wegener’s granulomatosis of the major salivary glands

Wegener’s granulomatosis of the major salivary glands

A. W. Barrett

Department of Histopathology, Queen Victoria Hospital, East Grinstead, UK

Wegener’s granulomatosis is one of the anti-cytoplasmic

autoantibodies (ANCA)-associated vasculitides. Although

it typically affects the lungs and kidneys, the head and

neck are also involved in most cases but the site usually

affected is the upper airway. However, there are 35 cases

with well-documented clinicopathological data in which

Wegener’s granulomatosis manifested in the major sali-

vary glands, most commonly the parotid. Twenty-four

patients presented with salivary signs and symptoms, in

eight of whom there was no other presenting manifes-

tation. These signs and symptoms may mimic infection or

neoplasia and laboratory investigations, including ANCA

serology and histopathology, may be non-specific; thus, in

21 of the 35 patients (60%) there was a delay in diagnosis.

Amongst the 21 were 11 of the 14 (78.6%) patients who

presented with unilateral parotid disease and three of the

five who died. Three other patients suffered permanent

pulmonary, two renal and five facial nerve damage. This

article reviews the literature on major salivary gland

involvement in Wegener’s granulomatosis, which should

be considered in the differential diagnosis of major sali-

vary gland disease particularly if commoner causes have

been excluded. A detailed medical history, and persis-

tently inconclusive laboratory tests, could provide the

clues that enable prompt diagnosis.

J Oral Pathol Med (2012)

Keywords: salivary glands; vasculitis; Wegener’s granulomatosis

Introduction

Wegener’s granulomatosis (WG) is a potentially lethaldisease characterised by aseptic, necrotising granulom-atous vasculitis of small and medium-sized vessels, theaetiology of which is associated with the production ofanti-cytoplasmic autoantibodies (ANCA) to polymor-phonuclear leucocytes. It is thus one of the ANCA-associated vasculitides (AAV), which also includeChurg-Strauss syndrome, microscopic polyangitis and

renal-limited vasculitis (1, 2). Although a fatal outcomeis no longer inevitable, prompt diagnosis and treatmentare essential if serious long-term sequelae, particularlyto the lungs and kidneys, are to be avoided. The diseaseis rare; a cohort of 216 patients with WG was only 8%of one author’s consultations for all systemic vasculi-tides (3). Giant cell arteritis was by far the commonest(41%), but WG was the second most frequentlyencountered. WG has a classical presentation affectingthe anatomical triad of the upper and lower respiratorytracts and kidneys, with 75–92% of patients havingmanifestations of otolaryngological, 63–85% pulmo-nary and 48–77% renal disease (3–5). Hence, the typicalpresenting symptoms are sinusitis, epistaxis, cough,haemoptysis and non-specific constitutional symptomssuch as arthralgia, fever, malaise and weight loss. Theconcept of a more localised, or limited, form of WG inwhich renal function is preserved and prognosis betterhas been described, but progression from a limited formto a systemic, life threatening, generalised vasculiticsyndrome with renal damage is unpredictable. Further-more, the term �limited WG’ has been inconsistentlyapplied, and it is more helpful to specify which organsare involved (4). Indeed, despite the classical anatomicaltriad, the disease may produce a constellation oflocalised and systemic symptoms. The head and neckis involved in nearly 90% of cases, the sites mostcommonly affected being the nose, eyes, ears and mouth(3). By contrast, the major salivary glands, usually theparotid and submandibular glands, are an uncommonand little appreciated site of involvement. In a Britishseries of 265 WG patients, none had disease of the majorsalivary glands (4), and there was only one instance ofbiopsy proven WG in a North American cohort of 158(5), although an earlier report on part of the samecohort reported two instances each of parotid pain orswelling (6). Lie (3) reported five cases of major salivarygland disease, and in a series of 70 patients with WGaffecting the head and neck, three had salivary involve-ment (7). However, involvement of the major salivaryglands may be the initial manifestation of WG, but withsigns and symptoms which are non-specific or whichmasquerade as malignancy. Laboratory investigations,including ANCA serology and histopathology, may beunhelpful in early WG and thus an atypical presenta-tion, such as salivary gland disease, may result in a

