Vasculitis is an inflammation of blood vessels, often with ischemia, necrosis and organ inflammation. The vasculitis can all blood vessels, whether arteries, arterioles, veins, small veins or capillaries concern. Clinical manifestations of specific vasculitic diseases are varied and depend on the size and location of the vessels involved and the extent of organ involvement and the degree and pattern of inflammation. Vasculitis etiology may Primary Secondary Primary vasculitis is the result of an inflammatory response, which is directed against the vessel walls and has no known cause. The secondary vasculitis can be triggered by an infection, a drug or a toxin, or occur as part of another inflammatory disease or cancer. Pathophysiology Histological Description of the affected vessel should include: a description of the damage to the vessel wall (e.g., the nature and localization of the inflammatory infiltrate, extent and type of damage, presence or absence of fibrinoid necrosis.) Describes the healing reactions (eg. .. intimal, fibrosis) Certain features (eg dominant inflammatory cells, the location of the inflammation) suggest a vasculitic process and can support the diagnosis (see table: Histological evidence for the diagnosis of vasculitis). So z. As in many acute lesions, the predominant inflammatory cells polymorphonuclear leukocytes, lymphocytes in chronic lesions are predominant. Inflammation may occur segmental or affect the entire vessel. In the area of ??inflammation, the extent of cellular infiltration and necrosis or scarring in one or more layers of the vessel wall is different. Inflammation within the media of muscular artery leading to the destruction of the internal elastic lamina. Some forms of vasculitis are characterized by giant cells in the vessel wall. The leukocytoclastic vasculitis is a histopathological term used to describe Vaskulitisbefunde in small vessels. It refers leave in and around the vessels to the reduction of inflammatory cells, the small nuclear fragments (nuclear detritus). Inflammation is transmural and nichtgranulomatös. First outweigh polymorphonuclear leukocytes, later outweigh lymphocytes. A healing of the inflammation usually leads to fibrosis and hypertrophy of the intima. An intimal hypertrophy or secondary clot formations can lead to vascular occlusion, the result is tissue ischemia or necrosis. Histological evidence for diagnosis of vasculitis findings possible diagnoses Mostly nichtnekrotisierende granulomatous inflammatory infiltrates with lymphocytes, macrophages and giant cells arteritis Primary vasculitis of the central nervous system (certain types) Takayasu’s arteritis fibrinoid vascular necrosis of the vessel wall with a mixed infiltrate of various combinations of leukocytes and lymphocytes EGPA (formerly Churg-Strauss syndrome) GPA (formerly Wegener’s granulomatosis) immune complex-associated vasculitis MPA polyarteritis nodosa RA IgA deposits * immunoglobulin-A-associated vasculitis (Henoch-Schonlein purpura formerly) detects Little or complete lack of immunoglobulins and Komplementablagerungen in the vessel walls *, EGPA GPA MPA * These findings are using immunofluorescent staining. Ekrankungen marked in this way are called Pauci-immune vasculitis. EGPA = eosinophilic granulomatosis with polyangiitis; GPA = granulomatosis with polyangiitis; MPA = microscopic polyangiitis. Classification Inflammatory disease can be classified based on the size of the vessels predominantly involved. However, there are often strong overlap (see Table: Classification of vasculitis). Classification of vasculitis size of the affected vessels disease symptoms and complaints bulk Behçet giant cell polymyalgia rheumatica, Takayasu’s arteritis claudication Unequal blood pressure measurements, or uneven pulse strength / missing pulse in the extremities ischemic symptoms of the CNS (eg., Stroke), medium-vessel wall Cutaneous vasculitis, polyarteritis nodosa symptoms of tissue infarction in the affected Organs such as: Muscles: myalgia Nervous: Multiple mononeuropathy (mononeuritis multiplex) gastrointestinal tract: mesenteric ischemia kidney: New-onset hypertension skin ulcers, nodules and livedo reticularis small eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome) Cyroglobulinämische vasculitis granulomatosis with polyangiitis (formerly Wegener’s granulomatosis), immunoglobulin-A-associated vasculitis (formerly Henoch-Schonlein purpura) Microscopic polyangiitis Cutaneous vasculitis of the small vessels symptoms of tissue infarction in affected organs, similar to those in medium-sized vessels except skin lesions rather purpura same Symptoms and complaints help the size of the vessels involved in determining the clinical presentation (see table: Classification of vasculitis). Regardless of the size of the vessels involved, patients can present with symptoms and signs of systemic inflammation (eg., Fever, night sweats, fatigue, loss of appetite, weight loss, joint pain, arthritis). Some manifestations are life-threatening and require immediate treatment. Alveolar hemorrhage Rapidly progressive glomerulonephritis mesenteric ischemia vision loss in patients with giant cell arteritis Small and medium-sized vasculitis often manifest with skin lesions as palpable purpura, urticaria, ulcers, livedo reticularis and nodules. Diagnosis Clinical evaluation Basic laboratory testing for the presence of