In medicine (rheumatology), Wegener's granulomatosis is a form of vasculitis that affects the lungs, kidneys and other organs. Due to its end-organ damage, it can be a serious disease that requires long-term immune suppression.^[1] The International Statistical Classification of Diseases and Related Health Problems (commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following codes are used with International Statistical Classification of Diseases and Related Health Problems. ... // M00-M99 - Diseases of the musculoskeletal system and connective tissue (M00-M25) Arthropathies (M00-M03) Infectious arthropathies (M00) Pyogenic arthritis (M01) Direct infections of joint in infectious and parasitic diseases classified elsewhere (M02) Reactive arthropathies (M023) Reiters disease (M03) Postinfective and reactive arthropathies in diseases classified elsewhere (M05-M14... The International Statistical Classification of Diseases and Related Health Problems (commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The Diseases Database is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... MedlinePlus (medlineplus. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... medicines, see medication and pharmacology. ... Rheumatology, a subspecialty of internal medicine, is devoted to the diagnosis and therapy of rheumatic diseases. ... In medicine (anatomical pathology), a granuloma is a group of epithelioid macrophages surrounded by a lymphocyte cuff. ... In medicine, vasculitis (plural: vasculitides) is a group of diseases featuring inflammation of the wall of blood vessels due to leukocyte migration and resultant damage. ... The lungs flank the heart and great vessels in the chest cavity. ... The kidneys are bean-shaped excretory organs in vertebrates. ... Immunosuppression is the medical suppression of the immune system. ...

It is part of a larger group of vasculitic syndromes that all feature the presence for an abnormal type of circulating antibody termed ANCAs (antineutrophil cytoplasmic antibodies) and affect small and medium-sized blood vessels. Apart from Wegener's, it includes Churg-Strauss syndrome and microscopic polyangiitis.^[1] Schematic of antibody binding to an antigen An antibody or immunoglobulin is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... For other uses, including the Australian company, ANCA Pty Ltd, see ANCA (disambiguation) Anti-neutrophil cytoplasmic antibodies (ANCAs) are a group of mainly IgG antibodies against antigens in the cytoplasm of neutrophil granulocytes (the most common type of white blood cell) and monocytes. ... The arterial system The blood vessels are part of the circulatory system and function to transport blood throughout the body. ... Churg-Strauss syndrome is a necrotizing vasculitis characterized by eosinophilia. ... Microscopic polyangiitis is an ill-defined autoimmune disease which usually presents with pulmonary bleeding and anemia. ...

Signs and symptoms

Initial signs are protean, and diagnosis can be severely delayed due to the non-specific nature of the symptoms. The rhinitis is generally the first sign in most patients.^[1] The term symptom (from the Greek syn = con/plus and pipto = fall, together meaning co-exist) has two similar meanings in the context of physical and mental health: Strictly, a symptom is a sensation or change in health function experienced by a patient. ...

• Upper airway, eye and ear disease:
  • Nose: pain, stuffiness, nosebleeds, rhinitis, crusting, saddle-nose deformity
  • Ears: conductive hearing loss due to Eustachian tube dysfunction, sensorineural hearing loss (unclear mechanism)
  • Eyes: pseudotumours, scleritis, conjunctivitis, uveitis, episcleritis
• Airways:
  • Trachea: subglottal stenosis
  • Lungs: pulmonary nodules, infiltrates (often interpreted as pneumonia), cavitary lesions, pulmonary hemorrhage causing hemoptysis), and rarely bronchial stenosis.
• Kidney: rapidly progressive segmental necrotising glomerulonephritis (75%), leading to chronic renal failure
• Arthritis: Pain or swelling (60%), often initially diagnosed as rheumatoid arthritis
• Skin: nodules on the elbow, purpura, various others (see cutaneous vasculitis)
• Nervous system: occasionally sensory neuropathy (10%) and rarely mononeuritis multiplex
• Heart, gastrointestinal tract, brain other organs: rarely affected.

