CASE REPORT

T. Carels Æ E. Verbeken Æ D. Blockmans

p-ANCA-associated periaortitis with histological proofof Wegener’s granulomatosis: case report

Received: 27 May 2004 / Accepted: 15 September 2004 / Published online: 24 November 2004� Clinical Rheumatology 2004

Abstract We describe a 63-year-old man who presentedwith an inflammatory aortic aneurysm. The patient hadp-ANCA antibodies directed against myeloperoxidase.A diagnosis of idiopathic periaortitis was made. Sevenyears later, he was rehospitalized because of fever,weight loss, and polyneuropathy. After revision of theaortic biopsy, which showed necrotizing vasculitis withpalisading granuloma, a diagnosis of Wegener’s granu-lomatosis (WG) was made. This case report illustratesan unusual disease course in WG, resembling largevessel vasculitis, and we discuss the possible mechanismsof large vessel involvement in this form of vasculitis.

Keywords ANCA Æ Aortitis Æ Giant cell arteritis ÆPeriaortitis Æ Vasculitis Æ Wegener’s granulomatosis

Introduction

Wegener’s granulomatosis (WG) is a systemic vasculitispredominantly of the small vessels. As such, aorticinvolvement in WG is not expected. In the Chapel HillConsensus Conference, WG was defined as a necrotizingvasculitis affecting small to medium-sized vessels (cap-illaries, venules, arterioles, and arteries) with granu-lomatous inflammation involving the respiratory tract.There is a strong association with antineutrophil cyto-plasmic autoantibodies (ANCAs) and necrotizing glo-

merulonephritis is common [1]. We describe a patientwith perinuclear-staining (p)-ANCA-associated peri-aortitis as a first presentation of WG.

Case report

A 63-year-old man was admitted to another hospitalwith a 2-month history of fatigue, fever (38�C), anor-exia, and weight loss of 8 kg. The patient also experi-enced low back pain radiating to the lower limbs,paresthesias in the lower limbs, and severe dyspnea onexertion. On admission the physical examination re-vealed a painful pulsatile abdominal mass and painfulpalpation of the calves.

Laboratory studies showed slight anemia (hemoglo-bin 12.7 g/dl, normal values 14–18), a raised erythrocytesedimentation rate (ESR) of 50 mm/h, and C-reactiveprotein (CRP) of 200 mg/l (normal <3). Renal functionwas normal, urine microscopy showed 30 red bloodcells/ll (normal <5) with 80% dysmorphic forms. Atrace of protein was detected in the urine. p-ANCAswere positive by immunofluorescence test. An enzyme-linked immunosorbent assay (ELISA) for detection ofanti-myeloperoxidase (MPO) antibodies was not avail-able at that time. Abdominal computed tomography(CT) scan showed a 4-cm aneurysm of the distal part ofthe aorta with inflammation of the surrounding adiposetissue suggestive of an inflammatory aneurysm (Fig. 1).Treatment with methylprednisolone 32 mg/day wasstarted.

As no improvement under this treatment wasobserved, the patient was referred to our hospital forfurther investigation. The dose of methylprednisolonewas increased to 48 mg/day.

CT scan of the chest disclosed a small round nodularparahilar opacity. With bronchoscopy no endobronchiallesions were seen. Gallium scintigraphy showed intenseuptake in both lungs and in the bowel. Electromyogra-phy showed a sensorimotor axonal polyneuropathy inthe lower limbs.

T. Carels Æ E. Verbeken Æ D. Blockmans (&)Department of Internal Medicine,University Hospital Gasthuisberg,Herestraat 49, 3000 Leuven, BelgiumE-mail: Daniel.Blockmans@uz.kuleuven.ac.beTel.: +32-16-344262Fax: +32-16-344230

E. VerbekenDepartment of Pathology,University Hospital Gasthuisberg, Leuven, Belgium

Clin Rheumatol (2005) 24: 83–86DOI 10.1007/s10067-004-0998-0

Exploration for underlying malignancy by prostateexamination, gastroscopy, and coloscopy was negative,and hence the diagnosis of idiopathic periaortitis asso-ciated with a sensorimotor polyneuropathy was made.

During the following months, under a tapering doseof steroids, the paresthesias persisted but the patient feltbetter and began to gain weight again. Inflammatoryparameters and inflammatory changes on abdominal CTscan normalized, as well as the urine sediment. Meth-ylprednisolone was progressively tapered down over9 months and stopped.

Surgery of the abdominal aneurysm, which had in-creased to 5.4 cm, was performed and an aortoiliac graftwas inserted. The histological examination of the re-sected specimen was reported as an inflammatoryaneurysm with substantial perianeurysmal inflammationand fibrosis. Postoperatively the patient made a slowrecovery and was then lost to follow-up.

