MHCPRED and IEDB were deployed, which makes the study more intensive in analyzing proteome of T. whipplei as these methods are based on robust result generating statistical algorithms ANN, HMM, and ML. This Immuno-Informatics approach leads us in the prediction of two epitopes: VLMVSAFPL and IRYLAALHL interacting with 4 and 6 HLA DRB1 alleles of MHC Class II respectively. VLMVSAFPL epitope is a part of DNA-directed RNA polymerase subunit beta, and IRYLAALHL epitope is a part of membranous protein insertase YidC of this bacterium. Molecular-Docking and Molecular-Simulation analysis yields the perfect interaction based on Atomic contact energy, binding scores along with RMSD values (0 to 1.5 Ǻ) in selection zone. The IEDB (Immune epitope database) population coverage analysis exhibits satisfactory relevance with respect to world population.
2014-09-29 | Tropheryma whipplei
Tropheryma whipplei is the causal agent of Whipple's disease – a systemic chronic infection affecting predominantly Caucasian middle-aged men and involving multiple organ systems. Although T. whipplei is ubiquitously present in the environment, only a small percentage of human individuals are affected, suggesting a role for host weaknesses such as inefficient cell-mediated immune responses in the disease process. Given Whipple's disease can be fatal without prompt antibiotic treatment, rapid and accurate diagnosis plays a vital role in implementing appropriate therapeutic regimens and reducing unnecessary human suffering. Future elucidation on the key elements in the initiation and progression of Whipple's disease will lead to the design of novel countermeasures for the improved control and prevention of T. whipplei infections in susceptible human population groups.
oligonucleotides
2025-12-22 | IRF4 haploinsufficiency in a multiplex family with Whipple's disease.
Tropheryma whipplei is the bacterial agent responsible for Whipple's disease (WD). However, WD occurs only very rarely in Tw-infected individuals. We investigated the cause of disease in two relatives with WD. We studied a son and his mother, both presenting an articular form of WD, at the ages of 38 and 60 years, respectively, these episodes occurring five years apart. Both were otherwise healthy. We performed whole-exome sequencing, characterized a candidate variant biochemically, and performed an immunological analysis on the patients' leukocytes. Both patients were heterozygous for a rare missense variant of the gene encoding the transcription factor IRF4 (p.R25S), for which haploinsufficiency was previously reported to underlie WD in a large multiplex family. This variant was hypomorphic for DNA binding and transcription induction. It did not exert negative dominance. Immunity was otherwise normal in these two patients. Haploinsufficiency for IRF4 can thus underlie WD in T. whipplei-infected individuals from at least two unrelated families.
2025-01-06 | An Incidental Finding of Whipple's Disease Masquerading as Nonspecific, Long-Standing Symptoms.
Whipple's disease is a rare bacterial infection that is often present for years prior to diagnosis. Symptoms are nonspecific in the early stages of presentation and are primarily gastrointestinal in nature. The disease may progress with more systemic symptoms including arthralgia, fever, lymphadenopathy, cardiovascular disease, and central nervous system involvement. This case describes a man with a history of long-standing, nonspecific symptoms who only began to show significant improvement after an incidental finding of Whipple's disease. Due to its rare nature, other instances of the disease have likely gone undiagnosed. A brief review of relevant literature is also included.
2024-07-17 | Supranuclear Vertical Gaze Palsy in Movement Disorders.
