Materiały źródłowe

• #1 Whipple’s disease – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/whipples-disease/symptoms-causes/syc-20378946

  Whipple disease is potentially life-threatening yet usually treatable. Contact your doctor if you experience unusual signs or symptoms, such as unexplained weight loss or joint pain. Your doctor can perform tests to determine the cause of your symptoms. […] Even after the infection is diagnosed and you’re receiving treatment, let your doctor know if your symptoms don’t improve. Sometimes antibiotic therapy isn’t effective because the bacteria are resistant to the particular drug you’re taking. The disease can recur, so it’s important to watch for symptoms that reappear.

• #1 Whipple Disease Workup: Approach Considerations, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/183350-workup

  Biopsy of the appropriate tissue is essential for establishing a diagnosis. These tissues may include small bowel, brain, endocardial, and synovial. Biopsies of tissue samples from the small bowel show expanded villi containing macrophages staining positive with periodic acid-Schiff stain. This finding leads to electron microscopy and then DNA testing for T whipplei. […] A baseline lumbar puncture to obtain cerebrospinal fluid (CSF) analysis for T whipplei should be obtained in newly diagnosed patients, even if the patient has a normal neurologic examination. […] The definitive test for the presence of malabsorption is the 72-hour fecal fat determination. […] No tests are specific for diagnosis except determining the presence of T whipplei DNA through PCR. […] The presence of T whipplei by PCR in patients who are clinically symptomatic is pathognomonic for the disease.

• #1 Whipple disease: Symptoms, causes, and diagnosis

  https://www.medicalnewstoday.com/articles/188228

  Diagnosis of the bacteria that causes Whipple was not possible until relatively recently. […] T. Whipplei was successfully recreated under laboratory conditions in 2000. This led to the development of a simple blood test to diagnose the disease. […] The appearance of Whipple diseases characteristic intestinal lesions also assists in its diagnosis. […] The best way to detect these lesions is to use an upper endoscopy to carry out a biopsy in the small intestine. During the procedure, a thin, flexible tube is passed through the mouth into the esophagus. […] Endoscopic findings of Whipple disease include areas of thickened folds with a granular, yellow-white shaggy covering. […] The polymerase chain reaction (PCR) method has been used to highlight DNA unique to T. Whipplei in various tissue samples of patients with Whipple disease.

• #1 Whipple Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441937/

  Whipple disease is a systemic disorder that not only involves malabsorption from the gastrointestinal tract but also affects other systems like the cardiovascular, central nervous system, joints, and vascular system. […] This activity covers the importance of making an accurate diagnosis of Whipple disease. […] The diagnosis of Whipple disease is made by a biopsy of the intestine and identification of the organism. Current diagnostic criteria require positive results for PAS-positive foamy macrophages in the small bowel biopsy. If it is negative, the diagnosis can also be made by showing positive results in for two of the following: […] It is important to know that T. whippelii quickly becomes negative after the initiation of therapy, which may lead to false negatives since many patients receive antibiotics before undergoing extensive diagnostic testing for this condition.

• #1 Whipple’s disease – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/whipples-disease/diagnosis-treatment/drc-20378950

  The process of diagnosing Whipple disease typically includes the following tests: […] An important step in diagnosing Whipple disease is taking a tissue sample (biopsy), usually from the lining of the small intestine. […] A DNA-based test known as polymerase chain reaction, which is available at some medical centers, can detect Tropheryma whipplei bacteria in biopsy specimens or spinal fluid samples. […] Your doctor may also order blood tests, such as a complete blood count. Blood tests can detect certain conditions associated with Whipple disease, particularly anemia, which is a decline in the number of red blood cells, and low concentrations of albumin, a protein in your blood. […] If your doctor is uncertain about the diagnosis, he or she may refer you to a doctor who specializes in digestive diseases or to another specialist depending on the symptoms you’re having. […] Whipple disease is rare, and the signs and symptoms can indicate other, more common disorders, so it can be hard to diagnose. As a result, it’s often diagnosed in its later stages. However, an early diagnosis reduces the risk of serious health effects associated with not treating the condition.

• #1 Immunohistochemistry in the Diagnosis of Whipple’s Disease | Propath

  https://www.propath.com/diagnostic-services/resources/immunohistochemistry-in-the-diagnosis-of-whipple-s-disease/

  Whipples disease is a rare multisystem infectious disorder, which tends to more commonly affect middle-aged Caucasian men, although current trends show increasing infection rates among females and in older patients. […] Unfortunately, there are currently no specific laboratory abnormalities which can be used to make the diagnosis of Whipples disease. Culture is often not feasible as this is a rather fastidious organism, and in cases in which patients have already started antibiotic therapy, the recovery can be very poor. […] Currently, most cases of Whipples disease are diagnosed on duodenal biopsy. The classically described, endoscopic finding is of thickened mucosal folds and multiple whitish-yellow plaques on the intestinal mucosa. […] Once the Whipples Bacillus had been cultivated, a group of physicians from Marseille France developed a highly specific and sensitive polyclonal rabbit anti-T. whipplei immunohistochemical stain. This immunoperoxidase stain can easily be performed on formalin-fixed paraffin-embedded biopsy tissue in a timely and cost-effective fashion, allowing for a specific diagnosis without waiting for culture, EM, or PCR.

