Modern Rheumatology

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Large-vessel involvement in granulomatosis with polyangiitis successfully treated with rituximab: A case report and literature review Takashi Ozaki, Keisuke Maeshima, Yasuhiro Kiyonaga, Masataka Torigoe, Chiharu Imada, Hajime Hamasaki, Miwa Haranaka, Koji Ishii & Hirotaka Shibata To cite this article: Takashi Ozaki, Keisuke Maeshima, Yasuhiro Kiyonaga, Masataka Torigoe, Chiharu Imada, Hajime Hamasaki, Miwa Haranaka, Koji Ishii & Hirotaka Shibata (2015): Largevessel involvement in granulomatosis with polyangiitis successfully treated with rituximab: A case report and literature review, Modern Rheumatology To link to this article: http://dx.doi.org/10.3109/14397595.2015.1021950

Accepted author version posted online: 04 Mar 2015. Published online: 02 Apr 2015. Submit your article to this journal

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Date: 11 November 2015, At: 07:55

http://informahealthcare.com/mor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2015; Early Online: 1–6 © 2015 Japan College of Rheumatology DOI: 10.3109/14397595.2015.1021950

CASE REPORT

Large-vessel involvement in granulomatosis with polyangiitis successfully treated with rituximab: A case report and literature review Takashi Ozaki, Keisuke Maeshima, Yasuhiro Kiyonaga, Masataka Torigoe, Chiharu Imada, Hajime Hamasaki, Miwa Haranaka, Koji Ishii & Hirotaka Shibata Downloaded by [University of Wisconsin Oshkosh] at 07:55 11 November 2015

Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Oita, Japan Abstract

Keywords

Granulomatosis with polyangiitis (GPA) is primary necrotizing vasculitis, which predominantly affects small to medium vessels. Herein, we describe a case of a 60-year-old female with GPA who developed inflammatory wall thickening localized in the aortic arch, upper abdominal aorta, and pulmonary artery. The wall thickening in the large vessels and other GPA lesions such as lung nodules and orbital mass had failed to respond to high-dose glucocorticoids combined with cyclophosphamide; however, all were successfully treated with rituximab. Our literature review identified 24 cases of large-vessel involvement associated with GPA. Luminal stenosis, occlusion, or wall thickening were observed in 8, periaortitis in 11, and aneurysms in 5 cases. The most commonly affected vessel was the abdominal aorta (12 cases), followed by the thoracic aorta (6 cases), subclavian artery (4 cases), and internal carotid artery (4 cases). Glucocorticoids were used in 23 cases, 20 of which received combination therapy with cyclophosphamide. Surgical or endovascular therapies were performed in 10 cases with aneurysmal dilatation. This is the first case showing the potential efficacy of rituximab for refractory large-vessel involvement associated with GPA.

Granulomatosis with polyangiitis, Large-vessel involvement, Rituximab History Received 15 October 2014 Accepted 19 February 2015 Published online 31 March 2015

Introduction

Case report

Granulomatosis with polyangiitis (GPA) is an autoimmune disease characterized by necrotizing granulomatous inflammation, which usually involves the upper and/or lower respiratory tract. It is categorized as a small-vessel vasculitis because it predominantly affects small-to-medium-sized vessels [1]. Therefore, large-vessel involvement is rare in patients with GPA. Combination therapy with glucocorticoids and cyclophosphamide is currently the standard regimen for remission induction in GPA [2]. In addition, it has been shown that rituximab, a chimeric monoclonal anti-CD20 antibody, is as effective for remission induction as conventional therapy with glucocorticoid and cyclophosphamide in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis [3–5]. However, it remains unknown whether rituximab would be effective in large-vessel involvement associated with GPA. We herein present a case of GPA with inflammatory wall thickening that was localized in the aorta and pulmonary artery, which was refractory to high-dose glucocorticoids and cyclophosphamide but responded well to rituximab therapy. In addition, we conducted a literature review to assess the clinical characteristics of large-vessel involvement with GPA.

