Whipple's Disease Research Articles

Whipple's disease: the great masquerader\u2014a high level of suspicion is the key to diagnosis

BackgroundWhipple'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 presentationWe 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.ConclusionsThis report aims to raise awareness of a very rare disease that presents with a combination of symptoms mimicking other and significantly more common diseases.

The Effect of Tocilizumab on Inflammatory Markers in Patients Hospitalized with Serious Infections. Case Series and Review of Literature.

Background: The human anti-IL-6 receptor antibody tocilizumab (TCZ) has been approved for the treatment of rheumatoid arthritis (RA) and giant cell arteritis (GCA). It is observed that CRP levels drop quickly after starting TCZ treatment. This may lead to misinterpretation of laboratory results when accessing the patient with infectious disease while on TCZ. We conducted this study to report cases treated with tocilizumab who developed serious infections with special reference to levels of CRP and to review the literature on the effect of tocilizumab on acute phase response (APR) during infections. Methods: The files of RA and GCA patients hospitalized in the Tel Aviv medical center between 2009–2019 were reviewed. Cases of patients with RA and GCA treated with tocilizumab who were hospitalized due to severe infections were reviewed with special emphasis on the duration of treatment, type of infection, and APR. Results: We identified nine admissions. Seven patients were treated with tocilizumab for RA, two for GCA. The diagnosis was pneumonia in three cases, osteomyelitis in one, cellulitis in one, endocarditis due to Whipple disease in one, abscess of cervix uteri in one, meningitis in one, and perforated diverticulitis in one. The mean CRP levels on admission were 4.75 mg/L (normal range, up to 5 mg/L). All cases were diagnosed correctly on admission. Conclusions: CRP levels may not correctly reflect the severity of infectious diseases during tocilizumab treatment. Increased awareness of the masking effect of tocilizumab on the APR during infection is needed in order to avoid a delay in the diagnosis.

HPLC methods for choloroquine determination in biological samples and pharmaceutical products.

Review and assess pharmaceutical and clinical characteristics of chloroquine including high-performance liquid chromatography (HPLC)-based methods used to quantify the drug in pharmaceutical products and biological samples. A literature review was undertaken on the PubMed, Science Direct, and Scielo databases using the following keywords related to the investigated subject: 'chloroquine', 'analytical methods', and 'HPLC'. For more than seven decades, chloroquine has been used to treat malaria and some autoimmune diseases, such as lupus erythematosus and rheumatoid arthritis. There is growing interest in chloroquine as a therapeutic alternative in the treatment of HIV, Q fever, Whipple's disease, fungal, Zika, Chikungunya infections, Sjogren's syndrome, porphyria, chronic ulcerative stomatitis, polymorphic light eruption, and different types of cancer. HPLC coupled to UV detectors is the most employed method to quantify chloroquine in pharmaceutical products and biological samples. The main chromatographic conditions used to identify and quantify chloroquine from tablets and injections, degradation products, and metabolites are presented and discussed. Research findings reported in this article may facilitate the repositioning, quality control, and biological monitoring of chloroquine in modern pharmaceutical dosage forms and treatments.

Whipple's disease.

Whipple's disease.

Multifocal secondary amyloidosis and Whipple disease: a case report

Background: Whipple disease (WD) is an exceedingly rare disease. Despite its rarity, there has been a longstanding allure with this disease. The classic form manifests with arthralgia, weight loss, abdominal pain, and diarrhea. However, the infection may involve other organs causing a great diversity of symptoms. Case Presentation: We report a case of a patient presenting to the emergency room with weight loss, abdominal pain and diarrhea. Duodenal biopsies revealed periodic acid Schiff-positive macrophages and Tropheryma whipplei was detected on a cervical lymph node. Diagnosis of WD was established. The patient also had multifocal secondary amyloidosis. We started the patient on a standardized antibiotic regimen for 1 year. Clinical improvement was seen early during the treatment. Conclusion: This case is an example of the protean nature of WD. To the authors’ knowledge, this is the first case report on WD with multifocal secondary amyloidosis affecting several digestive organs.

