232

BRIEF REPORT

SEVERE GIANT CELL VALVULITIS IN A PATIENT WITH REITER’S SYNDROME

TERRY E. PODELL, DANIEL J. WALLACE, MICHAEL C. FISHBEIN, KENT BRANSFORD, JAMES R. KLINENBERG. and SEYMOUR LEVINE

The presence of giant cells in heart valves has never been reported. In giant cell arteritis, giant cells can involve coronary arteries and the aorta, but they have never been demonstrated in heart valves ( 1,2). Takayasu’s arteritis is similar to giant cell arteritis, especially in its “pre-pulseless” phase; it often in- volves the aortic root and its branches and can cause aortic regurgitation ( 3 ) . We report a patient with Reiter’s syndrome who had severe giant cell valvulitis of aortic and mitral valves, necessitating valve re- placements.

CASE REPORT A 27-year-old black woman was well until July 1977,

when polyarthritis of her knees, ankles, wrists, and shoul- ders developed. She also had low back pain, recurrent

From the Division of Rheumatology. Department of Medi- cine, Cedars-Sinai Medical Center-UCLA School of Medicine. and the Department of Anatomic Pathology, Cedars-Sinai Medical Cen- ter, Los Angeles, CA 90048.

Terry E. Podell, MD: Fellow in Rheumatology, Division of Rheumatology, Department of Medicine, Cedars-Sinai Medical Center-UCLA School of Medicine; Daniel J . Wallace, MD: Attend- ing Physician, Division of Rheumatology, Department of Medicine, Cedars-Sinai Medical Center-UCLA School of Medicine, and As- sistant Clinical Professor, UCLA School of Medicine; Michael C. Fishbein, MD: Associate Pathologist, Department of Anatomic Pathology, Cedars-Sinai Medical Center; Kent Bransford, MD: Resident, Department of Medicine, Cedars-Sinai Medical Center- UCLA School of Medicine: James R. Klinenberg, MD: Professor and Chairman. Department of Medicine, Cedars-Sinai Medical Center-UCLA School of Medicine; Seymour Levine. MD: Attend- ing Physician, Division of Rheumatology, Department of Medicine, Cedars-Sinai Medical Center-UCLA School of Medicine. and As- sistant Clinical Professor, UCLA School of Medicine.

Address reprint requests to James ?. Klinenberg, MD, Department of Medicine, Cedars-Sinai Medica’ Center, 8700 Bever- ly Boulevard, Los Angeles, CA 90048.

Submitted for publication March 30, 1981: accepted in revised form August 4, 1981.

cystitis, and several episodes of conjunctivitis. Roentgeno- grams showed unilateral sacroiliitis and 2 erosions in her metacarpophalangeal joints. Her HLA-B27 antigen was positive, results of tests (latex) for rheumatoid factor were negative, and antinuclear antibodies were absent. Based on these findings, she was diagnosed as having Reiter’s syn- drome.

In October 1978, she had dyspnea on exertion, and ankle edema, and she was found to have systolic and diastolic heart murmurs. She was treated with digitalis and furosemide but needed to be admitted to the hospital many times for progressive congestive heart failure.

A cardiac catheterization at that time showed normal pulmonary-artery and capillary-wedge pressures, severe aortic regurgitation, moderate mitral regurgitation, and nor- mal coronary arteries.

On examination, abnormal findings included a point of maximal impulse displaced to the left anterior axillary line, a palpable diastolic thrill, S3 and S4 heart sounds, a grade 416 midsystolic murmur and a grade 4/6 diastolic blowing murmur-both heard at the LLSB and apex- “pistol-shot’’ femoral pulses, and a rapid runoff of her carotid pulses.

On October 3, 1979, when the patient had surgery, a dilated aortic root with a thickened ascending aorta was found. The aortic valve was very abnormal: it had only 2 thickened, enlarged cusps (which approximated poorly), located in the left and right coronary areas. An aortic valve replacement, a mitral valve replacement, and an aortic annuloplasty (Dacron graft) were performed. Nodules were noted on the free edges of the 2 megacusps.