A 60-year-old female developed several skin ulcers of the lower extremities in January 2013. A few weeks later, she presented with fever, bloody nasal discharge, and nasal obstruction. She showed no respiratory symptoms or chest or abdominal pain. She was referred to our department in February 2013. Her physical examination revealed marked nasal swelling, and no crackles in either lung. Laboratory tests indicated elevated C-reactive protein (CRP) level of 7.93 (normal, 0–0.3) mg/dL. The serum immunoglobulin G4 level was 60.9 (normal, 4.8–105) mg/dL. Her urine analysis revealed no abnormalities. The enzyme-linked immunosorbent assay for the detection of proteinase-3-ANCA (PR3-ANCA) was positive at 153 (normal, 0–3.5) U/mL. Her contrast-enhanced computed tomography (CT) showed sinusitis, multiple lung nodules with cavities in both lungs, and wall thickening with enhancement localized in the aortic arch and upper abdominal aorta (Figure 1a, b). Serologic tests for syphilis and blood cultures were negative. A biopsy specimen of the nasal mucosa demonstrated epithelioid granulomas with several giant cells and small vessels with fibrin deposition. She was diagnosed with GPA and administered oral prednisolone (50 mg/day) combined with intravenous cyclophosphamide (500–750 mg/body) every 3 weeks. Sinusitis and skin ulcers gradually improved, whereas her chest CT at 2 months after initiation of immunosuppressive therapy demonstrated that several lung nodules had enlarged and the aortic wall thickening showed no significant improvement. Furthermore, she subsequently developed diplopia and headache correlated with an increase in the serum levels of CRP and PR3-ANCA. Her head CT demonstrated orbital mass that was not observed by CT at

Correspondence to: Koji Ishii, Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan. Tel: ⫹ 81-97-586-5793. Fax: ⫹ 81-97-549-4480. E-mail:[email protected]

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Figure 1. CT scan of wall thickening of aortic arch, upper abdominal aorta, and bifurcation of main pulmonary artery (arrows). (a,b) On admission. (c–e) Two weeks after initiation of rituximab therapy. (f–h) Three months after initiation of rituximab therapy.

admission (Figure 2a). Contrast-enhanced brain magnetic resonance imaging also showed right orbital mass, but no dural thickening suggestive of hypertrophic pachymeningitis. Intravenous pulsed methylprednisolone at 125 mg/day for 4 days was added, which was ineffective. Consequently, the rituximab treatment at a dose of 375 mg/m2 weekly for 4 consecutive weeks was initiated as an alternative to cyclophosphamide. Moreover, dosage of concomitant oral prednisolone was returned to the initial dose (50 mg/day), because her CT findings at 2 weeks after the first infusion of rituximab revealed that the wall thickening of the aorta had slightly increased and similar wall thickening localized in the bifurcation of the main pulmonary artery was present (Figure 1c–e). After the four consecutive rituximab administrations, the headache disappeared and the diplopia gradually improved, and the levels of CRP and PR3-ANCA were normalized (Figure 3). A follow-up CT at 3 months after the first administration of rituximab demonstrated marked improvement of the orbital mass (Figure 2b), lung nodules, and wall thickening of the large vessels (Figure 1f–h). During the rituximab treatment, no adverse effects were observed. Azathioprine was added as maintenance therapy after four consecutive rituximab infusions, which was subsequently discontinued because of leukopenia. The dosage of prednisolone has been decreased to 10 mg/day and recurrence has not been observed with glucocorticoid monotherapy for 12 months.

Discussion GPA is necrotizing vasculitis that predominantly affects small-tomedium-sized vessels; thus, large-vessel involvement associated with GPA is a very rare complication. Our case developed an inflammatory wall thickening localized in the aortic arch, upper abdominal aorta, and pulmonary artery. We conducted a PubMed

