| Systemic vasculitis | |
|---|---|
| Other names | Necrotizing vasculitis |
 | |
| A case ofvasculitis on legs | |
| Specialty | Immunology,rheumatology |
Necrotizing vasculitis, also calledsystemic necrotizing vasculitis,[1] is a general term for theinflammation ofveins andarteries that develops intonecrosis and narrows the vessels.[2]
Tumors, medications,allergic reactions, and infectious organisms are some of the recognized triggers for these conditions, even though the precise cause of many of them is unknown. Immune complex disease,anti-neutrophil cytoplasmic antibodies, anti-endothelial cell antibodies, and cell-mediated immunity are examples of pathogenetic factors.[2]
Numerous secondary symptoms of vasculitis can occur, such asthrombosis,aneurysm formation, bleeding, occlusion of an artery, loss of weight,exhaustion,depression, fever, and widespread pain that worsens in the morning.[2]
Systemic vasculitides are categorized as small, medium, large, or variable based on the diameter of the vessel they primarily affect.[3]
The 2012Chapel Hill Consensus Conference defines large vessel vasculitis (LVV) as a type of vasculitis that can affect any sizeartery, but it usually affects the aorta and its major branches more frequently than other vasculitides.[4]Takayasu arteritis (TA) andgiant cell arteritis (GCA) are the two main forms of LVV.[5]
Takayasu arteritis (TA) is a large-vessel, idiopathic, granulomatous arteritis that primarily affects theaorta, significant branches of it, and (less frequently) thepulmonary arteries.[6] The disease's symptoms can range from catastrophic neurological impairment to an asymptomatic condition brought on by impalpable pulses orbruits.[7] Non-specific features include mildanemia,myalgia,arthralgia,weight loss,malaise,night sweats, andfever.[8]
Giant cell arteritis (GCA) is the most common type of systemic vasculitis in adults.Polymyalgia rheumatica (PMR), headache,jaw claudication, and visual symptoms are the classic manifestations; however, 40% of patients present with a variety of occult manifestations.[9]
Medium vessel vasculitis is a type of vasculitis that mostly affects the mediumarteries, which are the major arteries that supply theviscera and their branches. Any size artery could be impacted, though.[4] The two primary types arepolyarteritis nodosa andKawasaki disease.[5]
Polyarteritis nodosa is a type of systemic necrotizing vasculitis that primarily affects arteries of medium size. While small vessels likearterioles,capillaries, andvenules are not affected, smallarteries can be. The disease spectrum varies from failure of multiple organs to involvement of a single organ. Almost any organ could be impacted; however,polyarteritis nodosa rarely affects thelungs for unknown reasons.[10]
Kawasaki disease is a type of systemic vasculitis of medium-sized vessels with an acute onset that primarily affects young children.Fever,conjunctivitis, infection of the skin andmucous membranes, andcervical lymphadenopathy are the main symptoms.[11]
Small vessel vasculitis (SVV) is separated into immune complex SVV andantineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).[4]
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis linked to MPO-ANCA or PR3-ANCA that primarily affects small vessels and has few or no immune deposits. AAV is further classified aseosinophilic granulomatosis with polyangiitis,granulomatosis with polyangiitis, andmicroscopic polyangiitis.[4]
Eosinophilic granulomatosis with polyangiitis is a systemic small-vessel vasculitis linked toeosinophilia andasthma.Polyneuropathy, cardiac involvement, skin lesions, involvement of theupper respiratory tract, and lung are typical presentations ofeosinophilic granulomatosis with polyangiitis.[12]
Granulomatosis with polyangiitis, formerly known as Wegener's granulomatosis, is a rare immune-mediated systemic disease with an unclear etiology. It manifests pathologically as an inflammatory response pattern in the kidneys, upper and lowerrespiratory tracts, and granulomatous inflammation, which includesnecrosis.[13]
