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| {{SK}} vasculitis, angiitides, angiitis, arteritis, vasculitides | | {{SK}} vasculitis, angiitides, angiitis, arteritis, vasculitides |
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| ==Overview== | | ==[[Vasculitis overview|Overview]]== |
| '''Vasculitis''' (plural: ''vasculitides''), a group of diseases featuring [[inflammation]] of the wall of [[blood vessel]]s including veins ([[phlebitis]]), arteries ([[arteritis]]) and capillaries due to [[leukocyte]] migration and resultant damage. While most vasculitides are rare, they generally affect several organ systems and can cause severe disability.
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| ==Classification== | | ==[[Vasculitis historical perspective|Historical Perspective]]== |
| Vasculitides can be classified by the size of the blood vessel that they predominantly affect.<ref name="pmid8129773">{{cite journal |author=Jennette JC, Falk RJ, Andrassy K, ''et al'' |title=Nomenclature of systemic vasculitides. Proposal of an international consensus conference |journal=Arthritis Rheum. |volume=37 |issue=2 |pages=187-92 |year=1994 |pmid=8129773 |doi=}}</ref>
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| ===Large vessel vasculitis=== | | ==[[Vasculitis classification|Classification]]== |
| '''[[Takayasu arteritis]]'''. Primarily affects the [[aorta]] and its main branches. At least 3 out of 6 criteria yields sensitivity and specificity of 90.5 and 97.8%:
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| * Onset < 40 years
| | ==[[Vasculitis pathophysiology|Pathophysiology]]== |
| * [[Claudication]] of extremities
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| * Decreased pulsation of one or both [[brachial|brachial arteries]]
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| * At least 10 mmHg [[cardiac cycle|systolic]] difference in both arms
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| * [[Bruit]] over one or both [[carotid arteries]] or abdominal aorta
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| * Arteriographic narrowing of [[aorta]], its primary branches, or large arteries in upper or lower extremities
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| ----
| | ==[[Vasculitis causes|Causes]]== |
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| '''[[temporal arteritis|Giant cell (temporal) arteritis]]'''. Chronic vasculitis of both large and medium vessels, primarily affecting cranial branches of the arteries arising from the aortic arch. At least 3 out of 5 criteria yields sensitivity and specificity of 95 and 91%:
| | ==[[Vasculitis differential diagnosis|Differentiating Vasculitis from other Diseases]]== |
| * Age at onset ≥ 50 years
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| * New onset [[headache]] with localized tenderness
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| * [[Temporal artery]] tenderness or decreased pulsation
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| * Elevated [[ESR]] ≥ 50 mm/hour Westergren
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| * Temporal artery biopsy showing vasculitis with [[mononuclear cell]] infiltrate or granulomatous inflammation, usually with multinucleated giant cells
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| | ==[[Vasculitis epidemiology and demographics|Epidemiology and Demographics]]== |
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| ===Medium vessel vasculitis=== | | ==[[Vasculitis risk factors|Risk Factors]]== |
| '''[[Polyarteritis nodosa]]'''. Systemic necrotizing vasculitis and [[aneurysm]] formation affecting both medium and small arteries. If only small vessels are affected, it is called microscopic polyangiitis, although it is more associated with [[Wegener's granulomatosis]] than to classic [[PAN]]. At least 3 out of 10 criteria yields sensitivity and specificity of 82 and 87%:
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| * Unexplained [[weight loss]] > 4 kg
| | ==[[Vasculitis natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| * [[Livedo reticularis]]
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| * [[Testicular pain]]
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| * [[Myalgias]], [[weakness]]
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| * [[Mononeuropathy]] or [[polyneuropathy]]
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| * New onset diastolic blood pressure > 90 mmHg
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| * Elevated serum [[BUN]] (> 40 mg/dL) or serum [[creatinine]] (> 1.5 mg/dL)
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| * [[Hepatitis B infection]]
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| * Arteriographic abnormalities
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| * Arterial biopsy showing [[polymorphonuclear cells]]
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| '''[[Wegener's granulomatosis]]'''. Systemic vasculitis of medium and small arteries, including venules and arterioles. Produces granulomatous inflammation of the respiratory tracts and necrotizing, pauci-immune glomerulonephritis. Most common cause of saddle nose deformity in USA (nose flattened due to destruction of nasal septum by granulomatous inflammation). Almost all patients with WG has c-ANCA, but not vice versa. Current treatment of choice is cyclophosphamide. At least 2 out of 4 criteria yields sensitivity and specificity of 88 and 92%.