• #1 Orphanet: Whipple disease

  https://www.orpha.net/en/disease/detail/3452

  The gold standard for diagnosis was the histological recognition by an experienced pathologist of free or phagocytised rod-shaped bacteria with periodic-acid-SCHIFF (PAS) staining in macrophages from the duodenal mucosa. […] However, the combination of PAS staining in an intestinal mucosal biopsy plus a validated specific real time polymerase chain reaction (PCR) for TW will raise sensitivity and specificity of the diagnosis. […] An isolated positive PCR in an intestinal mucosal biopsy or in a stool specimen is not sufficient for diagnosis. […] The diagnosis in extraintestinal tissue is always made by PCR. […] Immunohistochemistry can be very useful. […] A positive PCR in pulmonary alveolar lavage or from the oral cavity may mean colonization with TW and not necessarily infection.

• #1 Gastrointestinal Diagnosis of Classical Whipple Disease: Clinical, Endoscopic, and Histopathologic Features in 191 Patients

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4602506/

  For the diagnosis of CWD, the conduction of several tests of which at least 2 should be positive to assure the diagnosis of CWD was suggested. However, the value of gastroscopy, histology, and molecularbiological methods for the diagnosis of CWD has not been systemically evaluated. But despite all advances, histological examination of duodenal biopsies seems the most reliable diagnostic method for the diagnosis of CWD. […] In this observational cohort study, CWD was defined as a systemic chronic infection with T whipplei and diagnosis required 2 independent positive tests. […] Primary diagnosis of CWD was based on histological examination and PAS staining of duodenal biopsies followed by T whipplei-specific PCR or immunohistochemistry (IHC) for confirmation. […] Cases without histological diagnosis from the duodenum required 2 independent PCR assays from sterile specimens targeting T whipplei sequences (eg, 16S rRNA gene amplification followed by sequencing and rpoB gene amplification with specific probe hybridization), positive PAS and T whipplei-specific IHC or PCR from affected organs, or the combination of at least 2 independent tests from 2 different locations.

• #1 Whipple’s Disease: Symptoms, Diagnosis, Treatment & More

  https://www.healthline.com/health/whipples-disease

  Polymerase chain reaction (PCR) is a highly sensitive test that amplifies the DNA of the T. whipplei from your tissue samples. If the bacteria have been in your tissue, there will be DNA evidence. […] This test can be used to confirm the existence of the T. whipplei bacteria in your tissue. […] Your doctor might order a complete blood count. This will help them determine if you have a low count of red blood cells and low amounts of albumin, which are both signs of anemia. […] Anemia is an indication that you might have Whipples disease.

• #1 Whipple disease Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/whipple-disease

  Whipple disease is a rare condition that mainly affects the small intestine. This prevents the small intestine from allowing nutrients to pass into the rest of the body. This is called malabsorption. […] Tests to diagnose Whipple disease may include: Complete blood count (CBC), Polymerase chain reaction (PCR) test to check for the bacteria that cause the disease, Small bowel biopsy, Upper GI endoscopy, Small bowel enteroscopy. […] This disease may also change the results of the following tests: Albumin levels in the blood, Unabsorbed fat in the stools (fecal fat), Intestinal absorption of a type of sugar (d-xylose absorption).

• #1 Whipple Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441937/

  The prompt diagnosis and successful treatment of Whipple disease require an interprofessional approach involving internal medicine, gastroenterology, and infectious disease specialists to work in a coordinated manner with nursing and pharmacy staff. […] The diagnosis of Whipple disease is not straightforward, as the disorder is rare and the symptoms are vague. Many organs can be involved, and hence awareness is vital.

• #1 Whipple’s disease: the great masquerader—a high level of suspicion is the key to diagnosis | BMC Gastroenterology | Full Text

  https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-021-01664-1

  PCR for T. whipplei becomes negative soon after antibiotic therapy has commenced. […] Before stopping antibiotic therapy, upper endoscopy with duodenal biopsy and PCR testing is recommended to ensure complete remission. […] Therefore, annual check-ups are recommended for at least some years after the end of treatment.

• #1 Whipple’s disease of the respiratory system: A case report

  https://www.spandidos-publications.com/10.3892/etm.2024.12421

  It has been suggested that: i) Positive macrophage peroxynitrite-staining in pathologic tissues; ii) anomalies in pathological specimens and a positive T. whipplei polymerase chain reaction (PCR); and iii) a positive T. whipplei PCR in sterile tissues can validate the diagnosis of WD. When one of the three aforementioned criteria are met, the diagnosis is verified. […] mNGS has performed well in identifying rare, novel, difficult-to-detect and co-infectious pathogens directly from clinical samples and has shown great potential in resistance prediction by sequencing antibiotic resistance genes, providing new diagnostic evidence that can be used to guide the treatment of infectious diseases. […] The treatment of WD is mainly antibiotic anti-infection treatment; commonly used drugs include penicillin, tetracycline, streptomycin, ceftriaxone, meropenem, hydroxychloroquine, doxycycline and cotrimoxazole.