Microscopic polyangiitis belongs to the group of vasculitides associated with ANCA. Its distinct histology reveals a pauci-immune vasculitis, or necrotizing small vessel vasculitis, with minimal or no immune deposits.[14] The most typical features of microscopic polyangiitis are renal manifestations and general symptoms; lung involvement is also frequently observed.[15]
Immune complex small vessel vasculitis (SVV) is a vasculitis that primarily affects small vessels and has moderate to significantimmunoglobulin and complement component deposits on the vessel wall.[4] Hypocomplementemicurticarial vasculitis,cryoglobulinemic vasculitis,IgA vasculitis, andanti-glomerular basement membrane disease are the categories of immune complex SVV.[5]
Hypocomplementemicurticarial vasculitis syndrome is a rare immune complex-mediated condition that has persistent acquiredhypocomplementemia andurticaria. Many systemic manifestations are linked to hypocomplementemic urticarial vasculitis syndrome, such asleukocytoclastic vasculitis,glomerulonephritis,laryngeal edema, severeangioedema, pulmonary involvement,arthritis,arthralgia, anduveitis.[16]
Cryoglobulinemic vasculitis is a type of small-vessel vasculitis that primarily affects the kidneys, skin, joints, andperipheral nervous system. Monoclonalimmunoglobulins associated with an underlyingB-cell lymphoproliferative disorder are known as type I cryovalent vasculitis.Cryoglobulins type II and III, also known as mixedcryoglobulinemia, are composed of polyclonalimmunoglobulin (Ig)G and either monoclonalIgM or both withrheumatoid factor activity. The disease can present with a wide range of symptoms, from minor ones likefatigue,purpura, orarthralgia to more serious ones likeglomerulonephritis and widespread vasculitis that can be fatal.[17]
Immunoglobulin A (IgA) vasculitis, formerly referred to asHenoch–Schönlein purpura, is a type of immune complex vasculitis that primarily affectsIgA deposits in small vessels. Acuteenteritis,glomerulonephritis,arthralgias and/orarthritis, and cutaneouspurpura are the most common clinical manifestations. Children are more likely than adults to develop IgA vasculitis, and adults tend to have a more severe case.[18]
Anti-glomerular basement membrane disease is an uncommon kind of small vessel vasculitis that affects the kidney and lung capillary beds. This illness is also known by its eponym, "Goodpasture syndrome".[19]
Variable vessel vasculitis is a kind of vasculitis that may impact vessels of all sizes (small, medium, and large) and any type (arteries,veins, andcapillaries), with no particular type of vessel being predominantly affected.[4] This category includesBehcet's disease andCogan's syndrome.[5]
Behçet's disease is a systemic illness marked by frequent episodes of severe inflammation. Genital ulcerations,uveitis, oral aphthous ulcers, and skin lesions are the main symptoms.[20]
Cogan's syndrome is an uncommon type of autoimmune systemic vasculitis that causes inflammation inside the eyes and malfunctions the vestibulo-auditory system, usually resulting inneurosensory deafness but alsotinnitus andvertigo.[21] Anupper respiratory tract infection, or less frequently,diarrhea, adental infection, or animmunization, precedes the onset of the disease.[22]
Kussmaul and Maier gave the first detailed description of systemic necrotizing arteritis in 1866.[23]
In 1919Karl Theodor Fahr[24] described acute arteriallesions which were always present inmalignantnephrosclerosis. These injuries were the most severe and widespread in thekidneys and occurred less frequently and severely in otherorgans, particularly in thepancreas,adrenals andintestines. Fahr believed that necrotizing arteriolitis was the primary cause of the lesions, malignant necrosis andhypertension in these cases by narrowing the renalvascular bed.[23]
Prodromal symptoms, constitutional abnormalities, and organ-specific manifestations are common invasculitis patients. Patients may show up at the emergency room with life-threatening symptoms (such as massivehemoptysis orrenal failure) or with nonspecific signs and symptoms (such as arash,fever,myalgia,arthralgia,malaise, orweight loss) at their family physician's office. The size, location, and extent of the vessels involved all affect the manifestations.[25]