Vertical gaze palsy, a neurological impairment affecting the upward and downward movement of the eyes, can be caused by various disorders. Understanding this phenomenon is essential for accurate diagnosis and effective management. This review aims to present a practical overview of vertical gaze palsy, its manifestation in various movement disorders, and the clinical relevance of such impairments. We did a thorough non-systematic search of the literature in PubMed with various keywords such as 'gaze palsy', 'vertical gaze palsy', 'gaze abnormality', and 'eye movement disorder'. Vertical gaze palsy can manifest in various disorders such as Parkinson's disease, atypical Parkinsonian syndromes, Niemann-Pick disease type C, Wilson's disease, Whipple's disease, prion disease, and several others. This comprehensive review elucidates the spectrum of movement disorders linked to vertical gaze palsy, exploring the specific ways it manifests and the complexities in diagnosing the condition. The list of movement disorders causing vertical gaze palsy is extremely wide, encompassing neurodegenerative, metabolic, infectious, autoimmune disorders, and intoxication with certain substances and specific medications. The differential diagnosis consists of various etiologies with heterogeneous presentations that may overlap and mimic each other. We hope that this paper will assist practitioners in managing the complex process of diagnosing a patient with vertical gaze palsy.
other
2023-06-30 | Two consecutive cases of mycotic aneurysms resulting from Whipple disease.
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.
1976-03-15 | The Whipple Riddle
Whipple disease (intestinal lipodystrophy) is a systemic disorder that involves not only the small bowel and lymph nodes but also the liver, spleen, heart, brain, and other organs. Histopathologically, the disease is characterized by the ubiquitous macrophages that give a positive diastase-resistant PAS staining reaction. Although Whipple disease can be treated with antibiotics, its etiology remains one of the unsolved riddles of medicine, that is, perhaps, until now. Clancy and associates1recently reported in theBritish Medical Journalthat a cell wall-deficient form (CWD) of an α-hemolyticStreptococcuswas grown from a prolonged monolayer cell culture of a lymph node taken from a patient with Whipple disease. Serological cross reactivity was shown between the organisms and the material within Whipple disease macrophages. In vitro studies characterized the organisms as a facultative intracellular parasite that caused the accumulation within cells of PASpositive material. Moreover, parenteral injection of this CWD organism into
small molecules
2026-08-13 | Exploring treatment challenges in Whipple's disease: two case reports and review of the literature.
To review the literature concerning the antimicrobial treatment of Whipple's disease and to highlight consequences of diagnostic delay (including inappropriate use of immunosuppressants). This in the context of two illustrative case reports in which the standard treatment regimen of intravenous (IV) ceftriaxone for two weeks followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) was either ineffective or poorly tolerated. A narrative review of the literature on antimicrobial treatment and the interplay of Whipple's disease with immunosuppressants was conducted alongside the clinical case descriptions. A review of the literature identified two principal treatment strategies in use: the standard IV ceftriaxone/TMP-SMX regimen and the doxycycline/hydroxychloroquine oral-only combination. Debate regarding optimal approach is ongoing, however several studies report on the failure or relapse of the standard IV regimen. Diagnostic delay and inappropriate use of immunosuppressants can lead to severe complications. In patients with Whipple's disease who fail or cannot tolerate the standard IV regimen, combination of doxycycline and hydroxychloroquine represents a viable and effective alternative in patients without cerebral involvement. Clinical awareness of this condition and its treatment options is essential for a timely diagnosis and appropriate management.
2026-07-30 | Oral Doxycycline Plus Low-dose Hydroxychloroquine Following Intravenous Ceftriaxone may be Effective for Whipple's Disease in Japan : A Case Report and Literature Review.
A 52-year-old woman presented with weight loss and fever of unknown origin that had persisted for one year. She presented with multiple lymphadenopathies, primarily within the abdominal cavity, but no joint symptoms were observed. A second upper endoscopy revealed diffuse white shaggy villi in the duodenum and the ileum. A definitive diagnosis of Whipple's disease was made based on electron microscopy and polymerase chain reaction (PCR) of the biopsy specimen. Treatment was initiated with doxycycline plus low-dose hydroxychloroquine oral therapy, followed by ceftriaxone intravenous infusion. Ten months after treatment, the patient responded successfully with no side effects.
2026-05-14 | Whipple's Disease Complicated by Severe Pulmonary Hypertension and Right Ventricular Failure.
