Granulomatous skin diseases: causes, symptoms, diagnosis, treatment

Granulomatous inflammation is based on immune disorders - mainly of the delayed-type hypersensitivity type, allergic and cytotoxic reactions. According to A.A. Yarilin (1999), the development of granuloma, as a rule, serves as an indicator of the ineffectiveness of immune protection. The appearance of granulomas during the inflammatory process is often associated with the failure of mononuclear phagocytes, which cannot digest the pathogen, as well as with the persistence of the latter in the tissues.

Due to the specificity of the body's reaction to a particular agent, granulomatous inflammation is also called specific. It is characterized by a specific pathogen, change and polymorphism of tissue reactions in accordance with the state of the body's immune system, chronic wave-like course, prevalence of productive granulomatous reaction and development of coagulation necrosis in the foci of inflammation. Infectious diseases characterized by specificity of reaction include tuberculosis, syphilis, leprosy, scleroma. The inflammatory process in these diseases has, as usual, all components: alteration, exudation and proliferation, but, in addition, a number of specific morphological signs in the form of granuloma - a fairly clearly delimited accumulation of histiocytes or epithelioid cells in the dermis against the background of chronic inflammatory infiltration, often with an admixture of giant multinucleated cells.

Epithelioid cells are a type of macrophage, contain a granular endoplasmic reticulum, synthesize RNA, but are poorly capable of phagocytosis, although they exhibit the ability to pinocytose small particles. These cells have an uneven surface due to the large number of microvilli that are in close contact with the microvilli of neighboring cells, resulting in them being closely adjacent to each other in the granuloma. It is believed that giant cells are formed from several epithelioid cells due to the fusion of their cytoplasm.

Classification of granulomatous inflammation is extremely difficult. As a rule, it is based on pathogenetic, immunological and morphological criteria. W. L. Epstein (1983) divides all skin granulomas, depending on the etiopathogenetic factor, into the following types: foreign body granuloma, infectious, immune, associated with primary tissue damage and not associated with tissue damage. O. Reyes-Flores (1986) classifies granulomatous inflammation depending on the immune status of the organism. He distinguishes between immunoincompetent granulomatous inflammation, granulomatous inflammation with unstable immunity and immunodeficiency.

A.I. Strukov and O.Ya. Kaufman (1989) divided all granulomas into 3 groups: by etiology (infectious, non-infectious, drug-induced, dust-induced, granulomas around foreign bodies, of unknown etiology); histology (granulomas from mature macrophages, with/without epithelioid or giant, multinucleated cells, with necrosis, fibrous changes, etc.) and pathogenesis (immune hypersensitivity granulomas, non-immune granulomas, etc.).

BC Hirsh and WC Johnson (1984) proposed a morphological classification that takes into account the severity of the tissue reaction and the prevalence of one or another cell type in this process, the presence of suppuration, necrotic changes and foreign bodies or infectious agents. The authors distinguish five types of granulomas: tuberculoid (epithelioid cell), sarcoid (histiocytic), foreign body type, necrobiotic (palisade) and mixed.

Tuberculoid (epithelioid cell granulomas) are found mainly in chronic infections (tuberculosis, late secondary syphilis, actinomycosis, leishmaniasis, rhinoscleroma, etc.). They are formed by epithelioid and giant multinucleated cells, among the latter, Pirogov-Langhans cells predominate, but foreign body cells are also encountered. This type of granuloma is characterized by the presence of a wide zone of infiltration by lymphocytic elements around clusters of epithelioid cells.

Sarcoid (histiocytic) granuloma is a tissue reaction characterized by the predominance of histiocytes and multinucleated giant cells in the infiltrate. In typical cases, individual granulomas are not prone to merging with each other and are surrounded by a rim of a very small number of lymphocytes and fibroblasts, which are not determined in the granulomas themselves. Granulomas of this type develop in sarcoidosis, zirconium implantation, and tattooing.

Necrobiotic (palisade) granulomas are found in annular granuloma, lipoid necrobiosis, rheumatic nodules, cat scratch disease and lymphogranuloma venereum. Necrobiotic granulomas can be of various genesis, some of them are accompanied by profound vascular changes, more often of a primary nature (Wegener's granulomatosis). Foreign body granuloma reflects the skin's reaction to a foreign body (exogenous or endogenous), characterized by accumulations of macrophages and giant cells of foreign bodies around it. Mixed granulomas, as the name suggests, combine features of different types of granulomas.

The histogenesis of granulomatous inflammation is described in detail by D. O. Adams. This author demonstrated experimentally that the development of granuloma depends on the nature of the causative agent and the state of the organism. In the initial phases of the process, a massive infiltrate of young mononuclear phagocytes appears, histologically resembling the picture of chronic non-specific inflammation. After several days, this infiltrate turns into a mature granuloma, and the aggregates of mature macrophages are compactly located, they turn into epithelioid, and then into giant cells. This process is accompanied by ultrastructural and histochemical changes in mononuclear phagocytes. Thus, young mononuclear phagocytes are relatively small cells, have dense heterochromatic nuclei and scanty cytoplasm, which contains a few organelles: mitochondria, Golgi complex, granular and smooth endoplasmic reticulum and lysosomes. Epithelioid cells are larger, have an eccentrically located euchromatic nucleus and abundant cytoplasm, which usually contains a large number of organelles.

Histochemical examination of mononuclear phagocytes at the beginning of their development reveals peroxidase-positive granules resembling those in monocytes; progressive dissolution of primary peroxidase-positive granules and an increase in the number of peroxisomes are noted in etpelioid cells. As the process progresses, lysosomal enzymes such as beta-galactosidase appear in them. Changes in the nuclei of granuloma cells from small heterochromatic to large euchromatic are usually accompanied by the synthesis of RNA and DNA.

In addition to the above-described granuloma elements, it contains varying amounts of neutrophilic and eosinophilic granulocytes, plasma cells, T- and B-lymphocytes. Necrosis is very often observed in granulomas, especially in cases of high toxicity of the agents that caused granulomatous inflammation, such as streptococci, silicon, mycobacterium tuberculosis, histoplasma. The pathogenesis of necrosis in granulomas is not precisely known, but there are indications of the influence of such factors as acid hydrolases, neutral proteases and various mediators. In addition, importance is attached to lymphokines, the influence of elastase and collagenase, as well as vascular spasms. Necrosis can be fibrinoid, caseous, sometimes accompanied by softening or purulent melting (abscess formation). Foreign material or pathogen in granulomas. are subject to degradation, but they can cause an immune response. If the harmful substances are completely inactivated, the granuloma regresses with the formation of a superficial scar.

If this does not happen, then the indicated substances may be located inside macrophages and are separated from the surrounding tissues by a fibrous capsule or sequestered.

The formation of granulomatous inflammation is controlled by T-lymphocytes, which recognize the antigen, transform into blast cells capable of informing other cells and lymphoid organs, and participate in the proliferation process due to the production of biologically active substances (interleukin-2, lymphokines), called macrophage-active chemotactic factors.

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