710. Non-invasive Diagnosis of Whipple Endocarditis Using Next-Generation Sequencing for Microbial Cell-free DNA in Plasma

Background Tropheryma whipplei is a gram-positive bacillus that causes Whipple’s disease, a protean multisystemic syndrome classically characterized by arthralgias, chronic diarrhea, malabsorption, and weight loss. T. whipplei infection has a wide spectrum of clinical manifestations including pleuropulmonary disease, skin hyperpigmentation and cardiac infection. Endocarditis has been diagnosed in a small number of patients and may represent an atypical presentation of T. whipplei infection. Diagnosis can be challenging and has typically been accomplished with histopathology on resected valvular tissue or GI tract biopsy. Next-generation sequencing (NGS) of microbial cell-free DNA (mcfDNA) in plasma offers a rapid, non-invasive means of diagnosis of this rare cause of culture-negative endocarditis and challenging clinical entity.MethodsMcfDNA analysis was performed in a patient with culture negative endocarditis. McDNA was extracted from plasma and NGS was performed by Karius, Inc. (Redwood City, California). Human sequences were removed and remaining sequences were aligned to a curated database of over 1,400 pathogens. Organisms present above a predefined statistical significance threshold were reported and quantified in DNA molecules per microliter (MPM). Chart review was performed for clinical correlation.ResultsA 64 year-old male with history of valve replacement presented with significant deterioration of the mitral valve. An exhaustive infectious workup including blood cultures was negative. Karius testing detected T. whipplei at 766 MPM within two days of sample receipt. The normal range for T. whipplei is 0 MPM based on a cohort of 684 healthy individuals. Blood PCR for T. whipplei was confirmatory.Table 1: Clinical Parameters of Case ConclusionNGS for mcfDNA in plasma offers a rapid, non-invasive method for identifying T. whipplei and, to our knowledge, the first diagnosis of Whipple disease using NGS of plasma mcfDNA.DisclosuresChristiaan R. de Vries, MD, PhD, Karius (Consultant, Independent Contractor)Stanford University (Employee) Ann Macintyre, DO, Karius (Employee)

Tropheryma whipplei: an unusual cause of the accumulation in positron emission tomography

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

Rational for meta-analysis and randomized treatment: the COVID-19 example

Rational for meta-analysis and randomized treatment: the COVID-19 example

S2790 Mycobacterium avium Complex Enteritis Mimicking Whipple's Disease in a Patient With Advanced AIDS

INTRODUCTION: Acquired Immunodeficiency Syndrome (AIDS) patients are susceptible to numerous opportunistic infections, including Mycobacterium avium complex (MAC). MAC infection usually presents as a disseminated disease with fever, nights sweats, diarrhea as well as lymphadenopathy which can be the presenting symptoms of various other diseases, such as Whipple's disease (WD). We present a case of MAC infection initially diagnosed as Whipple’s Disease in a patient resulting in delay in MAC treatment. CASE DESCRIPTION/METHODS: A 37 year old homosexual male presented with a one year history of progressively worsening abdominal pain accompanied by intermittent non bloody, non bilious vomiting, chronic diarrhea, fatigue and 60 lbs unintentional weight loss over several months. He underwent an elective EGD where abnormal appearing duodenal mucosa was seen with duodenal biopsy showing villous atrophy and period acid Schiff (PAS) stain positive macrophages, while abdominal imaging showed retroperitoneal and mesenteric lymphadenopathy (Image 1). Despite initiation on treatment for WD, he continued to clinically decline. Given his high risk social history and significant constitutional symptoms, HIV infection was considered as an alternative diagnosis. He was found to have HIV/AIDS (viral load of >100,000 copies/mL and CD4 count 9/μL) and blood cultures positive for MAC. On further review, his duodenal biopsies were positive for acid fast bacillus (AFB) confirming MAC enteritis. A CT chest revealed a 4.6 cm right lung mass with biopsy positive for AFB stain(Image 2). Patient was then initiated on appropriate treatment for disseminated MAC infection (azithromycin, rifabutin, ethambutol) as well as antiretroviral therapy resulting in clinical improvement. DISCUSSION: The differential diagnoses for villous atrophy include malabsorptive diseases, infections, malignancy, pancreatic insufficiency but other less common infectious entities such as MAC should be considered in the right clinical settings. MAC infections have become increasingly uncommon since the advent of highly effective antiretroviral therapy, control of HIV infection and appropriate antimicrobial prophylaxis. Due to the relative rarity, diagnosis and treatment may be delayed, especially when presenting symptoms are non-specific, which can result in morbidity and mortality.Figure 1.: View of duodenum during endoscopy which shows white color plaques in the second and third part of the duodenum (A). H&E stain (20X) of duodenal biopsy shows mildly blunted villi due to expansion of lamina propria by foamy macrophages in a patchy fashion (B). No fat vacuoles or increased intraepithelial lymphocytes seen. AFB stain (20X) of duodenal biopsy shows many positive bacillary forms confirming the presence of Mycobacterium avium intracellular complex (C). Abdominal lymphadenopathy noted on computed tomography of abdomen (red circle) (D).Figure 2.: Computed Tomography of Lung mass (red circle) (A). H&E stain (40X) lung mass biopsy shows florid lympho-histiocytic reaction (B) while CD68 stain (40X) shows many macrophages (C), and AFB stain (40X) confirms presence of mycobacterial organisms (D).