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| * nasal or oral inflammation (oral ulcers or purulent/bloody nasal discharge, may be painful)
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| * abnormal CXR showing nodules, infiltrates, cavities
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| * microscopic hematuria or RBC casts
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| * vessel biopsy shows granulomatous inflammation
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| '''[[Kawasaki disease]]'''. Usually in children, it affects large, medium, and small vessels, prominently the coronary arteries. Associated with a mucocutaneous lymph node syndrome. Diagnosis requires fever lasting five days or more with at least 4 out of 5 criteria:
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| * bilateral conjunctival injection
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| * injected or fissured lips, injected pharynx, or strawberry tongue
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| * erythema of palms/soles, edema of hands/feet, periungual desquamation
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| * polymorphous rash
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| * cervical lymphadenopathy (at least one node > 1.5 cm)
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| '''Isolated CNS vasculitis'''. Affects medium and small arteries over a diffuse CNS area, without symptomatic extracranial vessel involvement. Patients have CNS symptoms as well as cerebral vasculitis by angiography and leptomeningeal biopsy.
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| ===Small vessel vasculitis===
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| There are several vasculitides that affect small vessels.<ref name="pmid9366584">{{cite journal |author=Jennette JC, Falk RJ |title=Small-vessel vasculitis |journal=N. Engl. J. Med. |volume=337 |issue=21 |pages=1512-23 |year=1997 |pmid=9366584 |doi=}}</ref>
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| '''[[Churg-Strauss syndrome|Churg-Strauss arteritis]]'''. Affects medium and small vessels with vascular and extravascular granulomatosis. Classically involves arteries of lungs and skin, but may be generalized. At least 4 criteria yields sensitivity and specificity of 85 and 99.7%.
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| * [[Asthma]] (history of [[wheezing]] or presently wheezing)
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| * [[Eosinophilia]] > 10% on CBC
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| * [[Mononeuropathy]] or [[polyneuropathy]]
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| * Migratory or transient pulmonary opacities on [[CXR]]
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| * [[Paranasal sinus]] abnormalities
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| * Vessel biopsy showing eosinophils in extravascular areas
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| '''[[microscopic polyangiitis|Microscopic polyarteritis/polyangiitis]]'''. Affects [[capillaries]], [[venules]], or [[arterioles]]. Thought to be part of a group that includes [[Wegeners]] since both are associated with [[ANCA]] and similar extrapulmonary manifestations. Patients do not usually have symptomatic or histologic respiratory involvement.
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| '''[[Hypersensitivity vasculitis]]'''. Usually due to a [[hypersensitivity]] reaction to a known drug. There is presence of skin vaculitis with palpable [[petechiae]] or [[purpura]]. Biopsy of these lesions reveal inflammation of the small vessels, termed leukocytoclastic vasculitis, which is most prominent in postcapillary venules. At least 3 out of 5 criteria yields sensitivity and specificity of 71 and 84%:
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| * Age > 16
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| * Use of possible triggering drug in relation to symptoms
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| * Palpable [[purpura]]
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| * Maculopapular rash
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| * Skin biopsy showing [[neutrophils]] around vessel
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| '''[[Henoch-Schonlein purpura]]'''. Systemic vasculitis due to tissue deposition of [[IgA]]-containing immune complexes. Biopsy of lesions shows inflammation of small vessels. It is considered a form of hypersensitivity vasculitis but is distinguished by prominent deposits of IgA. This is the most common vasculitis in children. Presence of 3 or more criteria yielded sensitivity of 87% while less than 2 criteria yielded hypersensitivity vasculitis in 74%:
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| * Palpable [[purpura]] (usually of buttocks & legs)
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| * [[Mesenteric ischemia]]
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| * [[GI bleed]]
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| * [[Hematuria]]
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| * Onset < 20 years
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| * No new medications
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| '''[[Essential cryoglobulinemic vasculitis]]'''. Most often due to [[hepatitis C infection]], immune complexes of [[cryoglobulins]] --- proteins that consists of [[immunoglobulins]] and [[complement]] and precipitate in the cold while dissolving upon rewarming --- are deposited in walls of capillaries, venules, or arterioles. Therefore, complement will be low with histology showing vessel inflammation with immune deposits.