Takayasu arteritis (TA) is typically documented in three distinct phases. There are generalized constitutional inflammatory symptoms during the first stage. Patients may reportfever of unknown cause during this phase. Patients may refer to dorsal and thoracic pain in the following phase, and infrequently,neck pain as well.Arterial bruits, intermittent extremityclaudication, decreased or absent pulses, and/or variations in arterialblood pressure among upper extremities are the hallmarks of the final phase.[26]
Giant cell arteritis (GCA) often exhibits a wide range of symptoms in its early stages, all of which are related to the localized consequences of systemic and vascular inflammation. The symptoms of GCA includejaw claudication,headaches, and tenderness in the scalp. The most common symptom isheadache, which is restricted to the temporal region.[3]
Polyarteritis nodosa (PAN) can affect one organ or cause systemic failure as its clinical manifestation.[27] Although any tissue may be impacted, PAN rarely affects thelungs for unclear reasons.[28] A variety of clinical indicators, including common symptoms likefever,chills,weight loss,myalgia, andarthralgia, are typically present when PAN first manifests.Peripheral nerves and skin are typically involved in PAN. Skin manifestations includepurpura, necrotic ulcers, subcutaneous nodules, and livedoid.Mononeuritis multiplex is the main neurological symptom, typically presenting as a drop in the foot or wrist.[3]
Patients withKawasaki disease often have afever between 38 and 40 degrees Celsius and often show noprodromal symptoms. Within two to four days of the illness starting, bilateralconjunctival injections withoutexudate become visible. The term "modifications of the oral cavity" usually refers to conditions such as diffuseerythema of the oropharyngeal mucosa, strawberry-like tongue without vesicles or pseudo-membrane formation, bleeding of the lips, redness, fissuring, and dryness. From the first to the fifth day following the onset of fever, polymorphouserythema appears on the body and/or extremities.[3]
Malaise,arthralgia,sinusitis, andrhinitis are typically present at the beginning ofAnti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.Prodromes often occur weeks or months beforepulmonary-renal syndrome.[3]
Anti-glomerular basement membrane vasculitis patients usually report sudden onset ofanuria oroliguria. Typically,hematuria or tea-colored urine are noticed.[3]
Many cases ofcryoglobulinemia vasculitis are asymptomatic.[29]Hyperviscosity and/orthrombosis are the principal signs and symptoms of type Icryoglobulinemia. As a result, the conditions most frequently manifested asRaynaud's phenomenon, distalgangrene, ischemic ulcers,purpura,livedo reticularis,headache, retinal hemorrhages, andencephalopathy. Nonspecific systemic and musculoskeletal symptoms, such ascutaneous vasculitis andneuropathy, can also be seen in patients with mixed cryoglobulinemia.[30]
Ninety-five percent of cases ofimmunoglobulin A vasculitis start with a skin rash.[31] Additionally, the illness manifests as the standard tripartite of symptoms pertaining to the gastrointestinal, renal, and musculoskeletal systems.[32]
Recurrenturticaria, with skin eruptions primarily affecting the trunk, face, and upper extremities, is the primary clinical manifestation of hypocomplementemicurticarial vasculitis.[33]
Oralaphthae are the defining feature ofBehçet's disease and manifest in 98% of patients. Compared to oral lesions, genital aphthae are less common.[3]
Often, theupper respiratory tract infection is the initial sign of Cogan's syndrome.[3] Ocular and audio-vestibular symptoms are typical indicators. Non-syphiliticinterstitial keratitis (IK),uveitis,retinal vasculitis,conjunctivitis,scleritis,tinnitus,hearing loss, andvertigo are among the range of ocular manifestations.[34]
To confirm the diagnosis, the initial evaluation consists of a thorough clinical assessment,serological tests,histology when possible, andradiography when necessary.[35]
Individuals experiencing activevasculitis frequently exhibitanemia,thrombocytopenia, andleukocytosis. One of the main characteristics ofeosinophilic granulomatosis with polyangiitis iseosinophilia.[25]