search using the following terms: “Wegener’s granulomatosis,” “Granulomatosis with polyangiitis,” “large-vessel involvement,” “aortitis,” “periaortitis,” and “aneurysm” to investigate published cases which had been diagnosed with GPA (Wegener’s granulomatosis) complicated with large-vessel involvement. The references of retrieved articles were also screened for additional reports. Cases without detailed information such as age, sex, and affected large vessels were excluded. Our literature review revealed that 23 published cases had developed a large-vessel involvement with GPA [6–28] (Table 1). The mean age of the 24 cases was 46.25 (range, 22–68) years. The clinical manifestations of the large-vessel involvement included luminal stenosis, occlusion, wall thickening, aneurysm, and periaortitis. Stenosis, occlusion, or wall thickening was observed in 8 cases. Of these, 4 cases [7,9–11], which fulfilled the criteria for the classification of Takayasu arteritis [29], were described as an overlap between GPA and Takayasu arteritis. Periaortitis, which is characterized by the presence of a mantle of soft-tissue density surrounding the aorta by CT, was observed in 11 cases. Of these, 6 cases showed aneurysmal dilatation along with periaortic inflammation [18,21–24,28]. An aneurysm without perivascular inflammation was observed in 5 cases. The most commonly affected large vessel was the abdominal aorta (12 cases), followed by the thoracic aorta (6 cases), subclavian artery (4 cases), and internal carotid artery (4 cases). Large-vessel involvement was found more commonly at the time of initial diagnosis of GPA (14 cases) rather than prior to (5 cases) or after (5 cases) the GPA diagnosis. With respect to symptoms, 5 cases developed symptoms of vascular ischemia because of luminal stenosis or occlusion. In 11 cases with periaortitis, abdominal and back pain occurred in 7 and 4 cases, respectively. Aneurysmal rupture occurred in 2 cases

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Figure 2. CT scan of orbital mass (arrowheads). (a) Two months after combination therapy with glucocorticoids and cyclophosphamide (before initiation of rituximab therapy). (b) Three months after initiation of rituximab therapy.

[17,28]. All 24 cases had other organ involvement associated with GPA, including the ear, nose, or throat (19 cases), kidney (14 cases), and lung lesions (13 cases). Orbital mass was observed only in our case. The results of the ANCA assay detected by indirect immunofluorescence or enzyme-linked immunosorbent assay were described in 22 cases. Of these, cytoplasmic-ANCA (C-ANCA) or PR3-ANCA was positive in 15 cases, and perinuclear-ANCA (P-ANCA) or myeloperoxidase-ANCA (MPOANCA) was positive in 4 cases. A description regarding pattern or ANCA antigen was not available in 1 case, and ANCA was negative in the remaining 2 cases. A detailed description of the immunosuppressive treatment was available in 23 cases. Glucocorticoids were used in all cases; 20 of these cases received combination therapy with cyclophosphamide. One of the previous cases with refractory sinusitis had received rituximab therapy, but subsequently an aneurysm of the internal carotid artery developed, which required endovascular balloon occlusion [26]. Surgical or endovascular therapies were performed in 10 cases with aneurysmal dilatation because of the following causes: rapid aneurysmal enlargement or impending rupture (4 cases), aneurysm rupture (2 cases), suspicion of mycotic aneurysm (2 cases), thromboembolism (1 case), and unknown (1 case). No fatalities were observed among 24 cases with large-vessel involvement. Histological examination of the large-vessel involvement was performed in 7 cases [6,8,13,18,20,24,28], 6 of which showed the presence of necrotizing granulomatous inflammation of large vessel wall [6,20,24,28] or periaortic tissue [13,18]. However, the precise pathological mechanism of the large-vessel involvement has not yet been completely elucidated. Figure 3. Clinical course of the present case.

