Classification of Systemic Vasculitides
Because the underlying cause of vascular inflammation is often unknown, these conditions are categorized according to the size of the blood vessels involved. This is the primary criterion determining clinical presentation and prognosis.
- Large-vessel vasculitis: Includes giant cell (temporal) arteritis and Takayasu arteritis.
- Medium-vessel vasculitis: Includes polyarteritis nodosa and Kawasaki disease.
- Small-vessel vasculitis: The largest group, including granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome), leukocytoclastic vasculitis, and IgA vasculitis (Henoch–Schönlein purpura).
Kawasaki Disease (Mucocutaneous Lymph Node Syndrome)
Kawasaki disease is a systemic arteritis that can affect large, medium, and small arteries, though it is primarily recognized by its prominent mucocutaneous manifestations. It has the highest epidemiological significance in children aged 2–3 years. Its clinical presentation often mimics measles.
Clinical Presentation: The disease has an acute onset characterized by high fever and cervical lymphadenopathy. Mucocutaneous findings include dry, erythematous, cracked lips and a characteristic "strawberry tongue." Patients develop a polymorphic, erythematous, urticarial-like skin rash. Ophthalmic features include uveitis and photophobia. Musculoskeletal involvement manifests as arthritis and arthralgias.
The most severe complication is cardiovascular involvement—specifically, coronary artery inflammation, which carries a high risk of aneurysm rupture.
Immunopathogenesis of Vascular Injury:
- Unidentified causal antigens are processed and presented via MHC class I molecules.
- Cellular immune response is activated: macrophages become activated, and antigen-specific CD8+ T lymphocytes destroy infected cells.
- Concurrently, a humoral response is triggered. Antigen-specific IgA B lymphocytes transform into plasma cells, secreting antibodies that form pathogenic immune complexes.
- Macrophages and myofibroblasts release pro-inflammatory and profibrotic mediators: tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), and matrix metalloproteinases.
- The end result is disruption of the vascular intima and necrosis of endothelial cells. The damaged surface promotes cellular proliferation and active thrombus formation, leading to tightly adherent thrombi along the vessel wall.
IgA Vasculitis (Henoch–Schönlein Purpura)
IgA vasculitis is a small- and medium-vessel immune-complex-mediated necrotizing vasculitis. Children aged 2–8 years are predominantly affected. A preceding upper respiratory tract infection frequently serves as the trigger.
Pathogenesis: The disease is immune-complex-mediated. Circulating complexes composed of antigens, antibodies, and complement components form in the blood and deposit in vessel walls (predominantly affecting small dermal capillaries and renal glomeruli). Neutrophilic infiltrates accumulate at the sites of deposition, complement is activated, and localized intravascular coagulation (DIC) develops. Renal involvement shares pathogenic mechanisms with IgA nephropathy due to the deposition of IgA and the C3 complement component.
Clinical Manifestations:
- Cutaneous syndrome: Results from increased permeability of inflamed vessel walls. It presents as a palpable, symmetrical, purpuric, and papular erythematous rash (lesions typically 3 to 10 mm in diameter) distributed mainly on the lower extremities and buttocks.
- Articular syndrome: Marked arthralgia affecting large joints.
- Abdominal syndrome: Nausea, vomiting, and intense abdominal pain.
- General symptoms: Fever.
Laboratory Diagnostics of Systemic Inflammation
Laboratory tests are adjunctive but critical for assessing the severity of the systemic inflammatory response.
Complete blood counts typically show leukocytosis and thrombocytosis (an abnormal elevation in platelet count). Acute-phase reactants are markedly elevated: the erythrocyte sedimentation rate (ESR) rises significantly, and C-reactive protein (CRP) levels increase (often remaining elevated for 4–6 weeks). Serum protein electrophoresis and immunoglobulins generally show hypergammaglobulinemia.
To confirm the diagnosis of Henoch–Schönlein purpura, serum IgA levels may be assessed (typically elevated), and tissue biopsies can demonstrate IgA deposition in the skin or renal mesangium.