Microscopic Polyangiitis (MPA) is a rare and serious autoimmune disorder that causes widespread inflammation by mistakenly attacking healthy tissues. MPA affects the body’s small blood vessels. This condition can be challenging to identify because its symptoms often mimic those of other, more common illnesses. Understanding the nature of MPA is important, as it requires swift and focused medical intervention to prevent permanent organ damage.
Defining Microscopic Polyangiitis
MPA is defined as a systemic, necrotizing small-vessel vasculitis, involving inflammation and destruction of the walls of the smallest blood vessels (capillaries, venules, and arterioles). This inflammation restricts blood flow, damaging organs and tissues throughout the body. MPA is unique because it is considered a “pauci-immune” vasculitis, meaning there are little or no immune complex deposits in the affected tissue when examined.
This condition is categorized as one of the Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitides (AAV), a group of autoimmune diseases linked to specific antibodies. ANCA are blood proteins that target components within neutrophils, a type of white blood cell. The presence of these autoantibodies is a hallmark of MPA and is thought to play a direct role in causing vessel inflammation.
In MPA patients, ANCA are most frequently directed against myeloperoxidase (MPO), leading to MPO-ANCA positivity. Unlike related forms of vasculitis, MPA typically presents without granulomas, which are organized clusters of inflammatory cells. This distinction in the pattern of inflammation helps medical professionals differentiate MPA from other AAV disorders. MPA generally affects older adults, with the median age at diagnosis often around 65 years.
Causes and Underlying Mechanisms
The precise cause that initiates Microscopic Polyangiitis remains unknown, but it is established as an autoimmune disease where the body’s defenses turn inward. This misdirected immune response suggests a combination of genetic predisposition and environmental factors must align to trigger the disease. Certain genetic markers, such as specific human leukocyte antigen (HLA) types, indicate that some individuals inherit a higher susceptibility to the disorder.
In a genetically susceptible person, an outside factor is believed to act as a trigger, disrupting the immune system’s tolerance. Potential environmental triggers include infections, exposure to toxins like silica, or reactions to certain medications. Once activated, the immune system produces ANCA antibodies that target components within neutrophils.
The mechanism of vessel damage begins when ANCA antibodies bind to the surface of neutrophils, priming them. This interaction causes the activated neutrophils to attach to the walls of the small blood vessels. The activated neutrophils then release damaging enzymes and reactive oxygen species, leading to inflammation, necrosis, and rupture of the vessel walls. This process, known as leukocytoclastic inflammation, results in the characteristic destruction of the vessel wall.
How MPA Affects the Body (Clinical Presentation)
Because MPA is a systemic disorder, it most frequently and severely targets the kidneys and lungs. Initial symptoms are often non-specific, including malaise, fever, unexplained weight loss, and muscle or joint pain, which complicates early diagnosis. These constitutional symptoms may precede severe organ involvement by weeks or months.
Kidney involvement occurs in up to 90% of patients and often presents as rapidly progressive glomerulonephritis (RPGN). Glomerulonephritis is inflammation of the tiny filtering units within the kidney, leading to blood and protein leaking into the urine. This damage may be initially silent, but if left untreated, it can quickly progress to kidney failure, requiring urgent medical attention.
The lungs are the second most commonly affected organ. A life-threatening manifestation is diffuse alveolar hemorrhage, which is bleeding from the small capillaries into the air sacs. This can cause a cough, shortness of breath, and hemoptysis (coughing up blood).
MPA can manifest in other areas of the body beyond the kidneys and lungs. Skin involvement is frequent, often appearing as palpable purpura (a rash of small, raised purple spots, especially on the legs). Inflammation of the peripheral nerves, known as mononeuritis multiplex, can lead to numbness, tingling, or weakness in the extremities. Other manifestations include eye inflammation, gastrointestinal bleeding, and abdominal pain.
Diagnosis and Treatment Approaches
Diagnosing MPA requires combining a review of the patient’s symptoms with specific laboratory and imaging tests. The physician looks for the characteristic clinical presentation, particularly systemic symptoms combined with evidence of kidney or lung damage. Laboratory blood tests check for markers of inflammation, such as an elevated erythrocyte sedimentation rate or C-reactive protein.
The most specific laboratory test screens for ANCA, which are found in a majority of MPA patients. A positive test for MPO-ANCA strongly supports the diagnosis, though a small percentage of patients may test negative. Urinalysis is performed to detect blood and protein in the urine, serving as an early indicator of kidney inflammation and damage.
To confirm the diagnosis and assess organ damage, a tissue biopsy is frequently required, often taken from the kidney, lung, or skin. This sample is examined for evidence of necrotizing vasculitis and the characteristic lack of significant immune deposits. Imaging studies, such as a chest CT scan, are also employed to look for lung abnormalities, helping to identify alveolar hemorrhage or other pulmonary issues.
Treatment for MPA is divided into two phases: induction and maintenance, with the goal of rapidly achieving and sustaining remission. The induction phase controls active, life-threatening inflammation using high-dose corticosteroids, such as prednisone, to quickly suppress the immune response. This is combined with immunosuppressive medications, such as cyclophosphamide or the biologic agent rituximab, to halt disease activity and induce remission.
Once the disease is in remission, the patient transitions to the maintenance phase, designed to prevent relapses using lower doses of immunosuppressants. Common maintenance drugs include azathioprine or methotrexate, continued for an extended period, often one to two years or longer. Long-term monitoring is necessary due to the chronic nature of the condition and the potential for relapse. Management focuses on regular check-ups, blood tests, addressing lasting organ damage, and managing side effects from immunosuppressive therapies.