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| '''Vasculitis secondary to connective tissue disorders'''. Usually secondary to [[lupus erythematosus| systemic lupus erythematosus]] (SLE), [[rheumatoid arthritis]] (RA), relapsing [[polychondritis]], [[Behcet's disease]], and other connective tissue disorders.
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| '''Vasculitis secondary to viral infection'''. Usually due to [[hepatitis B]] and C, [[HIV]], [[cytomegalovirus]], [[Epstein-Barr virus]], and [[Parvo B19 virus]].
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| ==Pathophysiology==
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| ==Pathological Findings==
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| [http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
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| <div align="left">
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| <gallery heights="175" widths="175">
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| Image:Acute vasculitis due to transplant rejection 2.jpg|Kidney: Transplant: Micro H&E high mag excellent example acute vasculitis due to rejection
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| Image:Coronary artery vasculitis due to transplant rejection 1.jpg|Coronary artery: Transplant Rejection: Micro high mag H&E small muscular artery vasculitis
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| Image:Kidney petechia 1.jpg|Kidney: Petechiae: Gross natural color, an excellent example of flea bitten kidney case had necrotizing vasculitis
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| </gallery>
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| </div>
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| <div align="left">
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| <gallery heights="175" widths="175">
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| Image:Ricketsia vasculitis.jpg|Vasculitis, Rocky Mountain Spotted Fever, immunoperoxidase staining vessels for Rickettsia rickettsii
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| Image:Leucocytoclastic vasculitis 1.jpg|Skin:Leucocytolastic vasculitis; a close up view
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| Image:Leucocytoclastic vasculitis 2.jpg|Skin:Leucocytolastic vasculitis; legs
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| Image:Leucocytoclastic vasculitis pustular type.jpg|Leucocytoclastic vasculitis; pustular type
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| </gallery>
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| </div>
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| (Images courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, CA)
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| <div align="left">
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| <gallery heights="175" widths="175">
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| Image:Skin vasculitis.jpg|Vasculitis: In this instance, the vasculitic skin lesions were secondary to Haemophilus endocarditis.
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| Image:Skin vasculitis2.jpg|Vasculitis: In this instance, the vasculitic skin lesions were secondary to Haemophilus endocarditis.
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| Image:Skin vasculitis4.jpg|Vasculitis: In this instance, idiopathic with palpable purpura.
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| </gallery>
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| </div>
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| <div align="left">
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| <gallery heights="175" widths="175">
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| Image:skin_vasculitis6.jpg|Vasculitis: Palpable Purpura: Secondary to idiopathic leukocytoplastic vasculitis.
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| Image:Skin_vasculitis7.jpg|Vasculitis: In this instance, idiopathic.
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| Image:skin_vasculitis5.jpg|Vasculitis: In this instance, idiopathic with palpable purpura.
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| </gallery>
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| </div>
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| ==Diagnosis== | | ==Diagnosis== |
| ===Symptoms and signs===
| | [[Vasculitis history and symptoms| History and Symptoms]] | [[Vasculitis physical examination | Physical Examination]] | [[Vasculitis laboratory findings|Laboratory Findings]] | [[Vasculitis electrocardiogram|Electrocardiogram]] | [[Vasculitis chest x ray|Chest X Ray]] | [[Vasculitis CT|CT]] | [[Vasculitis MRI|MRI]] | [[Vasculitis echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Vasculitis other imaging findings|Other Imaging Findings]] | [[Vasculitis other diagnostic studies|Other Diagnostic Studies]] |
| Patients usually present with systemic symptoms with single or multiorgan dysfunction. Common (and nonspecific) complaints include fatigue, weakness, fever, arthralgias, abdominal pain, hypertension, renal insufficiency, and neurologic dysfunction. The following symptoms should raise a strong suspicion of a vasculitis:
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| *'''[[Mononeuritis multiplex]]'''. Also known as asymmetric polyneuropathy is highly suggestive of vasculitis, since diabetes is the only other cause of this.