• #1 What Is Whipple Disease? Symptoms, Causes, Diagnosis, Treatment, and Prevention

  https://www.everydayhealth.com/whipples-disease/guide/

  To diagnose Whipple disease, your doctor will begin by getting your medical history and conducting a physical examination, which may involve checking for enlarged lymph glands, a heart murmur, or swelling in your body tissues. Your doctor will use your symptoms to guide which diagnostic tests to order. […] A definitive diagnosis of Whipple disease requires a biopsy of an affected organ in which a tissue sample is viewed under a microscope as well as a PCR (polymerase chain reaction) test on the tissue. Depending on the results of your exam and tests, your doctor may refer you to a gastroenterologist, a doctor who specializes in digestive diseases. […] With Whipple disease, the earlier the diagnosis and treatment, the better the prognosis. While Whipple disease can be treated, and most people with the condition will likely have a good outcome, relapse is common. This is why it’s important for someone who has been treated for Whipple disease to be closely monitored and to undergo endoscopy with biopsy and other diagnostic tests a year after their first diagnosis and treatment.

• #1 What Is Whipple Disease? Symptoms, Causes, Diagnosis, Treatment, and Prevention

  https://www.everydayhealth.com/whipples-disease/guide/

  This is why early diagnosis is crucial for Whipple disease. If untreated, Whipple disease will progressively get worse and is most often fatal. […] The use of PCR testing as a tool to diagnose Whipple disease has made it possible for scientists to identify cases of Whipple disease that may have been previously missed.

• #1 Whipple’s Disease, One of Medicine’s Great Imitators: A Case Report – European Medical Journal

  https://www.emjreviews.com/flagship-journal/article/whipples-disease-one-of-medicines-great-imitators-a-case-report/

  The patient had a history of pulmonary hypertension diagnosed 7 years prior and had been treated with macitentan (an endothelin receptor antagonist) and sildenafil. […] Following an admission to the authors centre with severe anaemia and workup for suspected haematological malignancy, duodenal biopsy confirmed the diagnosis of Whipples disease. […] Whipples disease can be regarded as a great imitator, often with non-specific signs and symptoms, which can present a diagnostic challenge. […] The diagnosis was unexpected as there was a strong suspicion of malignancy given the nature of the presentation and investigation findings of mediastinal lymphadenopathy. […] WD can be seen as a great imitator given its multisystem presentation and is often challenging to diagnose. […] The organism has a predilection for small-bowel macrophages; hence, duodenal biopsy with periodic acid-Schiff staining is the gold-standard method for diagnosis. […] This case demonstrates the importance of considering investigating for WD in patients who present with evidence of severe systemic inflammation, anaemia, or malabsorption of chronic duration, even if the cardinal symptoms of arthralgia, fever, or diarrhoea are not reported.

• #2 Whipple Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/183350-overview

  Whipple disease is a systemic disease most likely caused by a gram-positive bacterium, Tropheryma whipplei (formerly T whippelii). […] Because fewer than 1000 reported cases have been described, clinical experience with this disorder is sparse. […] Diagnostic electron microscopy reveals coccobacillary bodies that represent the T whipplei organism. This is diagnostic because a positive polymerase chain reaction (PCR) for T whipplei will be present in the affected tissue. […] The organism has been cultured from affected cerebrospinal fluid (CSF) and vitreous humor of patients with Whipple disease. […] If Whipple disease is untreated, the prognosis is poor, and mortality approaches 100% after 1 year in patients who do not receive the correct diagnosis and therapy. […] Up to 30-40% of patients may relapse, and relapse appears to be more common in patients with central nervous system (CNS) related Whipple disease.

• #2 Whipple Disease – Gastrointestinal Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gastrointestinal-disorders/malabsorption-syndromes/whipple-disease

  Diagnosis is by small-bowel biopsy. […] Whipple disease should be suspected in middle-aged or older White individuals with arthritis and abdominal pain, diarrhea, weight loss, or other symptoms of malabsorption. Such patients should have upper endoscopy with small-bowel biopsy; the intestinal lesions are specific and diagnostic. […] Endoscopic small-bowel biopsy is necessary.

• #2 Whipple’s Disease: Symptoms, Diagnosis, Treatment & More

  https://www.healthline.com/health/whipples-disease

  A diagnosis of Whipples disease is complicated, especially because symptoms are similar to other more common conditions, which range from celiac disease to neurological disorders. […] A doctor will try to rule out these other conditions before diagnosing you with Whipples disease. They may refer you to the following procedures or tests. […] The first sign your doctor will look for to determine if you have Whipples disease is lesions. […] An endoscopy involves the insertion of a small flexible tube down your throat to the small intestine. The tube has a mini camera attached. […] Your doctor will observe the condition of your intestinal walls. Thick walls with creamy, ragged covers are a potential sign of Whipples. […] During an endoscopy, your doctor may remove tissue from your intestinal walls to test for the presence of the T. whipplei bacteria. This procedure is called a biopsy and can confirm an infection.