Correspondence: A. W. Barrett, Department of Histopathology,Queen Victoria Hospital NHS, Foundation Trust, Holtye Road, EastGrinstead, West Sussex RH19 3DZ, UK. Tel.: +44 1342 414 270,Fax: +44 1342 414 117, E-mail: [email protected] for publication February 14, 2012

doi: 10.1111/j.1600-0714.2012.01141.x

J Oral Pathol Med

ª 2012 John Wiley & Sons A/S Æ All rights reserved

wileyonlinelibrary.com/journal/jop

crucial delay in treatment. The aim of this article is tohighlight the fact that WG affects the major salivaryglands, to review previous reported cases and identifyfeatures that might facilitate prompt diagnosis in theface of a vague clinical presentation.

Clinical features

The first case of salivary gland involvement in WG wasprobably reported by Lindsay et al. (8) in 1944 and wasthat of a 60-year-old woman who developed an acuteparotitis amongst other, more typical symptoms of WG.However, the diagnosis made was �chronic granulomaassociated with periarteritis nodosa’, as the first paperscharacterising WG had been published in Germanduring the 1930s and the term WG was not introducedinto the English language literature until the work ofGodman and Churg in 1954 (9). Since then, 47 cases ofWG have been documented as involving the salivaryglands (Table 1). The case reported by Burlacoff &Wong (10), in which a symptomless parotid gland

showed increased uptake on gallium scanning and wasthus suspected as a site of recrudescent WG after18 months of maintenance treatment, has not beenincluded in the analysis that follows. Clinical data areavailable for 35 of the 47 patients, 20 of whom were menand 15 women (male ⁄ female ratio 1.33:1). Their meanage is 51.1 years, with a median of 54 and a range of 18–75. Twenty-eight (80.0%) patients were aged over 40.The mean age is similar to that in the series of Andersonet al. (4), but higher than that of Hoffman et al. (5)(mean 41 years) and Devaney et al. (7) (36 years, indisease restricted to the head and neck). The race of thepatient was stated, or deducible from clinical photo-graphs, in 17 of the 35 patients, 12 of whom were white,three Asian (one Chinese, one Japanese, one Indian) andtwo Jewish. The parotid gland was involved in 25patients (with bilateral involvement in nine), thesubmandibular gland in 14 (with bilateral involvementin nine). A combination of parotid and submandibulargland involvement was reported in five patients. There isonly one documented case of WG affecting the

Table 1 Clinical details of documented cases of Wegener’s granulomatosis (WG) of the major salivary glands

References Sex Age Duration prior to presentation Presenting feature? Salivary glands affected

15 M 75 Not stated No Unilateral parotid33 (case 2) F 55 4 weeks Yes Unilateral parotid21 (case 4) M 27 2–3 weeks No Unilateral parotid19 F 34 6 weeks Yes Unilateral parotid17 F 47 2 weeks Yes Unilateral parotida

13 M 69 9 months Yes Unilateral parotida

14 F 59 Not stated Yes Unilateral parotida

27 M 45 3 weeks Yes Unilateral parotida



28 M 59 4 months Yes Unilateral parotida

30 F 71 3 weeks Yes Unilateral parotid31 F 69 10 days Yes Unilateral parotida

18 M 47 4 weeks Yes Unilateral parotid43 (case 4) M 39 2 months No Bilateral parotid45 M 43 6 weeks No Bilateral parotid21 (case 5) F 75 Not stated Yes Bilateral parotid25 F 40 3 years No Bilateral parotid16 M 62 Not stated No Bilateral parotid46 F 18 Not stated Yes Bilateral parotida

44 F 53 About 2 years No Unilateral submandibular33 (case 1) M 23 8 weeks Yes Unilateral submandibular21 (case 3) F 24 2–3 weeks No Unilateral submandibular20 M 59 6 weeks Yes Bilateral submandibular21 (case 1) M 60 >3 months No Bilateral submandibular21 (case 2) M 64 1 month No Bilateral submandibular35 F 63 7 months Yes Bilateral submandibular22 F 60 6 weeks Yes Bilateral submandibular36 M 55 3 months Yes Bilateral submandibular24 M 68 6 weeks Yes Unilateral parotid, bilateral submandibular29 M 45 Several months No Bilateral parotid, unilateral submandibular47 F 48 48 h Yes Bilateral parotid, bilateral submandibular23 F 46 2 weeks Yes Bilateral parotid, bilateral submandibular42 (case 2) M 34 Not stated Yes Parotid and submandibularb

11 M 55 2 weeks Yes Unilateral sublingual7 (3 cases) No Details Given Parotid and submandibularb

3 (5 cases) No Details Given Glands Not specified6 (4 cases) No Details Given Parotidb

aFacial nerve weakness.bNo further details given.

