Pulmonary vasculitides

Role of ANCA in pathogenesis

Antineutrophil cytoplasmic antibodies (ANCA) are detected in most autoimmune vasculitides. The exact mechanism of their action is not fully understood, but the following cascade is hypothesized: antibodies bind to neutrophil cytoplasmic contents, leading to the activation of these cells. Activated neutrophils release hydrolytic enzymes that directly damage the vascular wall.

Two main types of antibodies are distinguished:

• cANCA (cytoplasmic): bind to proteinase 3 located in azurophilic granules of neutrophils. They are most specific for granulomatosis with polyangiitis (detected in 70–99% of patients) and are considered a poor prognostic factor.
• pANCA (perinuclear): produce a characteristic granular staining around the nucleus; their target is myeloperoxidase. These antibodies are typical for microscopic polyangiitis and Churg-Strauss syndrome.

Dependence of morphology on vessel caliber

Stereotypical pulmonary changes in vasculitis include hemorrhagic infarcts, foci of necrosis, hemorrhages, and hemosiderosis. However, the specific morphological picture strictly depends on the caliber of the vessels involved in the pathological process:

1. Medium and small branches of the pulmonary artery: inflammation is accompanied by thrombosis, leading to the development of classic pulmonary hemorrhagic infarcts.
2. Small vessels (capillaries): their involvement causes alveolitis, capillaritis, diffuse hemorrhages, and subsequent hemosiderosis.
3. Small branches of the bronchial artery: inflammation in this bed leads to necrosis and destruction of the bronchial wall.

Main nosologies with pulmonary involvement

Granulomatosis with polyangiitis A systemic necrotizing arteritis affecting the upper respiratory tract, respiratory tree, lung parenchyma, and kidneys. Isolated pulmonary involvement is extremely rare. It most commonly affects individuals around 50 years of age, with a peak incidence in winter. Macroscopically, multiple dark-red nodules and cavities are symmetrically defined in both lungs. The microscopic picture is represented by the histological triad: necrotic polymorphonuclear granulomas, vasculitis, and foci of necrosis. Without treatment, the disease progresses rapidly, leading to death from renal failure.

Microscopic polyangiitis The disease belongs to pulmonary-renal syndrome. Unlike classical polyarteritis nodosa, inflammation here extends down to arterioles, venules, and capillaries (including renal glomeruli). Hemorrhagic alveolitis develops in the lungs—a combination of diffuse alveolar damage, capillaritis, hemorrhages, and infarcts. In late stages, carnification and pulmonary fibrosis develop. Men are affected 1.5 times more often, with a mean age of 56 years.

Churg-Strauss syndrome An angiitis with granulomatous inflammation, presenting with the diagnostic triad: bronchial asthma, blood eosinophilia (greater than 10%), and systemic vasculitis. The disease goes through three stages: from allergic reactions (rhinitis, asthma) to systemic leukocytoclastic vasculitis and severe organ pathology. Specific infarcts with destructive thrombovasculitis, eosinophilic infiltration, and granulomas in the demarcation zone form in the lungs.

Vasculitides with specific pulmonary affinity

Certain systemic vasculitides have strict features of pulmonary vessel involvement:

• Polyarteritis nodosa: a chronic systemic vasculitis of small and medium arteries (associated with hepatitis B in 30% of cases). A critical diagnostic sign is that this disease never affects the vessels of the lesser circulation and renal glomeruli capillaries. In the lungs, vasculitis can occur only in bronchial artery branches. The classical morphological marker is the simultaneous presence of all stages of inflammation and regeneration in different vessels.
• Takayasu arteritis: a giant cell aortitis affecting predominantly young Asian women (under 40 years of age). In addition to the aortic arch, the pulmonary trunk is involved in 12–86% of cases. The walls of affected vessels thicken, and their lumen narrows significantly.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanisms of antineutrophil cytoplasmic antibody (ANCA) formation
• Pathogenesis of pulmonary-renal syndrome in microscopic polyangiitis
• Stages of Churg-Strauss syndrome development and prognostic significance of myocardial involvement
• Differential diagnosis of necrotizing pulmonary granulomas
• Morphology of renal lesions in systemic vasculitides (crescentic glomerulonephritis)

Other topics in the "Lung Diseases" section

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