• #2 Gastrointestinal Diagnosis of Classical Whipple Disease: Clinical, Endoscopic, and Histopathologic Features in 191 Patients

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4602506/

  Classic Whipple disease (CWD) is a systemic infection caused by Tropheryma whipplei. Different diagnostic tools have been developed over the last decades: periodic acid-Schiff (PAS) staining, T whipplei-specific polymerase chain reaction (PCR), and T whipplei-specific immunohistochemistry (IHC). Despite all these advances, CWD is still difficult to diagnose because of a variety of clinical symptoms and possibly a long time span between first unspecific symptoms and the full-blown clinical picture of the disease. […] Thus, despite efforts to diagnose CWD from alternative specimens, gastroscopy with duodenal biopsy and subsequent histological and molecularbiological examination is the most reliable diagnostic tool for CWD. […] Today, the diagnosis of CWD mainly is based on the histological investigation of the small bowel mucosa (ie, positive PAS staining of duodenal biopsies) but atypical cases require a more elaborate diagnostic scheme.

• #2 Whipple’s disease: the great masquerader—a high level of suspicion is the key to diagnosis | BMC Gastroenterology | Full Text

  https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-021-01664-1

  Whipple’s disease is a chronic infectious disease that primarily affects the small intestine, but several organs can simultaneously be involved. […] 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. […] The diagnosis is based on histopathological examination of biopsies from the small bowel and PCR analysis of the 16S rRNA gene for T. whipplei. […] The diagnosis of WD is therefore made histopathologically with the detection of PAS-positive inclusions in histiocytes/macrophages in the lamina propria from small intestinal mucosal biopsies, but also other tissues such as articular fluid, lymph nodes, CSF and, heart valves.

• #2

  https://journals.lww.com/md-journal/fulltext/2015/04030/gastrointestinal_diagnosis_of_classical_whipple.17.aspx

  Particularly, T whipplei-specific IHC is a diagnostic test with very high specificity and sensitivity and allows the identification of T whipplei in PAS-negative specimens and should be considered. […] In conclusion, histology with PAS staining of duodenal biopsies still can be considered as the most reliable diagnostic tool for CWD.

• #2 Rheumatological features of Whipple disease | Scientific Reports

  https://www.nature.com/articles/s41598-021-91671-9

  Whipple disease (WD) is a rare infectious systemic disease. Rheumatologists are at the frontline of WD diagnosis due to the early rheumatological manifestations. An early diagnosis is crucial, as usual anti-rheumatic drugs, especially TNF inhibitors, may worsen the disease course. […] The gold standard for CWD diagnosis is periodic acid-Schiff (PAS)-stained inclusions in foamy macrophages of the lamina propria on small-bowel (SB) biopsy, with possible confirmation by immunohistochemistry using specific anti-TW antibodies. […] Diagnosis was made by PAS staining of SB biopsy samples and by real-time quantitative PCR (qPCR) targeting TW sequences in various samples. […] All diagnoses were based on 1 rheumatologist expert diagnosis, according to clinical, biological, molecular and histological features; and 2 a spectacular response to antibiotics, including the healing of arthritis and the normalization of CRP levels.

• #2 Orphanet: Whipple disease

  https://www.orpha.net/en/disease/detail/3452

  As the majority of patients with infected cerebrospinal fluid (CSF) are asymptomatic at the time of diagnosis, CSF should be examined with PCR in every patient before antibiotic treatment. […] Synovial fluid or synovial tissue should be examined by PCR for TW in patients with rheumatic symptoms as the intestinal mucosa is not always involved. […] Positive PAS staining in cerebral tissues should never be accepted as sole diagnostic tool.

• #2

  https://link.springer.com/article/10.1007/s10620-018-5342-7

  The authors proposed a diagnostic classification of Whipples disease, with three groups: (1) definite classic (small intestinal biopsies positive for both PAS and PCR), (2) probable classic with small intestine positive for PCR or PAS, and (3) localized or extraintestinal with PCR or PAS positivity in a nongastrointestinal tissues and fluids such as plasma and synovial fluid. […] Overall, PCR-based tests were positive more frequently (88% of cases), compared with PAS-positive tissue (73%). […] The authors defined definite classic as PAS-positive macrophages in the intestinal lamina propria and positive PCR, an acknowledgment that PAS staining alone may be nonspecific. […] In actuality, it is much more likely that if a gastroenterologist today encountered PAS-positive small bowel biopsies, the etiology would be mycobacteria avium complex (MAC) rather than WD, especially in an immunocompromised patient.

• #2 An unusual presentation of Whipples disease: adenopathies, polyarthralgia and dermatomyositis-like symptoms

  https://www.explorationpub.com/Journals/em/Article/1001113

  The diagnosis is usually made with endoscopic procedures and biopsies of the affected tissue. However, in 30% of cases the duodenal biopsies can be normal. […] Screening for WD by duodenal biopsies with PAS stain plus PCR test (or immunohistochemistry) and the final diagnosis is made if it meets one of the following criteria: a positive PAS staining in duodenal tissue, two different positive tests of the same tissue or two positive tests of different tissues. […] In this case, biopsy had a key role to achieve the diagnosis, since both soft tissue mass and digestive endoscopy duodenal biopsies were conclusive and diagnostic (two positive tests of different tissues). The patient had a firm diagnosis of WD following PAS-positive macrophages demonstrated on mass biopsy and confirmed with positive PCR.