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| *'''Palpable purpura'''. If patients have this in isolation, it is most likely due to cutaneous leukocytoclastic vasculitis. If the purpura is in combination with systemic organ involvement, it is most likely to be Henoch-Schonlein purpura or microscopic polyarteritis.
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| *'''Pulmonary-Renal'''. Patients with hemoptysis and renal involvement are likely to have [[Wegener's granulomatosis]], [[microscopic polyangiitis]], or anti-GBM disease ([[Goodpasture's syndrome]]).
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| ==Natural History, Complications, Prognosis==
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| ===Prognosis===
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| If the involvement of the vasculitis is limited to the skin, the disorder should resolve within months and carries a good prognosis. Recurrences may appear at variable intervals. in contrast if the vascultis involves internal organs such as the kidney, lungs or brain, then the prognosis is poorer and the condition can be life-threatening.
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| ==Diagnosis==
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| A detailed history is important to elicit any recent medications, any risk of [[hepatitis]] infection, or any recent diagnosis with a connective tissue disorder such as [[lupus erythematosus| systemic lupus erythematosus]] ([[SLE]]). A thorough physical exam is needed as usual.
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| *'''Lab tests'''. Basic lab tests may include a CBC, chem-7 (look for creatinine), muscle enzyme, liver function tests, ESR, hepatitis seroloties, urinalysis, CXR, and EKG. Additional, more specific tests include:
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| ** [[Antinuclear antibody]] (ANA) test can detect an underlying connective tissue disorder, especially [[lupus erythematosus| SLE]]
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| ** Complement levels that are low can suggest mixed cryoglobulinemia, hepatitis C infection, and [[lupus erythematosus| SLE]], but not most other vasculitides.
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| ** [[Antineutrophil cytoplasmic antibody]] ([[ANCA]]) may highly suggest [[Wegener's granulomatosis]], [[microscopic polyangiitis]], [[Churg-Strauss syndrome]], or drug-induced vasculitis, but is not diagnostic.
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| *'''[[Electromyography]]'''. It is useful if a systemic vasculitis is suspected and neuromuscular symptoms are present.
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| *'''[[Arteriography]]'''. Arteriograms are helpful in vasculitis affecting the large and medium vessels but not helpful in small vessel vasculitis. Angiograms of mesenteri or renal arteries in polyarteritis nodosa may show aneurysms, occlusions, and vascular wall abnormalities. Arteriography are not diagnostic in itself if other accessible areas for biopsy are present. However, in Takayasu's arteritis, where the aorta may be involved, it is unlikely a biopsy will be successful and angiography can be diagnostic.
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| *'''Tissue biopsy'''. This is the gold standard of diagnosis when biopsy is taken from the most involved area.
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| == Complete Differential Diagnosis for Vasculitis ==
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| Causes include; <ref>Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:77 ISBN 1591032016</ref> <ref>Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:68 ISBN 140510368X</ref>
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| '''Large-sized vessel'''
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| *[[Takayasu's Arteritis]]
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| *[[Temporal Arteritis]]
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| '''Medium-sized vessel'''
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| *[[Kawasaki's Disease]]
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| *[[Polyarteritis Nodosa]]
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| '''Small-sized vessel'''
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| *[[Churg-Strauss Syndrome]]
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| *Cutaneous leukocytoclastic vasculitis
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| *[[Essential cryoglobulinemic vasculitis]]
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| *[[Henoch-Schonlein Purpura]]
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| *[[Microscopic polyangiitis]]
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| *[[Wegener's Granulomatosis]]
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| == Other causes==
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| *[[Allopurinol]]
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| *[[Amantadine]]
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| *[[Anti-cardiolipin antibodies]]
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| *[[Arthus reaction]]
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| *[[Bazin disease]]
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| *[[Behcet's disease]]
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| *[[Benzylthiouracil]]
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| *[[Buerger's disease]]
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| *C1 esterase inhibitor (C1-INH) deficiency
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| *[[Cefaclor]]
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| *[[Cholesterol embolism]]
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| *[[Cocaine]]
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| *[[Cryoglobulinemia]]
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| *[[Cutis marmorata telangiectatica congenita]]
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| *Degos' disease
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| *Diptheria & tetanus vaccine