Six years later, the patient was readmitted because ofa 4-week history of malaise, fatigue, fever (38.3�), andweight loss of 7 kg. The patient also experienced par-esthesias, muscular pain in the lower limbs, and girdle-type myalgia.

Laboratory studies showed a CRP of 137 mg/l, nor-mal renal function and urine microscopy, and slightdisturbances of liver function. Antinuclear antibodieswere negative, p-ANCAs were positive at a dilution of 1/80 (normal <1/40) and they were directed against MPO(28 U/l, normal <5). CT scan of the aorta showed theaortoiliac graft with slightly thickened wall interpretedas postoperative changes. A positron emission tomo-graphy (PET) scan was completely normal. Electro-myography once again showed a sensorypolyneuropathy of the lower limbs.

Temporal artery biopsy showed vasculitis of an arterytributary to the temporal artery with a spared main ar-tery (Fig. 2). On revision of the aortic biopsy performed6 years earlier, the pathologist concluded it to be char-acteristic for WG: multiple areas of ‘‘geographic necro-sis’’ were found, mainly within the tissue surroundingthe aortic wall. The latter showed also areas of fibrosis

and active inflammation (Fig. 3a). Vasculitis with walldestruction was also present, together with the hallmarkof WG: pallisading histiocytes surrounding polymor-phonuclear debris (Fig. 3b). Ziehl and Grocott stainingwere negative.

Treatment with methylprednisolone 1 mg/kg per day,cyclophosphamide 2 mg/kg per day orally, and tri-methoprim—sulfamethoxazole was initiated with afavorable course over the ensuing months. Undertapering doses of steroids, the patient is in remission atpresent and inflammation and p-ANCAs have disap-peared.

Discussion

Wegener’s granulomatosis is a systemic vasculitis of thesmall arterioles, capillaries, and venules. Large vesselinvolvement is very rare. A biopsy from affected tissue(kidney, nose, lung, etc.) may not be required for con-firmation of the diagnosis if the classic triad of upperairway, pulmonary, and renal disease is present andc-ANCAs directed against proteinase 3 (PR 3) arepositive. However, in many cases, including this one, theclinical findings are not completely typical, and a biopsyis indicated to establish the diagnosis.

Revision of the aortic biopsy showed a picture vir-tually diagnostic of WG, which had not been recognized6 years earlier by a less experienced pathologist. Thepresence of frank necrosis argues against a diagnosis ofgiant cell arteritis (GCA) or Takayasu’s arteritis.

Although our patient had no signs of nasal involve-ment, he fulfilled the American College of Rheumatol-ogy (ACR) criteria for WG at first presentation:vasculitis was biopsy proven, he had an abnormal chestradiograph, an abnormal urinary sediment, and granu-lomatous inflammation on biopsy [2]. Nasal involve-

Fig. 1 CT scan of the lower abdomen, showing a slightly dilatedaorta with a thickened wall and some calcifications

Fig. 2 Non-necrotizing arteritis in an artery bifurcating from thetemporal artery. The arterial wall is infiltrated by histiocytes andlymphocytes (H & E, ·200)

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ment is not obligatory in WG: in the first large study onWG involving 85 patients, followed up during 21 yearsby Fauci et al. [3], 22% of patients had nasal symptomsat presentation and 64% during follow-up. The vastmajority of WG patients have c-ANCA antibodies, di-rected against PR 3, but 5–10% of WG patients arereported to be p-ANCA positive, with antibodies di-rected against MPO, as our patient was [4]. Anti-MPOp-ANCAs are typically found in microscopic polyangi-itis, but the presence of granulomas on the aortic biopsyis not compatible with this diagnosis.

Aortic involvement is most frequently seen in largevessel vasculitides such as giant cell arteritis and Taka-yasu’s arteritis. Although less common, (peri)aortitis canbe seen occasionally in other vasculitides [5].

ANCA-associated periaortitis has been occasionallyreported. Nakabayashi et al. [6] described three late

middle-aged female patients with p-ANCA-associatedperiaortitis with thickened aortic wall on CT scan in twocases and stenosis or occlusion of the subclavian arteriesin all three cases. All patients had chronic inflammationand were p-ANCA positive (twice identified as anti-MPO antibodies). Two of three patients also had arapidly progressive glomerulonephritis. A definite diag-nosis could not be made due to a lack of histologicalsamples. Sakemi et al. [7] described a 63-year-oldp-ANCA-positive woman with a periaortic soft tissuestructure surrounding the aorta, extending from thedescending thoracic aorta to both common iliac arteries,responsive to steroid therapy. In a series of 16 patientswith chronic periaortitis, three patients were ANCApositive (two anti-MPO p-ANCA, one c-ANCA posi-tive, but negative for anti-PR 3 and anti-MPO). Thesethree patients presented with rapidly progressive renalfailure; renal biopsy performed in one revealed cresc-entic necrotizing glomerulonephritis. Aortic histopa-thology was not available in these three patients [8].

