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Joint Bone Spine 78 (2011) 88–91

ase report

orsal prevertebral lesions in Wegener granulomatosis: Report on four cases

aulo Barretoa,b, Christian Pagnouxa,∗, Luminata Lucac, Jessie Aouizeratea, Isabel Ortigueirab,ascal Cohena, Géraldine Mullerd, Loïc Guillevina

Department of Internal Medicine, National Referral Center for Necrotizing Vasculitides and Systemic Sclerosis, Hôpital Cochin, Assistance publique–Hôpitaux de Paris, Universitéaris Descartes, 27, rue du Faubourg Saint-Jacques, 75879 Paris cedex 14, FranceDepartment of Internal Medicine, Centro Hospitalar Lisboa Central, Lisbon, PortugalDepartment of Internal Medicine and Infectious Diseases, CHU de Poitiers, 86000 Poitiers, FranceDepartment of Internal Medicine, Hôpital Général, 21300 Dijon, France

r t i c l e i n f o

rticle history:ccepted 26 July 2010vailable online 18 September 2010

eywords:egener’s granulomatosis

ibrosing mediastinitis

a b s t r a c t

Retroperitoneal fibrosis has been reported in several patients with Wegener granulomatosis (WG), butonly three isolated cases of dorsal prevertebral lesions, closely resembling fibrosing mediastinitis, havebeen published so far. We describe four new WG patients (two men, two women), 49–59 years old at diag-nosis, with dorsal prevertebral lesions, mainly right-sided, and with adjacent pleural thickening in two.These lesions were detected on computed-tomography scans at diagnosis in two patients, and occurredlater in the two others. Only one of them had mild back pain. Two patients’ lesions were biopsied, reveal-ing granulomatous inflammation. In one patient, the lesion regressed under WG treatment. Lesion size

etroperitoneal fibrosisrevertebral lesions did not change in the remainings. Intralesional calcifications appeared in two. None of the patients had

local bone erosion, vascular or neurological complications. These prevertebral lesions might represent adorsal form of retroperitoneal fibrosis in WG, but usually with a more benign presentation and course.WG should be included in the differential diagnosis of fibrosing mediastinitis (with tuberculosis, neo-

sis, h

ncais

plastic diseases, sarcoidoradiological appearance.

© 2010 Société fra

. Introduction

Wegener granulomatosis (WG) is a rare systemic and necrotiz-ng small-sized–vessel vasculitis, associated with antineutrophilytoplasm antibodies (ANCA), mainly directed against proteinase(PR3) [1–3]. In addition to its typical clinical triade of ear, nose

nd throat, pulmonary and renal involvements, several other man-festations have been reported, some of which are suggestive, likerbital pseudotumor or pachymeningitis, but rather unusual [4–6].ost of these latter were caused by local granulomatous tissue

nfiltration and their responses to conventional treatment for WGaried widely.

Herein, we describe four WG patients with dorsal preverte-ral tissular lesions and discuss on the presentation and diagnosticork-up for these exceptional lesions.

∗ Corresponding author. Tel.: +33 1 58 41 13 21; fax: +33 1 58 41 14 50.E-mail address: christian.pagnoux@cch.aphp.fr (C. Pagnoux).

297-319X/$ – see front matter © 2010 Société francaise de rhumatologie. Published by Eoi:10.1016/j.jbspin.2010.07.017

istiocytosis and inflammatory pseudotumor), which may have a similar

e de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.

2. Case reports

2.1. Case 1

A 50-year-old woman consulted in 1996 for acute onsetlaryngeal stridor after a 2-year history of peripheral joint painand chronic sinusitis. Blood analyses revealed an inflammatorysyndrome but no renal abnormalities. ANCA with a cytoplas-mic immunofluorescence pattern (C-ANCA) were detected, withantiPR3 specificity. Computed-tomography (CT) scans of thesinuses and chest showed left maxillary destructive sinusitisand subglottic laryngeal stenosis, without bronchial or lung-parenchyma involvement. A prevertebral thoracic lesion wasalso detected, extending from dorsal vertebrae 3 to 7 (D3-D7).On magnetic resonance imaging (MRI), this lesion was regular,hypointense in T1- and T2-weighted sequences, with enhancementafter gadolinium contrast-medium injection (Fig. 1A). Vertebralbodies and intervertebral discs were normal. Tuberculin purifiedprotein derivative (PPD) skin test was negative. Granulomatous

lesions were found in laryngeal biopsies, supporting the clinicallysuspected diagnosis of WG.

She received glucocorticoids (GC) in combination with monthlycyclophosphamide (CYC) pulses for 6 months, with rapid laryn-geal lesion regression, but persistent rhinitis and sinusitis required

lsevier Masson SAS. All rights reserved.