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| *[[Familial Mediterranean fever]]
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| *[[Golfer's vasculitis]]
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| *[[Hepatitis C]]
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| *Hughes-Stovin syndrome
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| *[[Hydralazine]]
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| *[[Hypersensitivity vasculitis]]
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| *[[Isoniazid]]
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| *[[Isotretinoin]]
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| *[[Juvenile dermatomyositis]]
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| *[[Late congenital syphilitic oculopathy]]
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| *[[Lepromatous leprosy]]
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| *[[Livedoid vasculitis]]
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| *[[Lung cancer]]
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| *[[Methotrexate]]
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| *[[Metolazone]]
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| *[[Minocycline]]
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| *[[Necrobiosis lipoidica]]
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| *[[Neisseria meningiditis]]
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| *[[Pancreatic cancer]]
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| *[[Pancreatitis]]
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| *Parvovirus B19 infection
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| *[[Penicillamine]]
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| *[[Phenytoin]]
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| *[[Polychondritis]]
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| *[[Polymyalgia rheumatica]]
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| *[[Polymyositis]]
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| *[[Propylthiouracil]]
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| *[[Quinidine]]
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| *[[Rapidly progressive glomerulonephritis]]
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| *[[Rheumatoid arthritis]]
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| *[[Smoking]]
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| *[[Sneddon syndrome]]
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| *Streptococcus Group A
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| *[[Sweet's syndrome]]
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| *[[Systemic lupus erythematosus]]
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| *[[Thromboangiitis obliterans]]
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| *[[Trazodone]]
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| *[[Treponema pallidum]]
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| *[[Tuberculosis]]
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| ===Complete Differential Diagnosis of the Causes of Vasculitis===
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| (By organ system)
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| {|style="width:80%; height:100px" border="1"
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| |style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular''' | |
| |style="height:100px"; style="width:75%" border="1" bgcolor="Beige" |
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| [[Sneddon syndrome]],
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Chemical / poisoning'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue" | |
| | '''Dermatologic'''
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| |bgcolor="Beige"|
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| [[Bazin disease]], | |
| [[Sweet's syndrome]],
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| |- | |
| |-bgcolor="LightSteelBlue"
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| | '''Drug Side Effect'''
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| |bgcolor="Beige"|
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| [[Allopurinol]],
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| [[Amantadine]],
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| [[Benzylthiouracil]],
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| [[Isoniazid]],
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| [[Phenytoin]],
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| [[Quinidine]],
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| [[Trazodone]],
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| |- | |
| |-bgcolor="LightSteelBlue"
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| | '''Ear Nose Throat'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Endocrine'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Environmental'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Gastroenterologic'''
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| |bgcolor="Beige"|
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| [[Pancreatitis]], | |
| |- | |
| |-bgcolor="LightSteelBlue"
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| | '''Genetic'''
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| |bgcolor="Beige"| [[Juvenile dermatomyositis]],
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| | |
| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Hematologic'''
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| |bgcolor="Beige"| | |
| [[Cryoglobulinemia]], | |
| | |
| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Iatrogenic'''
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| |bgcolor="Beige"| No underlying causes
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| |- | |
| |-bgcolor="LightSteelBlue"
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| | '''Infectious Disease'''
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| |bgcolor="Beige"|
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| [[Hepatitis C]],
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| [[Tuberculosis]],