inflammation or of organ failure (z. B. blood count, ESR or C-reactive protein, serum albumin and total protein, AST and ALT, urea nitrogen and creatinine, urine analysis) laboratory tests to diagnose the type of vasculitis (eg. B. antineutrophil cytoplasmic antibodies [ANCA]) Laboratory and imaging tests, which determine the cause of vasculitis and the extent of organ involvement biopsy of the suspected systemic vasculitis, patients with the following appearance:. symptoms or signs of vasculitis (e.g. indicate times headache and claudication of the jaw to a giant out) Ischemic manifestations (eg., stroke, claudication of the extremities, mesenteric ischemia ) That are disproportionate to the risk factors of the patient for atherosclerosis inexplicable combinations of symptoms in more than one organ system associated with vasculitis are compatible (eg. As hypertension, myalgia), especially if symptoms of systemic disease are present Primary vasculitis are diagnosed based on characteristic symptoms, physical findings, appropriate laboratory values ??and the exclusion of other causes (d. E. A secondary vasculitis). Histological examination is, whenever possible, carried out, it can provide information about a specific vasculitis (see table: Histological evidence for the diagnosis of vasculitis). First, routine laboratory tests to be performed. Most tests provide results that are non-specific; However, the results can often help to support the diagnosis in order to determine the degree of organ involvement or suggest alternative diagnoses. The tests typically include total blood count, ESR or C-reactive protein, serum albumin and total protein, AST and ALT. Often the patients, increased platelets and low serum albumin present with increased ESR or C-reactive protein of anemia due to chronic inflammation. Fresh random urine must be examined for red blood cells, red blood cell casts and protein to identify renal involvement. The serum creatinine should be checked and monitored. Leukopenia and thrombocytopenia are not typical for a primary vasculitis and put a different diagnosis at hand. The detection of ANCA, the diagnosis of granulomatosis with polyangiitis (GPA, formerly known as Wegener’s granulomatosis), eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome) or microscopic polyangiitis (sometimes known as ANCA-associated vasculitis summarized) support. Among the standardized tests for ANCA include immunofluorescence staining and ELISA. By immunofluorescence staining of ethanol fixed neutrophils to cytoplasmic pattern of c-ANCA or perinuclear pattern of p-ANCA reveal. ELISA is used to test for antibodies specific to the major autoantigens: Proteinase 3 (PR3), which generates the staining pattern of c-ANCA, or myeloperoxidase (MPO), which generates the staining pattern of p-ANCA, the ethanol -fixed neutrophils are seen. Because ANCA-associated vasculitis are rare, and the ANCA TEst is nihct complete specific tests should be performed only on ANCA if the probability of ANCA-associated vasculitis is moderately high. Other useful laboratory tests include hepatitis B and C serology, serum and Urineiweißelektrophorese, antinuclear antibodies and anti-extractable nuclear antigen panel, a test for the presence of cryoglobulins and complement levels, a viral vasculitis, a cryoglobulinämische vasculitis, lymphoproliferative disorders or to diagnose a vasculitis that is based on other autoimmune diseases. Further tests will be determined by the clinical findings. If indicated by clinical findings, a radiograph should be made to track infiltrates; a high-resolution non-enhanced CT of the chest may be required to determine subtle findings such as small nodules or cavities. Bilateral diffuse infiltrates justify suspicion of possible alveolar hemorrhage, requiring immediate diagnosis and treatment. Other imaging tests may be required. So z. For example, a magnetic resonance angiography of the large vessels and the aorta to diagnose and monitor if these vessels seem to be affected useful. If the symptoms and studies suggest a neuropathy, electromyography may be helpful. Because vasculitis are rare and their treatment has severe side effects, for confirmatory diagnosis, a tissue biopsy is performed. Clinical findings help in tracking down the most appropriate biopsy site. The biopsy findings are most likely to be positive when they come from the affected lung, skin and kidney tissue. Blind biopsies of organs without clinical manifestations or the suspected involvement of the laboratory examination however, have a low probability to deliver positive results. Therapy induction of remission in life-threatening vasculitis with corticosteroids, often with cyclophosphamide or rituximab induction of remission in a less severe vasculitis with corticosteroids plus a less potent immunosuppressant (e.g., methotrexate, azathioprine, mycophenolate mofetil) or Rituximab maintenance of remission with methotrexate, azathioprine or rituximab plus tapering of corticosteroids the treatment depends on the etiology, the Zyp of vasculitis and the extent and severity of disease. When secondary vasculites eliminating the cause may (z. B. infection, medication, cancer) help. In primary vasculitis treatment aims to induce and maintain remission. Remission is initiated by use of cytotoxic immunosuppressive drugs and high-dose corticosteroids, usually given for 3-6 months