In humans the respiratory tract is the part of the anatomy that has to do with the process of respiration or breathing. ... A human eye. ... Bat ears come in different sizes and shapes The ear is the sense organ that detects sound. ... A nosebleed or nosebleedage, medically known as epistaxis, is the relatively common occurrence of hemorrhage (bleeding) from the nose, usually noticed when it drains out through the nostrils. ... Rhinitis is the medical term describing irritation and inflammation of the nose. ... Saddle nose is a condition associated with congenital syphilis and Wegeners granulomatosis, among other conditions. ... Hearing impairment or deafness is decreased or absent ability to perceive auditory information. ... Anatomy of the human ear. ... Scleritis is a serious inflammatory disease that affects the white outer coating of the eye, known as the sclera. ... Uveitis specifically refers to inflammation of the middle layer of the eye, termed the uvea but in common usage may refer to any inflammatory process involving the interior of the eye. ... This article or section does not cite its references or sources. ... Windpipe redirects here. ... A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure. ... The lungs flank the heart and great vessels in the chest cavity. ... Pneumonia is an illness of the lungs and respiratory system in which the alveoli (microscopic air-filled sacs of the lung responsible for absorbing oxygen from the atmosphere) become inflamed and flooded with fluid. ... This page meets Wikipedias criteria for speedy deletion. ... Hemoptysis (US English) or haemoptysis (International English) is the expectoration (coughing up) of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs (e. ... The kidneys are bean-shaped excretory organs in vertebrates. ... Glomerulonephritis is a primary or secondary autoimmune renal disease featuring inflammation of the glomeruli. ... Arthritis (from Greek arthro-, joint + -itis, inflammation; plural: arthritides) is a group of conditions where there is damage caused to the joints of the body. ... Rheumatoid arthritis (RA) is traditionally considered a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. ... It has been suggested that this article or section be merged with Epidermis (skin). ... Purple discolorations on the skin caused by bleeding underneath the skin. ... The nervous system of an animal coordinates the activity of the muscles, monitors the organs, constructs and also stops input from the senses, and initiates actions. ... Neuropathy, strictly speaking, is any disease that affects the nervous system. ... Mononeuritis multiplex is the clinical picture that arises from problems with multiple individual nerves serially or almost simultaneously. ... The heart and lungs, from an older edition of Grays Anatomy. ... The gastrointestinal tract (GI tract), also called the digestive tract, alimentary canal, or gut, is the system of organs within multicellular animals that takes in food, digests it to extract energy and nutrients, and expels the remaining waste. ... In animals, the brain, or encephalon (Greek for in the head), is the control center of the central nervous system. ...

Diagnosis

Vasculitis such as Wegener's granulomatosis is usually only suspected when a patient has had unexplained symptoms for a longer period of time. Determination of ANCAs can aid in the diagnosis, but positivity is not conclusive and negative ANCAs are not sufficient to reject the diagnosis. Cytoplasmic staining ANCAs that react with the enzyme proteinase 3 (cANCA) in neutrophils (a type of white blood cell) are associated with Wegener's.^[1] For other uses, including the Australian company, ANCA Pty Ltd, see ANCA (disambiguation) Anti-neutrophil cytoplasmic antibodies (ANCAs) are a group of mainly IgG antibodies against antigens in the cytoplasm of neutrophil granulocytes (the most common type of white blood cell) and monocytes. ... Proteinase 3 is a serine protease enzyme expressed mainly in neutrophil granulocytes. ... A scanning electron microscope (SEM) image of normal circulating human blood. ... White blood cells or leucocytes are cells which form a component of the blood. ...

If the patient has renal failure or cutaneous vasculitis, these are the most logical organs to obtain a biopsy from. Rarely, thoracoscopic lung biopsy is required. On histopathological examination, a biopsy will show leukocytoclastic vasculitis with necrotic changes and granulomatous inflammation (clumps of typically arranged white blood cells) on microscopy. The latter is the main reason for the appellation of "Wegener's granulomatosis", although it is not an essential feature. Unfortunately, many biopsies can be aspecific and 50% provide too little information for the diagnosis of Wegener's.^[1] Chronic renal failure (CRF, or chronic kidney failure, CKF, or chronic kidney disease, CKD) is a slowly progressive loss of renal function over a period of months or years and defined as an abnormally low glomerular filtration rate, which is usually determined indirectly by the creatinine level in blood serum. ... A biopsy (in Greek: bios = life and opsy = look/appearance) is a medical test involving the removal of cells or tissues for examination. ... Thoracoscopy is a medical procedure involving internal inspection of the pleural cavity. ... Histopathology is a field of pathology which specialises in the histologic study of diseased tissue. ... Necrosis (in Greek Νεκρός = Death) is the name given to accidental death of cells and living tissue. ... H&E section of non-caseasting granuloma seen in the colon of a patient with Crohns disease In medicine (anatomical pathology), a granuloma is a group of epithelioid macrophages surrounded by a lymphocyte cuff. ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ... Microscopy is any technique for producing visible images of structures or details too small to otherwise be seen by the human eye. ...