S2804 Brown Bowel Syndrome as a Result of Chronic Bowel Obstruction

INTRODUCTION: Brown bowel syndrome (BBS) is a rare condition characterized by deposition of lipofuscin in the smooth muscle cells of the muscularis propria and muscularis mucosa. This condition has been attributed to various chronic malabsorptive conditions that result in deficiency in vitamin E. Vitamin E normally acts as an antioxidant which helps stabilize the mitochondrial membranes. Lack of vitamin E leads to mitochondrial degeneration with release of lipofuscin that accumulates in the smooth muscle cells. This results in a form of myopathy with uncoordinated bowel function. There have been case reports of BBS attributed to celiac disease, IBD, chronic pancreatitis, Whipple's disease and malignancy. We present an interested case of BBS attributed to chronic bowel obstruction. CASE DESCRIPTION/METHODS: 56 yo Caucasian female who had been having chronic abdominal pain associated with a 20lb weight loss. CT scan showed a markedly dilated RLQ small bowel with air-fluid levels concerning for ileus vs partial small bowel obstruction (SBO). She subsequently under a small bowel follow through which showed a relatively high-grade partial SBO. She had an EGD and colonoscopy, both of which were unremarkable. Her medical history is notable for a congenital SBO that was repaired at birth as well as a history of ectopic pregnancy requiring removal. She eventually underwent ex-lap with extensive lysis of adhesions. There was one majorly dilated area of the small intestine measuring over 12 cm in diameter. This area was resected and histology was notable for extensive deposition of light brown granular, lipofuscin-like pigment within the smooth muscle cells of the muscularis propria. These pigments were highlighted by special stains for PAS and PAS-D. This was consistent with ceroidosis (BBS). Review of the bowel histology was unremarkable for celiac disease or Whipple’s disease. The patient also had no findings concerning for chronic pancreatitis. DISCUSSION: We describe a case of BBS that was attributed to malabsorption from a chronic partial SBO. Her bowel obstruction was believed to be caused by adhesions related to prior surgeries. While bowel dilation and atresia can occur from the myopathy associated with BBS, this patient's pathologic findings were actually attributed to a series of events that originated from her having chronic SBO. This case illustrates the impact of bowel obstructions on adequate absorption of nutrients as well as the consequences of chronic malabsorption, including the development of BBS.Figure 1.: Gross Pathology.Figure 2.: HE Stain.Figure 3.: PAS-D Stain showing lipofuscin deposition.

S2793 Sprue-Like Enteropathy Secondary to Lisinopril Use

INTRODUCTION: Diarrhea is reported as a rare adverse effect of angiotensin-converting enzyme (ACE) inhibitors, but there are few reports of sprue-like enteropathy from its use. In contrast, this has been well described with the angiotensin II receptor blocker (ARB), olmesartan. We describe a case of drug-induced enteropathy secondary to lisinopril. CASE DESCRIPTION/METHODS: A 76-year-old man with hypertension and coronary artery disease presented with one year of diarrhea, abdominal discomfort and a 35-pound unintentional weight loss. His first EGD yielded duodenal biopsies with villous blunting and increased IELs. Tissue transglutaminase antibody (tTg, IgA) was 22 U/mL (negative is <20 U/mL), and the patient was advised to follow a gluten free diet. He did so for 9 months without symptom improvement and so returned to a gluten-rich diet. Despite a gluten-rich diet for 4 months, the patient’s repeat tTg, IgA and deamidated gliadin peptide (DGP) IgA and IgG were negative. In addition, he was negative for HLA-DQ2 and HLA-DQ8 genotypes, making celiac disease unlikely. All immunoglobulin levels were normal. Then on repeat EGD and colonoscopy, duodenal and terminal ileal biopsies showed villous blunting and dense infiltrate of IELs. Biopsies were negative for Congo red and periodic acid-Schiff diastase stains, sent to evaluate for amyloid and Whipple's disease. Video capsule endoscopy identified diffuse small bowel villous flattening, though no erosions, ulcerations or strictures were seen. Stool testing was negative for giardia and fecal calprotectin. Glucose hydrogen breath test was negative. The patient had a normal fasting gastrin level, and his ANA and anti-enterocyte antibody were negative. We then considered lisinopril-induced enteropathy, as the patient had been on lisinopril since symptom onset. After lisinopril was stopped, the patient's symptoms resolved within 3 months. He gained back weight and no longer had abdominal discomfort. Repeat endoscopy is planned, but was postponed during the COVID-19 pandemic. DISCUSSION: It is important to maintain a high degree of suspicion for drug-induced enteropathy. One study from Italy and Germany examined patients on olmesartan, ARBs and ACE inhibitors and found rare instances of ACE inhibitors leading to intestinal malabsorption (Malfertheiner et al. Pharmacoepidemiol Drug Saf. 2018, 581-586). Olmesartan is classically the medication associated with sprue-like enteropathy, and our case highlights that lisinopril should be considered as well.

