Schoenlein-Genoch disease - Causes and pathogenesis

The causes of Henoch-Schonlein purpura are associated with infections, food allergies, drug intolerance, and alcohol consumption. In most cases, the disease is preceded by a nasopharyngeal or intestinal infection. The development of hemorrhagic vasculitis is associated with a number of bacteria and viruses. The most clearly traced connection of the disease with an infection caused by streptococci and staphylococci, cytomegalovirus, parvovirus B19, and human immunodeficiency virus. Less often, an association with intestinal bacteria, yersinia, and mycoplasma is noted.

The development of Henoch-Schonlein purpura has been described after the use of certain drugs, including vaccines and serums, antibiotics (penicillin), thiazide diuretics, and quinidine.

The pathogenesis of Henoch-Schonlein purpura has not been fully studied. Currently, an important pathogenetic role is attributed to IgA, its macromolecular polymers and IgA-containing immune complexes. It has been established that 40-50% of patients have an increased concentration of IgA in the blood, mainly due to an increase in polymeric forms of the IgA isotype _r. In some cases, these IgA exhibit the properties of rheumatoid factor, antibodies to the cytoplasm of neutrophils, and form complexes with fibronectin. The cause of the increase in IgA is both an increase in its synthesis and a decrease in clearance, possibly as a result of a defective biochemical structure of IgA, which contributes to an extension of the period of circulation of IgA polymers and IgA-containing immune complexes in the systemic bloodstream.

The development of glomerulonephritis in hemorrhagic vasculitis is associated with the deposition of IgA-containing immune complexes in the glomerular mesangium with subsequent activation of complement via the alternative pathway. The possibility of the formation of immune complexes in situ is also discussed. The latter mechanism is supported by the presence of mesangial IgA deposits in patients with normal IgA levels in the blood and the absence of IgA-containing immune complexes in the glomeruli of most HIV-infected individuals with high levels of polymeric IgA in the blood plasma. Based on these facts, a hypothesis was formulated about the existence of a mechanism facilitating the deposition of IgA in the glomeruli. The currently established defect in the glycosylation of IgA molecules in Henoch-Schonlein purpura is considered as such a mechanism. As a result, the structure of IgA may change, which in turn disrupts its interaction with proteins of the mesangial matrix, receptors on the surface of mesangial cells, complement (altered IgA, formed as a result of abnormal glycosylation, activates complement more effectively than normal), causing the deposition of immune complexes with subsequent damage to the glomerulus.

Changes in the concentration of IgA in the blood, the presence of its polymeric forms and IgA-containing deposits in the glomeruli of the kidney, and the clinical and morphological features of glomerulonephritis in Henoch-Schonlein purpura do not differ from those in IgA nephropathy. In this regard, discussions continue to this day about whether it is possible to consider Berger's disease as a local renal form of Henoch-Schonlein purpura. Recently, the possible role of chronic inflammation of the intestinal wall in the pathogenesis of Henoch-Schonlein purpura has been discussed, apparently caused by a dysfunction of its local immune system. This assumption is based on the increase in intestinal permeability for macromolecules during an exacerbation of the disease, established in recent studies, and the discovery of a relationship between the permeability of the intestinal mucosa and the severity of lymphocyte infiltration of the latter.

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Pathomorphology of Henoch-Schonlein disease

Morphological changes in the kidneys in Henoch-Schonlein purpura are varied.

The most frequently observed picture is focal or diffuse mesangioproliferative glomerulonephritis.

Less common is diffuse proliferative endocapillary glomerulonephritis, which is characterized by a combination of intense mesangial proliferation with an increase in the mesangial matrix, the presence of leukocytes in the lumen of the glomerular capillaries and foci of doubling of the glomerular basement membrane.

In a small proportion of patients, diffuse proliferative glomerulonephritis with endocapillary and extracapillary proliferation is detected, in which, depending on the severity of the damage, along with diffuse proliferative changes, the formation of crescents in less than or more than 50% of the glomeruli and mesangiocapillary glomerulonephritis are noted.

Tubulo-interstitial changes are minimally expressed in the early stages of the disease, and in later stages they are represented by tubular atrophy and interstitial sclerosis, which correlates with the severity of glomerular pathology. In adult patients, unlike children, arteriosclerosis and arteriole hyalinosis are often detected.

Immunofluorescence microscopy of patients with Henoch-Schonlein purpura reveals diffuse granular deposits containing predominantly IgA in the mesangium. These deposits can then penetrate the capillary wall, being located subendothelially. Subepithelial localization of deposits is extremely rare. In some cases, IgG deposits are detected in combination with IgA. Almost all patients with IgA nephritis in Henoch-Schonlein purpura have C3 deposits, and in more than 80% of cases, fibrinogen deposits in the mesangium, which indicates local intravascular coagulation in the glomeruli of the kidney.