P. Barreto et al. / Joint Bone Spine 78 (2011) 88–91 89

F pointense tissular lesion (arrow) anterior to D3–D7 vertebrae (initial CT scan images nota dly appeared unchanged, with the appearance of internal calcifications. C. CT scan of thec

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She received GC and a monthly CYC pulse for 6 months, withresolution of sinusitis and episcleritis. ANCA remained positive. CYCwas switched to AZA for maintenance, changed to methotrexateafter 4 months, because of hepatic toxicity.

ig. 1. Patient 1. A. Parasagittal T2-weighted MRI of the chest and spine showing hyvailable). B. CT scan of the chest obtained 8 years later. The lesion (arrow) reportehest obtained 2 years later, showing no further change.

witching to oral CYC, continued for a total of 42 months (cumula-ive dose, 96 g), followed by azathioprine (AZA). Her rhinitis neverotally resolved and ANCA remained positive.

She was referred to our department in 2007 because of renalbnormalities (serum creatinine, 189 �mol/L; proteinuria, 2 g/24 h;icroscopic hematuria) and a 7-mm diameter nodule in the inferior

obe of the left lung. Kidney biopsy showed necrotizing extra-apillary glomerulonephritis. The GC dose was increased and sheeceived rituximab (RTX), rather than CYC because of her alreadyigh cumulative CYC dose. She entered remission and the lungodule disappeared after 9 months.

Although the prevertebral mass size did not change, it remainedsymptomatic and intralesion calcifications appeared on the chestT scan (Fig. 1B and C).

.2. Case 2

A 49-year-old man, with a history of asthma, consulted in002 for cough, dysphonia and hemoptysis. Blood tests revealedn inflammatory syndrome, normal eosinophil count and C-ANCAith antiPR3 specificity. Chest CT scan showed a subglottic laryn-

eal stenosis and lung nodules. No renal involvement was detected.G was diagnosed and treatment combining oral CYC and GC

btained laryngeal lesion attenuation and disappearance of lungodules and ANCA. CYC was stopped after 8 months.

In 2004, WG relapsed with lung-nodule and C-ANCA reappear-nce, worsening of the laryngeal stenosis, and appearance of aight-sided prevertebral D3–D7 lesion, with lateral spreading tohe pleura but without bone erosion or disk involvement (Fig. 2A).T-guided needle-biopsy of the lesion revealed granulomatous

nflammation, and no mycobacteria. Treatment with a monthlyYC pulse for 6 months and GC achieved remission and markededuction of the prevertebral mass (Fig. 2B). CYC was switched toZA.

In 2007, the laryngeal stenosis worsened again but the resid-al prevertebral lesion remained stable on the CT scan. Endoscopicracheal dilation and a regimen combining oral CYC, initially, RTXnd GC achieved remission. CYC was stopped and maintenance RTXas continued, with no further relapse to date.

Fig. 2. Patient 2. A. Initial CT scan of the chest revealing a right-sided dorsal pre-vertebral lesion (arrow). B. Five years later, after WG treatment, showing some sizereduction.

2.3. Case 3

A 59-year-old woman consulted in 2004 with asthenia, sinusitisand episcleritis of the right eye. Blood analyses revealed inflamma-tory syndrome but no renal abnormalities. C-ANCA with antiPR3specificity were detected. Chest CT scan showed no lung involve-ment but a right-sided prevertebral D2–D7 lesion, spreading to thepleura (Fig. 3A), without invasion of vertebrae or intervertebraldisks. The surgical biopsy showed granulomatous inflammation,without mycobacteria, supporting the diagnosis of WG.

Fig. 3. Patient 3. A. Initial CT scan of the chest revealing a right-sided dorsal prever-tebral lesion (arrow). B. CT scan obtained 4 years later, showing no (or only minor)size reduction.

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In 2006, WG relapsed with right episcleritis, cough and dyspnea.hest CT scan showed lung nodules and persistence of the prever-ebral mass. She received a second, but ineffective, cycle of CYCulses, then RTX as rescue therapy, with a semestrial RTX infusionor maintenance. The prevertebral lesion only modestly diminishedFig. 3B), and residual lung nodules persisted on the CT scan.

.4. Case 4

A 57-year-old man, with a history of hypertension and chronicbstructive lung disease (tobacco intoxication, 40 pack-years), con-ulted in 2005 with asthenia, fever, diffuse arthralgias, skin purpurand mononeuritis multiplex. Blood tests revealed an inflam-atory syndrome. Serum creatinine was 143 �mol/L and urine

nalyses showed proteinuria (> 1 g/24 h) and microscopic hema-uria. C-ANCA were detected with antiPR3 specificity. Chest CTcan showed no lung involvement. Kidney biopsy revealed focalegmental glomelurosclerosis. WG was diagnosed and AZA, com-ined with GC, was started. Joint pain and skin lesions resolved.enal abnormalities regressed, with persistent mild renal insuffi-iency (serum creatinine, 125 �mol/L). Motor deficit disappearedut paresthesias persisted, as did the fluctuating inflammatoryyndrome (C-reactive protein, 10–30 mg/L), and ANCA remainedositive.