The aortic valve, mitral valve, and a biopsy of the aorta were sent to pathology for histologic study. The aorta showed intimal proliferation, destruction of medial elastic tissue with vascular proliferation, and infiltration of chronic inflammatory cells. No giant cells were seen. The aortic valve (Figure 1) showed prominent infiltration by multinu- cleated giant cells, plasma cells, lymphocytes, eosinophils, and occasional neutrophils. There were multiple areas of fibrinoid necrosis of collagen and areas of fibrosis and thick- walled vessels. The overall architecture of the valve leaflets

Arthritis and Rheumatism, Vol. 25, No. 2 (February 1982)

BRIEF REPORTS 233

Figure 1. Histologic section of aortic valve. Note fibrinous exudate on the surface (asterisk), numerous multinucleated giant cells (ar- row) and infiltration of the valve by mononuclear inflammatory cells (hematoxylin and eosin, magnification X40).

was destroyed. The mitral valve showed fibrosis, focal myxomatous change, firbrinoid necrosis, and chronic in- flammatory cell infiltration, including giant cells. The sub- valvular myocardium also showed fibrosis and inflammatory cell infiltrates. There was coagulative necrosis of a papillary muscle with central mummification of myocardium sur- rounded by granulation tissue and chronic inflammatory cells, suggesting subacute infarction.

On October 29, 1979, prednisone therapy 60 mgiday was started. The patient’s erythrocyte sedimentation rate ESR was 128 mm/hour at that time, and she was discharged from the hospital. The prednisone was slowly tapered to 20 mg every other day by April 1980. At last followup (Decem- ber 1980), she was still receiving this dosage because the arthritis flared when attempts were made to taper the medication. Her erythrocyte sedimentation rate had fallen to 12 mm/hour, and there had been no exacerbation in the cardiac or vascular component of the disease.

DISCUSSION

Even though this patient’s disease does not meet the criteria for Takayasu’s arteritis, it fits no other heretofore-described entity. For literature re- view and discussion purposes, we will describe the current views on large vessel arteritis in young pa- tients.

Although mild aortic insufficiency has been a frequent clinical observation in Takayasu’s arteritis, we are aware of only 3 reports (4-6) of the histologic findings in abnormal valves in Takayasu’s disease. Deposition of fibrous tissue containing mononuclear cells was found in all 4 valves in 1 patient (4) and only in the aortic valve in another (7). In 2 other cases the histology was normal in 1 aortic valve and there was some fibrosis in the other (6). Our patient’s mitral and

aortic valves showed this fibrous tissue deposition but also revealed marked inflammation that included mul- tinucleated giant cells-the first time these have been noted in valve tissue.

Examination of a mitral papillary muscle in our patient showed at 2- to 3-week-old infarction, suggest- ing the presence of coronary arteritis with occlusion. There have been several reports of myocardial infarc- tions occurring in patients with Takayasu’s disease (3). Congestive heart failure was common among these patients, sometimes with systemic hypertension or aortic regurgitation. Coronary artery narrowing, espe- cially of the ostia alone, and angina pectoris have also been noted (2-4,7).

Myocarditis has been observed occasionally in Takayasu’s arteritis (7-10). Our patient’s subaortic myocardium showed infiltration with chronic inflam- matory cells, vascular proliferation, and giant cells.

Severe valvular involvement has been rare (6). We are aware of only 2 other reports (6,l I ) of aortic valve replacement, and none of mitral valve replace- ment in patients with Takayasu’s arteritis.

Of additional interest is the associated arthropa- thy in our patient. We felt that this rheumatic disease was most consistent with Reiter’s syndrome, consider- ing her episodes of conjunctivitis, possible urethritis, positive HLA-B27 antigen, sacroiliitis, negative re- sults of tests for rheumatoid factor, and the absence of skin manifestations of psoriasis or symptoms of in- flammatory bowel disease. Reiter’s syndrome has not to our knowledge been reported in association with any giant cells or large vessel arteritis.