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sublingual gland (11). The duration of symptoms priorto presentation was stated in 29 cases and ranged from48 h to 3 years, but 24 (82.8%) cases presented between2 weeks and 4 months after the onset of symptoms. Inonly three cases was there already an establisheddiagnosis of WG and in eight swelling of the majorsalivary glands developed at a later stage in the naturalhistory of the disease. However, in 24 cases, salivarygland swelling with or without pain was a presentingfeature of WG, in eight of which it was the onlypresentation. In the other 16 patients there wereconcurrent manifestations of the ear, nose and throatin 14 cases, lung in six, eyes in three and gastrointestinaltract in one (Table 2). Nine patients also sufferedgeneral malaise. Despite apparent normal renal functionclinically, four of the 26 patients for whom data areavailable had haematuria or proteinuria at presentation,and in another five initially normal renal functiondeteriorated as the disease progressed. Facial nerveweakness occurred in nine cases of parotid disease(Table 1), although one of these may have been because

of direct injury to an exposed nerve (12) and one tosurgical manipulation (13) rather than WG. In onepatient, brain stem involvement caused not only facialnerve weakness, but deficits in the fifth and eighth cranialnerves too (14). The sixth cranial nerve was affected inanother patient (15), the ninth and tenth nerves in a third(16). In several cases, the medical history suggested that amultisystem process was involved, and between 5 weeksand 4 years before WG was finally recognised there werehistories of pericarditis (17), chronic blepharitis (18),myalgic encephalitis (19), recurrent polyarticularsynovitis (20), bronchial asthma (16) and, in the first caseof Specks et al. (21), signs and symptoms of prostate, lungand ocular disease as well as ulceration of the lip.

Haematological, chemical pathological andmicrobiological findings

These have seldom proved helpful, although theerythrocyte sedimentation rate is consistently raised;this was the case in 20 of the 22 cases where the data arereported. However, in the other two it was normal.Neutrophilia was reported in twelve patients, eosino-philia in one. C-reactive protein was raised in seven ofthe eight patients for whom the result was stated, withone normal. Microbiological investigations have onseveral occasions proved frankly misleading; in onepatient, there was a positive antibody titre to cyto-megalovirus (11).

ANCA serology

This test became available in the mid-1980s and appliesindirect immunofluorescence to ANCA on ethanol-fixedneutrophils. One of two positive staining patterns maybe produced, namely the cytoplasmic (c-ANCA) and theperinuclear (p-ANCA). Most patients with a c-ANCApattern have an ANCA directed against proteinase-3(PR3), as determined by enzyme-linked immunosorbentassay. Those with the p-ANCA pattern usually have anANCA directed against myeloperoxidase (MPO).However, Asian WG patients are more likely to produceMPO-ANCA, and northern Caucasian patients tend tohave PR3-ANCA even if their AAV is not WG. PR3-ANCA levels are not necessarily a guide to the activityof the disease or in the planning of immunosuppressivetherapy (1). Amongst the 27 results of serology reportedin patients with WG of the major salivary glands, theANCA titre was raised in 19 patients and initiallynormal in eight, but in seven of the latter it subsequentlyrose.

