Vasculitis

Autoimmune mechanisms of vascular wall damage

Systemic vasculitis frequently presents as a manifestation of organ-nonspecific autoimmune diseases, in which antigens are widely represented in tissues (e.g., as nucleoproteins and DNA). The process is triggered by a generalized breakdown of natural immunological tolerance.

A key role in pathogenesis is played by defects in cellular apoptosis mechanisms and negative selection (specifically, failures in Fas and p53 protein systems). This leads to the survival of 'forbidden clones' of immune cells. A pronounced imbalance of lymphocyte subpopulations occurs: the $Th17 / Treg$ ratio is disrupted against the background of a T-suppressor deficit.

Concurrently, hyperproduction of B-cell survival factors (BAFF/BLyS) is observed, leading to polyclonal activation of B lymphocytes. They begin to massively synthesize autoantibodies that attack the body's own tissues. In some cases, the triggering mechanism of autoaggression can be the disruption of blood-tissue barriers, leading to the release of previously sequestered antigens into the systemic circulation.

Basic morphology of destructive vasculitis

The pathomorphology of vascular lesions in autoimmune aggression features distinct stages and characteristic histological manifestations.

The basic substrate is perivascular lymphohistiocytic infiltration of the stroma. Immunocompetent cells—T lymphocytes, B lymphocytes, plasma cells, and macrophages—concentrate around the affected vessel. Their excessive activity provokes destructive inflammation.

A key histological marker of severe disease is fibrinoid necrosis of the vessel wall. As an outcome of this destructive stage, when acute inflammation subsides, damaged areas undergo irreversible changes: sclerosis and hyalinosis develop, permanently depriving the vessel of elasticity.

Polyarteritis nodosa and vascular lesions in SLE

Individual nosological forms of systemic autoimmune diseases have specific features of vascular bed involvement:

• Polyarteritis nodosa: characterized by the selective involvement of small and medium-sized arteries. Segmental fibrinoid necrosis followed by the formation of multiple microaneurysms is typical. An important diagnostic feature is evolutionary polymorphism—the simultaneous presence of blood vessels in completely different stages of inflammation and scarring within the tissue.
• Systemic lupus erythematosus (SLE): vascular inflammation is pronounced and systemic in nature. Vasculitis of the synovial membranes and central nervous system vessels is characteristic. Involvement of CNS arteries is complicated by thrombosis and infarctions, leading to irreversible destruction of neurocytes. Additionally, SLE can cause systemic coronary artery vasculitis, triggering true episodes of angina pectoris in patients.

Indicated separately in the classification is the drug-induced form of SLE (M32.0), where a pharmacological trigger induces a lupus-like syndrome in predisposed individuals.

Clinical masks and systemic associations

In clinical practice, vasculitis requires rigorous differential diagnosis. Due to non-specific symptoms (fever, various skin rashes, lymphadenopathy, serositis), it must be strictly differentiated from occult infectious processes and oncohematological diseases (lymphomas and leukemias). It is always included in the differential diagnostic set for non-infectious febrile conditions.

Pathological immune complexes, autoaggressive immunoglobulins, and complement components are capable of depositing in tissues, provoking the development of secondary conditions. Vasculitis and systemic immune inflammation can act as a trigger for:

1. Pericarditis;
2. Dilated cardiomyopathy;
3. Glomerulonephritis and nephrotic syndrome;
4. Atypical hemolytic-uremic syndrome (as a 'second hit' factor);
5. Secondary osteoporosis.

Principles of therapy and drug interactions

The pathophysiological rationale for treating vasculitis is based on immunosuppression. Since the underlying pathology involves hyperreactivity of the immune system against the body's own tissues, pharmacological suppression of the immune response is the primary therapeutic tool.

When managing patients, it is necessary to consider the interactions and side effects of baseline medications:

• Glucocorticoids significantly increase the risk of infectious complications and exacerbate secondary osteoporosis.
• Cytostatics (azathioprine, cyclophosphamide, mycophenolate mofetil) require constant strict monitoring of renal function and hematological blood parameters.
• Antimalarial drugs (hydroxychloroquine) serve as baseline therapy to reduce the frequency of flare-ups, control skin manifestations, and manage articular syndrome.

Class and exam questions

What else to study on this topic

• Mechanisms of immunological tolerance breakdown in Fas and p53 gene defects
• Polyclonal activation of B lymphocytes and the role of BAFF/BLyS factors in autoaggression
• The role of blood-tissue barrier disruption in the pathogenesis of autoimmune reactions
• Laboratory algorithms for determining autoantibody titers (ANA, anti-dsDNA, rheumatoid factor) and their interpretation
• Pathogenetic similarities between autoimmune aggression and graft rejection reactions

Other topics in the "Additional Topics" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.