One question is whether the aortic and valvular lesions can be explained by the presence of seronega- tive spondylarthropathy alone. One can see a thick- ened and dilated aorta in ankylosing spondylitis, as well as aortic insufficiency with shortened, thickened aortic valve cusps (12). Mitral regurgitation is less common and rarely severe (12-15). However, histo- logically one seens intimal proliferation and adventitial scarring in the aorta, and while lymphocytes and plasma cells may appear, there are no giant cells (12). There is an increase in fibrous tissue in the aortic valve; the anterior mitral valve leaflet may also show this, but here again there are no giant cells.

Lesions similar to those of ankylosing spondyli- tis in the aorta and aortic valve have been noted in patients with Reiter’s syndrome (13,14,16); no giant cells were reported. There are also reports of aortitis and aortic insufficiency in psoriatic arthritis and in- flammatory bowel disease (16).

234 BRIEF REPORTS

There are several clinical implications of our case. Diagnosing Takayasu’s arteritis can often be difficult. There is often a pre-pulseless phase and the disease can have primarily cardiac manifestions that simulate other causes of valvular, myocardial, or coronary artery disease.

This case report represents a new disease mani- festation-giant cell valvulitis. Whether it is a unique disorder or a rare manifestation of Takayasu’s disease, giant cell arteritis, or one of the seronegative spondyl- arthropathies remains to be determined.

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REFERENCES

Klein RG, Hunder GG, Stanson AW, Sheps SG: Large artery involvement in giant cell (temporal) arteritis. Ann Intern Med 83:806-812, 1975 Hamilton CR, Shelley WM, Tumulty PA: Giant cell arteritis: including temporal arteritis and polymyalgia rheumatica. Medicine 50: 1-26, 1971 Cipriano PR, Silverman JF, Perlroth MG, Griepp RB, Wexler L: Coronary arterial narrowing in Takayasu’s aortitis. Am J Cardiol 39:744-750, 1977 Roberts WC, MacGregory RR, DeBlanc JR HJ, Beiser GD, Wolf SM: The prepulseless phase of pulseless disease with pulses. Am J Med 44:313-324, 1969 Yamashita K: Two autopsy cases of “pulseless dis- ease.” Acta Pathol Jpn 23:415-420, 1973 Honig HS, Weintraub AM, Comes MN, Hufnagel CA, Roberts WC: Severe aortic regurgitation secondary to idiopathic aortitis. Am J Med 63:623-633, 1977

7. Fraga A, Mintz G, Valle L, Izquirdo GF: Takayasu’s arteritis: frequency of systemic manifestations and fa- vorable response to maintenance therapy with adreno- corticosteroids. Arthritis Rheum 15:617-624, 1972

8. Castleman B: Case record of the Massachusetts General Hospital. N Engl J Med 264:664-671, 1961

9. Palmer HP, Michael IE: Giant-cell myocarditis with multiple organ involvement. Arch Intern Med 116:444- 447, 1965

10. Roberts WC, Wibin EA: Idiopathic panaortitis, supra- aortic arteritis, granulomatous myocarditis and pericar- ditis. Am J Med 41:453-461, 1966

11. Austen WG, Blennerhassett JB: Giant-cell aortitis caus- ing an aneurysm of the ascending aorta and aortic regurgitation. N Engl J Med 272:80-83, 1965

12. Buckley BH, Roberts WC: Ankylosing spondylitis and aortic regurgitation: description of the characteristic cardiovascular lesion from study of eight necropsy pa- tients. Circulation 48: 1014-1027, 1973

13. Rodnan G, Benedek TG, Shaver JA, Fennel1 RH: Rei- ter’s syndrome and aortic insufficiency. JAMA 189:889- 894, 1964

14. Paulus HE, Pearson CM, Pitts W: Aortic insufficiency in 5 patients with Reiter’s syndrome. Am J Med 53:464- 472, 1972

15. Roberts WC, Hollingsworth JF, Buckley BH, Jaffe RB, Epstein SE, Stinson EB: Combined mitral and aortic regurgitation in ankylosing spondylitis: angiographic and anatomic features. Am J Med 56:237-243, 1974

16. Zvaifler NJ, Weintraub AM: Aortitis and aortic insuffi- ciency in the chronic rheumatic disorders: a reappraisal. Arthritis Rheum 6:241-245, 1963