Imaging

Where imaging is reported, there has been no consistentor specific feature that has identified WG in the majorsalivary glands. Both diffuse (12, 13, 19, 22–24) anddiscrete (25–28) swellings have been reported withcomputerised tomography (CT) and magnetic resonanceimaging (MRI). A discrete lesion is suggestive of anabscess or tumour, and a primary malignancy of the

Table 2 presenting signs and symptoms other than those of salivaryorigin, and working diagnoses

ReferencesOther presenting signs

& symptoms Working diagnosis

15 ENT, general malaise Infection, malignancy,vasculitis

33 (case 2) ENT WG21 (case 4) ENT Not stated19 ENT, ocular Myalgic encephalitis17 ENT TMJ dysfunction, malignancy13 None Infection, malignancy14 ENT Infection27 Lung Parotid abscess26 Lung Infection, malignancy12 None Infection28 Ocular Episcleritis, parotid abscess30 None Infection31 None Infection18 None Malignancy, obstructive

sialadenitis43 (case 4) Known WG WG45 Known WG WG21 (case 5) Lung, general malaise Not stated25 Known WG for 3 years Sjogren’s syndrome16 Lung Churg-Strauss syndrome46 ENT Sarcoidosis44 General malaise Sclerosing sialadenitis33 (case 1) ENT Lymphoma, WG21 (case 3) ENT Not stated20 Lung, general malaise Relapsing polychondritis21 (case 1) Lung, general malaise Not stated21 (case 2) ENT Not stated35 Ocular Sjogren’s syndrome22 None Reaction to contrast medium36 None Tuberculosis24 ENT, general malaise,

ocularSarcoidosis (Heerfordtsyndrome)

29 General malaise,gastrointestinal,renal

Not stated

47 ENT, general malaise WG23 ENT Tuberculosis42 (case 2) ENT Not stated11 None Dental abscess


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parotid was the working diagnosis in the case of Bergeet al. (17) because of the appearances of a cavitated,infiltrating mass. Both the parotid and submandibularglands may show changes, even if only one is affectedclinically (28, 29). MRI can produce low signal intensityin T2-weighted imaging suggestive of necrotic foci, andas they found none in their case, Gassling et al. (24)concluded there was evidence of neither an abscess norneoplasia in the affected submandibular glands, despitemarked enhancement with contrast medium. Whereasultrasound may produce a circumscribed, cystic or fluid-filled mass even in a clinically unaffected gland (25, 30),no such collection was seen in the case ofGeyer et al. (31).

Histopathological findings

Detailed analyses of the histopathology of WG havebeen made by Devaney et al. (7) and Carlson (32). WGis characterised histologically by a neutrophilic (or�leucocytoclastic’) vasculitis affecting the walls of smalland ⁄ or muscular blood vessels, and foci of scattered,so-called �geographic’ necrosis of the stromal tissue, thatis, basophilic, necrotic foci with irregular borders,typically surrounded by granulomatous inflammationcomprising histiocytes (which may be palisaded) andgiant cells. There may also be more dispersed, poorlyformed granulomas, giant cells and micro-abscesses.The latter may also be surrounded by granulomas, andpossibly represent early stromal necrosis that willdevelop into geographic necrosis. There may also bestoriform or angiocentric (�onion ring’) fibrosis. How-ever, Devaney et al. (7) found that a combination ofvasculitis, stromal necrosis and granulomatous inflam-mation was present in only 16% of 126 cases from thehead and neck. Scattered eosinophils were a commonfinding, but were prominent in <5% (7) and are more afeature of other AAV. Only three of the 126 biopsiesemanated from the major salivary glands, of which twoshowed geographic necrosis, poorly formed granulo-mas, scattered giant cells and micro-abscesses. Noneshowed micro-abscesses with surrounding granulomasor fibrinoid necrosis.Histological data on salivary biopsies are recorded in

33 of the 35 case reports. Several reported the histolog-ical changes to be reactive and non-specific. WGremained undiagnosed after two biopsies in the case ofJones et al. (28), and three in that of Chegar and Kelley(12), the third biopsy of the parotid showing necrotisinggranulomatous inflammation and small vessel arteritis.Other authors have identified histological features ofWG in the salivary glands, but the changes wereregarded as consistent with, rather than pathognomonicof, WG (26, 33). The case of Murty et al. (33)demonstrated fibrosis, which was absent in the threesamples documented by Devaney et al. (7). Xanthogra-nulomatous lesions, which may be seen in lung biopsiesdiagnostic of WG (34), may also occur in salivaryWG (18).Giant cells may be absent (18), but if present their

nature and significance may not be recognised and theyhave been interpreted as a foreign body reaction to

contrast medium (22) or mucous extravasation (11). Bycontrast, Specks et al. (21) found that salivary glandbiopsy alone was diagnostic of WG in three of theircases, and commented that a parotid or submandibulargland biopsy had the advantage of reduced morbiditycompared to an open lung biopsy. Lustmann et al. (25)reckoned that 30% of parotid biopsies showed vascu-litis, with giant cells in 50%. It is of particularsignificance therefore that in five cases (18, 20, 25, 35,44), the salivary histology was originally reported asnon-specific but, on retrospective review once thediagnosis of WG had become established by othermeans, it was recognised that there was, in fact, goodhistological evidence of WG which had been missed orignored.