Differential diagnosis (alternative possible diagnoses) can be extensive. ANCAs can be positive after the use of certain drugs, and other forms of vasculitis can present with very similar symptoms. The saddle nose deformity may also seen in cocaine abuse and in congenital syphilis. In medicine, differential diagnosis (sometimes abbreviated DDx or ΔΔ) is the systematic method physicians use to identify the disease causing a patients symptoms. ... In medicine, vasculitis (plural: vasculitides) is a group of diseases featuring inflammation of the wall of blood vessels due to leukocyte migration and resultant damage. ... Saddle nose is a condition associated with congenital syphilis and Wegeners granulomatosis, among other conditions. ... Cocaine (or crack in its impure freebase form) is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. ...

Criteria

In 1990, the American College of Rheumatology accepted classification criteria for Wegener's. They were not intended for diagnosis, but for inclusion in randomised controlled trials. Two or more positive criteria have a sensitivity of 88.2% and a specificity of 92.0% of describing Wegener's.^[2] ... A randomized controlled trial (RCT) is a form of clinical trial, or scientific procedure used in the testing of the efficacy of medicine, used because of its record of reliability. ...

• Nasal or oral inflammation:
  • painful or painless oral ulcers or
  • purulent or bloody nasal discharge
• Lungs: abnormal chest X-ray with:
  • nodules,
  • infiltrates or
  • cavities
• Kidneys: urinary sediment with:
  • microhematuria or
  • red cell casts
• Biopsy: granulomatous inflammation
  • within the arterial wall or
  • in the perivascular area

According to the Chapel Hill Consensus Conference (CHCC) on the nomenclature of systemic vasculitis (1992), establishing the diagnosis of Wegener's granulomatosis demands:^[3] Pus is a whitish-yellow or yellow substance that can be found in regions of bacterial infection, including superficial infections, such as pimples. ... Microscopic hematuria is a medical condition in which urine contains small amounts of blood. ... To meet Wikipedias quality standards, this article or section may require cleanup. ...

• a granulomatous inflammation involving the respiratory tract, and
• a vasculitis of small- to medium-sized vessels.

Several investigators have compared the ACR and Chapel Hill criteria.^[4] In medicine (anatomical pathology), a granuloma is a group of epithelioid macrophages surrounded by a lymphocyte cuff. ... In medicine, vasculitis (plural: vasculitides) is a group of diseases featuring inflammation of the wall of blood vessels due to leukocyte migration and resultant damage. ...

Pathophysiology

Inflammation with granuloma formation against a nonspecific inflammatory background is the classical tissue abnormality in all organs affected by Wegener's granulomatosis.^[1] Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ... H&E section of non-caseasting granuloma seen in the colon of a patient with Crohns disease In medicine (anatomical pathology), a granuloma is a group of epithelioid macrophages surrounded by a lymphocyte cuff. ...

It is now widely presumed that the anti-neutrophil cytoplasmic antibodies (ANCAs) are responsible for the inflammation in Wegener's.^[1] The typical ANCAs in Wegener's are those that react with proteinase 3, an enzyme prevalent in neutrophil granulocytes.^[5] This type of ANCA is also known as cANCA, with the c indicating cytoplasmic (in contrast to pANCA, which is perinuclear). For other uses, including the Australian company, ANCA Pty Ltd, see ANCA (disambiguation) Anti-neutrophil cytoplasmic antibodies (ANCAs) are a group of mainly IgG antibodies against antigens in the cytoplasm of neutrophil granulocytes (the most common type of white blood cell) and monocytes. ... Proteinase 3 is a serine protease enzyme expressed mainly in neutrophil granulocytes. ... A scanning electron microscope (SEM) image of normal circulating human blood. ... Cytoplasm is a water-like cell wall that fills cells. ...