Large-vessel involvement in granulomatosis with polyangiitis 3 In our case, the wall thickening of large vessels increased in parallel with the increase in the serum PR3-ANCA levels and the progression of other GPA lesions such as the orbital mass and lung nodules; all of these markedly improved after rituximab therapy. This clinical course demonstrated that large-vessel involvement could be a part of GPA, although we could not perform a biopsy. Furthermore, in our case, findings related to wall thickening of the large vessels appeared to be uncommon for Takayasu arteritis and giant-cell arteritis on the CT, both of which are major variants of large-vessel vasculitis [1]. It has been reported that concentric wall thickening of the large vessels on CT is a typical finding in Takayasu arteritis and giant-cell arteritis [30–32]. In our case, however, wall thickening of the aorta and pulmonary artery was not concentric (Figure 1), suggesting that the wall thickening might be associated with a unique mechanism of GPA. Although our literature review identified 4 published cases with wall thickening of the large vessels, none of them presented with similar findings as those of the present case. Rituximab has been proven to be highly effective in the induction therapy of patients with ANCA-associated vasculitis [3–5]. A few recent reports demonstrated the efficacy of rituximab for large-vessel vasculitis such as Takayasu arteritis and chronic periaortitis [33–36]. To the best of our knowledge, there has been no report that showed the therapeutic benefit of rituximab for large-vessel involvement with GPA. Onodera et al. [26] reported a case with refractory sinusitis, which responded well to rituximab therapy but subsequently developed an aneurysm of the internal carotid artery requiring endovascular treatment because of the rapid aneurysm expansion. According to our literature review, improvement of wall thickening and periaortic inflammation after immunosuppressive therapy alone was observed in 4 and 6 cases, respectively. In contrast, all 5 cases with aneurysm received surgical or endovascular treatment combined with immunosuppressive therapies, suggesting that immunosuppressive therapy alone might be insufficient for cases with aneurysm associated with GPA. In the present case, the wall thickening of the large vessels, orbital mass, and lung nodules resolved after the administration of rituximab, while the dosage of concomitant prednisolone was increased to the starting dose during the rituximab treatment. Therefore, whether rituximab contributed to remission induction more than increased glucocorticoids (oral prednisolone, 50 mg/day) combined with cyclophosphamide should also be considered.

Abdominal aorta

Subclavian artery

45/M 27/F

29/F

29/F 56/F 42/M

37/M

47/M

58/F

34/M

63/M

61/M

67/M

33/M

51/M 61/F

43/M

68/F 22/F

48/M

Logar et al. [7]

Fink et al. [8] Yamasaki et al. [9]

Dábague et al. [10]

Jolly et al. [11] Ohta et al. [12] Blockmans et al. [13]

Schmidt et al. [14]

De Roux-Serratrice et al. [15] Shitrit et al. [16]

Takei et al. [17]

Carels et al. [18]

Levin et al. [19]

Luebke et al. [20]

Durai et al. [21]

Minnee et al. [22] Kasagi et al. [23]

Unlü et al. [24]

Shmagel et al. [25] Onodera et al. [26]

Kim et al. [27]

Thoracic aorta

Abdominal aorta Internal carotid artery

Abdominal aorta

Wall thickening

Periaortitis Aneurysm

Periaortitis

Periaortitis Periaortitis

Periaortitis

Aneurysm

Periaortitis

Periaortitis

Aneurysm (ruptured)

Aneurysm

Stenosis, wall thickening Periaortitis

Stenosis Wall thickening Periaortitis

Occlusion

Stenosis, occlusion Periaortitis Occlusion, wall thickening

Manifestations Aneurysm

Simultaneity

Simultaneity After 7 months

After 11 years

Simultaneity Simultaneity

Simultaneity

After 5 years

After 10 months

Simultaneity

Before 1 month

Simultaneity

Before 2 years

Simultaneity

Before 14 years Simultaneity Simultaneity

Before 2 years

Simultaneity Simultaneity

Simultaneity

Time of diagnosis (Duration from GPA diagnosis) Before 5 months

Atrioventricular block

Abdominal pain None

Abdominal pain

Back pain Back pain

Abdominal pain

Abdominal pain, back pain Leg pain

Headache (subarachnoid hemorrhage) Back pain

Arm pain

Transient right arm paresis Abdominal pain

Arm claudication NA Abdominal pain

Loss of consciousness

Symptoms Abdominal pain, tenesmus, nausea Hemiplegia, aphasia, seizure Abdominal pain Arm claudication