• #2 Whipple’s disease of the respiratory system: A case report

  https://www.spandidos-publications.com/10.3892/etm.2024.12421

  Whipple’s disease (WD) is a multiplesystem chronic disease caused by Tropheryma whipplei (T. whipplei) infection. […] To the best of our knowledge, there are few reports on WD of the respiratory system caused by T. whipplei, and differential diagnosis is the key to clinical diagnosis. When WD of the respiratory system is difficult to diagnose, metagenomic secondgeneration sequencing (mNGS) may be a better choice, which can achieve early diagnosis and early treatment. […] The imaging manifestations of WD lung involvement are also diverse, with the most common chest imaging manifestations being nodules, interstitial changes and patchy infiltrates, of which nodules are the most commonly observed, with cavitation-like changes, pleural thickening and pleural effusion being less common. […] Laboratory results of WD showed that 90% of patients have combined anemia as well as iron, folate or vitamin B12 deficiencies, and ~1/3 had neutrophilia with decreased lymphocyte counts, hypoalbuminemia and elevated C-reactive protein being more common; if T. whipplei nucleic acid is not detected before treatment, some patients may test negative for T. whipplei nucleic acid after broad-spectrum antibiotic therapy, but this may be a false negative.

• #2 Whipple disease Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/whipple-disease

  Whipple disease is a rare condition that mainly affects the small intestine. This prevents the small intestine from allowing nutrients to pass into the rest of the body. This is called malabsorption. […] Tests to diagnose Whipple disease may include: Complete blood count (CBC), Polymerase chain reaction (PCR) test to check for the bacteria that cause the disease, Small bowel biopsy, Upper GI endoscopy, Small bowel enteroscopy. […] This disease may also change the results of the following tests: Albumin levels in the blood, Unabsorbed fat in the stools (fecal fat), Intestinal absorption of a type of sugar (d-xylose absorption).

• #2 Orphanet: Whipple disease

  https://www.orpha.net/en/disease/detail/3452

  The gold standard for diagnosis was the histological recognition by an experienced pathologist of free or phagocytised rod-shaped bacteria with periodic-acid-SCHIFF (PAS) staining in macrophages from the duodenal mucosa. […] However, the combination of PAS staining in an intestinal mucosal biopsy plus a validated specific real time polymerase chain reaction (PCR) for TW will raise sensitivity and specificity of the diagnosis. […] An isolated positive PCR in an intestinal mucosal biopsy or in a stool specimen is not sufficient for diagnosis. […] The diagnosis in extraintestinal tissue is always made by PCR. […] Immunohistochemistry can be very useful. […] A positive PCR in pulmonary alveolar lavage or from the oral cavity may mean colonization with TW and not necessarily infection.

• #2 The great masquerader: What is Whipple’s disease?

  https://www.gideononline.com/blogs/the-great-masquerader-what-is-whipples-disease/

  Diagnosing Whipple’s disease is not easy since symptoms are similar to many other conditions. The steps to diagnose the infection is through physical examination, a tissue biopsy from the small intestine, and blood tests to help determine if a patient is anemic. […] Since Whipple’s disease is often misdiagnosed, differential diagnosis is important. […] The features of Whipple’s disease may be similar to: Systemic inflammation, Celiac disease, CNS neoplasm, Rheumatoid arthritis, Chronic inflammatory rheumatism, Crohn’s vasculitis, Lymphoma, Sepsis, and more.

• #2 Whipple’s disease differential diagnosis – wikidoc

  https://www.wikidoc.org/index.php/Whipple%27s_disease_differential_diagnosis

  Whipple’s disease must be differentiated from other diseases that cause malabsorption, chronic diarrhea, multisystem involvement, such as celiac disease, cystic fibrosis, inflammatory bowel disease and systemic infections. […] Whipple’s disease must be differentiated from other diseases that cause malabsorption, chronic diarrhea, abdominal pain and multisystem involvement. […] Small intestine biopsy for Tropheryma whipplei testing is the gold standard diagnosis for Whipple’s disease.

• #2 Whipple Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441937/

  Whipple disease is a systemic disorder that not only involves malabsorption from the gastrointestinal tract but also affects other systems like the cardiovascular, central nervous system, joints, and vascular system. […] This activity covers the importance of making an accurate diagnosis of Whipple disease. […] The diagnosis of Whipple disease is made by a biopsy of the intestine and identification of the organism. Current diagnostic criteria require positive results for PAS-positive foamy macrophages in the small bowel biopsy. If it is negative, the diagnosis can also be made by showing positive results in for two of the following: […] It is important to know that T. whippelii quickly becomes negative after the initiation of therapy, which may lead to false negatives since many patients receive antibiotics before undergoing extensive diagnostic testing for this condition.

• #2 The Great Unknown, Whipple’s Disease | Reumatología Clínica

  https://www.reumatologiaclinica.org/en-the-great-unknown-whipple39s-disease-articulo-S2173574317300655

  Whipple’s disease was first described by George Hoyt Whipple in 1907. It is a multisystem infectious disease, produced by Tropheryma whipplei, which was identified for the first time in 1991. The clinical signs include arthralgia, weight loss, diarrhea and abdominal pain, although the clinical manifestations can vary widely. Thus it may take up to 6 years to be diagnosed. […] The diagnosis was Whipple’s disease. Treatment was begun with ceftriaxone and imipenem, and included cefixime during the first 2 months. […] When the diagnosis is uncertain, it is important to rule out this disease in patients with seronegative arthritis and signs associated with the digestive tract prior to initiating biological therapies, since the use of the latter can have a negative effect on the disease course.

