Allergic necrotizing vasculitis: causes, symptoms, diagnosis, treatment

Allergic necrotic vasculitis is a heterogeneous group of diseases related to immunocomplex diseases and is characterized by segmental inflammation and fibrinoid necrosis of the vascular walls.

The severity of clinical symptoms depends on the depth of the skin lesion, the degree of alteration of the vascular walls and the nature of hematologic, biochemical, serological and immune disorders. Vessels of different caliber are affected, but the hypersensitivity reaction involves mainly the microvasculature, in particular the venules.

The clinical manifestations of this type of vasculitis, as a rule, are polymorphic, the elements are combined: petechiae, erythematous spots, erythematoma-urticaria and erythemato-nodular, nodular elements, in some patients - with hemorrhagic character, superficial necrosis and ulceration. There may be bubbles, bubbles, including hemorrhagic contents, reminiscent of the manifestations of multiform exudative erythema. Close-lying necrotic foci may merge. The rash is more often on the skin of the legs, less often the hands, but the skin of the trunk can be involved in the process. The color of the rashes depends on the duration of their existence, at first they are bright red, then they become cyanotic with a brownish tinge. On the site of the regressed elements, pigmentation may remain, after ulceration, scars, often ossyphenous. Subjective sensations are minor, there may be itching, burning, soreness, mainly with necrotic changes. There can be a lesion of internal organs, joints.

Pathomorphology of allergic necrotic vasculitis. In the initial stages of the process swelling of endotheliocytes with a violation of the structure of the vascular walls, infiltration of them and perivascular tissue with lymphocytes with an admixture of neutrophilic and individual eosinophilic granulocytes are noted. In the next stage, a characteristic pattern is revealed, which is expressed in the necrosis of the walls of blood vessels with fibrinoid deposition, massive infiltration by mononuclear cells with an admixture of a large number of neutrophilic granulocytes. In this case, the characteristic histological criterion of necrotic vasculitis is pronounced leukoclasis with the formation of "nuclear dust", located in the infiltrates around the vessels and diffusely in the dermis between the collagen fibers. In addition, extravases of erythrocytes are often observed. The fibrinoid material in the walls of the vessels and perivascular tissue consists mainly of fibrin. The epidermis in fresh cells is almost unchanged, with the exception of a slight swelling, swelling of the basal layer and exocytosis. In necrotic foci, the epidermis undergoes necrosis. The process begins in its upper sections and extends to the entire thickness. Necrotic masses are separated from the underlying tissue by a powerful neutrophil granulocyte shaft with leucocla- sia phenomena.

With electron microscopy in the lesions, a significant increase in the volume of the capillary zondotheliocytes protruding into the lumen almost closes it. The surface of epithelial cells is uneven, sometimes with a large number of microvilli, the cytoplasm contains a large number of ribosomes, a lot of pinopitotic vesicles, vacuoles, and sometimes lysosomal structures in different stages of development. In some cells, a lot of mitochondria, mostly with a dense matrix, there is an expansion of the cisterns of the zondoplasmic reticulum. The nuclei of such endothelial cells are large with uneven contours, sometimes with marked invaginations of the nuclear rim and the location of the condensed chromatin of the bowl near the nuclear envelope. Similar changes are found in pericytes. The basal membrane is multilayered over a large length, is seen indistinctly, has a lower electron density than the norm, sometimes intermittent and appears as separate fragments. Subendothelial space, as a rule, is widened, fragments of the basement membrane can be seen in it, sometimes it is completely filled with a basal membrane of average electron density thickened with indistinct boundaries. With pronounced necrobiotic processes in the capillaries, destructive changes are observed, manifested in the sharp swelling of endotheliocytes completely covering the lumen of the capillary. Their cytoplasm with the phenomena of cytolysis is filled with small and larger vacuoles, sometimes merging with each other with the loss of membrane structures. Similar changes occur in the nucleus. Organelles in such cells are almost not detected, there are only single small mitochondria with a dark matrix and a fuzzy structure of cristae. The subendothelial space in such capillaries is greatly expanded and is completely filled with homogeneous masses of average electron density. In some of its areas, an electron-dense substance resembling immune complexes or fibrinoid substance is revealed, described by G. Dobrescu et al. (1983) for allergic vasculitis. Around the vessels in such lesions, the destruction of some cellular elements of the inflammatory infiltrate (in the form of scraps with lysis phenomena) is revealed. Among the latter are fine-fibrous, increased electron density of the mass, possibly fibrinoid substance. The deposits of immune complexes in the investigated material were not found. This is probably due to the fact that immune complexes, according to some authors, can be detected only at the beginning of the process. Then, after the appearance of an allergic inflammatory reaction, they become morphologically undetectable, possibly in connection with phagocytosis by their cellular elements.