ENT, L

ENT ENT

P, S, orchitis ENT, L, K, SCL ENT, K

ENT, L

K, S

ENT, L, SCL

NA

PR3-ANCA PR3-ANCA

Negative

PR3-ANCA MPO-ANCA

PR3-ANCA

Negative

C-ANCA

MPO-ANCA

PR3-ANCA

ENT, L, K L, K, P

P-ANCA

PR3-ANCA

PR3-ANCA

C-ANCA C-ANCA PR3-ANCA

P-ANCA

Positive† C-ANCA

PR3-ANCA

ANCA C-ANCA

ENT, L, K

L

ENT, K

ENT ENT, K ENT, L, K, P

ENT, L, K

ENT, L, K ENT

ENT, K

Other organ involvement L, K

GC, CSA

GC, CYC, MTX GC, CYC, RTX

GC, MPA

GC, CYC GC, CYC

GC, CYC

GC, CYC, MPA

GC, CYC

GC, CYC

GC, CYC

GC, CYC

GC, CYC, AZA

GC, CYC

GC, CYC GC, CYC GC, CYC

GC, CYC

NA GC, CYC

GC, CYC

Treatment Immunosuppressive therapy GC, CYC

None

Surgery (graft) None Endovascular balloon occlusion

Surgery (venous bypass) Surgery (graft) None None

Surgery (graft) None

Endovascular stent graft Surgery (clipping)

None

None None Surgery (graft) None

None

None None

None

Surgery (bypass)

Others

(Continued)

Survived

Survived Survived

Survived

Survived Survived

Survived

Survived

Survived

Survived

Survived

Survived

Survived

Survived

Survived Survived Survived

Survived

Survived Survived

Survived

Outcome Survived

T. Ozaki et al.

Abdominal aorta Abdominal aorta

Abdominal aorta

Superficial femoral artery

Abdominal aorta

Abdominal aorta

Internal carotid artery

Internal carotid artery

Abdominal aorta Thoracic aorta, subclavian artery, pulmonary artery, common carotid artery Thoracic aorta, brachiocephalic artery, subclavian artery, common carotid artery Subclavian artery Thoracic aorta Abdominal aorta

Internal carotid artery

32/F

Sieber et al. [6]

Affected vessels Abdominal aorta

Age/Sex 59/M

Table 1. Summary of large-vessel involvement in patients with GPA.

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4 Mod Rheumatol, 2015; Early Online: 1–6

Simultaneity Thoracic aorta, abdominal aorta, pulmonary artery 60/F Present case

ENT ear, nose, and throat, L lung, K kidney, P peripheral nervous system, S skin, SCL spinal cord lesion, OP orbital pseudotumor, ANCA antineutrophil cytoplasmic antibody, C-ANCA cytoplasmic-ANCA, P-ANCA perinuclear-ANCA, PR3-ANCA proteinase-3-ANCA, MPO-ANCA myeloperoxidase-ANCA, GC glucocorticoid, CYC cyclophosphamide, AZA azathioprine, MPA mycophenolic acid, MTX methotrexate, CSA cyclosporine, RTX rituximab, NA not available. †Detailed information was unavailable.

Outcome

Survived GC, CYC, RTX, AZA PR3-ANCA ENT, L, S, OP

NA ENT, K

Chest pain, loss of consciousness None After 22 years

Periaortitis (ruptured) Wall thickening Thoracic aorta 38/M Ohta et al. [28]

Table 1. (Continued)

Age/Sex

Affected vessels

Manifestations

Time of diagnosis (Duration from GPA diagnosis)

Symptoms

Other organ involvement

ANCA

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Treatment Immunosuppressive therapy GC