Whipple's disease is a rare, chronic systemic infection caused by Tropheryma whipplei that commonly presents with gastrointestinal manifestations but may involve multiple extraintestinal organs. Cardiac involvement, particularly culture-negative endocarditis, is described; however, pulmonary complications such as pulmonary hypertension (PH) are uncommon. We report a case of Whipple's disease presenting with severe pre-capillary pulmonary hypertension and right ventricular (RV) failure with reversibility following antimicrobial therapy. A 62-year-old woman with seropositive rheumatoid arthritis on adalimumab, presented with one month of profuse watery diarrhoea, abdominal pain, dizziness and weakness. Imaging revealed diffuse mesenteric and para-aortic lymphadenopathy. Upper endoscopy demonstrated oedematous whitish granular villi in the duodenum, and biopsies showed periodic acid-Schiff-positive, acid-fast bacillus-negative foamy macrophages diagnostic of Whipple's disease. Transthoracic echocardiography revealed RV dilation and dysfunction with pulmonary hypertension, which was confirmed on right heart catheterisation as severe pre-capillary PH with elevated pulmonary vascular resistance and normal wedge pressure. The patient developed RV-predominant cardiogenic shock requiring inotropic and vasopressor support. Following initiation of intravenous ceftriaxone her haemodynamics improved rapidly, with normalisation of cardiac output and marked reduction in pulmonary pressures on repeat catheterisation. Gastrointestinal symptoms resolved, immunosuppressive therapy was discontinued, and she was discharged on prolonged antimicrobial therapy. This case underscores PH as a rare but potentially reversible manifestation of Whipple's disease. Recognition of this entity is critical, as PH-specific vasodilator therapy alone is often ineffective, whereas early targeted antimicrobial treatment can result in rapid and profound clinical and haemodynamic recovery, even in cases presenting with severe RV failure. Whipple's disease should be considered in the differential diagnosis of otherwise unexplained pre-capillary pulmonary hypertension, particularly when accompanied by chronic diarrhoea, arthralgia or systemic features.Unlike idiopathic pulmonary arterial hypertension, Whipple's disease-associated pulmonary hypertension is often driven by a reversible inflammatory process and may present with severe right ventricular failure and haemodynamic compromise.Recognition of this rare entity is critical, as pulmonary hypertension-specific vasodilator therapy alone is frequently insufficient, whereas timely initiation of targeted antimicrobial treatment can result in rapid and profound clinical and haemodynamic recovery.
2026-04-15 | Pulmonary infection caused by Tropheryma whipplei in a child before hematopoietic stem cell transplantation: a case report.
Tropheryma whipplei (TW) triggers Whipple's disease (WD), a rare, chronic multisystemic infection with heterogeneous clinical presentations that can be easily overlooked, particularly Whipple's pneumonia. The advent of metagenomic next-generation sequencing (mNGS) technology applied to bronchoalveolar lavage fluid (BALF) analysis has enabled the identification of an increasing number of patients with acute pneumonia due to TW. Most reports describe symptomatic middle-aged males with cough, while asymptomatic pediatric cases remain exceptionally rare. Without adequate antibiotic therapy, WD is invariably fatal, especially in patients undergoing hematopoietic stem cell transplantation (HSCT). There is no established consensus on the optimal treatment regimen or duration, particularly for pediatric patients. An 8-year-old boy with primary immunodeficiency due to a genetic mutation presented without respiratory symptoms. Yet, high-resolution computed tomography (HRCT) revealed nodular lesions. Initially misdiagnosed as a fungal infection, subsequent mNGS analysis of BALF identified TW as the sole pathogen, leading to a diagnosis of TW-associated pneumonia. Following a combined anti-infective therapy regimen, the patient successfully underwent the myeloablative conditioning (MAC) regimen. Neutrophil and platelet engraftment occurred promptly, with no severe transplant-related complications. This retrospective analysis describes a clinical scenario involving a pediatric patient who exhibited no respiratory symptoms prior to transplantation but showed characteristic nodular lesions on imaging studies, ultimately confirming acute pneumonia caused by TW. Under a combination anti-infection regimen consisting of intravenous ceftriaxone, oral doxycycline, and oral hydroxychloroquine, the child tolerated the MAC regimen well. Neutrophil and platelet engraftment proceeded without delay, and follow-up imaging confirmed complete resolution of the pulmonary lesions.