ANCAs activate neutrophils, increase their adherence to endothelium, and lead to their degranulation. This causes extensive damage to the vessel wall, particularly of arterioles.^[1] Neutrophil granulocytes (commonly referred to as neutrophils) are a class of white blood cells and are part of the immune system. ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ... An arteriole is a blood vessel that extends and branches out from an artery and leads to capillaries. ...

The exact cause for the production of ANCAs is unknown, although some drugs have been implicated in secondary forms of Wegener's. As with many autoimmune disorders, the cause is probably genetic predisposition combined with molecular mimicry caused by a virus or bacterium. Oral medication A medication is a licenced drug taken to cure or reduce symptoms of an illness or medical condition. ... Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ... Molecular mimicry is a phenomenon associated with some pathogens, where the antigens evoking an immune response have enough similarity to the bodys own proteins to cause an autoimmune reaction, such as in rheumatoid arthritis, mediated by cross reactive T cells and/or circulating antibodies. ... Groups I: dsDNA viruses II: ssDNA viruses III: dsRNA viruses IV: (+)ssRNA viruses V: (-)ssRNA viruses VI: ssRNA-RT viruses VII: dsDNA-RT viruses A virus (Latin, poison) is a microscopic particle that can infect the cells of a biological organism. ... Phyla/Divisions Actinobacteria Aquificae Bacteroidetes/Chlorobi Chlamydiae/Verrucomicrobia Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Nitrospirae Omnibacteria Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Bacteria (singular, bacterium) are a major group of living organisms. ...

Treatment

Initial treatment is generally with corticosteroids and oral cyclophosphamide (CYC), 1 mg/kg/day and 2 mg/kg/day respectively. Occasionally CYC is given in monthly IV doses. Monitoring of the white blood count is essential during CYC therapy. Once remission is attained (normally 3 to 6 months), treatment is frequently changed to azathioprine or methotrexate, which are less toxic drugs. Total duration of therapy should be at least 1 year, or longer in high risk patients. Corticosteroids are tapered to a low maintenance dose, 5-10 mg/day. Plasmapheresis may be beneficial in severe disease or pulmonary hemorrhage. Experience with other treatment agents is very limited.^[1] In physiology, corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. ... Cyclophosphamide (the generic name for Cytoxan, Neosar) is a nitrogen mustard alkylating agent, used to treat various types of cancer and some autoimmune disorders. ... White blood cells or leucocytes are cells which form a component of the blood. ... Azathioprine is a chemotherapy drug, now rarely used for chemotherapy but more for immunosuppression in organ transplantation, autoimmune disease such as rheumatoid arthritis or inflammatory bowel disease such as Crohns disease. ... Methotrexate (rINN) (IPA: ), abbreviated MTX and formerly known as amethopterin, is an antimetabolite drug used in treatment of cancer and autoimmune diseases. ... Plasmapheresis is the removal of (components of) blood plasma from the circulation. ... This page meets Wikipedias criteria for speedy deletion. ...

Alternative treatments include:

• Rituximab: a very promising drug currently in clinical trials. It has been successful when used several times as a compassionate treatment for those who cannot tolerate CYC.
• Chlorambucil: a powerful immunosuppressant that has been used instead of cyclophosphamide in some cases.
• Mycophenolate mofetil: a drug similar to azathioprine

Non-immunosuppressive therapies are: Rituximab, sold under the trade names Rituxan® and MabThera®, is a monoclonal antibody used in the treatment of B cell non-Hodgkins lymphoma, B cell leukemia, and some autoimmune disorders. ... Chlorambucil (marketed as Leukeran by GlaxoSmithKline) is a chemotherapy drug that has been mainly used in the treatment of chronic lymphocytic leukemia. ... Mycophenolate mofetil (MMF, trade name Cellcept®) is an immunosuppresant drug used to prevent rejection in organ transplantation. ... Azathioprine is a chemotherapy drug, now rarely used for chemotherapy but more for immunosuppression in organ transplantation, autoimmune disease such as rheumatoid arthritis or inflammatory bowel disease such as Crohns disease. ...

• Co-trimoxazole: a wide-range antibiotic often administered in conjunction with immunosuppressants. Sometimes even administered as a treatment for Wegener's^{[citation needed]}.
• Folic acid: often administered in addition to some of the above immunosuppressants.
• Intravenous immunoglobulin (IVIG): A blood product containing immunoglobulins given to patients to bolster their immune system.

