What is microscopic polyangiitis?

 Microscopic Polyangiitis

Microscopic polyangiitis is a necrotizing vasculitis that generally affects capillaries, as well as small arterioles and venules. It also is called hypersensitivity vasculitis or leukocytoclastic vasculitis.

Unlike in PAN (polyarteritis nodosa), all lesions of microscopic polyangiitis tend to be of the same age in any given patient. The skin, mucous membranes, lungs, brain, heart, gastrointestinal tract, kidneys, and muscle all can be involved; necrotizing glomerulonephritis (seen in 90% of patients) and pulmonary capillaritis are particularly common Microscopic angiitis can be a feature of a number of immune disorders, such as Henoch-Schönlein purpura, essential mixed cryoglobulinemia, or the vasculitis associated with connective tissue disorders.

In some cases, antibody responses to antigens such as drugs (e.g., penicillin), microorganisms (e.g., streptococci), heterologous proteins, or tumor proteins have been implicated. These reactions can either lead to immune complex deposition or trigger secondary immune responses (e.g., the development of ANCAs) that are pathogenic. Indeed, most cases of microscopic polyangiitis are associated with MPO-ANCA. Recruitment and activation of neutrophils within affected vascular beds is probably responsible for the disease manifestations.

Morphology of Microscopic Polyangiitis

1. Vascular Changes:

• Affects small vessels: arterioles, capillaries, and venules.

• Necrotizing vasculitis with fibrinoid necrosis of the vessel wall.

• No granulomas (important distinction from granulomatosis with polyangiitis).

2. Organs Commonly Affected:

• Kidneys:

  • Necrotizing glomerulonephritis (pauci-immune type).

• Lungs:

  • Capillaritis with alveolar hemorrhage.

• Skin:

  • Palpable purpura due to dermal small vessel vasculitis.

• Other sites: GI tract, nerves, muscles (depending on vessel involvement).

Pathogenesis of Microscopic Polyangiitis (MPA):

1. Trigger: Likely initiated by drugs, infections, or other unknown antigens in genetically predisposed individuals.

2. Immune response:

   • Production of anti-neutrophil cytoplasmic antibodies (ANCAs), mainly p-ANCA (anti-MPO).

   • ANCAs activate neutrophils, especially in small vessels.

3. Vessel damage:

   • Activated neutrophils adhere to endothelium and release reactive oxygen species and enzymes.

   • This causes fibrinoid necrosis and inflammation of small vessels (capillaries, venules, and arterioles).

4. Tissue injury:

   • Results in necrotizing vasculitis in multiple organs.

   • Minimal immune complex deposition → known as pauci-immune vasculitis.

Clinical Features

Depending on the vascular bed involved, major features include hemoptysis, hematuria, proteinuria, abdominal pain or bleeding, muscle pain or weakness, and palpable cutaneous purpura. 

With the exception of patients with widespread renal or CNS involvement, immunosuppression and removal of the offending agent induce durable remission.