2026-04-14 | Whipple's disease with multiple serous effusions as the clinical manifestation: a case report and literature review.
Whipple's disease, caused by Tropheryma whipplei, is a rare multisystem infectious disorder with diverse clinical manifestations. Typical symptoms include arthralgia, nausea, vomiting, diarrhoea, and weight loss, while nonspecific features such as fever, anaemia, and lymphadenopathy may also occur. Presentations with multiple serous effusions are exceedingly rare. Diagnosis remains particularly challenging in resource-limited regions because of nonspecific symptoms and limited access to advanced diagnostic techniques. A 34-year-old male presented with fever, vomiting, diarrhoea, mild dry cough, and anorexia. Whole-body computed tomography revealed systemic inflammatory changes that mimicked vasculitis, including multiple serous effusions (pleural, peritoneal, pericardial, and pelvic) and omental thickening. Initial anti-infective therapy failed. Serological tests, pleural fluid analysis, and thoracoscopic pleural biopsy excluded systemic vasculitis and pleural malignancy. Given the diagnostic uncertainty, subsequently 18F-fluorodeoxyglucose positron emission tomography demonstrated diffuse peritoneal thickening accompanied by hypermetabolism, which prompted a biopsy. Definitive diagnosis was achieved via laparoscopic omental biopsy with histopathology, periodic acid-Schiff staining, and polymerase chain reaction. Despite receiving targeted antibiotic therapy for T. whipplei, the patient showed suboptimal clinical improvement. We speculated that the recurrence of the patient's condition was more likely attributable to immune reconstitution inflammatory syndrome. Combination therapy with doxycycline, hydroxychloroquine, and short-term glucocorticoids induced sustained remission. After more than 2 years of targeted anti-T. whipplei therapy, the patient demonstrated a favourable recovery. Multiple serous effusions are uncommon clinical manifestations of Whipple's disease. Early identification of T. whipplei infection and timely targeted therapy are critical for improving patient prognosis.
antibodies
2026-04-12 | Whipple's disease in rheumatology: insights from a Portuguese multicenter series.
Whipple's disease (WD) is a rare chronic infection caused by Tropheryma whipplei, often presenting initially with musculoskeletal (MSK) manifestations that precede gastrointestinal (GI) or systemic symptoms by years. Its protean features and response to immunosuppression make it a diagnostic challenge in rheumatology. We conducted a national, multicenter, retrospective study of WD cases initially assessed for suspected rheumatic disease in Portuguese Rheumatology departments. Diagnosis was confirmed by duodenal histopathology and/or polymerase chain reaction (PCR) detection of T. whipplei. Demographic, clinical, laboratory, and therapeutic data were analyzed descriptively. Seven patients were identified (71.4% male; mean age 59.9 ± 8.2 years). The median diagnostic delay from MSK symptom onset was 4 years. MSK presentations included migratory arthritis/arthralgia (n=4), polymyalgia rheumatica-like symptoms (n=1), asymmetric sacroiliitis (n=1), and rheumatoid arthritis mimics (n=2). GI symptoms occurred in 57.1% and systemic manifestations in 85.7%, all with weight loss. One patient had central nervous system involvement. All showed anemia and elevated inflammatory markers. The median interval between MSK and extra-articular symptoms was 2.6 years. Five patients received immunosuppressive therapy; notably, earlier systemic/GI involvement occurred in those without such exposure, while the only patient treated with biologics did not develop extra-articular symptoms. WD may mimic diverse rheumatic diseases, causing diagnostic delay. A high index of suspicion is warranted in patients with refractory rheumatic symptoms, anemia, and weight loss. The observed variability in systemic progression highlights a potentially complex relationship between immunosuppression and host immune response to T. whipplei, warranting further investigation.
