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Whipple's disease - Diagnosis
Medical expert of the article
Last reviewed: 06.07.2025
Whipple's disease may be suspected based on the history, clinical manifestations, laboratory, endoscopic and radiological data. The cardinal clinical manifestations of the disease are diarrhea, mesogastric pain, increasing weakness, weight loss, polyarthritis (or arthralgia) and lymphadenopathy.
Laboratory data
- Complete blood count: anemia (usually hypochromic due to iron deficiency, less often hyperchromic, macrocytic, caused by impaired absorption of vitamin B12 ); hyperleukocytosis; sometimes eosinophilia, more often thrombocytosis; increased ESR.
- General urine analysis: in severe cases of malabsorption syndrome, slight proteinuria is possible.
- Coprological analysis: polyfecalia, steatorrhea; possible appearance of undigested muscle fibers, sometimes occult blood is detected.
- Biochemical blood test: decreased levels of total protein, albumin, calcium, iron, potassium, sodium, prothrombin, glucose (not in all patients), increased levels of bilirubin, aminotransferases.
- The absorption function of the small intestine is reduced.
Instrumental data
- X-ray examination. When examining the small intestine, dilation of the small intestinal loops is determined, its contours are coarsely serrated, and marginal filling defects may be disrupted with enlarged mesenteric lymph nodes. The folds of the small intestinal mucosa are dilated, it is unevenly thickened (a “granularity” pattern) due to infiltration. The elasticity of the small intestinal wall is significantly reduced. With an increase in retroperitoneal lymph nodes, dilation of the duodenal flexure is possible.
- Ultrasound of abdominal organs. May reveal enlargement of mesenteric, parapancreatic, retroperitoneal lymph nodes.
- Lymphography. Reveals non-specific inflammatory changes in the retroperitoneal lymph nodes, as well as signs of subdiaphragmatic lymph stasis.
- Biopsy of the small intestinal mucosa. Currently, biopsy of the small intestinal mucosa is the only method that allows to verify the diagnosis of Whipple's disease. Biopsy is performed during endoscopy of the small intestine in the area of the duodenal junction. This area of the small intestine is affected in all patients, both in the early and late stages of the disease. Histological evidence of Whipple's disease is the following signs detected in biopsy specimens:
- infiltration of the proper layer of the small intestinal mucosa by large PAS-positive macrophages ("foamy" macrophages); these granules in macrophages are detected using brilliant fuchsin staining. Macrophages can also be detected in biopsies of other organs - lymph nodes, spleen, liver;
- detection in biopsies using electron microscopy of bacilli-like Whipple bodies, which are rod-shaped cells (1-2 µm x 0.2 µm) with a three-layer membrane. They are determined in the intercellular space and are also present inside macrophages. PAS-positive material of macrophages is lysosomal material containing bacteria at various stages of destruction;
- intra- and extracellular accumulation of fat in the mucous membrane of the small intestine, as well as in the mesenteric lymph nodes;
- dilation of lymphatic vessels.
- FEGDS. Signs of chronic gastritis and duodenitis are revealed.
- Determination of hormone levels in the blood. In severe cases of malabsorption syndrome, the levels of cortisol, thyroxine, triiodothyronine, and sex hormones in the blood decrease.
Differential diagnosis. The clinical triad of diarrhea, weight loss and increasing weakness requires differential diagnosis, primarily with malignant tumors of the gastrointestinal tract, chronic inflammatory bowel disease, sprue, and Zollinger-Ellison syndrome.
Endoscopic and radiological examination of the gastrointestinal tract can exclude cancer, Crohn's disease, and nonspecific ulcerative colitis. The absence of recurrent ulcers in the upper gastrointestinal tract, gastric hypersecretion and hyperacidity, hypergastrinemia, and pancreatic tumors in ultrasound or computed tomography allows us to rule out Zollinger-Ellison syndrome.
In differential diagnostics with Whipple's disease, Addison's disease should also be excluded. Laboratory data help to establish the correct diagnosis - hormonal studies, detection of hyperkalemia in Addison's disease, signs of blood thickening, absence of steatorrhea.
Whipple's disease should be suspected in patients with arthralgias or arthritis if diarrhea, malabsorption, or unexplained weight loss develops, especially if the type of arthritis cannot be determined. In Whipple's disease, tests for rheumatoid factor are negative or weakly positive. Rheumatic tests are negative. Serum uric acid levels are normal.
Fever often precedes the development of intestinal manifestations. In case of fever of unknown genesis, the possibility of this disease developing should also be kept in mind.
Patients with Whipple's disease often have fever, lymphadenopathy, and a tumor-like formation may be detected in the abdominal cavity. In this regard, it is necessary to exclude a lymphoproliferative disease, primarily lymphogranulomatosis.
The final diagnosis of Whipple's disease in all cases is made only on the basis of a histological examination of the affected organs, primarily the small intestine.