1454 LETTERS

She was well thereafter. She had a miscarriage in 1980 and, at that time, was noted to have a platelet count of 120 x 109/liter. This observation was not investigated fur- ther. Her mitral valve prosthesis (Stented homograft) was replaced with a Starr-Edwards prosthesis in 1981 because of the development of mitral incompetence. The question of obstruction of the homograft prosthesis had been raised on the basis of echocardiographic findings (posterior movement at end-diastole and at the beginning of systole).

At surgical exploration, the left auricle was very large, and a mural thrombus was found posterior to the mitral valve and around the orifices of the pulmonary veins. The clot was friable. There were abnormalities of the homo- graft itself, and 2 of the buttresses had become detached. She became pregnant soon after and LAC was demon- strated. When the activated partial thromboplastin time was noted to be prolonged, her treatment was switched from warfarin to heparin. The question of whether she had previ- ously had rheumatic fever at all was raised. The suggestion was made that she possibly had developed SLE with endo- cardial involvement, complicated later by SBE. She had no joint symptoms at this time.

She had a normal blood pressure level and no overt signs of arthritis, but there was a definite butterfly rash on the malar area of her face. There were no other positive findings, and her mitral valve prosthesis was functioning normally. At that time, laboratory investigations showed a hemoglobin level of 11.2 gm%, white blood cell count of 1 I .7 x lO9/Iiter, and a platelet count of 122 x lO’/liter. The antinuclear antibody test result was positive (1 :64), but results of tests for antibodies to double-stranded DNA were negative. LAC was present. She was discharged from the hospital a month after an unsuccessful delivery by cesarean section, at 24 weeks after gestation. She was feeling well and had no signs of mitral valve dysfunction. The placenta showed multiple infarcts.

Six weeks later, the patient was again admitted; she was moribund, with markedly reduced prosthetic valve sounds. She had a cardiac arrest soon after arriving at the hospital. Permission for autopsy was not given.

This patient had been thought to have had rheumatic fever, but there were no records of a test for antistreptolysin 0 titer being performed. She presented with solitary mitral incompetence at the age of 21, followed 2 years later by the development of bacterial endocarditis. Histologic evaluation of the valve that had been replaced showed only nonspecific thickening. At further surgery in 1981, a mural thrombosis was found posterior to the mitral valve and obstructing the orifices of the pulmonary veins.

She was readmitted 6 weeks after hospital discharge, having discontinued her warfarin therapy. On examination, she had developed markedly reduced prosthetic valve sounds. She then had a cardiac arrest and died. It was believed that she had developed a further intracardiac event, on this occasion, a thrombosis of the prosthesis itself.

The development of recurrent thrombosis (either venous or arterial) after the discontinuation of warfarin has been documented in patients with elevations of anticardioli- pin antibody levels (6 ) .

This appears to be the first reported case of intracar- diac thrombosis occurring in a patient with LAC who had a

probable thrombosis of the prosthetic valve that appears to have been precipitated by the cessation of warfarin therapy.

Since submission of this paper, Ford et a1 (7) de- scribed 2 patients with severe valvular heart disease and systemic lupus erythematosus associated with LAC. Their second patient, a woman with SLE who had a mechanical mitral valve prosthesis replacement for severe mitral regur- gitation, developed a pulmonary embolus and hemiparesis 8 and 18 months postoperatively, respectively. Apparently, she was receiving warfarin therapy. Four years after the valve replacement, sudden hypotension developed and she died. Investigations and necropsy revealed obstruction of the valve by thrombus. Thrombosis occurring during warfa- rin therapy has been seen in a number of patients in our unit recently (8), and in most, but not all, patients this was due to poor anticoagulation control.

Willem F. Lubbe, MD, FCP(SA), FRACP Green Lane Hospital Auckland, N Z Ronald A. Asherson, MD, FACP, FCP(SA) The Rayne Institute London. UK

1. Chartash EK, Paget SA, Lockshin MD: Lupus anticoagulant associated with aortic and mitral valve insufficiency (abstract). Arthritis Rheum 29 (suppl 4):S95, 1986

2. Cronin ME, Biswas R, van der Straeton C, Fleisher TA, Klippel JH: IgG and IgM anticardiolipin antibodies in patients with lupus with anticardiolipin associated clinical syndromes. J Rheumatol

3. Carreras LO, Vermylen JG: “Lupus” anticoagulant and throm- bosis: possible role of inhibition of prostacyclin formation. Thromb Haemost 48:28-40, 1981

4. Asherson RA, Lubbe WF: Cerebral and valve lesions in SLE: association with antiphospholipid antibodies. J Rheumatol 15:

5 . Anderson D, Bell D. Lodge R, Grant E: Recurrent cerebral ischaemia and mitral valve vegetation in a patient with anti- phospholipid antibodies. J Rheumatol 14:839-841, 1987

6. Asherson RA, Harris EN, Gharavi AE, Hughes GRV: Anticar- diolipin antibody, recurrent thrombosis and warfarin withdrawal. Ann Rheum Dis 44:823-825, 1985

7. Ford PM, Ford SE, Lillicrap DP: Association of lupus anticoag- ulant with severe valvular heart disease in systemic lupus ery- thematosus. J Rheumatol 15:597400, 1988

8. Baguley E, Asherson RA, Hughes GRV: Thrombotic events in patients with antiphospholipid antibodies on warfarin therapy. Br J Rheumatol (in press)

15: 795-798. 1988

539-543, 1988

Comment on the letter by Calin et a1

To the Editor: We noted with interest the recent communication

reporting the occurrence of reactive arthropathy following Salmonella vaccination (1). We have observed a patient with HLA-B27-associated ankylosing spondylitis (AS) who de- veloped recurrent attacks of anterior uveitis after repeated immunization with Salmonella typhi.