Patients with vasculitis frequently have increasederythrocyte sedimentation rate and elevatedC-reactive protein levels; however, these symptoms are nonspecific and can arise in a variety of circumstances, most notably infection. When vasculitis is not active, normalerythrocyte sedimentation rate orC-reactive protein level can occur and should not rule out the diagnosis. When paired with congruent clinical features, an elevatederythrocyte sedimentation rate ingiant cell arteritis patients can both support the diagnosis and aid in disease monitoring.[25]
In any patient suspected of havingvasculitis, measurements ofblood urea nitrogen,serum creatinine, and urine should be taken.Hematuria andproteinuria raise the risk ofglomerulonephritis.Serum bilirubin andliver enzyme levels (ó-glutamyltransferase,alkaline phosphatase, andaspartate andalanine transaminase) can give indications for liver-related vasculitis, likepolyarteritis nodosa.[25]
Antineutrophil cytoplasmic antibodies (ANCAs) are a diverse collection ofautoantibodies that targetneutrophil enzymes and have been detected in the serum of many vasculitis patients. The conditions known as ANCA-associated vasculitides, which are characterized by circulating ANCAs, comprisegranulomatosis with polyangiitis,microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis.[25]
Chest radiography may reveal nonspecific abnormalities such ascardiomegaly, patchy consolidation, nodules, and infiltrates. These results can happen in a variety of situations, but if they go undiagnosed, they could point to vasculitis.[25]
Aneurysms andvascular occlusion can be seen withangiography.Polyarteritis nodosa can be verified by looking foraneurysms in therenal andmesenteric arteries. While conventionalangiography remains the accepted standard diagnostic modality, there is potential for superiority withcomputed tomography angiography andmagnetic resonance angiography, as they can offer important insights into intraluminal pathology and vessel wall thickening. These methods have been applied toKawasaki disease andTakayasu arteritis diagnosis and follow-up.[25]
WhenKawasaki disease is present,transthoracic echocardiography can identify coronary artery abnormalities.[25]Echocardiography reveals coronary artery lesions (ectasia oraneurysm) in about 40% of children withKawasaki disease.[36] In patients withTakayasu arteritis,echocardiography is used to measure the degree of coronarystenosis andcoronary artery blood flow.[37]
For the diagnosis and ongoing observation of large vessel vasculitis,ultrasonography may be helpful. Individuals diagnosed withgiant cell arteritis may present with superficial temporal arterystenosis, occlusion, or halo sign (a dark patch surrounding the artery due to vessel walledema).[25]
When diagnosing patients withgranulomatosis with polyangiitis,computed tomography is useful. Results include destruction of punctate bone, primarily in the midline, and thickening of thenasal mucosa.[25] In about 90% of patients with granulomatosis with polyangiitis, a chest computed tomography scan will show nodules or masses.[38]
Systemic vasculitides, such aspolyarteritis nodosa,granulomatosis with polyangiitis, andeosinophilic granulomatosis with polyangiitis, can result in motor andsensory neuropathy. Neurological manifestations should be evaluated bynerve conduction testing.[25]
Abiopsy of the affected tissue (such as the skin, the sinuses, lung, artery, nerve, or kidney) is used to make a definitive diagnosis of vasculitis by identifying the pattern of vessel inflammation. Determining the precise type of vasculitis may be made easier by looking forimmunoglobulins and complement on the tissue section as detected byimmunofluorescence. Although a negative biopsy cannot rule out vasculitis, biopsies are especially useful in ruling out other causes.[25]
Treatment is targeted at the underlying cause. However, most vasculitides, in general, are treated withsteroids (e.g.,methylprednisolone) because the underlying cause of the vasculitis is due to hyperactive immunological damage. Immunosuppressants such ascyclophosphamide andazathioprine may also be given.
Asystematic review ofantineutrophil cytoplasmic antibody-positive vasculitis identified the best treatments depending on whether the goal is to induce remission or maintenance and depending on the severity of the vasculitis.[39]