until remission occurs or the disease activity is reduced to an acceptable level. The duration of remission is difficult to predict and depends on the type of vasculitis. For many patients, the maintenance of remission requires a continuation of immunosuppressive therapy with or without a small dose of corticosteroids. During this time, the goal is to discontinue corticosteroids or reduce their dose and less potent (and less toxic) immunosuppressants to use as long as necessary. All patients being treated with immunosuppressive drugs should be monitored for opportunistic and other infections. Testing for TB and hepatitis B, which can be aggravated by immunosuppressive therapy should be considered. Prophylaxis against Pneumocystis jirovecii should be considered when patients receive potent and prolonged immunosuppressive therapy. Induction of remission For less severe forms of vasculitis low doses of corticosteroids and few potent immunosuppressive agents (e.g., methotrexate, azathioprine, mycophenolate mofetil) or Rituximab be used. The severe, rapidly progressive and life-threatening vasculitis (z. B. causes alveolar hemorrhage, a rapidly progressive glomerulonephritis, or mesenteric ischemia) is a medical emergency that requires a hospital admission and immediate treatment. Treatment usually consists of the following measures: Corticosteroids: High-dose corticosteroids (also called steroid pulse therapy) are often prescribed. Methylprednisolone 15 mg / kg or 1 g i.v. once a day is applied for 3 days, followed by 1 mg / kg prednisone or methylprednisolone p.o. (Or in the hospital sometimes iv) once a day for about 4 weeks. The dose is then tapered off slowly when it tolerates the patient, usually at 10 mg per week up to 40 mg / day, followed by 5 mg every 2 weeks up to 20 mg / day to 2.5 mg every 2 weeks to 10 mg / day and about 1 mg per month from then on, until the means is stopped. Changes to this schedule for discontinuation may be necessary if the patient’s condition does not improve or relapse occurs. Cyclophosphamide: One dose of 2 mg / kg p.o. is recommended or generally for at least 3 months until the onset of remission. once a day The leukocytes should be closely monitored and the dose should be adjusted to prevent leukopenia. (The white blood cell count of> 3500 / ul should be maintained.) Alternatively bhandlet with Cyclophosphami, i.v. used of 0.5-1 g / m2 in the 2- to 4-week intervals. The dose should be reduced in patients with significant renal failure, and the white blood cell count should be monitored frequently. Patients taking chronic high-dose corticosteroids, especially with cyclophosphamide should receive a prophylactic treatment against Pneumocystis jirovecii. Mesna: Mesna is with i.v. Cyclophosphamide mixed to bind acrolein, a product of Cyclophosphamidabbaus, which is toxic to the Blaseenepithel and can lead to a hemorrhagic cystitis urothelial to and occasionally. The long-term use of cyclophosphamide increases the risk of bladder cancer. One milligram per milligram Mesna cyclophosphamide is added. A recurrence of hematuria, especially without cylinder and dysmorphic red blood cells should be cause for a urological evaluation. Cystoscopy and renal imaging should be performed to rule out cancer. Rituximab: Rituximab, a B-cell depleting anti-CD20 monoclonal antibody, has not inferior as compared with cyclophosphamide proved with respect to the initiation of a remission of the heavy ANCA-associated vasculitis. Rituximab is administered in a dose of 375 mg / m2 i.v. administered once weekly for 4 weeks. A widely used alternative treatment regimen consists of two infusions of 1000 mg administered at an interval of 2 weeks. Maintenance of remission The corticosteroids are tapered down to zero or to the lowest dose that can maintain a remission. In some forms of vasculitis (shown very clearly in ANCA-associated disease) is a weekly methotrexate (folic acid) or azathioprine prescribed daily to replace cyclophosphamide, because these drugs have a better side effect profile. A periodic infusion of rituximab can be applied also to maintain remission. The duration of treatment varies from one year to several years, depending on the patient, diagnosis and recurrences. Patients with frequent recurrences may need to take indefinitely immunosuppressants. A long-term use of corticosteroids can have serious side effects. Patients who are taking daily, or equivalent doses of other corticosteroids 7.5 mg prednisone ? should calcium, vitamin D supplements and bisphosphonates are administered in order to prevent osteoporosis or minimize the risk of osteoporosis; Monitoring of bone density should be considered. Summary vasculitis can be a primary or secondary disease occur as a result of other causes. Clinical manifestations can be systemic and / or organ-specific, depending on which blood vessels are affected. Vasculitis tends to infect small, medium or large vessels, with each certain patterns of organ involvement are observed. to determine the cause of vasculitis (including diseases such as infections and cancer) and the extent of organ involvement, blood tests, imaging methods and, if indicated, a tissue biopsy to be performed. To treat glucocorticoids and immunosuppressants are used. Meet an increased risk of infection and osteoporosis, caused by a Vaskulitisbehandlung with control and / or prophylactic treatments.