LETTERS 1455

The patient, a 41-year-old woman, had recurrent anterior uveitis involving each eye over a 12-year period. During the 7-year period prior to 1981, she had 5 episodes of acute anterior uveitis that was not associated with an iden- tifiable triggering event. Over the last 8 years, she has had lower back pain and radiologic evidence of sacroiliitis. The patient has made several trips overseas which have necessi- tated immunization against cholera and typhoid. In 1981, the patient was first vaccinated with combined cholera and typhoid vaccine, and this was followed a few days later by a severe attack of anterior uveitis in the right eye. She traveled overseas again in 1982 and was vaccinated only against cholera; she did not develop uveitis. In 1986, she was again immunized against typhoid, and 8 days later a severe attack of acute anterior uveitis occurred in the left eye. She has not had a subsequent attack of uveitis nor has she had any further vaccinations. She has been advised not to have further typhoid vaccinations.

The sequence of events observed in this patient, provides intriguing, indirect evidence that exposure to a suitable environmental antigen can trigger attacks of anterior uveitis. It is of great interest that in this patient, immuniza- tion against Vibrio cholera alone did not induce an attack of uveitis, whereas immunization with S typhi alone or com- bined with V cholera did provoke an attack.

It is well recognized that there is a close association between anterior uveitis, AS, and the HLA-B27 phenotype. We and others have reported that both anterior uveitis and AS may be associated with infection by Chlamydia tracho- matis andfor gram-negative bacteria, particularly Klebsiella pneumoniae (2,3). There is in vitro evidence that there are antibodies to C trachomatis and K pneumoniae that cross- react with the lymphocytes of patients who are HLA-B27 positive and have AS andlor anterior uveitis (3,4).

Our findings support the view that there is a strong link between exposure to selected environmental infective agents and the initiation of uveitis attacks in certain geneti- cally susceptible patients.

Peter McCluskey, MBBS, FRACO, FRACS Denis Wakefield, MD, FRACP, FRCPA University of NSW Kensington, Australiq

1. Calin A, Goulding N , Brewerton D: Reactive arthropathy follow- ing Salmonella vaccination (letter). Arthritis Rheum 30: 1197, 1987

2. Wakefield D, Penny R: The cell mediated immune response to chlamydia in HLA B27 anterior uveitis. Clin Exp Immunol 51:

3. Geczy AF, Alexander K, Bashir HV, Edmonds JP, Upfold L, Sullivan J: HLA B27 Klebsiella and ankylosing spondylitis: biological and chemical studies. Immunol Rev 70:23-50, 1983

4. Wakefield D, Easter J, Robinson J, Graham D, Penny R: Chla- mydial antibody crossreactivity with peripheral blood mono- nuclear cells of patients with ankylosing spondylitis: the role of HLA B27. Clin Exp Immunol63:49-55, 1986

191-196, 1983

Absence of abnormal Epstein-Barr virus serologic findings in patients with fibrositis

To the Editor: We read with interest the article by Buchwald and

colleagues (11, on the possible relationship between chronic fatigue syndrome and primary fibromyalgia (fibrositis). These syndromes often have similar clinical manifestations, including arthralgias, myalgias, fatigue, abnormal sleep pat- tern, headaches, sicca symptoms, depression, temperature intolerance, and irritable bowel symptoms. Fibrositis is distinguished mainly by the presence of trigger points. Patients with chronic fatigue syndrome are known to have serologic evidence of acute or persistent infection with the Epstein-Barr virus (EBV) (2,3).

Because of the clinical similarity between patients with fibrositis syndrome and chronic fatigue syndrome, we undertook a study (supported in part by a grant from Smith Kline & French) to determine whether patients with fibro- sitis might also have serologic findings consistent with per- sistent EBV infection. Our study population included 19 patients with fibrositis syndrome, 21 with chronic fatigue syndrome, 20 with osteoarthritis (OA), 20 with rheumatoid arthritis (RA), and 20 normal control subjects. The patients with fibrositis syndrome, RA, or OA were selected sequen- tially from the private practice of one of us (KHF).

All fibrositis syndrome patients had at least 7 of a possible 14 trigger points, an abnormal sleep pattern, gen- eralized myalgias, severe fatigue, and normal laboratory findings, including complete blood count, erythrocyte sedi- mentation rate (Westergren), rheumatoid factor analysis, antinuclear antibody assay, urinalysis, electrolyte levels, liver function, and levels of creatinine, blood urea nitrogen, calcium, and phosphorous. All the RA patients met the American Rheumatism Association criteria for a diagnosis of definite or classic RA (4). The diagnosis of OA was based on clinical presentation, standard radiographic criteria, and the absence of evidence of inflammatory arthropathy.

Patients with chronic fatigue syndrome were selected from the chronic fatigue syndrome clinic at Mount Zion Hospital (San Francisco, CA) and were entered into the study based on clinical findings. All chronic fatigue syn- drome patients had severe fatigue, myalgias, arthralgias, recurrent sore throats, abnormal sleep pattern, headache, and normal findings on the same battery of laboratory tests as assessed in the fibrositis patients. Tests for EBV were obtained only after patients had been accepted into the study. Control subjects were the healthy staff and colleagues of the investigators.

Sera from all patients were assayed for IgG anti-viral capsid antigen (anti-VCA), anti-early antigen diffuse (anti- EAD), and anti-early antigen restricted (anti-EAR) anti- bodies by indirect immunofluorescence (51, and for anti- Epstein-Barr nuclear antigen (anti-EBNA) antibodies by anticomplement indirect immunofluorescence (6). These se- rologic tests were done by Virolab (Berkeley, CA). Serologic determinations were performed in a blinded manner, except for those of the controls.