VASCULITIS INTRODUCTION  

• Last update 9 May 2010
• Definition
  • Vasculitis is a condition in which blood vessel walls are inflamed.

FIGURE 1 - RESULTS OF VESSEL DAMAGE

• Results
  • Vasculitis leads to poor blood flow or even blockages (ischemia) which will damage organs unless controlled adequately or put into remission with medications.
  • Almost all autoimmune vasculitides are incurable and require life-long follow-up.
  • ANCA related vasculitides can cause increased blood clotting.
  • The incidence of venous thromboembolism (VTE) is higher in patients with active and non-active AAV. This finding cannot be explained by the presence of classic risk factors, but is probably associated with endothelial changes or hypercoagulability caused by AAV or its treatment.
  • Vasculitis patients should be evaluated not only with electrocardiography but also with echocardiography or cardiac MRI.  Cardiac involvement was documented in 74% of CSS patients negative for antineutrophil cytoplasmic antibodies (ANCA) but in only 23% of ANCA-positive patients. 
  • In the absence of complaints and major ECG abnormalities, cardiac involvement could still be detected in nearly 40% of the patients, indicating that the absence of complaints or a normal ECG does not exclude cardiac involvement,
  • A March 2009 study in Scandinavia found the most common damage due to vasculitis was cardiovascular, followed by renal, neuropsychiatric, ear nose and throat (ENT), and musculoskeletal.
    • Major vascular and treatment-related damage was associated with advanced age.
    • ENT damage was more prevalent in younger patients.
    • There was an almost complete separation between ENT damage and cardiac and renal damage.
• Major types
  • Hypersensitivity vasculitis is an allergic process and perhaps not always considered autoimmune.
  • infection or injury may cause vasculitis.
  • Autoimmune vasculitis (AV)in which the immune system is not properly regulated, causing blood cells to adhere to blood vessel walls, and subsequently damage tissue due to an inflammatory cascade. There are other autoimmune (AI) diseases distinct from AVs. 
• Causes
  • Causes of autoimmune vasculitides are largely unknown, but thought to be due to a combination of factors including infection, genetic predisposition,  and environmental.
  • Systemic autoimmunity appears to be the inevitable consequence of over-stimulating the host's immune 'system' by repeated immunization with antigen, to the levels that surpass system's self-organized criticality.
  • Click here to view an html file with a 2006 abstract on the various causes of vasculitis (not all autoimmune).
  • • An August 2008 article stated that human parvovirus B19 can cause vasculitis by molecular mimicry.
    • A June 2008 publication indicated NBI (CD177) was required for the inflammation cascade to proceed, identifying a possible therapeutic target.
    • A January 2007 study implicated the complement system (IgG) in ANCA related vasculitis.
    • A 2007 study discovered mast cells have a major role in controlling inflammatory conditions, and it may be speculated that manipulation of mast cell chemistry might prove useful in treating AVs.
  • Since identification of the hepatitis C virus (HCV) in 1989, it has become clear that the chronic infection can be accompanied by a variety of systemic auto-reactive phenomena, most notably vasculitis [Feb. 2007 article].
    • This virus replicates very rapidly, turning over billions of times each day, chronically stimulating the immune system.  In approximately half of patients, this chronic immune stimulation leads to the development of auto-reactivity and the appearance of rheumatoid factor (RF) in serum.
  • Infection by fimbriated bacteria results in the production of autoantibodies and may be involved in developing an AV. Such infection may trigger cross-reactive autoimmunity to a previously characterized ANCA antigen, lysosomal membrane protein-2, which is contained in the same vesicles that harbor MPO and PR3. 
  • Researchers at Imperial College London said evidence is mounting that, in addition to gene mutations, variation in the number of copies of individual genes can influence susceptibility to common diseases.
    • British geneticists have found in 2007 that people with fewer than two copies of the gene FCGR3B are more susceptible to autoimmune disorders, including lupus.