• #2 Whipple’s disease: the great masquerader—a high level of suspicion is the key to diagnosis | BMC Gastroenterology | Full Text

  https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-021-01664-1

  PCR for T. whipplei becomes negative soon after antibiotic therapy has commenced. […] Before stopping antibiotic therapy, upper endoscopy with duodenal biopsy and PCR testing is recommended to ensure complete remission. […] Therefore, annual check-ups are recommended for at least some years after the end of treatment.

• #2 Whipple disease: Symptoms, causes, and diagnosis

  https://www.medicalnewstoday.com/articles/188228

  The PCR method can confirm a diagnosis of Whipple disease when the diagnosis cannot be confirmed histologically, or by looking at the tissue through a microscope. PCR is highly sensitive and specific and is useful in suspicious, inconclusive cases. […] In 1997, researchers suggested that a negative PCR result after therapy may predict a low clinical relapse rate. Patients who received treatment but still had a positive PCR result after therapy may be more likely to face a recurrence, they said. […] Up to 50 percent of patients with Whipple disease have central nervous system infection, but not all of them develop clinical or radiologic evidence of the disease. […] In these cases, it may be helpful to carry out a PCR analysis of the cerebrospinal fluid. This may help detect those with cerebral Whipple disease.

• #2 SciELO Brazil – Whipple’s disease: rare disorder and late diagnosis Whipple’s disease: rare disorder and late diagnosis

  https://www.scielo.br/j/rimtsp/a/M6VVJ4WyhLgvZRvRHSQYGwb/?lang=en

  Thus, the antibiotic selection was based on the fact that trimethoprim/sulfamethoxazole is an antibiotic that crosses the blood-brain barrier, with probability of being effective in the CNS involvement. […] Whipple’s disease is an infectious disease with an excellent clinical response within a few weeks after initiation of antibiotic therapy. […] The typical evolution of the treatment is the improvement of the classic symptoms (such as arthralgia and diarrhea) within two weeks after appropriate treatment is initiated. […] Thus a negative PCR may exclude disease relapse (100% negative predictive value), whereas the visualization of intact bacilli by means of electron microscopy may be a sign of active disease. […] In addition, all patients should be monitored for life because relapses may occur after long-term remission with severe involvement of the CNS.

• #2 Research In Geelong Leads To A Worldwide Advance In Diagnosing Whipple’s Disease | Barwon Health Research

  https://research.barwonhealth.org.au/news/research-in-geelong-leads-to-a-worldwide-advance-in-diagnosing-whipples-disease/

  An innovative research project by the Australian Rickettsial Reference Laboratory at Barwon Health has uncovered a new and simpler method to diagnose Whipples Disease without the standard invasive, expensive and painful procedure that patients have previously endured. […] Currently a biopsy of the affected tissue is required whenever Whipples Disease is suspected, which is an invasive, expensive and painful procedure. […] Prof Graves explained, This novel finding means that if someone has symptoms that suggest possible Whipples Disease, a simple blood test may now be used to exclude the disease, instead of a biopsy, and could be used as the first step towards the diagnosis. […] The test is currently available at the ARRL at Barwon Health, and will continue to be validated to ensure that it is indeed a useful method to help exclude or diagnose suspected cases of Whipples Disease.

• #2 Whipple’s disease of the respiratory system: A case report

  https://www.spandidos-publications.com/10.3892/etm.2024.12421

  It has been suggested that: i) Positive macrophage peroxynitrite-staining in pathologic tissues; ii) anomalies in pathological specimens and a positive T. whipplei polymerase chain reaction (PCR); and iii) a positive T. whipplei PCR in sterile tissues can validate the diagnosis of WD. When one of the three aforementioned criteria are met, the diagnosis is verified. […] mNGS has performed well in identifying rare, novel, difficult-to-detect and co-infectious pathogens directly from clinical samples and has shown great potential in resistance prediction by sequencing antibiotic resistance genes, providing new diagnostic evidence that can be used to guide the treatment of infectious diseases. […] The treatment of WD is mainly antibiotic anti-infection treatment; commonly used drugs include penicillin, tetracycline, streptomycin, ceftriaxone, meropenem, hydroxychloroquine, doxycycline and cotrimoxazole.

• #2 Whipple disease | MedLink Neurology

  https://www.medlink.com/articles/whipple-disease

  The diagnosis of secondary Whipple disease of the brain might be confirmed on tissue biopsy, such as of an abdominal lymph node, and in both primary and secondary cases by the application of molecular biological techniques to confirm active infection in the central nervous system. […] The authors believe that patients with Whipple disease of the brain are likely to be overlooked if this diagnostic approach is not used and, further, that this disease may be more common than realized. […] Dolmans and colleagues emphasized the importance of molecular techniques in the diagnosis of Whipple disease, as periodic acid-Schiff (PAS) staining may have poor specificity and sensitivity. […] The PCR on CSF and blood can also be used to monitor the response to treatment. […] Therefore, the diagnosis of Whipple disease of the brain depends on the following: 1. Asking the question: could it be Whipple? 2. Looking for evidence of systemic involvement. 3. PCR and DNA sequencing for T whipplei in CSF and blood.