Others

Surgery (graft) None

Survived

DOI 10.3109/14397595.2015.1021950

Large-vessel involvement in granulomatosis with polyangiitis 5 Although combination therapy with the same dosage of prednisolone with intravenous cyclophosphamide had been administered before initiating rituximab treatment, the wall thickening in the aorta showed no marked improvement and the progression of the orbital mass and lung nodules was observed. Moreover, all those lesions failed to respond to intravenous pulsed methylprednisolone at 125 mg/day for 4 days immediately before the start of rituximab therapy. These clinical courses suggest that those GPA lesions were refractory to high-dose glucocorticoids and rituximab significantly contributed to remission induction (Figure 3). Nonetheless, although current standard induction therapy for GPA consists of high-dose glucocorticoids and cyclophosphamide [2], our case was initially treated with glucocorticoid monotherapy for 4 weeks and subsequently treated with combination therapy with cyclophosphamide. Therefore, it cannot be concluded that our case was totally refractory to the conventional induction regimen in which treatment with cyclophosphamide and glucocorticoids is initiated simultaneously. Whether maintenance therapy with other immunosuppressing agents should be added after remission induction with rituximab therapy is unclear [37]. In our case, azathioprine was initiated to maintain remission, which was discontinued due to leukopenia. Nonetheless, the patient has remained in remission for 12 months while the dosage of prednisolone has been decreased to 10 mg/day, suggesting that rituximab contributes to long-term remission with glucocorticoid monotherapy. In the present case, the orbital mass was also refractory to combination treatment with glucocorticoids and cyclophosphamide and disappeared after the rituximab therapy. Orbital masses are rare but significant manifestations of GPA. Holle et al. [38] reported that among 1142 patients with GPA, 58 (5%) developed orbital masses during a median follow-up of 101.5 months. They demonstrated that 15 patients (40.5%) were refractory to first-line intensive immunosuppressive therapy. With respect to the rituximab treatment for orbital masses with GPA, although a few published reports showed poor response with rituximab [39,40], there have been more studies demonstrating the benefits of rituximab [41–44]. In conclusion, although the incidence is rare, large-vessel involvement, such as wall thickening, luminal stenosis, occlusion, aneurysm, and periaortitis, can occur in patients with GPA. Our case developed wall thickening of the aorta and pulmonary artery that was refractory to conventional therapy with high-dose glucocorticoids combined with cyclophosphamide but was markedly relieved after the rituximab therapy; this suggested the potential of rituximab for large-vessel involvement with GPA. Further studies will be required to confirm the efficacy of rituximab for largevessel involvement.

Conflict of interest None.

References 1. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1–11. 2. Mukhtyar C, Guillevin L, Cid MC, Dasgupta B, de Groot K, Gross W, et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. 2009;68(3):310–7. 3. Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010;363(3):211–20. 4. Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221–32. 5. Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013;369(5):417–27.