    • It was previously shown variation in the copy number of FCGR3B is associated with susceptibility to a kidney disease called glomerulonephritis.
    • In the new study, Timothy Aitman and colleagues determined variation in the number of FCGR3B copies is associated more broadly with autoimmune disorders, including lupus, microscopic polyangiitis, and Wegener's granulomatosis.
    • The small group of individuals who have no copies of FCGR3B have a dramatically elevated risk of autoimmune disease.
    • Some vasculitis patients also are found to have cryoglobulins, and a subset develop autoimmune conditions such as cryoglobulinemic vasculitis with symptoms of purpura, glomerulonephritis, peripheral neuropathy, and polyarthritis.  B-cell lymphomas also can occur.
  • Ross River virus was the first microbe linked with ANCA-positive disease.
    • Other anti-sense regions complementary to PR-3 included sequences from Entamoeba histolytica, and  Staphylococcus aureus, the two pathogens that have been most closely linked to the development of PR-3-ANCA in humans.
  • A 2002 study reported four cases of vasculitis (probably hypersensitivity) due to antigen inhalation.
  • The presence of myeloperoxidase–antineutrophil cytoplasmic antibodies, IgM anticardiolipin antibody, and antihistone antibodies in combination was found to be characteristic of drug-induced vasculitic syndromes caused by the antithyroid drugs propylthiouracil and methimazol. Clinically, skin vasculitis and arthralgias predominated and renal vasculitis was rare.
  • A 2009 study suggests the drug-induced hypersensitivity syndrome (DIHS) makes persons more liable to viral infection, particularly herpes viruses, and suggests patients with DIHS need close monitoring because of possible progression to autoimmune diseases even after the complete resolution of the DIHS.
  • A 2009 study of T1D (Type 1 Diabetes) associated SNPs in AAV has confirmed CTLA4 and PTPN22 as susceptibility loci in AAV. These genes encode two key regulators of the immune response and are associated with many autoimmune diseases, including T1D, autoimmune thyroid disease, celiac disease, rheumatoid arthritis, and now AAV. Across different autoimmune diseases some genes with immunomodulatory roles, such as PTPN22, are frequently associated with multiple diseases, whereas specific HLA associations, such as HLA-B27, tend to be disease restricted.  
  • A June 2009 study titled, “Exercise-induced Vasculitis Associated with Auto-Immune Disease” noted that, “Exercise-induced vasculitis (EIV) is an underreported and frequently misdiagnosed condition that occurs on the lower extremities shortly after exercise. 
  • Chromatin fibers, so-called neutrophil extracellular traps (NETs), are released by ANCA-stimulated neutrophils and contain the targeted autoantigens proteinase-3 (PR3) and myeloperoxidase (MPO). Deposition of NETs in inflamed kidneys and circulating MPO-DNA complexes suggest that NET formation triggers vasculitis and promotes the autoimmune response against neutrophil components in individuals with SVV.
  • Clinicians should recognize Exercise-Induced Vasculitis and consider the possibility that this disorder may be the presenting sign of subclinical connective-tissue diseases.
  • Mortality is higher in infection-triggered AV than in idiopathic systemic ANCA AV patients (ISAV). 
    • Clinical presentation is similar in ISAV and ITAV group, but serological markers are different.
    • In ITAV, anti-PR3, anti-MPO, ANA, aCL, anti beta-2 GP I antibodies and cryoglobulins can be detected in the same patient. 
    • In ISAV, autoimmune response is monospecific (anti-PR3 or MPO), in contrast to polyclonal activation in ANCA vasculitis triggered by infection.
• Prognosis
  • Once considered a death sentence, most autoimmune vasculitis can be controlled with medications.
    • The earlier the disease is diagnosed and treatment begun, the more likely the outcome will be good.
    • Some damaged organs and tissues may heal.  Some  damages may be permanent.
  • Some patients require life-long low dosage medications even after remission to keep the disease from becoming active.
  • Age doesn't usually preclude a satisfactory resolution.
    • A 2006 study showed polyartertis nodosa (PAN) patients with ages > 65 yr at diagnosis carry a poor prognosis.
    • That may be due to lack of knowledge and experience of physicians, delaying diagnoses thus permitting more damage than if the patient had been diagnosed earlier.