Histological differential diagnoses have included non-specific chronic inflammation, a consequence of eitherobstructive sialadenitis or mucin extravasation, tuber-culosis, other infections (including viral), sarcoidosisand foreign body reactions. Xanthogranuloma andRosai–Dorfman disease were also considered in onecase (18). The features of one parotid biopsy werethought to be those of Sjogren’s syndrome, but theidentification of Langhan’s type giant cells led theauthors to preclude this (25). The presence of granu-lomatous inflammation in a submandibular gland sam-ple prompted a definitive diagnosis of WG when themain differential diagnosis after a renal biopsy waspolyarteritis nodosa (35).

Not surprisingly, the features in fine needle aspira-tions have been interpreted as non-specific (13, 14, 23,27, 28, 36) or misleadingly malignant (18). Frozensections have also proved non-diagnostic (13, 18).Special stains for elastin and vascular smooth muscle,and immunohistochemistry for smooth muscle actinand ⁄ or endothelial markers might prove helpful, butdirect immunofluorescence is not. This is because thevasculitis in WG is �pauci-immune’, that is, in WG, as inthe other AAV, there is no immune complex depositionand so direct immunofluorescence is negative (32).

Association of WG with Sjogren’s syndrome

Five apparent �collision’ cases of WG with Sjogren’ssyndrome have been reported (35, 37–40). Whilst at leasttwo had salivary gland abnormalities on sialoscintigra-phy (39, 40), only one (35) presented with parotidswelling, the salivary abnormalities in the other casesbeing attributed to Sjogren’s syndrome rather than WG,which appeared to be confined to the lungs. Minorsalivary gland biopsies confirmed the features of Sjo-gren’s syndrome in two cases (38, 40), with no evidenceof salivary WG, whereas lung biopsies were diagnosticof WG in these two and one other patient (39). 11% ofSjogren’s syndrome patients may have ANCA antibod-ies (41), and whilst all are negative for antinuclear factorover half of WG patients may be positive for rheuma-toid factor (6), as was the case in the patients reportedby Bucolo et al. (14) and Bulbul et al. (27). In two morepatients, the clinicopathological picture raised the pos-sibility of Sjogren’s or �Mikulicz’ syndrome (25, 42).


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Outcomes

Five patients died of WG: of these, one predatedtreatment (43), one was treated solely with steroids,the only available therapy at the time (42) and onepatient refused further treatment after an initial courseof steroid therapy, WG being diagnosed at autopsy (24).Of the other two fatal outcomes, one had been treatedwith cyclophosphamide, prednisolone, trimethoprimand sulphamethoxazole (27), the other with cyclophos-phamide and prednisolone (26). Thus, 30 (85.7%)patients survived. However, three showed permanentlung changes on chest radiography (21, 29, 45) andanother two suffered permanent renal damage (18, 23).Facial nerve palsy persisted in five patients (12, 13, 17,28), of which one also had hearing loss and facialparaesthesia (14). There was lasting damage to oneparotid (26) and one submandibular gland (33), a thirdpatient suffering permanently reduced function of all themajor salivary glands although only the parotids wereinvolved clinically (25). In 21 of the 35 (60.0%) cases,there is evidence that the unusual salivary glandpresentation caused a delay in the diagnosis of WG,including 11 of the 14 (78.6%) cases of unilateral parotiddisease. The delay ranged from 2 weeks to over a year.Three of the five patients who died are amongst these 21,death being as a result of pulmonary complications intwo patients (26, 27) and renal sequelae in the other (24).These three deaths occurred at a time when moderntherapeutic regimes had become available.

