Allergic necrotizing vasculitis: causes, symptoms, diagnosis, treatment

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

The severity of clinical symptoms depends on the depth of skin damage, the degree of alteration of vascular walls and the nature of hematological, biochemical, serological and immune disorders. Vessels of different calibers are affected, but the hypersensitivity reaction mainly involves the microcirculatory bed, in particular venules.

Clinical manifestations of this type of vasculitis are usually polymorphic, combining elements of various nature: petechiae, erythematous spots, erythematous-urticarial and erythematous-nodular, nodular elements, in some patients - with a hemorrhagic nature, superficial necrosis and ulceration. Blisters, vesicles, including those with hemorrhagic contents, may occur, resembling manifestations of erythema multiforme exudative. Closely located necrotic foci may merge. The rash is more often located on the skin of the legs, less often on the arms, but the skin of the trunk may also be involved in the process. The color of the rash depends on the duration of its existence, at first they are bright red, then become bluish with a brownish tint. Pigmentation may remain at the site of regressed elements, after ulcerations - scars, often smallpox-like. Subjective sensations are insignificant, there may be itching, burning, pain, mainly with necrotic changes. Damage to internal organs and joints may be observed.

Pathomorphology of allergic necrotic vasculitis. In the initial stages of the process, swelling of endotheliocytes with disruption of the structure of vascular walls, their infiltration and perivascular tissue by lymphocytes with an admixture of neutrophils and single eosinophilic granulocytes are observed. In the next stage, a characteristic picture is revealed, expressed in necrosis of the walls of blood vessels with fibrinoid deposition, massive infiltration by mononuclear elements with an admixture of a large number of neutrophils granulocytes. In this case, a characteristic histological criterion of necrotic vasculitis is pronounced leukoclasia with the formation of "nuclear dust" located in infiltrates around the vessels and diffusely in the dermis between collagen fibers. In addition, erythrocyte extravasates are often observed. Fibrinoid material in the walls of vessels and perivascular tissue consists mainly of fibrin. The epidermis in fresh elements is almost unchanged, with the exception of its slight thickening, edema of the basal layer and exocytosis. In necrotic foci, the epidermis undergoes necrosis. The process begins in its upper sections and spreads to the entire thickness. Necrotic masses are separated from the underlying tissue by a powerful shaft of neutrophilic granulocytes with leukoclasia phenomena.

Electron microscopy reveals a significant increase in the volume of capillary endothelial cells protruding into the lumen, almost covering it, in the lesions. The surface of the epithelial cells is uneven, sometimes with a large number of microvilli, the cytoplasm contains a large number of ribosomes, many pinopitic vesicles, vacuoles, and sometimes lysosomal structures in various stages of development. Some cells have many mitochondria, mostly with a dense matrix, and expansion of the endoplasmic reticulum cisterns is noted. The nuclei of such endothelial cells are large with uneven contours, sometimes with pronounced invaginations of the nuclear rim and the location of the compacted chromatin usually near the nuclear membrane. Similar changes are found in pericytes. The basal membrane is multilayered over a large area, is not clearly visible, has a lower electron density than normal, is sometimes discontinuous and appears as separate fragments. The subendothelial space is usually widened, fragments of the basement membrane may be visible in it, sometimes it is completely filled with a thickened basement membrane of medium electron density with unclear boundaries. In case of pronounced necrobiotic processes in the capillaries, destructive changes are observed, expressed in a sharp swelling of endotheliocytes, completely closing the lumen of the capillary. Their cytoplasm with cytolysis phenomena is filled with small and larger vacuoles, in places merging with each other with the loss of membrane structures. Similar changes occur in the nucleus. Organelles in such cells are almost not detected, only single small mitochondria with a dark matrix and unclear structure of the cristae are found. The subendothelial space in such capillaries is sharply widened and completely filled with homogeneous masses of medium electron density. In some of its areas, an electron-dense substance is detected, resembling immune complexes or fibrinoid substance described by G. Dobrescu et al. (1983) in allergic vasculitis. Around the vessels in such lesions, destruction of some cellular elements of the inflammatory infiltrate is detected (in the form of fragments with lysis phenomena). Among the latter are fine-fibrous, high-electron-density masses, possibly fibrinoid substance. No deposits of immune complexes were detected in the studied material. This is probably explained by 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 due to phagocytosis by their cellular elements.

