Systemic vasculitis is a group of rare disorders defined by inflammation of the blood vessel walls. This inflammation can affect arteries, veins, arterioles, venules, or capillaries across the body. The term “systemic” emphasizes that the disease is not confined to a single area, having the potential to impact virtually any organ or body system. These conditions can range from mild to life-threatening, making accurate diagnosis and management important.
Understanding the Inflammatory Mechanism
Systemic vasculitis is fundamentally an autoimmune process where the body’s own immune system mistakenly targets the cells lining the blood vessels. This misdirected attack leads to the infiltration of inflammatory cells, such as leukocytes, into the vessel wall, causing the swelling and thickening that defines vasculitis.
The inflammation damages the structure of the vessel, which can have several mechanical consequences. Damage can cause the vessel’s interior to narrow (stenosis) or lead to complete blockage (occlusion). Alternatively, the vessel wall can weaken and bulge outward, forming an aneurysm, which risks rupture and hemorrhage. These changes restrict or stop blood flow, depriving downstream tissues of oxygen and nutrients, resulting in tissue death (ischemia).
In some forms of vasculitis, specific autoantibodies like anti-neutrophil cytoplasmic antibodies (ANCA) play a direct role in this process. ANCA target components within neutrophils, causing them to activate and release destructive enzymes and reactive oxygen species. This activation leads to a necrotizing inflammation, characterized by tissue destruction in the vessel wall.
Categorizing Systemic Vasculitis
To organize this diverse group of diseases, clinicians use the Chapel Hill Consensus Classification, which primarily categorizes vasculitis based on the size of the blood vessels predominantly affected. This size-based system creates three main groups: large, medium, and small vessel vasculitis, although some overlap can occur.
Large Vessel Vasculitis (LVV) mainly affects the aorta and its major branches, such as the arteries leading to the head and limbs. The recognized forms are Giant Cell Arteritis (GCA) and Takayasu Arteritis (TAK). The inflammation in LVV is often granulomatous, involving the accumulation of specialized immune cells, and can lead to diminished or absent pulses and vascular bruits.
Medium Vessel Vasculitis (MVV) primarily targets the main visceral arteries, which are the vessels supplying internal organs, and their immediate branches. Polyarteritis Nodosa (PAN) and Kawasaki Disease (KD) are the two main examples within this category. This form of vasculitis frequently results in the formation of inflammatory aneurysms and areas of stenosis in the affected arteries.
Small Vessel Vasculitis (SVV) affects the smallest vessels, including the capillaries, venules, arterioles, and intraparenchymal arteries. This group is further subdivided, including the ANCA-associated vasculitides (AAV) like Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA). Small vessel inflammation is often associated with a necrotizing pattern and can lead to rapidly progressive damage in organs like the kidneys and lungs.
Common Signs and Manifestations
The symptoms of systemic vasculitis are highly diverse because they depend entirely on the specific location and extent of the affected blood vessels. The onset of the disease is frequently marked by non-specific signs of widespread inflammation, making initial diagnosis often difficult.
Patients commonly report constitutional symptoms such as persistent fever, profound fatigue, and unexplained weight loss. Joint pain (arthralgia) and muscle aches (myalgias) are also frequent initial complaints. These general symptoms often precede or accompany the more specific manifestations of organ involvement.
When the disease targets specific organs, the symptoms become more localized. Skin involvement is common, often presenting as palpable purpura (small, raised purple spots), ulcers, or rashes. Nervous system involvement can cause numbness, tingling, or weakness due to nerve damage. Kidney dysfunction may manifest as blood in the urine, while inflammation in the lungs can cause coughing or shortness of breath.
Diagnostic Procedures and Management
Diagnosis of systemic vasculitis begins with a thorough medical history and physical examination, looking for specific patterns of organ involvement and signs of systemic illness. Laboratory tests support the suspicion of vasculitis, often revealing general markers of inflammation, such as elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).
Specialized blood tests search for autoantibodies, particularly Antineutrophil Cytoplasmic Antibodies (ANCA), characteristic of certain small vessel vasculitides. Imaging techniques (CT scans, MRI, and specialized angiography) visualize affected vessels, detecting narrowing or aneurysms and determining the extent of organ damage. The most definitive diagnostic tool is a biopsy, where a small piece of the affected tissue or vessel is examined under a microscope for signs of inflammation.
The primary goal of managing systemic vasculitis is to stop the immune-driven inflammation and prevent further organ damage. The standard treatment approach involves powerful immunosuppressive drugs. High-dose corticosteroids, such as prednisone, are typically prescribed to rapidly control the initial inflammation.
For more severe or organ-threatening disease, corticosteroids are often combined with other specialized immunosuppressive agents, such as cyclophosphamide or rituximab, to induce remission. Treatment is generally divided into two phases: an induction phase to quickly bring the disease under control, followed by a maintenance phase with less potent medications to keep the disease suppressed and prevent relapses.