In late 2008, the patient reported mild and fluctuating dor-al pain. The chest CT scan showed no signs of lung disease,ut detected a right-sided prevertebral, fusiform D5–D10 lesion,ithout bone erosion or intervertebral disk invasion (Fig. S1A).

nterferon-gamma tuberculosis blood test was negative. The WGegimen was not modified.

In mid-2009, left exophthalmia occurred due to an infil-rating orbital lesion, whose surgical removal revealed a non-pecific inflammatory infiltration of lymphocytes, plasmocytes andosinophils. Renal function was stable. The prevertebral mass wasnchanged and lungs remained unaffected. AZA was switched toonthly CYC pulses and the GC dose was increased. After six CYC

ulses, the chest CT scan showed that the thoracic prevertebralass had the same size (or slightly diminished), and contained

ome calcifications (Fig. S1B); the reappearance of the orbital lesioned to a switch to oral CYC.

. Discussion

Prevertebral lesions like those described above are rare in WG.o our knowledge, only three similar cases have been published7–9]. All these cases are very similar radiologically, especially inheir location and appearance (Table 1).

Cardenal-Urdampilleta et al. [9] reported on a 40-year-old WGatient with antiPR3 ANCA, who initially had a painful D8–D10revertebral mass, and later developed lung nodules and glomeru-

onephritis. The mass disappeared after therapy combining CYC andC. Kerkeni et al. [8] reported a 55-year-old antimyeloperoxidaseNCA-positive patient, diagnosed with WG because of associatedinusitis, glomerulonephritis and a painful D4–D10 prevertebralass that regressed under treatment for WG. Finally, Tojima et

l. [7] reported an ANCA-negative 63-year-old man with episcle-itis, pleural effusion, lung nodules (showing vasculitis in a surgicaliopsy) and a mass in the posterior mediastinum, adjacent to ver-ebrae. The lesions in our patients were also dorsal, with pleuralxtension for two of them. Intriguingly, the lesions were predomi-

antly right-sided in all our patients, and one previously reported9].

Infiltrating lesions in WG patients have been described in severalocations, like the central nervous system, orbital cavity, gingival

ucosa, breasts, anterior and middle mediastinum and retroperi- Tab

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oneum [5,6,10,11]. Granulomatous inflammation is often seen inhe biopsies of such patients, when feasible and done, and, morearely, vasculitis. Whether dorsal prevertebral lesions, as describedn our patients, should be considered fibrosing mediastinitis or likeetroperitoneal fibrosis remains to be determined, with the lattereing reported more frequently in WG. Their locations in the pre-ertebral areas could suggest a parallel, but none of our patients,or those previously reported, had true associated retroperitonealbrosis. In addition, dorsal prevertebral lesions did not lead toompression of nearby structures, as opposed to retroperitonealbrosis (with possible ureteral and/or vessel compression and infil-ration). The differential diagnoses to rule out also overlap withhose of fibrosing mediastinitis or retroperitoneal fibrosis, and

ainly include neoplastic diseases, infections, especially tubercu-osis, other granulomatous diseases, like sarcoidosis, inflammatoryseudotumor or histiocytosis [12–15]. Imaging studies, especiallyRI, can be helpful to exclude spondylodiscitis [15,16]. Common

ertebral osteoarthritis can also sometimes mimic these appear-nces, when internal calcifications are present.

Biopsy of such lesions is not easy and carries a non-negligibleisk of complication(s), because of the difficulty in accessing thehoracic prevertebral area. None of the three previously reportedases and “only” two of ours had biopsies, one surgical and thether CT-guided because the adjacent pleural spreading alloweduch a procedure. These two patients’ biopsies showed granulo-atous inflammation. In addition to histology, when positive, the

ink between these lesions and WG is further supported by lesionegression under WG treatment, as in two of the previously pub-ished cases, whose lesion outcomes were clearly reported [8,9],nd in one of our patients, who had granulomatous inflamma-ion on biopsy. By contrast, the prevertebral mass remained almostnchanged in the remaining patients, with intralesion calcifica-ions, as a hypothetical scarring process.

In conclusion, dorsal prevertebral, possibly granulomatous, tis-ular lesions can be observed at WG onset, even rarely as the firstanifestation, or during its course. These are very rare lesions but

heir frequency may be underestimated, as they are often asymp-omatic and not associated with bone erosion or compression of

earby vessels. Biopsy to establish the relationship between such

esions and WG is a delicate undertaking, and several differentialiagnoses must be excluded. Lesions can disappear under adequateG treatment or remain stable, sometimes with internal calcifica-

ions, but usually without further related symptoms.

[

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pine 78 (2011) 88–91 91

Conflict of interest statement

None of the authors has any conflicts of interest to declare.

Appendix A. Supplementary material

Supplementary material (Fig. S1) associated with this articlecan be found at http://www.sciencedirect.com, at doi:10.1016/j.jbspin.2010.07.017.

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