Histogenesis of allergic necrotic vasculitis. Most often, local deposits of circulating immune complexes play a role in the development of allergic necrotic vasculitis. It is known that immune complexes can activate the complement system with the formation of C3a and C5a complement components, leading to degranulation of tissue basophils. In addition, the C5a complement component can act on neutrophilic granulocytes, which, in turn, release lysosomal enzymes, damaging tissues. The formation of the chemoattractant leukotriene B4 in neutrophilic granulocytes promotes an increase in the influx of the latter into the inflammation site. Other immune complexes can interact with the Fc fragment and lymphocytes with the release of lymphokines with chemotactic and cytolytic activity. Circulating immune complexes are present in the blood serum as cryoglobulins, and in the affected skin immune complexes are detected by electron microscopy as electron-dense deposits and as deposits of immunoglobulins M, G, A and C3-component of complement by direct immunofluorescence. As a result of these interactions, vascular endothelial cells are damaged, in which adaptive changes occur at the beginning of the process in the form of mitochondrial hypertrophy, intense pinocytic activity, an increase in the number of lysosomes, active cytoplasmic transport and even phagocytosis. Then these changes are replaced by 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, also damage the basal membrane and the pericyte layer, causing a violation of the permeability of the vascular wall. It is assumed that the basement membrane can be damaged by immune complexes. This process can be repeated, and the disease becomes chronic. Direct immunofluorescence with antiserum 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 non-specific sign.

Special forms of allergic (necrotic) vasculitis are hemorrhagic vasculitis of Schonlein-Henoch, allergic vasculitis of the skin associated with focal streptococcal infection of the upper respiratory tract, necrotic urticarial-like vasculitis, and livedo vasculitis.

Allergic vasculitis of the skin associated with focal streptococcal infection of the upper respiratory tract was classified by L.Kh. Uzunyan et al. (1979) as a special form of vasculitis. It is characterized by damage to the vessels of the dermis and subcutaneous tissue with a relapsing course, which is closely related to focal streptococcal infection of the upper respiratory tract. The authors distinguish three clinical and morphological forms of the disease: deep vasculitis, superficial and bullous. Clinically, in patients with damage to the deep vessels of the skin, the process develops as erythema nodosum, the main changes are observed on the shins in the form of bright pink spots 2-5 cm in diameter, then acquiring a bluish color, the foci subsequently become denser, and become painful to the touch. In the superficial form, bright pink areas with a pronounced pattern of the vascular network appear on the skin. In chronic course, skin changes are characterized by polymorphism, as in all types of allergic vasculitis. The bullous form is characterized by an acute course.

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

Histogenesis. Immunomorphological examination of skin lesions reveals IgA and IgG deposits in the vascular basement membranes and in the infiltrate cells. Circulating antibodies to cellular elements of infiltrates and vessels are also detected, which indicates the role of immune disorders in this type of vasculitis.

Livedovasculitis (syn.: segmental hyalinizing vasculitis, livedoangiitis) is clinically manifested by the presence, predominantly in the skin of the lower extremities, of reticularly dilated superficial vessels, hemorrhages, nodular elements, painful ulcers and various forms of sharply defined areas of atrophy of white color with a yellowish tint, surrounded by a pigmented rim. In the atrophy zone - telangiectasias, punctate hemorrhages, hyperpigmentation.

Pathomorphology. The number of capillaries in the dermis is increased, their endothelium proliferates, the walls are thickened due to the deposition of eosinophilic masses in the area of the basement membranes. These deposits are PAS-positive, diastasis-resistant. Subsequently, the lumens of the capillaries thrombose, the thrombi undergo 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 are found, and in old ones - hemosiderosis and fibrosis. Livedo vasculitis is differentiated from dermatitis in chronic venous insufficiency, when there is a slight thickening of the capillary walls and their proliferation.

Histogenesis. Livedo vasculitis is based on hyalinosis of the capillary basement membranes, and inflammatory phenomena are secondary in nature, which is why some authors classify this disease not as vasculitis, but as dystrophic processes.

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