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| | |
| |- | |
| |-bgcolor="LightSteelBlue"
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| | '''Musculoskeletal / Ortho'''
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| |bgcolor="Beige"|
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| [[Polychondritis]], | |
| | |
| |- | |
| |-bgcolor="LightSteelBlue"
| |
| | '''Neurologic'''
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| |bgcolor="Beige"| No underlying causes
| |
| |-
| |
| |-bgcolor="LightSteelBlue"
| |
| | '''Nutritional / Metabolic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
| |
| |-bgcolor="LightSteelBlue"
| |
| | '''Obstetric/Gynecologic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
| |
| |-bgcolor="LightSteelBlue"
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| | '''Oncologic'''
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| |bgcolor="Beige"|
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| [[Pancreatic cancer]],
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| [[Lung cancer]],
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| | |
| |-
| |
| |-bgcolor="LightSteelBlue"
| |
| | '''Opthalmologic''' | |
| |bgcolor="Beige"|
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| [[Late congenital syphilitic oculopathy]], | |
| | |
| |- | |
| |-bgcolor="LightSteelBlue"
| |
| | '''Overdose / Toxicity'''
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| |bgcolor="Beige"| No underlying causes
| |
| |-
| |
| |-bgcolor="LightSteelBlue"
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| | '''Psychiatric'''
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| |bgcolor="Beige"| No underlying causes
| |
| |-
| |
| |-bgcolor="LightSteelBlue"
| |
| | '''Pulmonary'''
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| |bgcolor="Beige"| No underlying causes
| |
| |-
| |
| |-bgcolor="LightSteelBlue"
| |
| | '''Renal / Electrolyte'''
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| |bgcolor="Beige"|
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| [[Rapidly progressive glomerulonephritis]],
| |
| | |
| |- | |
| |-bgcolor="LightSteelBlue"
| |
| | '''Rheum / Immune / Allergy'''
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| |bgcolor="Beige"|
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| [[Anti-cardiolipin antibodies]],
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| [[Arthus reaction]], | |
| [[Behcet's disease]],
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| [[Churg-Strauss Vasculitis]],
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| Diptheria & tetanus vaccine,
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| [[Hypersensitivity vasculitis]],
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| [[Kawasaki disease]],
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| [[Microscopic polyangiitis]],
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| [[Polyarteritis nodosa]],
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| [[Rheumatoid arthritis]],
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| [[Systemic lupus erythematosus]],
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| [[Takayasu's Arteritis]],
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| [[Temporal arteritis]],
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| [[Wegener's granulomatosis]],
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| | |
| | |
| |- | |
| |-bgcolor="LightSteelBlue"
| |
| | '''Sexual'''
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| |bgcolor="Beige"| No underlying causes
| |
| |-
| |
| |-bgcolor="LightSteelBlue"
| |
| | '''Trauma'''
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| |bgcolor="Beige"| No underlying causes
| |
| |-
| |
| |-bgcolor="LightSteelBlue"
| |
| | '''Urologic'''
| |
| |bgcolor="Beige"| No underlying causes
| |
| |-
| |
| |-bgcolor="LightSteelBlue"
| |
| | '''Miscellaneous'''
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| |bgcolor="Beige"|
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| [[Buerger's disease]],
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| [[Golfer's vasculitis]],
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| [[Smoking]],
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| | |
| |-
| |
| |}
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| ==Treatment== | | ==Treatment== |
| Treatment is targeted to the underlying cause. However, most vasculitis in general are treated with [[steroid]]s (e.g. [[methylprednisolone]]) because the underlying cause of the vasculitis is due to hyperactive immunological damage. Immunosuppressants such as [[cyclophosphamide]] and [[azathioprine]] may also be given.
| | [[Vasculitis medical therapy|Medical Therapy]] | [[Vasculitis surgery|Surgery]] | [[Vasculitis primary prevention|Primary Prevention]] | [[Vasculitis secondary prevention|Secondary Prevention]] | [[Vasculitis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Vasculitis future or investigational therapies|Future or Investigational Therapies]] |
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| A [[systematic review]] of [[antineutrophil cytoplasmic antibody]] (ANCA) positive vasculitis indentified best treatments depending on whether the goal is to induce remission or maintenance and depending on severity of the vasculitis.<ref name="pmid17684188">{{cite journal |author=Bosch X, Guilabert A, Espinosa G, Mirapeix E |title=Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review |journal=JAMA |volume=298 |issue=6 |pages=655-69 |year=2007 |pmid=17684188 |doi=10.1001/jama.298.6.655}}</ref>
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| == References ==
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| {{Reflist|2}}
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| ==External links==
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| * [http://www.vasculitis.org/ European Vasculitis Study Group]
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| * [http://www.vasculitisfoundation.org/ Vasculitis Foundation]
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| {{Systemic connective tissue disorders}} | | {{Systemic connective tissue disorders}} |
