Microscopic Polyangiitis (MPA) is a severe, systemic autoimmune disease belonging to the category of vasculitis, which is characterized by the inflammation of blood vessels. As a form of small-vessel vasculitis, MPA specifically targets the capillaries, venules, and arterioles throughout the body. This condition occurs when the immune system mistakenly attacks the lining of these small blood vessels, causing inflammation and disrupting normal blood flow. MPA represents a serious health concern due to its potential to cause rapid and widespread organ damage.
How Microscopic Polyangiitis Damages the Body
The damage in Microscopic Polyangiitis is driven by the misguided action of the immune system, particularly the presence of Anti-Neutrophil Cytoplasmic Antibodies (ANCA). In the majority of MPA cases, these autoantibodies are directed against myeloperoxidase (MPO-ANCA), a specific enzyme found within white blood cells. The underlying cause is believed to involve a genetic predisposition combined with an environmental trigger, such as an infection, which initiates this autoimmune response.
Once produced, MPO-ANCA antibodies circulate and bind to neutrophils, a type of white blood cell, that have been primed by inflammatory signals. This binding activates the neutrophils, causing them to adhere to the inner walls of small blood vessels (endothelium). The activated neutrophils then release destructive substances, including reactive oxygen species and lytic enzymes, directly onto the vessel wall.
This process results in necrotizing vasculitis, characterized by inflammation and cell death in the blood vessel walls. The damage is often described as “pauci-immune” because it lacks the large immune-complex deposits seen in other forms of vasculitis. Vessel walls become weakened, leading to leaks, or they narrow and restrict blood flow, resulting in tissue death and organ failure.
Recognizing the Symptoms
The initial signs of Microscopic Polyangiitis are often non-specific and mimic those of a viral infection, making early diagnosis challenging. Patients commonly experience constitutional symptoms such as persistent fatigue, unexplained fever, night sweats, and unintentional weight loss.
The disease quickly progresses to involve specific organs, with the kidneys being the most frequently affected, occurring in up to 90% of cases. Kidney involvement often manifests as rapidly progressive glomerulonephritis, where the filtering units become inflamed and damaged. This can present as hematuria (blood in the urine) and proteinuria (excess protein in the urine), often without noticeable symptoms until function is significantly impaired.
Pulmonary involvement is also common and can be life-threatening, presenting as capillaritis that leads to diffuse alveolar hemorrhage (bleeding into the lungs). Symptoms include a cough, shortness of breath, and sometimes hemoptysis (coughing up blood). When both the lungs and kidneys are affected simultaneously, this is referred to as a pulmo-renal syndrome.
The disease can also affect other organs, including the skin, where inflammation causes a rash known as palpable purpura (raised, non-blanching red or purple spots). The peripheral nervous system may also be affected, leading to peripheral neuropathy that causes numbness, tingling, or weakness, often in the hands and feet.
Confirming the Diagnosis
Confirming a diagnosis of Microscopic Polyangiitis requires a combination of clinical evaluation and specific laboratory tests. A blood test for Anti-Neutrophil Cytoplasmic Antibodies (ANCA) is a primary step. A positive result for MPO-ANCA strongly supports the diagnosis in the context of clinical symptoms, though a small percentage of patients may test negative or positive for a different ANCA type.
A comprehensive urinalysis is routinely performed to check for signs of kidney damage, such as red blood cells, red blood cell casts, and excessive protein. Blood tests measure kidney function, specifically serum creatinine levels, which indicate how well the kidneys are filtering waste. Imaging studies, such as a high-resolution CT scan of the chest, may also be used to assess the extent of pulmonary involvement.
The definitive confirmation of MPA typically relies on obtaining a tissue biopsy from an affected organ, most commonly the kidney or skin. Pathologists examine the sample under a microscope to look for the characteristic pattern of necrotizing vasculitis, which shows inflammation and destruction of the small vessel walls. The biopsy must also confirm the “pauci-immune” nature of the inflammation.
Treatment Strategies
Treatment for Microscopic Polyangiitis is intensive and generally follows a two-phased approach: halting the active disease and preventing future relapses. The initial phase, known as induction therapy, aims to rapidly achieve disease remission and prevent further organ damage using high-dose immunosuppressive medications.
Glucocorticoids, such as high-dose prednisone or intravenous methylprednisolone, are used to quickly suppress widespread inflammation. These are combined with a potent immunosuppressant: either cyclophosphamide (a traditional chemotherapy agent) or rituximab (a monoclonal antibody that targets B-cells). The choice between these agents depends on disease severity and patient-specific factors.
Once remission is achieved, the patient transitions to maintenance therapy, a longer-term strategy to prevent disease recurrence. This phase involves lower doses of immunosuppressants for an extended period, often lasting for years. Common maintenance agents include azathioprine or methotrexate, which are less toxic than cyclophosphamide, or continued, less frequent infusions of rituximab. The goal is to keep immune system inflammation controlled while minimizing medication side effects and preserving long-term organ function.