Whipple disease: a 15-year retrospective study on 36 patients with positive polymerase chain reaction for Tropheryma whipplei

Our institution has performed microbiological diagnosis of Tropheryma whipplei since 2001, initially with a PCR targeting 16S rRNA before the development of a quantitative PCR in 2012. Here we report the clinical characteristics of a cohort of patients suffering from Whipple disease (WD) and evaluate the impact of these molecular techniques. Patients with a positive PCR for T. whipplei between 2001 and 2016 were retrospectively collected from microbiological databases. Two infectious diseases specialists reviewed their medical records and classified them as definite WD, probable WD or carriage of T. whipplei without disease. A total of 1153 samples were tested for T. whipplei; 76 samples taken from 36 patients were positive. Fifteen were considered as presenting a definite WD, seven as a probable WD and 14 as carriers. Median age was 56.4 years (extremes, 6.6–76.1). Median time from symptoms to diagnosis was 3 years (2.5 months to 13.3 years). About 60% were immunosuppressed. The most frequent clinical presentations were joint pain (16/22), weight loss (15/22) and/or digestive tract disorder (15/22); 41% had neurological manifestations, 32% pulmonary involvement and 32% lymphadenopathies. Bacterial load in faeces or saliva were 88 425 copies/mL (IQR 6175-292 725) in definite and probable WD and 311 copies/mL (IQR 253–2090) in carriers, respectively. We observed a 90% PPV above 32 200 copies/mL in faeces. WD is a chronic multisystemic disease with frequent pulmonary involvement. Underlying immunodeficiency is commonly observed leading to more complex clinical presentation. Positive T. whipplei PCR in both stool and saliva has a high positive predictive value. Moreover, patients with WD present higher bacterial load in faeces with a threshold of >32 200 copies/mL predicting ongoing infection.

Whippleova choroba – dvě kazuistiky

Whippleova choroba – dvě kazuistiky

Whippleova choroba – dvě kazuistiky

Whippleova choroba – dvě kazuistiky

A Case of Whipple's Disease Related Infectious Endocarditis

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

Long-term morbidity and mortality in Whipple's disease: a single-centerexperience over 20years.

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 of35 patients with WD (9F, 54±11years) were followed-up for a median of 104months. Nine patients developed ten complications; three patients died. A total of31 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.

Whipple disease diagnosed by enteroscopy: first case report in Colombia of an underdiagnosed disease and literature review

BackgroundWhipple’s disease is a rare systemic disease caused by a gram-positive bacillus called Tropheryma whipplei. First described in 1907 as an intestinal lipodystrophy with histological finding of vacuoles in the macrophages of the intestinal mucous. Usually the symptoms are localized according to the compromised organ. The differential diagnosis is wide. It can be fatal without proper treatment. Recurrence can occur in up to 33% of the cases and usually compromises the neurological system.Case presentationThis article reports the case of a 46-year-old female patient with a history of a 6-month hypochromic microcytic anemia of unknown cause. She consulted for a 6-months oppressive abdominal pain located in the mesogastrium as well as abdominal distention associated with nausea and liquid stools; in addition, she had an 8-month small and medium joint pain, without edema or erythema. Physical examination without relevant findings. Multiple esophagogastroduodenoscopies with normal gastric and duodenal biopsies findings and a normal colonoscopy were performed. Endoscope capsule showed red spots in the duodenum and ulcerations in the jejunum and proximal ileum covered by fibrin; histological report showed macrophages with positive periodic acid-schiff reaction staining (PAS staining), disgnosing Whipple’s disease. Antibiotics were initiated. The patient is currently in the second phase of treatment without gastrointestinal and joint symptoms.ConclusionThis is the first case reported in Colombia. It is a rare entity and difficult to diagnose reason why it is important to continue with clinical investigations to give more clarity about the onset and appropriate diagnose to avoid the delay in treatment of this entity.

