Granulomatous skin diseases: causes, symptoms, diagnosis, treatment

At the heart of granulomatous inflammation are immune disorders - mainly by the type of delayed-type hypersensitivity, allergic and cytotoxic reactions. According to A.A. Yarilina (1999), the development of granuloma, usually serves as an indicator of the ineffectiveness of immune defense. The appearance of granulomas during the inflammatory process is often associated with the inadequacy of mononuclear phagocytes, which can not digest the pathogen, as well as with the persistence of the latter in the tissues.

In connection with the characteristics of the body's reaction to an agent, granulomatous inflammation is also called specific. It is characterized by a specific causative agent, a change and polymorphism of tissue reactions in accordance with the state of the body's immune system, a chronic undulating course, the prevalence of a productive granulomatous reaction and the development of coagulation necrosis in inflammatory foci. To infectious diseases, characterized by the specificity of the 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 definite morphological signs in the form of granuloma - a fairly clearly delineated cluster of histiocytes or epithelioid cells in the dermis against chronic inflammatory infiltration, often with an admixture of giant multinucleated cells.

Epithelioid cells are a variety of macrophages, they contain a granular endoplasmic reticulum, they synthesize RNA, but they are not very capable of phagocytosis, but they have the ability to pinocytosis small particles. These cells have an uneven surface due to a large number of microvilli, tightly in contact with the microvilli of neighboring cells, resulting in the granuloma, they are closely adjacent to each other. 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, they are based on pathogenetic, immunological and morphological criteria. WL Epstein (1983) divides all granulomas of the skin, depending on the etiopathogenetic factor, on 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 immunocompetent granulomatous inflammation, granulomatous inflammation with unstable immunity and immunodeficiency.

A.I. Strukov and O.Ya. Kaufmann (1989) divided all granulomas into 3 groups: on etiology (infectious, non-infectious, medicinal, dust, granulomas around foreign bodies, unknown etiology); Histology (granulomas from mature macrophages, with or without epithelioid, or giant, multinucleated cells, with necrosis, fibrotic changes, etc.) and pathogenesis (immune hypersensitive granulomas, non-immune granulomas, etc.).

BC Hirsh and WC Johnson (1984) proposed a morphological classification, taking into account the severity of the tissue reaction and the prevalence of this or that type of cells, the presence of suppuration, necrotic changes and foreign bodies or infectious agents. The authors distinguish five types of granulomas: tuberculoid (epithelioid-cell), sarcoid (histiocytic), type of foreign bodies, necrobiotic (palisadic) 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 multinucleate cells, among the latter the Pirogov-Langhans cells predominate, but cells of foreign bodies also occur. For this type of granuloma, there is a wide zone of infiltration by lymphocytic elements around the accumulations of epithelioid cells.

Sarcoid (histiocytic) granuloma is a tissue reaction characterized by a predominance of histiocytes and multinucleated giant cells in the infiltrate. In typical cases, individual granulomas are not prone to fusion and are surrounded by a whisk of a very small number of lymphocytes and fibroblasts that are not detected in the granulomas themselves. Granulomas of this type develop with sarcoidosis, the introduction of zirconia, with tattooing.

Necrobiotic (palisad-like) granulomas occur in the annular granuloma, lipoid necrobiosis, rheumatic nodules, cat scratch disease and venereal lymphogranuloma. Necrobiotic granulomas can be of different genesis, some of them are accompanied by deep changes in blood vessels, more often of a primary nature (Wegener's granulomatosis). The granuloma of foreign bodies reflects the reaction of the skin to a foreign body (exogenous or endogenous), characterized by accumulations of macrophages and giant cells of foreign bodies around it. In mixed granulomas, as the name suggests, features of different types of granulomas are combined.

The histogenesis of granulomatous inflammation is described in detail by DO Adams. Experimentally, this author showed that the development of granuloma depends on the nature of the invoking agent and the state of the organism. In the initial phases of the process appears a massive infiltration of young mononuclear cells, phagocytes, histologically reminiscent of a picture of chronic non-specific inflammation. A few days later, this infiltrate turns into a mature granuloma, and the aggregates of mature macrophages are compact, 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 heterochromatin nuclei and a scant cytoplasm, which contains a few organelles: mitochondria, Golgi complex, granular and smooth endoplasmic reticulum and lysosomes. Epithelioid cells are larger, have an eccentrically located euchromatin nucleus and abundant cytoplasm, containing, as a rule, a large number of organelles.

In a histochemical study in mononuclear phagocytes, at the beginning of their development, peroxidase-positive granules resembling those in monocytes are detected, progressive dissolution of the primary peroxidase-positive granules and an increase in the amount of peroxisomes are noted in the etpelioid cells. When 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 ones are usually accompanied by the synthesis of RNA and DNA.

In addition to the granuloma elements described above, neutrophilic and eosinophilic granulocytes, plasmocytes, T- and B-lymphocytes are found in various amounts. In granulomas, necrosis is very often observed, especially in cases of high toxicity of agents that caused granulomatous inflammation, such as streptococci, silicon, mycobacterium tuberculosis, histoplasm. The pathogenesis of necrosis in granulomas is not known exactly, but there are indications of the influence of such factors as acid hydrolases, neutral proteases and various mediators. In addition, they attach importance to lymphokines, the influence of elastase and collagenase, as well as vasospasm. Necrosis can be fibrinoid, caseous, sometimes accompanied by softening or purulent melting (abscessing). Foreign matter or pathogen in granulomas. They are degraded, but they can cause an immune response. If the harmful substances are completely inactivated, then the granuloma regresses with the formation of a superficial scar.

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

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

[1], [2], [3], [4], [5]