• #2 The Great Unknown, Whipple’s Disease | Reumatología Clínica

  https://www.reumatologiaclinica.org/en-the-great-unknown-whipple-s-disease-articulo-S2173574317300655

  Whipple’s disease was first described by George Hoyt Whipple in 1907. It is a multisystem infectious disease, produced by Tropheryma whipplei, which was identified for the first time in 1991. […] Thus it may take up to 6 years to be diagnosed. We report 2 cases in which the final diagnosis was Whipple’s disease. […] When the diagnosis is uncertain, it is important to rule out this disease in patients with seronegative arthritis and signs associated with the digestive tract prior to initiating biological therapies, since the use of the latter can have a negative effect on the disease course. […] The improvement of the symptoms with the administration of antibiotics taken for another reason, as well as the lack of improvement or clinical deterioration with immunosuppressive therapy should lead to the suspicion of Whipple’s disease.

• #2 SciELO Brazil – Whipple’s disease: rare disorder and late diagnosis Whipple’s disease: rare disorder and late diagnosis

  https://www.scielo.br/j/rimtsp/a/M6VVJ4WyhLgvZRvRHSQYGwb/?lang=en

  Whipple’s disease is a rare systemic infectious disorder caused by the bacterium Tropheryma whipplei. […] An endoscopic biopsy was suggestive of Whipple’s disease. Diagnosis was confirmed based on a positive serum polymerase chain reaction. […] Whipple’s disease should be considered a differential diagnosis in patients with prolonged constitutional and/or gastrointestinal symptoms. […] Diagnosis is based on the presence of typical signs and symptoms and identification of Tropheryma whipplei in the histopathological examination of duodenal biopsies. […] When there is clinical suspicion without histological findings, the use of molecular biology tests is recommended, especially polymerase chain reaction (PCR). […] The infiltration of the lamina propria of the small intestine by macrophages filled with bacilliform bodies, positive PAS, and diastase-resistant structures, accompanied by dilated lymphatic ducts, are specific and diagnostic aspects of Whipple’s disease.

• #3 Immunohistochemistry in the Diagnosis of Whipple’s Disease | Propath

  https://www.propath.com/diagnostic-services/resources/immunohistochemistry-in-the-diagnosis-of-whipple-s-disease/

  Whipples disease is a rare multisystem infectious disorder, which tends to more commonly affect middle-aged Caucasian men, although current trends show increasing infection rates among females and in older patients. […] Unfortunately, there are currently no specific laboratory abnormalities which can be used to make the diagnosis of Whipples disease. Culture is often not feasible as this is a rather fastidious organism, and in cases in which patients have already started antibiotic therapy, the recovery can be very poor. […] Currently, most cases of Whipples disease are diagnosed on duodenal biopsy. The classically described, endoscopic finding is of thickened mucosal folds and multiple whitish-yellow plaques on the intestinal mucosa. […] Once the Whipples Bacillus had been cultivated, a group of physicians from Marseille France developed a highly specific and sensitive polyclonal rabbit anti-T. whipplei immunohistochemical stain. This immunoperoxidase stain can easily be performed on formalin-fixed paraffin-embedded biopsy tissue in a timely and cost-effective fashion, allowing for a specific diagnosis without waiting for culture, EM, or PCR.

• #3 WHIPB – Overview: Tropheryma whipplei, Molecular Detection, PCR, Blood

  https://www.mayocliniclabs.com/test-catalog/overview/87974

  Aiding in the diagnosis of Whipple disease, especially for identifying inconclusive or suspicious cases, using whole blood specimens. […] Whipple disease is a chronic, systemic illness that, in the majority of cases, involves the small intestine and its lymphatic drainage. The disease primarily affects adults of middle age, with a peak incidence in the third and fourth decades of life. Clinical findings may include malabsorption, chronic diarrhea, abdominal pain, arthralgia, fever, and central nervous system symptoms. […] Test results should be used as an aid in diagnosis and not be considered diagnostic in themselves. The single assay should not be used as the only criteria to form a clinical conclusion, but results should be correlated with patient symptoms and clinical presentation. A negative result does not negate the presence of the organism or active disease.

• #3 Test guide | Eurofins Biomnis

  https://www.eurofins-biomnis.com/en/services/test-guide/page/WHIBM/

  Tropheryma whipplei is a Gram-positive bacillus that cannot be cultivated on standard culture media. […] Whipple’s disease is characterised by positive PAS staining and anti-T. whipplei immunohistochemistry of small intestinal biopsies. […] PCR in saliva and stools is a very good way of detecting Whipple’s disease: a negative PCR in saliva and stools rules out Whipple’s disease, while a positive PCR in saliva and/or stools should lead to anatomopathological examination of a duodenal biopsy to confirm the diagnosis. […] A negative PCR on stool or saliva does not rule out a localised infection. […] PCR must be performed on an appropriate sample: – Endocarditis: PCR on valve biopsy or blood. – Encephalitis or neurological disorders: PCR on cerebrospinal fluid or brain biopsies – Uveitis: PCR on aqueous humour – Adenopathies : PCR on puncture fluid or lymph node biopsies – Arthritis: PCR on joint fluid. […] Methodology: Real-time PCR.