Discussion

WG has been described as one medicine’s greatmasqueraders (10, 28). The differential diagnosis of aswollen parotid or submandibular gland is wide, and ascan be seen in Table 2, the working diagnosis is oftenone of an infective or neoplastic process. A unilateralparotid presentation of WG appears particularly liableto a delayed or misdiagnosis. �Dependable’ specialinvestigations may not be so; eight of the 27 patientswith major salivary gland disease in whom serology isreported were ANCA-negative on first testing, and thehistopathologist will be fortunate if a fifth of WGbiopsies contain all the principal diagnostic features (7).

The reports of Bulbul et al. (27), Specks et al. (21) andVanhauwaert et al. (22) illustrate the diagnostic dilem-ma. In the first (27), despite lung changes and parotidswelling, WG was not considered and the patient wasprescribed teicoplanin after a parotid pus swab grewmethicillin-resistant Staphylococcus aureus. In thesecond, the first patient of a series of five (21), therewere signs and symptoms of multisystem disease, andhistopathological changes of WG not only in thesubmandibular gland but also the lungs and prostate.WG was considered, yet a diagnosis of TB was made. Inthe third (22), both a submandibular gland and a nasalbiopsy showed microscopic features of WG, but thisdiagnosis was rejected because of negative c-ANCAserology. By the time a renal biopsy finally clinched thediagnosis, c-ANCA was positive.

Retrospectively, of course, the diagnosis may seemobvious! So are there clues which might facilitatediagnosis? The medical history and clinical examinationare crucial, since they might provide evidence of diseasein other systems. Paradoxically, the very non-specificityof imaging and the laboratory tests might be helpful.Berge et al. (17) recommended that, if histology doesnot confirm a primary malignancy in the face of a CTor MRI scan which shows an infiltrating mass, WG andsarcoid should be considered. If an erroneous diagnosisof infection is made initially, Bucolo et al. (14) sug-gested that WG should be considered when antibiotictreatment fails. They also advocated that an initiallynegative ANCA result be repeated if the ESR remainsraised and the serum creatinine monitored for any risewhich could herald incipient renal failure. Close clini-copathological liaison is essential, as the risk to thekidneys cannot be over-emphasised. Because renalcomplications did not befall any of their five cases,Specks et al. (21) proposed that salivary disease repre-sented a �limited’ form of WG. By contrast, Berge et al.(17) felt that salivary involvement as a presentingfeature of WG meant the disease was at an early stageand that, if treatment was instigated promptly, thekidneys could be spared. The available data clearlyshow that salivary WG cannot be assumed to representa limited form of the disease because renal, and other,damage can ensue.

Conclusions

Wegener’s granulomatosis of the major salivary glandsmay present with a sequence of mystifying signs andsymptoms, but it must be considered in the differentialdiagnosis of major salivary gland disease if disastrousconsequences are to be avoided. Review of the medicalhistory and histopathology may make the diagnosisinfuriatingly obvious in retrospect. The former inparticular is crucial in identifying a multisystem disease.Negative or contradictory special investigations couldbe masking the seriousness of the patient’s condition,especially in a unilateral presentation of the parotid, andrepeated serology for ANCA antibodies may be neces-sary. Histopathologically, necrotising lesions combinedwith granulomas, giant cells and ⁄ or unusual patterns ofinflammatory cell infiltration should bring WG to mind,even in apparently unlikely locations such as the majorsalivary glands.

References

1. Chen M, Kallenberg CGM. New advances in the patho-genesis of ANCA-associated vasculitides. Clin Exp Rheu-matol 2009; 27(Suppl 52): S108–14.

2. Gomez-Puerta JA, Bosch X. Anti-neutrophil cytoplasmicantibody pathogenesis in small vessel vasculitis. Am JPathol 2009; 175: 1790–8.

3. Lie JT. Wegener’s granulomatosis: histological documen-tation of common and uncommon manifestations in 216patients. Vasa 1997; 26: 261–70.


Barrett

5

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4. Anderson G, Coles ET, Crane M, et al. Wegener’sgranuloma. A series of 265 British cases seen between1975–1985. Q J Med 1992; 83: 427–38.

5. Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener’sgranulomatosis: an analysis of 158 patients. Ann InternMed 1992; 116: 488–98.

6. Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener’sgranulomatosis: prospective clinical and therapeutic expe-rience with 85 patients for 21 years. Ann Intern Med 1983;98: 76–85.

7. Devaney KO, Travis WD, Hoffman G, Leavitt R,Lebovics R, Fauci AS. Interpretation of head and neckbiopsies in Wegener’s granulomatosis: a pathologic studyof 126 biopsies in 70 patients. Am J Surg Pathol 1990; 14:555–64.

8. Lindsay S, Aggeler PM, Lucia SP. Chronic granulomaassociated with periarteritis nodosa. Report of a case withrenal failure. Am J Pathol 1944; 20: 1057–71.

9. Godman GC, Churg J. Wegener’s granulomatosis: pathol-ogy and review of the literature. Arch Pathol 1954; 58:533–53.

10. Burlacoff SG, Wong FSH. Wegener’s granulomatosis. Thegreat masquerade: a clinical presentation and literaturereview. J Otolaryngol 1993; 22: 94–105.

11. Crean SJ, Adams R, Bennett JH. Sublingual glandinvolvement in systemic Wegener’s granulomatosis. Int JOral Maxillofac Surg 2002; 31: 104–6.

12. Chegar BE, Kelley RT. Wegener’s granulomatosis pre-senting as unilateral parotid enlargement. Laryngoscope2004; 114: 1730–3.

13. Saravanappa N, Bibas A, Singhal A, Davis JP. Unilateralparotid swelling as initial manifestation of Wegener’sgranulomatosis. J Otolaryngol 2000; 29: 396–7.

14. Bucolo S, Torre V, Montemagno A, Beatrice F. Wegener’sgranulomatosis presenting with otologic and neurologicsymptoms; clinical and pathological correlations. J OralPathol Med 2003; 32: 438–40.

15. Kavanaugh AF, Huston DP. Wegener’s granulomatosispresenting with unilateral parotid enlargement. Am J Med1988; 85: 741–2.

16. Yamamoto M, Takahashi H, Suzuki C, Shinomura Y.Facial cutaneous and parotid gland involvement inWegener’s granulomatosis. J Rheumatol 2008; 35: 365–7.

17. Berge S, Niederhagen B, Von Lindern JJ, Appel T, ReichRH. Salivary gland involvement as an initial presentationof Wegener’s disease. Int J Oral Maxillofac Surg 2000; 29:450–2.

18. Barrett AW, Barbaccia C, Lavery KM. Wegener’s gran-ulomatosis of the parotid gland and surrounding tissues.Br J Oral Maxillofac Surg 2011; 49: 241–2.

19. Benson-Mitchell R, Tolley N, Croft CB, Roberts D.Wegener’s granuloma presenting as a unilateral parotidswelling. J Laryngol Otol 1994; 108: 431–2.

20. Small P, Black M, Davidman M, Brisson De ChamplainML, Kapusta MA, Kreisman H. Wegener’s granuloma-tosis and relapsing polychondritis. J Rheumatol 1980; 7:915–8.

21. Specks U, Colby TV, Olsen KD, De Remee RA. Salivarygland involvement in Wegener’s granulomatosis. ArchOtolaryngol Head Neck Surg 1991; 117: 218–23.

22. Vanhauwaert BG, Roskams TA, Vanneste SB, KnockaertDC. Salivary gland involvement as initial presentation ofWegener’s disease. Postgrad Med J 1993; 69: 643–5.

23. Liu SY, Viantis AC, Lee WC. Bilateral parotid andsubmandibular gland enlargement: rare features ofWegener’s granulomatosis. J Laryngol Otol 2003; 117:148–50.

24. Gassling V, Wiltfang J, Hampe J, Brasen JH, Both M,Moosig F. Salivary gland swelling in Wegener’s granulo-matosis: a rare cause of a frequent symptom. J Rheumatol2010; 37: 2633–6.

25. Lustman J, Segal N, Markitziu A. Salivary gland involve-ment in Wegener’s granulomatosis. A case report andreview of the literature. Oral Surg Oral Med Oral Pathol1994; 77: 254–9.

26. Imamoglu M, Bahadir O, Reis A. Parotid gland involve-ment as an initial presentation of Wegener’s granuloma-tosis. Otolaryngol Head Neck Surg 2003; 4: 451–3.