THU0591 CENTRAL NERVOUS SYSTEM VASCULITIS IN WHIPPLE DISEASE: A CASE REPORT

Background:Whipple disease (WD) is a rare systemic infection with possible involvement of the central nervous system (CNS). The neurological manifestations of the disease are various and can mimic any neurologic condition.Objectives:To describe the severe neurological complications occurred in a patient with WD misdiagnosed as a chronic inflammatory immune-mediated disorder.Methods:Case reportResults:A 46-year-old woman developed acute right-sided hemiparesis and dysarthria. She had a 10-year history of ill-defined rheumatic condition (defined as seronegative rheumatoid arthritis, spondyloarthritis, and adult onset Still’s disease) presenting with polyarthritis, episodic fever &gt; 38°C and rash of unclear etiology poorly responsive to different immunotherapies including methotrexate, anti-IL6 and anti-IL1 inhibitors. Brain MRI demonstrated multiple anterior circulation infarctions and stenosis of the bilateral M1 segments of the middle cerebral artery on MR angiography. Black blood sequences revealed contrast enhancement of the vessel walls consistent with vasculitis (Figure 1). Cerebrospinal fluid (CSF) analysis was unrevealing, including PCR for viruses and bacteria. A working diagnosis of primary CNS vasculitis and progressive neurologic deterioration with abnormal behavior and altered mental status prompted the initiation of intravenous (IV) methylprednisolone followed by cyclophosphamide without significant improvement. Re-evaluation of the long-standing history of joint symptoms unresponsive to immunotherapy, along with recurrent fevers and chronic diarrhea raised the suspicion of unrecognized Whipple’s disease. PCR for Tropheryma Whippleii was positive in stool, urine, blood and CSF, and duodenal mucosal biopsies confirmed the diagnosis. A combination of ceftriaxone, doxycycline, and hydroxychloroquine was initiated. Three days later the patient developed periocular burning pain and cutaneous vesicles consistent with shingles. Varicella-zoster virus DNA was detected in CSF and IV acyclovir was started. At 3 months follow-up neurologic examination was unremarkable except for a slightly fatuous behavior.Conclusion:Recognition of rare manifestations of WD is important to avoid diagnostic delay and inappropriate, potentially harmful treatments.Disclosure of Interests:Alessandro Giollo: None declared, Cecilia Zivelonghi: None declared, Davide Cardellini: None declared, Gian Marco Schiavi: None declared, Gaetano Vattemi: None declared, Ombretta Viapiana: None declared, Maurizio Rossini Speakers bureau: AbbVie, Abiogen, Amgen, BMS, Eli-Lilly, Novartis, Pfizer, Sanofi, Sandoz and UCB

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.

Enfermedad de Whipple

Whipple's disease (WD) is a multisystemic chronic disease caused by Tropheryma whipplei, a bacterium taxonomically closely related to the group of Actinomyces. Pathogen is transmitted by the oral-faecal route. Bacteria reaches the small intestine, spreads to bloodstream and is disseminated to the different organs and systems. There are different entities of infection: asymptomatic carrier, self-limited WD, classical-digestive WD, localized WD, and others. In classical WD (76% of the cases) the digestive system is usually affected. Diarrhea, abdominal pain and weight loss are the major symptoms, frequently preceded or accompanied by polyarthritis and fever (25-40%). Central nervous system (CNS) involvement is a delayed and advanced form and can manifest as supranuclear ophthalmoplegia or as choreiform movements, hypersomnia, ataxia, seizures or extrapyramidalism, among others. Induction treatment consists in ceftriaxone (2g per day intravenously), along 2 weeks (extendable up to 4 weeks if CNS or cardiac valves impaired). Doxycycline 100 mg/12hours plus hydroxychloroquine 200 mg/8hours at least for 12 months are used in maintenance treatment.