  • Autoimmune vasculitides in general will make blood more "sticky"�, leading to easy clotting or thromboses that can break loose and become emboli.  Deep Vein Thromboses (DVT) can occur in vasculitis patients.  Long periods of inactivity can lead to DVT.
  • As with WG and MPA, CSS patients are at greater risk of thomboses, than those with PAN.  Prognostic five-factor score; factor: add 1 point for each.
    • Proteinuria >1 g/24 h
    • Serum creatinine >140 µmol/l
    • Specific gastrointestinal involvement
    • Specific cardiomyopathy
    • Specific CNS involvement
    • Devised based on the analysis of 342 patients with polyarteritis nodosa or Churg–Strauss syndrome [55] , and subsequently also validated for microscopic polyangiitis patients.
• Life-long follow up
  • Remission for AV patients has very different implications from its regarding other disease, such cancer
    • A European League Against Rheumatism (EULAR) consensus report in 2007 said  remission is the suppression of the overt expression of vasculitis by ongoing therapy if needed, rather than the disappearance of the disease.  Continued remission may require continued medications in "maintenance"� dosages.
  • After remission, AV patients require life-long follow-up to make sure there are no "hidden" relapses, especially in kidneys, heart, and lungs where AV may be without symptoms until serious damage has already occurred.
    • Blood and urine lab work is perhaps weekly at the start, but less frequently as remission is achieved and sustained.
  • New or aggravated symptoms should be reported to one's physician(s) right away.
  • After the disease has been in remission for some time, the frequency of checks of key indicators might be decreased to quarterly or semi-annually in accord with the physician's judgment.
  • Click here to view a page on medical information to be carried on your person at all times.
  • Sudden vision changes should probably be considered a medical emergency and so require an ophthalmologist's immediate evaluation and care.
    • Giant cell or temporal arteritis (GCA/TA) may cause vision loss despite blood levels of ESR and CRP being in "normal"� ranges.
  • New test procedures may be come available to better monitor disease activity.
  • Several kinds of AVs can affect kidneys.  Most AV patients (even those without kidney involvement) should ask their physicians about use of inexpensive urine dip-sticks.
    • Click here to go to "Dipsticks" under "Scheduled tests in the section on "MEDICAL TESTS.
  • Other monitoring tests are needed to detect asymptomatic disease relapse.
    • For persons with lung involvement or undergoing a relapse, a CT scan, X-ray, PET scan or MRI imaging annually are reasonable.
      • MRI with contrast is perhaps better, if tolerated by the patient.
    • Periodic tests for CBC, creatinine, BUN, cANCA, anti-PR-3, pANCA, anti-MPO, ESR and CRP are usual to monitor disease activity and effects of medications.
    • An annual bone scan may be appropriate if the patient is on Prednisone or similar.
    • Reduction or withdrawal of therapy is the most potent predictor of the return of overt disease
• Other AI diseases
  • Persons with one autoimmune disease are predisposed to develop a second one.
    • Autoimmune thyroid disease is the most common autoimmune disease in the U.S. (and perhaps other countries).
      • A constant feeling of being cold and of lethargy may indicate hypothyroidism.  If one experiences those symptoms, it's best to have one's thyroid function evaluated.
        • Replacement therapy is indicated in most cases of hypothyroidism.
      • New symptoms could conceivably be the result of some new autoimmune condition other than an AV, such as "pseudovasculitis", which often closely mimic autoimmune vasculitis.
      • Various syndromes can mimic vasculitis such as cholesterol embolism, fibromuscular dysplasia, antiphospholipid syndrome, ergotism, neurofibromatosis, primary amyloidosis, and numerous others
• PowerPoints
  • Click here to download a slide show, "Primer on Vasculitis",
    • After opening the downloaded file, Click on "View" and select "slide show".
  • Click here to view more slide presentations on vasculitis available for downloading.
• AVs Briefly
  • Four by nine inch cards are available on request from the Vasculitis Foundation describing each of the 15 supported AVs, each on a separate card and suitable for friends and family. Call 1-800-277-9474.