27. Bulbul Y, Ozlu T, Oztuna F. Wegener’s granulomatosiswith parotid gland involvement and pneumothorax. MedPrinc Pract 2003; 12: 133–7.

28. Jones GL, Lukaris AD, Prabhu HV. Wegener’s granulo-matosis mimicking a parotid abscess. J Laryngol Otol2005; 119: 746–9.

29. Stuckey SL, Smart PJ. Wegener’s granulomatosis: parotidinvolvement and associated pancreatitis with CT findings.Australas Radiol 1992; 36: 343–6.

30. Frantz MC, Frank H, Von Weyhern C, Kiefer J. Unspe-cific parotitis can be the first indication of Wegener’sgranulomatosis. Eur Arch Otorhinolaryngol 2008; 265:131–4.

31. Geyer M, Kulamarva G, Davis A. Wegener’s granuloma-tosis presenting with an abscess in the parotid gland: a casereport. J Med Case Reports 2009; 3: 19–22.

32. Carlson JA. The histological assessment of cutaneousvasculitis. Histopathology 2009; 56: 3–23.

33. Murty GE, Mains BT, Bennett MK. Salivary glandinvolvement in Wegener’s granulomatosis. J LaryngolOtol 1990; 104: 259–61.

34. Travis WD. Common and uncommon manifestations ofWegener’s granulomatosis. Cardiovasc Pathol 1994; 3:217–25.

35. Bottinger EP, Niles JL, Collins AB, McCluskey RT,Arnaout MA. Antineutrophil cytoplasmic antibody-associated vasculitis presenting as Sjogren’s syndrome.Arthritis Rheum 1992; 35: 1373–6.

36. Singh S, Kaura D, Kumari S, Gupta D, Dey P, Suri S.Wegener’s granulomatosis presenting as submandibularswelling. Sarcoidosis Vasc Diffuse Lung Dis 1997; 14: 81–2.

37. Young C, Hunt S, Watkinson A, Beynon H. Sjogren’ssyndrome, cavitating lung disease and high sustained levelsof antibodies to serine proteinase 3. Scand J Rheumatol2000; 29: 267–9.

38. Karargyris G, Stamatopoulos K, Kittas C, LoukopoulosD, Vaiopoulos G. Sjogren’s syndrome coexisting withlimited Wegener’s granulomatosis. Rheumatology 2000;39: 805–6.

39. Sato Y, Sakamoto S, Kotajima F, et al. A case ofSjogren’s syndrome with Wegener’s granulomatosis-likepulmonary involvement. Allergol Int 2005; 54: 339–42.

40. Yasisiz V, Ozbudak IH, Nizam I, et al. A case of primarySjogren’s syndrome with pulmonary-limited Wegener’sgranulomatosis. Rheumatol Int 2010; 30: 1235–8.

41. Font J, Ramos-Casals M, Cervera R, et al. Antineutrophilcytoplasmic antibodies in primary Sjogren’s syndrome:prevalence and clinical significance. Br J Rheumatol 1998;37: 1287–91.

42. Berman DA, Rydell RE, Eichenholz A. Wegener’s gran-ulomatosis: a clinicopathological study of four cases. AnnIntern Med 1963; 59: 521–30.

43. Fahey JL, Leonard E, Churg J, Godman G. Wegener’sgranulomatosis. Am J Med 1954; 17: 168–79.

44. Smith GA, Konrad HR. Pathologic quiz case 2. ArchOtolaryngol 1976; 102: 320–1.


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45. Kovarsky J. Parotid nodules in Wegener’s granulomatosis.Arthritis Rheum 1978; 21: 864–5.

46. Saha AK, Rachapelli S, Steer S, Gordon P. Bilateralparotid gland involvement in Wegener’s granulomatosis.Ann Rheum Dis 2009; 68: 1233–4.

47. Ah-See KW, McLaren K, Maran AG. Wegener’s granu-lomatosis presenting as major salivary gland enlargement.J Laryngol Otol 1996; 110: 691–3.

Acknowledgements

The help of Patricia Rey and Karen Clements, library staff at Queen

Victoria Hospital NHS Foundation Trust, is gratefully acknowledged.


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wegener’s granulomatosis of the major salivary glands

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