Downloaded by [University of Wisconsin Oshkosh] at 07:55 11 November 2015

6

T. Ozaki et al.

6. Sieber SC, Cuello B, Gelfman NA, Garfinkel HB. Pulmonary capillaritis and glomerulonephritis in an antineutrophil cytoplasmic antibody-positive patient with prior granulomatous aortitis. Arch Pathol Lab Med. 1990;114(12):1223–6. 7. Logar D, Rozman B, Vizjak A, Ferluga D, Mulder AH, Kallenberg CG. Arteritis of both carotid arteries in a patient with focal, crescentic glomerulonephritis and anti-neutrophil cytoplasmic autoantibodies. Br J Rheumatol. 1994;33(2):167–9. 8. Fink AM, Miles KA, Wraight EP. Indium-111 labelled leucocyte uptake in aortitis. Clin Radiol. 1994;49(12):863–6. 9. Yamasaki S, Eguchi K, Kawabe Y, Tsukada T, Nagataki S. Wegener’s granulomatosis overlapped with Takayasu arteritis. Clin Rheumatol. 1996;15(3):303–6. 10. Dábague J, Arévalo RM, García-Torres R, Reyes PA. Takayasu’s arteritis and Wegener’s granulomatosis. A coincidental case. Clin Exp Rheumatol. 1995;13(3):413–4. 11. Jolly SS, Brownstein S, Jordan DR, Munro SM, Keystone EC. Scleritis in a patient with limited Wegener’s granulomatosis and Takayasu’s arteritis. Can J Ophthalmol. 1995;30(7):371–3. 12. Ohta H, Shirai S, Nasu K, Tei M, Kambara H, Ono T, Shintaku M. Ga-67 uptake in the aorta in Wegener’s granulomatosis: overlap with Takayasu’s arteritis? Clin Nucl Med. 1998;23(12):859–60. 13. Blockmans D, Baeyens H, Van Loon R, Lauwers G, Bobbaers H. Periaortitis and aortic dissection due to Wegener’s granulomatosis. Clin Rheumatol. 2000;19(2):161–4. 14. Schmidt WA, Seipelt E, Molsen HP, Poehls C, Gromnica-ihle EJ. Vasculitis of the internal carotid artery in Wegener’s granulomatosis: comparison of ultrasonography, angiography, and MRI. Scand J Rheumatol. 2001;30(1):48–50. 15. de RS, Serratrice J, Granel B, Disdier P, Bartoli JM, Pache X, et al. Periaortitis heralding Wegener’s granulomatosis. J Rheumatol. 2002;29(2):392–4. 16. Shitrit D, Shitrit AB, Starobin D, Izbicki G, Belenky A, Kaufman N, Kramer MR. Large vessel aneurysms in Wegener’s granulomatosis. J Vasc Surg. 2002;36(4):856–8. 17. Takei H, Komaba Y, Kitamura H, Hayama N, Osawa H, Furukawa T, et al. Aneurysmal subarachnoid hemorrhage in a patient with Wegener’s granulomatosis. Clin Exp Nephrol. 2004;8(3):274–8. 18. Carels T, Verbeken E, Blockmans D. p-ANCA-associated periaortitis with histological proof of Wegener’s granulomatosis: case report. Clin Rheumatol. 2005;24(1):83–6. 19. Levin A, Kasem S, Mader R, Naparstek Y, Friedman G, Ben-Yehuda A. Wegener granulomatosis with back pain, periaortitis, and dural inflammation developing while receiving monthly cyclophosphamide. J Clin Rheumatol. 2006;12(6):294–7. 20. Luebke T, Aleksic M, Brunkwall J. Superficial femoral artery aneurysm: a rare complication of wegener granulomatosis. Vascular. 2009;17(4):213–7. 21. Durai R, Agrawal R, Piper K, Brohi K. Wegener’s granulomatosis presenting as an abdominal aortic aneurysm: a case report. Cases J. 2009;2:9346. 22. Minnee RC, van den Berk GE, Groeneveld JO, van Dijk J, Turkcan K, Visser MJ, Vahl AC. Aortic aneurysm and orchitis due to Wegener’s granulomatosis. Ann Vasc Surg. 2009;23(6):786.e15–9. 23. Kasagi S, Saegusa J, Tsuji G, Sendo S, Miura N, Hayashi H, et al. Epidural spinal tumor and periaortitis as rare complications of Wegener’s granulomatosis. Mod Rheumatol. 2011;21(6):678–83. 24. Unlü C, Willems M, Ten Berge IJ, Legemate DA. Aortitis with aneurysm formation as a rare complication of Wegener’s granulomatosis. J Vasc Surg. 2011;54(5):1485–7. 25. Shmagel A, Kokebie R, Meyer C. Granulomatosis with polyangiitis (Wegener’s) presenting as a periaortic mass. J Clin Rheumatol. 2011;17(8):442–3. 26. Onodera H, Hiramoto J, Morishima H, Tanaka Y, Hashimoto T. Treatment of an unruptured fusiform aneurysm of the internal carotid

Mod Rheumatol, 2015; Early Online: 1–6

27. 28.

29.

30. 31. 32.

33.

34. 35. 36. 37.

38.

39.

40.

41. 42.