2026-01-03 | When it's not RA: unmasking Whipple's disease in seronegative, difficult-to-treat rheumatoid arthritis.
Whipple's disease (WD) is a rare systemic infection caused by Tropheryma whipplei, often misdiagnosed as seronegative rheumatoid arthritis (RA) due to overlapping clinical features. Delayed diagnosis may lead to multisystem complications, particularly in patients treated with immunosuppressive or biologic therapies. We describe two cases of WD initially misdiagnosed as refractory seronegative rheumatoid arthritis. Both patients were middle-aged men with persistently elevated inflammatory markers and poor responses to multiple biologic treatments. One developed constrictive pericarditis-the first reported to be successfully treated with anakinra-while the other presented with immune reconstitution inflammatory syndrome (IRIS)-related myositis, representing the first reported IRIS myositis in WD. A literature review of 215 cases of WD misdiagnosed as RA or RA-like arthritis (including the two current cases) revealed that 77% were male, and most were seronegative. Among 139 patients with serologic data, 13.6% were RF-positive; of 132 with ACPA results, only 3.7% were positive. Erosive disease was reported in 33%. The median diagnostic delay was 7 years (range: 3-35 years). Gastrointestinal and constitutional symptoms were the most frequent triggers for reevaluation. Non-invasive PCR testing (saliva, stool) has emerged as a sensitive and practical diagnostic approach, particularly in localized or rheumatology-predominant presentations. WD remains underrecognized in rheumatology practice. Early consideration in patients with refractory seronegative arthritis-especially middle-aged men with persistent inflammation-may prevent unnecessary immunosuppression and life-threatening complications. Based on accumulated evidence, we propose a pragmatic, tiered diagnostic algorithm to guide screening and confirmation of WD in rheumatologic settings, emphasizing the integration of noninvasive PCR-based testing to improve diagnostic yield and reduce delays. Key Points • Whipple's disease should be considered in inflammatory arthritis that is refractory to treatment and often seronegative with elevated CRP despite multiple immunosuppressive therapies. • Structured screening strategies may be warranted in rheumatology settings for patients meeting "high-risk criteria". Further studies are needed to assess the utility and cost-effectiveness of such approaches. • Saliva and stool PCR testing demonstrate high negative predictive value in the literature and are proposed as suitable non-invasive tools for initial screening. • Immune reconstitution inflammatory syndrome (IRIS) is a potentially serious complication following antimicrobial therapy for Whipple's disease, especially in patients previously treated with immunosuppressive agents. Early recognition is critical for appropriate management.
2023-10-30 | Use of bevacizumab in a patient with Whipple's disease: managing diagnostic uncertainty.
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.
2018-05-29 | Architectural and functional alterations of the small intestinal mucosa in classical Whipple's disease.
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.
2015-07-09 | Nearly Fatal Case of Whipple's Disease in a Patient Mistakenly on Anti-TNF Therapy.
Whipple's disease is a rare cause of chronic diarrhea and abdominal pain that may be confused with inflammatory bowel disease. We report a Whipple's case misdiagnosed as Crohn's disease in which treatment with anti-tumor necrosis factor (anti-TNF) therapy led to nearly fatal progression. Lymph node tissue obtained during laparotomy for suspected bowel necrosis stained dramatically with periodic acid-Schiff (PAS), and electron microscopy showed a bacterium consistent with Trophyrema whipplei. The patient made a remarkable recovery complicated only by cholestatic hepatitis, which was likely a treatment-associated inflammatory response. This case serves as a reminder that all granulomatous infections should be considered prior to initiation of anti-TNF therapies.
vaccines
2024-10-26 | Pangenome analysis of five representative Tropheryma whipplei strains following multiepitope-based vaccine design via immunoinformatic approaches.
