SPECIAL REVIEW

Marathon of eponyms: 23 Wegener granulomatosis

C Scully1, J Langdon

2, J Evans

1

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, 214–216

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 affected.

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 influencing the cellcycle, differentiation and cell death. MPO-ANCA isrelated mainly to MPA and AGA. PR3 might functionas an endogenous �danger⁄alarm’ 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 proinflammatory cytokine IL-32,an important factor in innate and adaptive immuneresponses. A number of endogenous and exogenousfactors (HLA-DPB1*0401⁄PTPN22*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 (neutrophils⁄monocytes) sur-rounded by antigen-presenting cells, Th1-typeCD4+CD28) effector memory T-cells and maturingB- and plasma cells are found in WG-granulomata ofthe upper respiratory tract. Thus, WG-granulomatamight provide the necessary �pro-inflammatory 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 affect mainly smallarteries, 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 produceinflammatory mediators, leading to recruitment of

Correspondence: Crispian Scully, UCL-Eastman Dental Institute,University College London, London, UK. Tel: 02079151170, Fax:02079151232, E-mail: crispian.scully@eastman.ucl.ac.uk

Oral Diseases (2012) 18, 214–216 doi:10.1111/j.1601-0825.2009.01555.x� 2012 John Wiley & Sons A/S

All rights reserved

www.wiley.com

monocytes and T cells and increased endothelialdamage. Non-specific inflammation 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-specific nature but rhinitis is generally the first 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, infiltrates, 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 differentiated from polyarteritis nodosa, lym-phomatoid granulomatosis, midline granulomas andlymphomas. WG is usually diagnosed by ANCA pos-itivity, but negative ANCAs are not sufficient 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-specific and 50% provide inadequate information forthe diagnosis. According to the Chapel Hill ConsensusConference (CHCC), establishing the diagnosis of We-gener’s granulomatosis demands the following:

• Granulomatous inflammation 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 infliximab may be effective.

Background to eponym

The clinical condition was first 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 specificclinical and histopathological criteria was offered 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 adifferent 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 firstdescribed 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 in1907, and studied at the University of Berlin.

Marathon of eponymsC Scully et al

215

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-associatedvasculitis – diagnosis and therapy. Ther Umsch 65: 295–301.

Friedmann I (1982). McBride and the midfacial granulomasyndrome. (The second �McBride Lecture’, Edinburgh,1980). J Laryngol Otol 96: 1–23.

Scully C, Langdon J, Evans J (2009). Editorial. Oral Dis 15:

185–186.Woywodt A, Matteson EL (2006). Wegener’s granulomatosis–probing the untold past of the man behind the eponym.Rheumatology (Oxford) 45: 1303–1306.

http://emedicine.medscape.com/article/1085290-overviewhttp://emedicine.medscape.com/article/1146811-overviewhttp://www.whonamedit.com, http://rarediseases.about.comhttp://medcosmos.blogspot.com/2008/09/1000-eponyms-in-medicine.html

http://insidesurgery.com/index.php?itemid=264http://en.wikipedia.org/wiki/List_of_eponyms

Marathon of eponymsC Scully et al

216

Oral Diseases