43. 44.

artery associated with Wegener’s granulomatosis by endovascular balloon occlusion. Case report. Neurol Med Chir (Tokyo). 2012;52(4):216–8. Kim JB, Kim W, Park MJ. Reversal of aortic root inflammation after treatment of Wegener’s granulomatosis. Heart. 2013;99(7):507. Ohta N, Waki T, Fukase S, Suzuki Y, Kurakami K, Aoyagi M, Kakehata S. Aortic aneurysm rupture as a rare complication of granulomatosis with polyangiitis: a case report. J Med Case Rep. 2013;7:202. Arend WP, Michel BA, Bloch DA, Hunder GG, Calabrese LH, Edworthy SM, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 1990;33(8):1129–34. Park JH, Chung JW, Im JG, Kim SK, Park YB, Han MC. Takayasu arteritis: evaluation of mural changes in the aorta and pulmonary artery with CT angiography. Radiology. 1995;196(1):89–93. Zhu FP, Luo S, Wang ZJ, Jin ZY, Zhang LJ, Lu GM. Takayasu arteritis: imaging spectrum at multidetector CT angiography. Br J Radiol. 2012;85(1020):e1282–92. Prieto-González S, Arguis P, García-Martínez A, Espígol-Frigolé G, Tavera-Bahillo I, Butjosa M, et al. Large vessel involvement in biopsyproven giant cell arteritis: prospective study in 40 newly diagnosed patients using CT angiography. Ann Rheum Dis. 2012;71(7):1170–6. Hoyer BF, Mumtaz IM, Loddenkemper K, Bruns A, Sengler C, Hermann KG, et al. Takayasu arteritis is characterised by disturbances of B cell homeostasis and responds to B cell depletion therapy with rituximab. Ann Rheum Dis. 2012;71(1):75–9. Ernst D, Greer M, Stoll M, Meyer-Olson D, Schmidt RE, Witte T. Remission achieved in refractory advanced takayasu arteritis using rituximab. Case Rep Rheumatol. 2012;2012:406963. Caltran E, Di Colo G, Ghigliotti G, Capecchi R, Catarsi E, Puxeddu I, Migliorini P, Tavoni A. Two Takayasu arteritis patients successfully treated with rituximab. Clin Rheumatol. 2014;33(8):1183–4. Maritati F, Corradi D, Versari A, Casali M, Urban ML, Buzio C, et al. Rituximab therapy for chronic periaortitis. Ann Rheum Dis. 2012;71(7):1262–4. Guerry MJ, Brogan P, Bruce IN, D’Cruz DP, Harper L, Luqmani R, et al. Recommendations for the use of rituximab in anti-neutrophil cytoplasm antibody-associated vasculitis. Rheumatology (Oxford). 2012;51(4):634–43. Holle JU, Voigt C, Both M, Holl-Ulrich K, Nölle B, Laudien M, et al. Orbital masses in granulomatosis with polyangiitis are associated with a refractory course and a high burden of local damage. Rheumatology (Oxford). 2013;52(5):875–82. Aries PM, Hellmich B, Voswinkel J, Both M, Nölle B, Holl-Ulrich K, Lamprecht P, Gross WL. Lack of efficacy of rituximab in Wegener’s granulomatosis with refractory granulomatous manifestations. Ann Rheum Dis. 2006;65(7):853–8. Brihaye B, Aouba A, Pagnoux C, Cohen P, Lacassin F, Guillevin L. Adjunction of rituximab to steroids and immunosuppressants for refractory/relapsing Wegener’s granulomatosis: a study on 8 patients. Clin Exp Rheumatol. 2007;25(1 Suppl 44):S23–7. Seo P, Specks U, Keogh KA. Efficacy of rituximab in limited Wegener’s granulomatosis with refractory granulomatous manifestations. J Rheumatol. 2008;35(10):2017–23. Martinez Del Pero M, Chaudhry A, Jones RB, Sivasothy P, Jani P, Jayne D. B-cell depletion with rituximab for refractory head and neck Wegener’s granulomatosis: a cohort study. Clin Otolaryngol. 2009;34(4):328–35. Taylor SR, Salama AD, Joshi L, Pusey CD, Lightman SL. Rituximab is effective in the treatment of refractory ophthalmic Wegener’s granulomatosis. Arthritis Rheum. 2009;60(5):1540–7. Baslund B, Wiencke AK, Rasmussen N, Faurschou M, Toft PB. Treatment of orbital inflammation with rituximab in Wegener’s granulomatosis. Clin Exp Rheumatol. 2012;30 (1 Suppl 70):S7–10.