Whipple disease caused by Tropheryma whipplei a gram-positive bacterium is a systemic disorder that impacts not only the gastrointestinal tract but also the vascular system, joints, central nervous system, and cardiovascular system. Due to the lack of an approved vaccine, this study aimed to utilize immunoinformatic approaches to design multiepitope -based vaccine by utilizing the proteomes of five representative T. whipplei strains. The genomes initially comprised a total of 4,844 proteins ranging from 956 to 1012 proteins per strain. We collected 829 nonredundant lists of core proteins, that were shared among all the strains. Following subtractive proteomics, one extracellular protein, WP_033800108.1, a WhiB family transcriptional regulator, was selected for the chimeric-based multiepitope vaccine. Five immunodominant epitopes were retrieved from the WhiB family transcriptional regulator protein, indicating MHC-I and MHC-II with a global population coverage of 70.61%. The strong binding affinity, high solubility, nontoxicity, nonallergenic properties and high antigenicity scores make the selected epitopes more appropriate. Integration of the epitopes into a chimeric vaccine was carried out by applying appropriate adjuvant molecules and linkers, leading to the vaccine construct having enhanced immunogenicity and successfully eliciting both innate and adaptive immune responses. Moreover, the abilityof the vaccine to bind TLR4, a core innate immune receptor, was confirmed. Molecular dynamics simulations have also revealed the promising potential stability of the designed vaccine at 400 ns. In summary, we have designed a potential vaccine construct that has the ability not only to induce targeted immunogenicity for one strain but also for global T. whipplei strains. This study proposes a potential universal vaccine, reducing Whipple's disease risk and laying the groundwork for future research on multi-strain pathogens.
2020-05-18 | In-Silico Proteomic Exploratory Quest: Crafting T-Cell Epitope Vaccine Against Whipple’s Disease
Whipple's disease is one of the rare maladies in terms of spread but very fatal one as it is linked with many disorders (like Gastroenteritis, Endocarditis etc.). Also, current regimens include less effective drugs which require long duration follows up. This exploratory study was conducted to commence the investigation for crafting multi target epitope vaccine against its bacterial pathogen Tropheryma whipplei. The modern bioinformatics tools like VaxiJen, NETMHCII PAN 3.2, ALLERGEN-FP, PATCH-DOCK, TOXIC-PRED, MHCPRED and IEDB were deployed, which makes the study more intensive in analyzing proteome of T. whipplei as these methods are based on robust result generating statistical algorithms ANN, HMM, and ML. This Immuno-Informatics approach leads us in the prediction of two epitopes: VLMVSAFPL and IRYLAALHL interacting with 4 and 6 HLA DRB1 alleles of MHC Class II respectively. VLMVSAFPL epitope is a part of DNA-directed RNA polymerase subunit beta, and IRYLAALHL epitope is a part of membranous protein insertase YidC of this bacterium. Molecular-Docking and Molecular-Simulation analysis yields the perfect interaction based on Atomic contact energy, binding scores along with RMSD values (0 to 1.5 Ǻ) in selection zone. The IEDB (Immune epitope database) population coverage analysis exhibits satisfactory relevance with respect to world population.
2014-09-29 | Tropheryma whipplei
Tropheryma whipplei is the causal agent of Whipple's disease – a systemic chronic infection affecting predominantly Caucasian middle-aged men and involving multiple organ systems. Although T. whipplei is ubiquitously present in the environment, only a small percentage of human individuals are affected, suggesting a role for host weaknesses such as inefficient cell-mediated immune responses in the disease process. Given Whipple's disease can be fatal without prompt antibiotic treatment, rapid and accurate diagnosis plays a vital role in implementing appropriate therapeutic regimens and reducing unnecessary human suffering. Future elucidation on the key elements in the initiation and progression of Whipple's disease will lead to the design of novel countermeasures for the improved control and prevention of T. whipplei infections in susceptible human population groups.
oligonucleotides
2025-12-22 | IRF4 haploinsufficiency in a multiplex family with Whipple's disease.