Histogenesis of allergic necrotic vasculitis. The most common occurrence of allergic necrotic vasculitis is the local deposition of circulating immune complexes. It is known that immune complexes can activate the complement system with the formation of complementary C3a and C5a components leading to the degranulation of tissue basophils. In addition, the complement C5a component can act on neutrophilic granulocytes, which in turn release lysosomal enzymes and damage tissues. The formation of chemoattractant leukotriene B4 in neutrophilic granulocytes promotes an increase in the inflow of the latter into the focus of inflammation. Other immune complexes can interact with the Fc-fragment and lymphocytes with release of lymphokines with chemotactic and cytolytic activity. Circulating immune complexes are found in the blood serum as cryoglobulins, and in the affected skin, immune complexes are detected by electron microscopy in the form of electronically dense deposits and as deposits of immunoglobulins of M, G, A and C3 complement components with direct immunofluorescence. As a result of these interactions, vascular endothelial cells are damaged in which adaptive changes take place at the beginning of the process in the form of mitochondrial hypertrophy, intense pinocytosis activity, increased lysosome number, active cytoplasmic transport, and even phagocytosis. Further, these changes are replaced by the alteration of these cells with partial disintegration of the endothelial network and aggregation of platelets on their surface, which also migrate through the vascular wall. They release vasoactive substances, damage also the basal membrane and the pericyte layer, causing a violation of the permeability of the vascular wall. It is suggested that the basal membrane may be damaged by immune complexes. This process can be repeated, while the disease becomes chronic. Direct immunofluorescence with antisera against IgG, IgM and IgA, C3 and fibrin in most patients with allergic vasculitis gives luminescence in the walls of the vessels of the dermis and subcutaneous tissue, which is, however, a nonspecific sign.

Special forms of allergic (necrotic) vasculitis are hemorrhagic Schenlein-Henoch vasculitis, allergic skin vasculitis associated with focal streptococcal infection of the upper respiratory bullet, necrotizing urticariform vasculitis, and lisudo-vasculitis.

Allergic skin vasculitis associated with focal streptococcal infection of the upper respiratory tract, L.Kh. Uzunyan et al. (1979) was attributed to a particular form of vasculitis. It is characterized by the defeat of the vessels of the dermis and subcutaneous tissue with a recurrent course, which has a close connection with focal streptococcal infection of the upper respiratory tract. The authors distinguish three clinical and morphological forms of the disease: a type of deep vasculitis, superficial and bullous. Clinically, in patients with lesions of deep vessels of the skin, the process develops as a type of erythema nodosum, the main changes are observed on the shins in the form of bright pink spots 2-5 cm in diameter, then acquire a cyanotic color, the foci are further compacted, and become painful when palpated. With a superficial form, bright pink areas with a pronounced pattern of the vascular network appear on the skin. In chronic course, skin changes differ in polymorphism, as with all types of allergic vasculitis. Bullous form is characterized by acute course.

Pathomorphology. In the acute period, as in other types of vasculitis, fibrinoid changes in the walls of the vessels are found, in chronic cases, a granulomatous process characteristic of a delayed-type hypersensitivity reaction is found.

Histogenesis. In the immunomorphological study of lesions of the skin, IgA and IgG deposits are detected in the basal vessels of the vessels and in the infiltrate cells. There are also circulating antibodies to cellular elements of infiltrates and blood vessels, which indicates the role of immune disorders in this form of vasculitis.

Livedovuskulit (syn: segmental gyaliniziruyuschy vasculitis, livedoangiitis) is clinically manifested by the presence predominantly in the skin of the lower extremities of the network-widened superficial vessels, hemorrhage, nodular elements, painful ulceration and various forms of sharply delineated areas of atrophy of white with a yellowish tinge surrounded by a pigmented rim. In the zone of atrophy - telangiectasia, pinpoint hemorrhage, hyperpigmentation.

Pathomorphology. The number of capillaries in the dermis is increased, their endothelium proliferates, the walls are thickened by the deposition of eosinophilic masses in the region of basal membranes. These deposits are Schick-positive, diastasis-resistant. In the future, the lumens of capillaries are thrombosed, the thrombi undergoes recanalization. The affected vessels are surrounded by moderately expressed inflammatory infiltrates, consisting mainly of lymphoid cells and histiocytes. In fresh lesions in the dermis, hemorrhages and necrosis occur, and in old hemosiderosis and fibrosis. Livedo vasculitis is differentiated from dermatitis in chronic venous insufficiency, when there is a small thickening of the capillary walls and their proliferation.

Histogenesis. At the heart of whether the vasculitis of the vasculitis is the hyalinosis of the basal membranes of the capillaries, and the inflammatory phenomena are secondary in nature, in connection with which some authors refer this disease not to vasculitis, but to dystrophic processes.

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