marathon of eponyms: 23 wegener granulomatosis

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    Marathon of eponyms: 23 Wegener granulomatosis

    C Scully1, J Langdon2, J Evans1

    1University College London, London, UK; 2Kings College London, London, UK

    The use of eponyms has long been contentious, but many

    remain in common use, as discussed elsewhere (Editorial:

    Oral Diseases. 2009: 15; 185). The use of eponyms in

    diseases of the head and neck is found mainly in special-

    ties dealing with medically compromised individuals

    (paediatric dentistry, special care dentistry, oral and

    maxillofacial medicine, oral and maxillofacial pathology

    and oral, oral and maxillofacial radiology and maxillofa-

    cial surgery) and particularly by hospital-centred practi-

    tioners. This series has selected some of the more

    recognized relevant eponymous conditions and presents

    them alphabetically. The information is based largely on

    data available from MEDLINE and a number of internet

    websites as noted below: the authors would welcome any

    corrections. This document summarizes data about

    Wegener granulomatosis.

    Oral Diseases (2012) 18, 214216

    Keywords: oral; eponyms; Wegener granulomatosis

    Also known as

    ANCA-associated granulomatous vasculitisKlinger syndromeKlinger-Wegener syndromeWegener diseaseWegener syndromeWegener-Churg-Klinger syndromeWegener-Klinger syndrome

    The condition

    Wegener granulomatosis (WG) is a rare disorder withan incidence of approximately one case per 1 000 000population, characterized by necrotising vasculitis,granulomatous lesions of the respiratory tract andglomerulonephritis. WG is mostly reported in whitepeople. The disease commonly occurs in mid-adulthood.Either gender may be aected.

    Wegener granulomatosis is part of a larger group ofvasculitic syndromes. Among the small-vessel vasculit-ides, microscopic polyangiitis (MPA), Wegener granu-lomatosis (WG), Churg-Strauss-syndrome and allergicgranulomatous angiitis (AGA) are collectively known asANCA-associated vasculitis (AAV) because of thepathogenic involvement of anti-neutrophil cytoplasmicantibodies (ANCA), which appear to induce vasculitisby directly activating neutrophils. Major target antigensof AAV are myeloperoxidase (MPO) and proteinase 3(PR3) in neutrophils. PR3-ANCA (cANCA) is themarker antibody in WG and is a multifunctionalneutrophil-derived serine protease inuencing the cellcycle, dierentiation and cell death. MPO-ANCA isrelated mainly to MPA and AGA. PR3 might functionas an endogenous dangeralarm signal that communi-cates the presence of tissue injury to dendritic cells (DC)via protease-activated receptor-2 (PAR-2), triggers theirmaturation and instructs DC to induce Th1-type cellresponses in WG. Furthermore, PR3 has the capacity tobind and activate the proinammatory cytokine IL-32,an important factor in innate and adaptive immuneresponses. A number of endogenous and exogenousfactors (HLA-DPB1*0401PTPN22*620W, respiratoryepithelial barrier dysfunction, Staphylococcus aureus,PR3) might favour initial formation of granulomata inthe respiratory tract and a break of immune tolerance.Clusters of PR3+ cells (neutrophilsmonocytes) sur-rounded by antigen-presenting cells, Th1-typeCD4+CD28) eector memory T-cells and maturingB- and plasma cells are found in WG-granulomata ofthe upper respiratory tract. Thus, WG-granulomatamight provide the necessary pro-inammatory environ-ment for the break of tolerance and display features oflymphoid-like tissue neoformation in which autoimmu-nity to PR3 could be sustained.ANCA-associated vasculitides aect mainly small

    arteries, venules and capillaries, showing a lack ofimmune complex formation on immunohistology, theso-called pauci-immune vasculitis. In vitro studies havefound that ANCAs can activate neutrophils, increasetheir adherence to endothelium and induce their degran-ulation that can damage endothelial cells. Endothelialcell damage and activation of neutrophils produceinammatory mediators, leading to recruitment of

    Correspondence: Crispian Scully, UCL-Eastman Dental Institute,University College London, London, UK. Tel: 02079151170, Fax:02079151232, E-mail:

    Oral Diseases (2012) 18, 214216 doi:10.1111/j.1601-0825.2009.01555.x 2012 John Wiley & Sons A/S

    All rights reserved

  • monocytes and T cells and increased endothelialdamage. Non-specic inammation and granulomato-sis are seen in WG, particularly initially in the upperrespiratory tract (localized phase) and this progressesto systemic disease with PR3-AAV (generalizedphase).The lesions of WG closely resemble those in polyar-

    teritis nodosa. The symptoms are weakness, malaise,progressive weight loss, purulent rhinitis, sinusitis,polyarthralgia, ulcerations of the nasal septum, signsof severe progressive renal disease and fever. Initial signsare protean, and diagnosis is often delayed due to theirnon-specic nature but rhinitis is generally the rst sign.Clinical features may include:

    Upper respiratory lesions in nearly 75% ofpatients: Subglottic tracheal stenosis Sinusitis and nasal mucosal disease with puru-

    lent or sanguinous nasal discharge Otitis media Salivary gland lesions Oral involvement, though rare, is classical as

    strawberry gingival swellings, ororal ulceration Pulmonary nodules, inltrates, cavitary lesions orhaemorrhage

    Renal rapidly progressive segmental necrotisingglomerulonephritis

    Joint pain or swelling Skin nodules or petechiae or splinter haemorhages Ophthalmic vasculitis of the eye includes orbitalgranuloma with exophthalmos, episcleritis, uveitisand retinal vasculitis

    Neurological mainly cranial and peripheral neur-opathies occur in about one-third of cases. Cranialnerves II, VI and VII are affected most commonly,either by vasculitic injury, compression, extension ofdisease from adjacent sinuses or cavernous sinusthrombosis

    Other organs heart and gastrointestinal tract arerarely affected

    Wegener granulomatosis, if not treated early, leads torenal damage and death in a matter of months. WGmust be dierentiated from polyarteritis nodosa, lym-phomatoid granulomatosis, midline granulomas andlymphomas. WG is usually diagnosed by ANCA pos-itivity, but negative ANCAs are not sucient to rejectthe diagnosis. Cytoplasmic staining ANCAs that reactwith proteinase 3 (cANCA) in neutrophils are associatedwith WG. Renal, skin or lung biopsy may showleukocytoclastic vasculitis with necrosis and granulom-atous changes but many biopsies, particularly thosetaken from the upper respiratory tract, can be non-specic and 50% provide inadequate information forthe diagnosis. According to the Chapel Hill ConsensusConference (CHCC), establishing the diagnosis of We-geners granulomatosis demands the following:

    Granulomatous inammation involving the respira-tory tract, and

    Vasculitis of small to medium-sized vessels

    Untreated, WG has a mortality within one year ofover 90%, with an average survival of 5 months.Despite little evidence of an infectious aetiology, WGhas been successfully treated with trimethoprim andsulfamethoxazole and in some studies, relapse rateshave been associated with chronic nasal carriage ofStaphylococcus aureus. In localized disease, treatmentwith co-trimoxazole is recommended, with corticosteroids in case of treatment failure. In generalizednon-organ threatening disease, remission can beinduced with steroids and methotrexate. In organ-threatening disease, treatment is by pulsed IV cyclo-phosphamide with steroids, followed by azathioprine tomaintain remission. In severe disease not responsive tothe above treatment, mycophenolate mofetil, 15-deoxy-spergualin (Gusperimus), anti-thymocyte globulin, rit-uximab or iniximab may be eective.

    Background to eponym

    The clinical condition was rst described by PeterMcBride in 1897, while the pathological-anatomicalpicture in 1931 by a German medical student, Heinz KarlErnst Klinger, who thought it was a variant of polyarter-itis nodosa, and a detailed description with specicclinical and histopathological criteria was oered byFriedrich Wegener in 1936 and 1939. A limited form hasbeen known as Carrington-Liebow syndrome, and alymphoid variant has been known as the Liebow-Carrington syndrome.Churg described Churg-Strauss syndrome a small-

    vessel vasculitis frequently associated with ANCA andsometimes with a focal glomerulonephritis, but with abetter prognosis than WG and now considered to be adierent disease.

    The main persons

    Friedrich Wegener was born in Germany in 1907.Wegener worked as a pathologist in Berlin, Breslauand Lubeck and, when in Breslau in the 1930s, he rstdescribed the condition that carries his name. DuringWorld War II, Wegener worked as a military patholo-gist in Lodz, where he also held a position in theGesundheitsamt, later being suspected of being a warcriminal. He died in 1990.Jacob Churg was born on 16 July 1910, Dolhinow,

    then in Russia, now Poland. He graduated in Medicinefrom the University of Wilno in 1933 and subsequentlyspent 2 years in internship in internal medicine at localhospitals. He became an assistant in the pathologicaldepartment of the university and received his medicaldoctorate in 1936, after which he migrated to the USAand moved to New York. Churg worked in thebacteriological laboratory at Mount Sinai Hospital.Churg was appointed as clinical professor of pathologyin 1966. He died on 27 July 2005.Heinz Karl Ernst Klinger was born in Germany in

    1907, and studied at the University of Berlin.

    Marathon of eponymsC Scully et al


    Oral Diseases

  • Associated persons

    Jacob ChurgHeinz Karl Ernst KlingerFriedrich Wegener

    Source internet sites (accessed 21 February 2009) andfurther reading

    Eisenberger U, Hess C (2008). Systemic ANCA-associatedv


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