Tropheryma whipplei is the bacterial agent responsible for Whipple's disease (WD). However, WD occurs only very rarely in Tw-infected individuals. We investigated the cause of disease in two relatives with WD. We studied a son and his mother, both presenting an articular form of WD, at the ages of 38 and 60 years, respectively, these episodes occurring five years apart. Both were otherwise healthy. We performed whole-exome sequencing, characterized a candidate variant biochemically, and performed an immunological analysis on the patients' leukocytes. Both patients were heterozygous for a rare missense variant of the gene encoding the transcription factor IRF4 (p.R25S), for which haploinsufficiency was previously reported to underlie WD in a large multiplex family. This variant was hypomorphic for DNA binding and transcription induction. It did not exert negative dominance. Immunity was otherwise normal in these two patients. Haploinsufficiency for IRF4 can thus underlie WD in T. whipplei-infected individuals from at least two unrelated families.
2025-01-06 | An Incidental Finding of Whipple's Disease Masquerading as Nonspecific, Long-Standing Symptoms.
Whipple's disease is a rare bacterial infection that is often present for years prior to diagnosis. Symptoms are nonspecific in the early stages of presentation and are primarily gastrointestinal in nature. The disease may progress with more systemic symptoms including arthralgia, fever, lymphadenopathy, cardiovascular disease, and central nervous system involvement. This case describes a man with a history of long-standing, nonspecific symptoms who only began to show significant improvement after an incidental finding of Whipple's disease. Due to its rare nature, other instances of the disease have likely gone undiagnosed. A brief review of relevant literature is also included.
2024-07-17 | Supranuclear Vertical Gaze Palsy in Movement Disorders.
Vertical gaze palsy, a neurological impairment affecting the upward and downward movement of the eyes, can be caused by various disorders. Understanding this phenomenon is essential for accurate diagnosis and effective management. This review aims to present a practical overview of vertical gaze palsy, its manifestation in various movement disorders, and the clinical relevance of such impairments. We did a thorough non-systematic search of the literature in PubMed with various keywords such as 'gaze palsy', 'vertical gaze palsy', 'gaze abnormality', and 'eye movement disorder'. Vertical gaze palsy can manifest in various disorders such as Parkinson's disease, atypical Parkinsonian syndromes, Niemann-Pick disease type C, Wilson's disease, Whipple's disease, prion disease, and several others. This comprehensive review elucidates the spectrum of movement disorders linked to vertical gaze palsy, exploring the specific ways it manifests and the complexities in diagnosing the condition. The list of movement disorders causing vertical gaze palsy is extremely wide, encompassing neurodegenerative, metabolic, infectious, autoimmune disorders, and intoxication with certain substances and specific medications. The differential diagnosis consists of various etiologies with heterogeneous presentations that may overlap and mimic each other. We hope that this paper will assist practitioners in managing the complex process of diagnosing a patient with vertical gaze palsy.
other
2023-06-30 | Two consecutive cases of mycotic aneurysms resulting from Whipple disease.
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.
1976-03-15 | The Whipple Riddle
Whipple disease (intestinal lipodystrophy) is a systemic disorder that involves not only the small bowel and lymph nodes but also the liver, spleen, heart, brain, and other organs. Histopathologically, the disease is characterized by the ubiquitous macrophages that give a positive diastase-resistant PAS staining reaction. Although Whipple disease can be treated with antibiotics, its etiology remains one of the unsolved riddles of medicine, that is, perhaps, until now. Clancy and associates1recently reported in theBritish Medical Journalthat a cell wall-deficient form (CWD) of an α-hemolyticStreptococcuswas grown from a prolonged monolayer cell culture of a lymph node taken from a patient with Whipple disease. Serological cross reactivity was shown between the organisms and the material within Whipple disease macrophages. In vitro studies characterized the organisms as a facultative intracellular parasite that caused the accumulation within cells of PASpositive material. Moreover, parenteral injection of this CWD organism into
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Drug Discovery Landscape
1 orphan drug designation for Whipple disease.
1 orphan drug designation for Whipple disease.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
emodepside | — | FDA | 2025-04-17 | — | Bayer HealthCare Pharmaceuticals Inc. |
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