• #3

  https://journals.lww.com/md-journal/fulltext/2015/04030/gastrointestinal_diagnosis_of_classical_whipple.17.aspx

  For the diagnosis of CWD, the conduction of several tests of which at least 2 should be positive to assure the diagnosis of CWD was suggested. […] However, the value of gastroscopy, histology, and molecularbiological methods for the diagnosis of CWD has not been systemically evaluated. […] Thus, here we report on our experience and the value of gastroscopy, macroscopic appearance of the duodenum, and histological and molecularbiological examination of duodenal biopsies for the diagnosis of Whipple disease in CWD patients with typical gastrointestinal involvement and atypical cases with no explicit hint toward Whipple disease based on intestinal symptoms. […] In this observational cohort study, CWD was defined as a systemic chronic infection with T whipplei and diagnosis required 2 independent positive tests.

• #3 Whipple’s disease | Altru Health System

  https://www.altru.org/health-library/conditions/whipples-disease

  The process of diagnosing Whipple disease typically includes the following tests: […] An important step in diagnosing Whipple disease is taking a tissue sample (biopsy), usually from the lining of the small intestine. […] A DNA-based test known as polymerase chain reaction, which is available at some medical centers, can detect Tropheryma whipplei bacteria in biopsy specimens or spinal fluid samples. […] Your doctor may also order blood tests, such as a complete blood count. Blood tests can detect certain conditions associated with Whipple disease, particularly anemia, which is a decline in the number of red blood cells, and low concentrations of albumin, a protein in your blood.

• #3 Whipple’s disease | EBSCO Research Starters

  https://www.ebsco.com/research-starters/health-and-medicine/whipples-disease

  Diagnosis typically involves a combination of medical history, physical exams, and laboratory tests, including biopsies that reveal characteristic inclusions in tissue samples. […] Diagnosis is based on medical history, physical examination, and laboratory evaluations. The initial diagnostic procedure requires an upper endoscopy with a small bowel mucosal biopsy, which shows periodic acid-Schiff-positive inclusions in the macrophages of lamina propria, representing the causative bacteria. T. whipplei can also be detected through specific polymerase chain reaction, immunohistochemistry, and electron microscopy. Whipples disease should be distinguished from malabsorptive and rare disorders such as celiac disease, Crohns disease, lymphoma, acquired immunodeficiency syndrome enteropathy, parasitic disorders, amyloidosis, hypogammaglobulinemia, and abetaproteinemia.

• #3

  https://link.springer.com/article/10.1007/s10620-018-5342-7

  Whipples disease (WD) is a condition of which all gastroenterologists likely learn about in medical school, occasionally investigate for, and very rarely see. […] The first small bowel biopsy diagnosis of Whipples was made in 1958; since then, the causative organism has been identified and cultured, its genome sequenced, and new polymerase chain reaction (PCR)-based bacterial identification and immunohistochemical diagnostic tests developed. […] The criteria for the diagnosis of WD vary, and the possibility of unrecognized cases must be acknowledged; the most recent studies suggest a prevalence of 3/1,000,000 and an incidence of 0.10.6/1,000,000 new cases in Western populations. […] Of the 33 cases identified by Hujoel et al., the diagnosis was made either by PCR analysis of mucosal biopsies in 88% and by PAS-positive staining of intestinal mucosal biopsies in 48%, although not all subjects had both tests performed on all samples.

• #3 Whipple disease | MedLink Neurology

  https://www.medlink.com/articles/whipple-disease

  The diagnosis of secondary Whipple disease of the brain might be confirmed on tissue biopsy, such as of an abdominal lymph node, and in both primary and secondary cases by the application of molecular biological techniques to confirm active infection in the central nervous system. […] The authors believe that patients with Whipple disease of the brain are likely to be overlooked if this diagnostic approach is not used and, further, that this disease may be more common than realized. […] Dolmans and colleagues emphasized the importance of molecular techniques in the diagnosis of Whipple disease, as periodic acid-Schiff (PAS) staining may have poor specificity and sensitivity. […] The PCR on CSF and blood can also be used to monitor the response to treatment. […] Therefore, the diagnosis of Whipple disease of the brain depends on the following: 1. Asking the question: could it be Whipple? 2. Looking for evidence of systemic involvement. 3. PCR and DNA sequencing for T whipplei in CSF and blood.

• #3 Immunohistochemistry in the Diagnosis of Whipple’s Disease | Propath

  https://www.propath.com/diagnostic-services/resources/immunohistochemistry-in-the-diagnosis-of-whipple-s-disease/

  At ProPath we now have this remarkable antibody and have titered it successfully within our laboratory. We are ready to offer this highly sensitive and specific immunohistochemical stain which can be performed on formalin-fixed paraffin-embedded tissue (even from remote cases) often with a turn around time of less than 24 hours.

• #3 Rheumatological features of Whipple disease | Scientific Reports

  https://www.nature.com/articles/s41598-021-91671-9

  By definition, 100% of patients with CWD had positive PAS staining of SB biopsy samples, whereas no patients with NCWD did. Saliva and stool PCR sensitivity were both 100% for CWD and 75% for NCWD. SB biopsy sample PCR sensitivity was 89% for CWD versus 60% for NCWD. […] As the rheumatologist is at the frontline for WD diagnosis, with most patients presenting with NCWD, these findings prompt, in patients with suspected rheumatism, an expansion of the panel of TW PCR tests to samples from specific and nonspecific sites.

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