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Critical Coronary Artery Stenosis and Aortitis in a Patient with Relapsing Polychondritis

To the Editors:

Relapsing polychondritis (RP) is a multisystem autoimmune disease with cartilage inflammation. Cardiovascular manifestations are associated with significant morbidity and mortality^1,2. Vasculitis involving the coronary arteries is rare. Our patient developed severe ostial lesions in 2 major coronary arteries and aortitis requiring surgical intervention despite intensive medical treatment.

A 30-year-old male Caucasian dental surgeon developed a painful, swollen left ear in January 2001. He was otherwise asymptomatic. Initial laboratory investigations were normal. A clinical diagnosis of relapsing polychondritis was made. His ear inflammation resolved after prednisone 30 mg daily for 3 weeks. Over the next 5 years he had 2 further episodes of left ear inflammation, pain and swelling of the bridge of his nose (2002), and uveitis (2003). He did not smoke. There was no family history of cardiac disease.

In the summer of 2006, he developed unaccustomed shortness of breath on exertion, fatigue, a recurrence of his left ear inflammation, and diffuse abdominal pain. Pulmonary function tests and a computed tomography (CT) of the chest were normal. He then complained of chest discomfort while walking progressively shorter distances and was referred for urgent cardiac assessment.

Examination was unremarkable with a blood pressure of 120/80. He was in sinus rhythm and breathing comfortably on room air. His body mass index was 21. There were no lymphadenopathy, or joint, eye, or ear abnormalities. Heart sounds were normal with no murmurs or added sounds. Chest examination was normal with no stridor, wheezing, or crackles.

Laboratory investigations revealed normal erythrocyte sedimentation rate, C-reactive protein, troponin, fasting glucose, C3 and C4 levels, and fasting lipid profile. Antinuclear antibodies, extractable nuclear antigen, antineutrophil cytoplasmic antibodies, rheumatoid factor, and antiphospholipid antibodies were negative, and repeated 12 weeks later. An electrocardiogram displayed normal sinus rhythm with Q waves in the inferior leads.

Echocardiogram showed a left ventricular ejection fraction of 53%, mild aortic regurgitation (AR), and normal right ventricular systolic pressure. Cardiac CT showed extensive, asymmetric wall thickening at the aortic root and proximal ascending aorta. There was severe stenosis of the ostium of both right and left main coronary arteries (Figure 1). Cardiac magnetic resonance imaging (MRI) showed subendocardial infarction of the inferior and inferoseptal segments at the base and mid-cavity (Figure 2). Abdominal CT revealed 50% narrowing of the proximal right external iliac artery.

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Figure 1. Coronary artery CT angiogram with multiplanar reformation. Critical and severe stenosis is seen at the ostium of the right coronary artery (arrowhead) and left main coronary artery (long arrow) respectively. There is irregular, asymmetric wall thickening of the aortic root due to aortitis (double arrow) that extends to involve the ostia of both coronary arteries.

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Figure 2. Cardiac MRI, short axis oblique projection of the basal left ventricle (LV), post gadolinium using a prepared inversion recovery gradient echo pulse sequence. There is a well defined area of subendocardial enhancement (arrow) in the territory of the right coronary artery, involving 60-75% of the thickness of the infero-septal wall of the LV consistent with subendocardial infarction. RV: right ventricle.

He was initially treated with prednisone (1 mg/kg/day), oral methotrexate (titrated up to 25 mg weekly), and a beta blocker. His angina improved over the next several days. He received 3 intravenous infusions of infliximab (5 mg/kg/dose) over the next 2 months. Although he was asymptomatic at 12 weeks into therapy, an exercise stress test (Naughton protocol) was positive. The patient refused early catheterization and surgery in favor of further immunosuppressive therapy. Infliximab and methotrexate were discontinued, and he began taking oral cyclophosphamide 100 mg daily.

Cardiac catheterization and aortography in February 2007 showed critical left main stem ostial disease, modest disease in the mid left arterial descending, and moderate aortic regurgitation. The right coronary artery was too tight to be cannulated. Elective surgery was carried out in April 2007 with triple coronary artery bypass and composite replacement of the aortic valve and ascending aorta. Pathological examination showed the presence of a pan-aortitis with a perivascular infiltrate, predominantly of lymphocytes, macrophages, and few plasma cells (Figure 3).

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Figure 3.A. Surgically excised segment of aorta showing an area of ulceration with a thrombus seen in the base of the ulcerated region. The surrounding aortic intima appears grossly unremarkable. B. Section of aorta from the grossly ulcerated area seen in A. There is a break in continuity of the aorta, with the gap bridged by new fibrovascular tissue (arrow). This area shows thick walled arteries and an infiltrate of mononuclear cells. The adjacent area shows features of panaortitis. I: intima; M: media; Stain: Movat pentachrome, original magnification ´2.5.