In some patients with severe subglottic stenosis, tracheotomy is required to maintain an airway. Co-trimoxazole (abbreviated SXT) is a bacteriostatic antibiotic combination of trimethoprim and sulfamethoxazole, in the ratio of 1 to 5, used in the treatment of a variety of bacterial infections. ... Folic acid and folate (the anion form) are forms of a water-soluble B vitamin. ... Intravenous immunoglobulin (IVIG) is a blood product administered Intravenously. ... Completed tracheostomy: 1 - Vocal cords 2 - Thyroid cartilage 3 - Cricoid cartilage 4 - Tracheal cartileges 5 - Balloon cuff A tracheotomy or tracheostomy is a surgical procedure performed on the neck to open a direct airway through an incision in the trachea (the windpipe). ...

Follow-up: general wellbeing and laboratory organ markers are checked on a regular basis to ascertain the patient has remained in remission.

Epidemiology

The incidence is 8.5 cases per million per year. 90% of the patients are whites. While it mainly occurs in the middle-aged, it has been reported in much younger and older patients. In optics one considers angles of incidence. ...

Prognosis

25 to 40% of patients suffer from flare-ups, but a majority responds well to treatment. Anatomical problems (sinusitis, tracheal stenosis) may require surgery in a small proportion. Relapses can be long and troublesome. Sinusitis is an inflammation of the paranasal sinuses, which may or may not be as a result of infection, from bacterial, fungal, viral, allergic or autoimmune issues. ...

Long-term complications are very common (86%): mainly chronic renal failure, hearing loss and deafness.^[1] An editor has expressed a concern that the topic of this article may be unencyclopedic. ...

History

A certain Peter McBride (1854-1946) first described the condition in 1897 in a British medical journal, especially the characteristic nasal deformation. Heinz Karl Ernst Klinger (1907-) would add information on the anatomical pathology, but the full picture was presented by Friedrich Wegener (1907-1990), a German pathologist, in two reports in 1936 and 1939.^[6] 1854 (MDCCCLIV) was a common year starting on Sunday (see link for calendar). ... Year 1946 (MCMXLVI) was a common year starting on Tuesday. ... 1897 (MDCCCXCVII) was a common year starting on Friday (see link for calendar). ... 1907 (MCMVII) was a common year starting on Tuesday (see link for calendar) of the Gregorian calendar (or a common year starting on Wednesday of the 13-day-slower Julian calendar). ... Anatomical pathology is the branch of pathology that is concerned with the diagnosis of disease based on the gross and microscopic examination of cells and tissues. ... Friedrich Wegener (1907-1990) was a German pathologist who is known for his documentation of Wegeners granulomatosis. ... 1907 (MCMVII) was a common year starting on Tuesday (see link for calendar) of the Gregorian calendar (or a common year starting on Wednesday of the 13-day-slower Julian calendar). ... ... To meet Wikipedias quality standards, this article or section may require cleanup. ... 1936 (MCMXXXVI) was a leap year starting on Wednesday (link will take you to calendar). ... 1939 (MCMXXXIX) was a common year starting on Sunday (link will take you to calendar). ...

References

1. ^ ^{a b c d e f g h i j} Seo P, Stone JH. The antineutrophil cytoplasmic antibody-associated vasculitides. Am J Med 2004;117:39-50. PMID 15210387.
2. ^ Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis Rheum 1990;33:1101-7. PMID 2202308.
3. ^ Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, Hoffman GS, Hunder GG, Kallenberg CG, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994;37:187-92. PMID 8129773.
4. ^ Bruce IN, Bell AL. A comparison of two nomenclature systems for primary systemic vasculitis. Br J Rheumatol 1997;36:453-8. PMID 9159539.
5. ^ van der Woude FJ, Rasmussen N, Lobatto S, Wiik A, Permin H, van Es LA, van der Giessen M, van der Hem GK, The TH. Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis. Lancet 1985;1(8426):425-9. PMID 2857806.
6. ^ synd/2823 at Who Named It

Who Named It is a Norwegian database of several thousand eponymous medical signs and the doctors associated with their identification. ...

External links

• Classification criteria by the American College of Rheumatology
• Wegener's Granulomatosis Association
• Wegener's Granulomatosis Info
• fluorescence images of ANCA