Fink et al. [9] described a 45-year-old man with typ-ical WG with pulmonary involvement presenting withabdominal pain caused by a periaortitis. Periaortitis wasdetected by 111indium-labeled leukocyte scan and con-firmed by CT scan. Surgical biopsies of the periaorticand periureteric tissue showed extensive vasculitis [9].Sieber et al. described a 59-year-old man with asyn-chronous development of granulomatous aortitis withaneurysm formation, followed 9 months later byc-ANCA-positive pulmonary capillaritis and glomeru-lonephritis typical for WG. The inflammatory granu-lomatous process was centralized within the media andadventitia of the aortic wall, with focal destruction ofthe medial elastic lamellae. The authors suggested thattheir patient had a systemic necrotizing vasculitis over-lap syndrome characterized by features of both GCAand WG [10].

We reported previously on a patient with nasal,pulmonary, and renal WG involvement presenting withabdominal periaortitis and intramural dissection andwho was anti-PR 3 c-ANCA positive. Surgical biopsiestaken from the retroperitoneal inflammatory tissue sur-rounding the aorta showed granulomatous vasculitis ofthe retroperitoneal muscular arteries with invasion ofthe aortic wall [11]. Granulomatous inflammation can bevery aggressive and destructive in WG as is sometimesseen in the case of nasal involvement or eye involvement.A very similar patient was presented by de Roux-Ser-ratrice et al. [12].

One does not expect to find ANCAs, which wereshown to play an important role in the pathogenesis ofsmall vessel vasculitis, in periaortitis. Apart from inva-sion of the aortic wall by granulomatous tissue in WGpatients, ANCAs may be involved in the pathogenesis ofperiaortitis by inducing vasculitis of the vasa vasorum ofthe aortic wall, which are indeed small vessels, suscep-tible to ANCA-associated vasculitides. In their series of16 patients with chronic periaortitis, Vaglio et al. [8] hadperiaortic retroperitoneal samples from nine patients

Fig. 3 a Low power view of the aorta and the periaortic tissue.Multiple areas of so-called geographic necrosis are seen in theperiaortic tissue. Also sclerosis and areas of active inflammation areevident (H & E, ·50). b A vessel wall is barely recognizable. It isreplaced by histiocytes palisading around polymorphonucleardebris (H & E, ·200)

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available for histologic examination (all ANCA nega-tive). Vasculitis with fibrinoid necrosis involving thevasa vasorum of the aorta and small and medium ret-roperitoneal vessels was found in seven of nine samples[8]. Pasquinelli et al. [13] found—apart from athero-sclerosis—vasculitis of the adventitial vessels in all of theaortic samples taken from seven patients with inflam-matory aneurysms of the abdominal aorta. These fea-tures confirm that at least in some patients periaortitiscan occur due to small vessel vasculitis. Necrotizingvasculitis of the vasa vasorum, causing aortic dissectionin a patient with hepatitis B-positive polyarteritis nod-osa, has been reported as well [14].

Our current patient presented several years after hisfirst attack of vasculitis (which could later, on revision ofthe aortic surgical specimen, be classified as WG), with aclinical picture compatible with GCA. Therefore, atemporal artery biopsy was performed which showedinflammation of a tributary artery, while the temporalartery itself was normal. WG presenting as GCA wasreported previously, as well as small vessel vasculitissurrounding a spared temporal artery [15–18]. Althoughat readmission our patient had no other signs of WG, itis reasonable to assume that the same type of vasculitisreoccurred, even more since p-ANCAs were again po-sitive, which is not seen in true GCA.

In conclusion, we present a p-ANCA-positive patientwho experienced two attacks of systemic vasculitis, thefirst time with prominent periaortitis and 7 years laterwith a clinical picture of GCA. At both occasions, vas-culitis was histologically proven. This vasculitis had allpathologic features of WG. All clinical classificationsand even histological classifications however have theirlimitations. This case shows that the different forms ofsystemic vasculitis, as they were identified by the ACR,are probably not completely separate entities and thatthey may melt together in one single patient.

Take home message

The different forms of systemic vasculitis, as they aredescribed by the American College of Rheumatologyand the Chapel Hill Conference, are probably notcompletely separate entities. One form of vasculitis mayhide another.

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