The patient recovered uneventfully from surgery, remains asymptomatic, and has returned to work. He is being maintained with a tapering dose of prednisone, methotrexate 20 mg weekly, atorvastatin, acetylsalicylic acid (ASA), metoprolol, and coumadin. Echocardiogram 6 months post surgery showed mild improvement in left ventricular function.

Vasculitis is estimated to occur in 11-56%^1,2 of patients with RP and has a 5 and 10 year survival probability of 74% and 55%, respectively². A literature review indicates that aortic valve (AV) involvement occurs in 4–6% of patients with RP, and severe regurgitation is a frequent indication for surgical intervention³. Mortality secondary to cardiovascular manifestations is estimated at 18%, second only to laryngotracheal involvement^4,5. Coronary ostial lesions are uncommon and presumed related to involvement of the adjacent aorta. The main histological findings are a lymphocytic infiltration around the vasa vasorum of the outer media with loss of elastic tissues⁵. To our knowledge there are only 4 other cases reported in the literature ^6-9.

Reported medical management of RP with coronary vasculitis has included high doses of corticosteroids, methotrexate, and/or cyclophosphamide^3,6. We chose infliximab prior to cyclophosphamide because of anecdotal reports¹⁰ and personal success in the treatment of severe RP. Despite aggressive medical management, most patients with cardiovascular involvement require surgical intervention because of severe, irreversible structural damage.

Reported surgical outcomes for cardiac manifestations of RP are limited. Postoperative complications, including prosthetic dehiscence and perivalvular leakage, are in part due to corticosteroid therapy causing aortic tissue fragilization³. It is recommended that all patients requiring surgery for disease involving the ascending aorta or sinuses of Valsalva have a prophylactic Bentall-type operation with composite aortic graft, along with coronary button re-implantation technique³. All patients need close followup because of the relapsing nature of the disease.

The fact that the clinical presentation of cardiovascular manifestations usually occurs late, and there is often no elevation in inflammatory markers, makes it extremely difficult to detect such lesions and to monitor disease activity. A favorable outcome is dependent on awareness, early diagnosis, aggressive medical treatment, and surgical correction when stable.

JONATHAN D. STEIN, MD, FRCPC, MHSc, University Health Network; PETER LEE, MD, FRCPC, FRACP, Mount Sinai Hospital; BINDEE KURIYA, MD, FRCPC, University Health Network; JERRY TENENBAUM, MD, FRCPC, Mount Sinai Hospital; LORRETTA B. DANIEL, MD, FRCPC, FACC, FASE; JAGDISH BUTANY, MBBS, MS, FRCPC; YVES L. PROVOST, MD, FRCPC; TYRONE E. DAVID, MD, University Health Network, Toronto, Ontario, Canada. Address reprint requests to Dr. P. Lee, Mount Sinai Hospital, 60 Murray Street, Box 9, Toronto, ON M5T 3L9.

REFERENCES

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2. Michet CJ. Vasculitis and relapsing polychondritis. Rheum Dis Clin North Am 1990;16:441-4. [MEDLINE]

3. Lang-Lazdunski L, Hvass U, Paillole C, Pansard Y, Langlois J. Cardiac valve replacement in relapsing polychondritis. A review. J Heart Valve Dis 1995;4:227-35. [MEDLINE]

4. Dib C, Moustafa SE, Mookadam M, Zehr KJ, Michet CJ Jr, Mookadam F. Surgical treatment of the cardiac manifestations of relapsing polychondritis: overview of 33 patients identified through literature review and the Mayo Clinic records. Mayo Clin Proc 2006;81:772-6. [MEDLINE]

5. Selim AG, Fulford LG, Mohiaddin RH, Sheppard MN. Active aortitis in relapsing polychondritis. J Clin Pathol 2001;54:890-2. [MEDLINE]

6. Bowness P, Hawley IC, Morris T, Dearden A, Walport MJ. Complete heart block and severe aortic incompetence in relapsing polychondritis: clinicopathologic findings. Arthritis Rheum 1991;34:97-100. [MEDLINE]

7. Yung A, Charleson HA, Ullal R, Doube A. A case of relapsing polychondritis with coronary ostial stenosis and severe aortic incompetence. Semin Arthritis Rheum 2000;30:144-6. [MEDLINE]

8. Vaidyanathan RK, Byalal JR, Sundaramoorthi T, et al. Rapidly progressive coronary ostial stenosis after aortic valve replacement in relapsing polychondritis. J Thorac Cardiovasc Surg 2006;131:1395-6. [MEDLINE]

9. Sasirekha D, Meenakshi NA, Thomas JM, Jagannath BR, Nayar S, Cherian KM. Multiple cardiovascular involvement in a case of relapsing polychondritis. J Assoc Physicians India 2006;54:817-9. [MEDLINE]

10. Saadoun D, Deslandre CJ, Allanore Y, Pham XV, Kahan A. Sustained response to infliximab in 2 patients with refractory relapsing polychondritis. J Rheumatol 2003;30:1394-5. [MEDLINE]