Whipple's disease: causes

In 1992, the bacterial nature of the disease was established (Relman, Schmidt, MacDermott, 1992). As an infectious agent identified Gram-positive actinomycetes Tropheryna whippelii. These small Gram-positive bacilli are found in the active phase of the disease in large quantities in the mucosa of the small intestine and other organs and disappear after intensive antibiotic therapy. Predisposing to the development of the disease factor is a violation of the immune system of different genesis.

Whipple's disease occurs sporadically and so rarely that no epidemic features are established. There are no cases of direct transmission from one person to another, the entrance gate of the infection is unknown.

Probably, microorganisms are the main, but only a partial etiologic factor. For the development of the disease, additional predisposing factors, possibly defects in the immune system, are necessary, but the results of the relevant studies are contradictory. Violations of humoral immunity in Whipple's disease are excluded, while disorders of cellular immunity, primarily the interaction of lymphocytes and macrophages, have not been sufficiently studied.

In response to invasion by microorganisms in the affected organs, reactive changes develop. Infiltration of tissues with large macrophages promotes the appearance of clinical manifestations. For example, infiltration of one's own layer of the mucous membrane of the small intestine can not but affect absorption. Absorption occurs through a little modified enterocytes. However, further transport of nutrients through the infected own layer into the vessels of the mucous membrane and lymphatic space is hampered, it is even more disturbed by infiltration and enlarged lymph nodes, since lymphatic drainage of the small intestine suffers, which prevents the normal release of absorbed substances. However, the exact mechanism for the development of violations found in the organs has not yet been established. As a rule, the maximum changes are found in the small intestine and mesenteric lymph nodes. The small intestine with Whipple's disease is compacted, the folds of the mucous membrane coarse, edematous. On the serous membrane, small yellowish nodules are sometimes seen. The lymph nodes of the mesentery are sharply enlarged, there may be an increase in periportal, retroperitoneal and other groups of lymph nodes, as well as peritonitis.

Histological examination clearly reveals damage to the structure of the intestinal mucosa. Vorsils of the small intestine are shortened, thickened, sometimes deformed. The crypts are flattened. The intrinsic layer of the mucosa is diffusely infiltrated by large polygonal macrophages. Their cytoplasm is filled with a large number of glycoprotein PAS-positive granules, which gives the cells a frothy appearance. These macrophages in the intestinal mucosa are pathognomonic for Whipple's disease. The native layer may contain accumulations of polymorphonuclear leukocytes. The usual cellular elements of its own layer of the mucous membrane - plasma cells, lymphocytes, eosinophils - have a normal appearance. However, their content is markedly reduced, because they are replaced by a large number of macrophages. In all layers of the intestinal wall, separate enlarged lymphatic vessels with fatty vacuoles are found. In the extracellular space of its own layer are located fatty clusters of various sizes. Some of them have the appearance of cavities lined with endothelium. The capillaries are enlarged. Although the architecture of the villi is visibly impaired, the superficial epithelium is preserved. There are only its focal nonspecific changes. The height of the enterocytes is reduced. The brush border is sparse. In the cytoplasm, the accumulation of a moderate amount of lipids.

Electron microscopic examination reveals a large number of bacilliform bodies 1-2.5 μm long and 0.25 μm wide in their own layer of the intestinal mucous membrane in untreated patients. Bacilli are localized in different areas, but most of them are found in the subepithelial zone and around the vessels in the upper half of the mucosa. They are also found in PAS-positive macrophages, with which they are phagocytosed and in which they degenerate and decay. "Whipple bacilli" and the products of their construction are responsible for PAS-positive granules of macrophages. In some cases, the bacilli can be seen in epithelial cells and between them, as well as in polymorphonuclear leukocytes, plasma and endothelial cells of its own layer.

Under the influence of treatment, the structure of the mucous membrane gradually normalizes. The bacilli disappear from the intercellular space and after 4-6 weeks only degenerative organisms in the cytoplasm of macrophages can be identified. The number of specific macrophages in the native layer gradually decreases, and usually the cells present are restored. The structure of villi and enterocytes is normalized. However, in a number of cases, despite the absence of clinical manifestations, the structure of the intestinal mucosa can not be completely restored. Persistent foci of PAS-positive macrophages may persist around the intestinal crypts and enlarged lymphatic vessels, as well as fat accumulations.

With Whipple's disease, the colon is often involved in the pathological process. In the affected areas, its mucosa is infiltrated by characteristic macrophages and bacilli. Detection in the large intestine of only PAS-positive macrophages without bacilli is not enough to make a diagnosis. Similar macrophages can occur in the mucous membrane of the rectum and colon in healthy individuals and are constantly detected during histiocytosis and melanosis of the large intestine.

With Whipple's disease, a systemic lesion was proven. In many organs, PAS-positive macrophages and bacilli can be found in patients: in peripheral lymph nodes, heart, adrenal glands, CNS, etc.

In many systems of the body, with Whipple's disease, nonspecific pathological changes develop secondary to nutrient absorption disorders: muscle atrophy, parathyroid glandular hyperplasia, adrenal cortex atrophy, follicular skin hyperkeratosis, bone marrow hyperplasia, etc.