  • Click here to view a Cleveland Clinic brochure on vasculitis.

  • Click here to view a Univ. of North Carolina brochure on vasculitis.
  • Click here to view a booklet on vasculitis by the Arthritis Research Campaign.
  • Click here to view a booklet "Living With Vasculitis" (University of Birmingham, U.K.)
  • A March 2009 study in Scandinavia found the most common damage due to vasculitis was cardiovascular, followed by renal, neuropsychiatric, ear nose and throat (ENT), and musculoskeletal.
    • Major vascular and treatment-related damage was associated with advanced age whereas ENT damage was more prevalent in younger patients.
    • There was an almost complete separation between ENT damage and cardiac and renal damage.

THIS SITE

• Intent
  • To assist vasculitis patients in getting early diagnoses, effective treatments, and to advise of patient, organization, and scientific resources concerning vasculitis.
• Sources Used
  • The following information is derived from a variety of sources over some ten+ years and is not to be considered as medical advice, but merely the opinions or experiences or findings of the writer who is not a physician and has no medical training.
  • Much comes from Medline abstracts and medical journal articles on vasculitis.  Some is from autoimmune vasculitis patients and carers, some from newsgroups,  internet web pages, etc. that also deal with vasculitis.
  • The compiler has attempted to use only recent valid medical information regarding vasculitis, but cannot guarantee the validity nor the currency in every case
• Limitations
  • No medical decisions should be made on the basis of information on this web page or on associated linked documents and web pages unless those are from a recognized medical professional or professional medical publication.
  • Limits to this web page concerning vasculitis:
    • The author/compiler/editor of this web page and related pages has had NO medical training.
    • Only autoimmune vasculitides will be considered, not hypersensitivity vasculitis nor vasculitis as a result of an allergic reaction to medication or vaccine..
    • Most sections apply to most autoimmune vasculitides.
      • One refers specifically to Wegener’s granulomatosis.
• Terminology
  • Some abbreviations and equivalencies are:
    • Hereafter, “autoimmune vasculitis” may be abbreviated “AV” or “AVs” for plural.
    • The term “Prednisone” is sometimes used where it or a similar glucocorticoid might be prescribed to treat vasculitis.
    • “Immunosuppressives” used to  treat vasculitis are sometimes abbreviated “ISs”.
• Updates
  • This update was on June 1, 2009 and is a complete rewrite of the former web page at http://www.wegenersgranulomatosis.net that also dealt with vasculitis.
• Files & links – Vasculitis related.
  • Click here to view a web page listing all the links and files from this page.
• Tables & Figures – Vasculitis related
  • Click here to view a listing of the tables and figures in this web page.
• Disclaimer
  • ALL MEDICAL QUESTIONS, SYMPTOMS, CONCERNS AND PROBLEMS SHOULD BE DIRECTED TO APROPRIATE LICENSED MEDICAL PROFESSIONALS.
  • The writer/editor/compiler does not vouch for the accuracy, completeness, nor applicability of the information included on this site to any person, whether a vasculitis patient or otherwise. 

This website and all content - © Copyright 2009, Bruce Macdonald. All Rights Reserved.
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Compilations, Observations & Suggestions by a Vasculitis Patient This web page hosted courtesy of Andrew MacLean at www.andrewmaclean.com Please use the SITE PLAN for advanced navigation if slide-out menus do not appear.

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