Annals of Medicine
ISSN: 0785-3890 (Print) 1365-2060 (Online) Journal homepage: http://www.tandfonline.com/loi/iann20
Toxoplasma Pericarditis Mimicking Systemic Lupus Erythematosus.: Diagnostic and Treatment Difficulties in One Patient Kirsten K. Lyngberg, Birgitte J. Vennervald, Ib C. Bygbjerg, Troels Mørk Hansen & Ole Østergaard Thomsen To cite this article: Kirsten K. Lyngberg, Birgitte J. Vennervald, Ib C. Bygbjerg, Troels Mørk Hansen & Ole Østergaard Thomsen (1992) Toxoplasma Pericarditis Mimicking Systemic Lupus Erythematosus.: Diagnostic and Treatment Difficulties in One Patient, Annals of Medicine, 24:5, 337-340, DOI: 10.3109/07853899209147833 To link to this article: http://dx.doi.org/10.3109/07853899209147833
Published online: 08 Jul 2009.
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Citing articles: 1 View citing articles
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Date: 30 March 2016, At: 03:34
Toxoplasma Pericarditis Mimicking Systemic Lupus Erythematosus. Diagnostic and Treatment Difficulties in One Patient Kirsten K. Lyngberg’, Birgitte J. Vennervald2,Ib C. Bygbjerg3,Troels Mark Hansen4 and Ole 0stergaard Thomsen4
Downloaded by [University of Western Ontario] at 03:34 30 March 2016
A life-threatening T. gondii pericarditis developed in a patient with symptoms corre-
sponding to systemic lupus erythematosus (SLE) with high concentrations of antinuclear antibodies and lymphadenopathy. The diagnosis would have been SLE-associated serositis, had not perlcardial fluid been inoculated into mice, because pericarditis is frequently seen in SLE and false positive toxoplasma seroreactions may occur in ANA positive patients. High IgG T. gondii antibodies without increased IgM antibodies indicated reactivation rather than primary infection. Prolonged high-dose treatment with pyrimethamine-sulphadiazine was needed. Interestingly, the patient‘s SLE symptoms, including high ANA antibodies, declined to an unexpected remission after treatment for toxoplasmosis. This may not be mere coincidence, but may point to a causative role of toxoplasmosis in some cases of SLE. Key words: toxoplasmosis; systemic lupus erythematosus; antinuclear antibodies; toxoplasma antibodies; pericarditis. (Annals of Medlcine 24: 337-340,1992)
Introduction The clinical manifestations in toxoplasmosis and systemic lupus erythematosus (SLE) are interchangeable, being lymphadenopathy, low grade fever, and vague symptoms such as weakness, arthralgia and weight loss. Symptomatic toxoplasmosis can be caused by both newly acquired infection and reactivation. Muscular symptoms may precede the diagnosis of SLE and toxoplasmosis. In order to classify SLE four criteria out of 11 are needed (American Rheumatism Association’s (ARA) 1982 revised criteria)(1 ). In toxoplasmosis the antibody production usually leads to the diagnosis, but it may be difficult with a disease lasting several months where no IgM antibodies are found and the IgG titre are still high after earlier Toxoplasma gondii (T. gondio infection (2, 3). The present case story describes a verified toxoplasmatic pericarditis in a patient with SLE symptoms and antibodies, where treatment induced an
From the ‘Department of Clinical Chemistry, Herlev Hospital, University of Copenhagen; ‘Department of Toxoplasmosis, Statens Serurninstitut, Copenhagen; 3Department of Infectious Diseases. Rigshospitalet, University of Copenhagen; and 4Division of Rheurnatology, Medical Department C, Herlev Hospital, University of Copenhagen, Denmark. Address and reprint requests: K. K. Lyngberg, M.D., Division of Rheurnatology, Medical Dept. C, Herlev Hospital, DK-2730 Herlev, Denmark. Received: March 3, 1992; revision accepted May 21, 1992.
unexpectedly positive result not only to the serious pericarditis but also regarding SLE.
Case Story A 61-year old woman was referred to the department of rheumatology after 8 months of unsuccessful treatment with non-steroidal anti-inflammatory drugs and sulphasalarin for a suspected sero-negative rheumatoid arthritis. The previous symptoms and signs were synovitis of the right knee, bursitis olecranii, stiffness of the fingers and general weakness. At admission the complaints were: restlessness, general malaise, muscular pain, decreased appetite and weight loss. Physical examination revealed tender extremities, no joint effusions, slight generalized lymphadenopathy and a low grade fever. Abnormal laboratory analyses were: haemoglobin 5.4 (7-1 0) mmol/l, serum albumine 342 (550-760) pnolll, IgG 23.8 (5.8-14) g/l. ESR, thrombocytes count, and serum lactic-dehydrogenase were slightly elevated. X-ray examinations of the thorax and colon, gastro- and sigmoidoscopy, intravenous urography, ultrasound examination of the abdomen, and echocardiography at admission were all normal. A CTscan of the brain showed signs of a small nonspecific infarct. Non-specific slight alterations were found in both bone marrow and in an axillary lymph node biopsy. Serum-autoantibodies determined by indirect immunofluorescence (IIF) showed the following titres: antinuclear antibodies (ANA) on in vitfo cultured human fibroblasts (organ-non-specific (ON))1280, ANA on
Downloaded by [University of Western Ontario] at 03:34 30 March 2016
338
Lyngberg
Vennervald
Bygbjerg
Hep-2 cells 1280, and anti-double-stranded DNA antibodies 10. The ratio of T-helper/T-suppressor lymphocytes was decreased to 0.57 (normally > 1.00). Granulocyte-specific (GS) IgG titre and complementbinding granulocyte-specific (GS compl) ANA decreased during the disease period (Table 1). Autoantibodies were all negative to cytoplasmic and cytoskeletal cell components such as nucleoproteins (anti-ENA), nuclear ribonucleoprotein (anti-RNP), and SM-antigen (anti-SM). Furthermore, IgM rheumatoid factor, anti-cardiolipin antibodies IgG and IgM, direct Coombs' test, tuberculin skin test (Mantoux), and antibodies to Borrelia, human immunodeficiency virus (HIV), and cytomegalo virus (CMV) were also negative. Reactivated toxoplasmosis was suspected when finding very high IgG antibody titre against toxoplasma, and normal IgM antibody titre using the indirect immunofluorescence antibody test (IFAT), the Sabin-Feldman dyetest (dye-test), the enzyme-linked immunosorbent assay (ELISA) and the complement fixation test (CF) (4) (Table 1). Pyrimethamine, 50 mg initially and later 25 mg daily, sulphadiazine, 1.5 g initially and later 0.5.9 daily, and leucovorin 7.5 mg once weekly were given for 3 weeks. One week after completing this treatment the patient was readmitted with increasing symptoms, including a weight loss of 5 kg, dyspnoea and psychosomatic reactions. Clinical examination revealed a pericardial rub and ECG changes as found with pericarditis. Initially the patient refused further examinations and treatment, but a few days later she developed a serious right-sided cardiac tamponade with low arterial blood pressure. X-ray examination showed an enlarged heart, and ECG disclosed general ST segment elevation and low voltage. Echocardiography showed signs of severe exudative pericarditis but normal valves and myocardium, and in particular no hypokinetic areas were seen. At pericardial centesis 340 ml of fluid was aspirated. The following day
Hansen
Thomsen
another 250 ml was aspirated during pericardial catheter insertion. The pericardial fluid showed marked polymorphonuclear leucocytosis, but bacterial culture was negative. Treatment with prednisolone 40 mg twice daily, leucovorin 7.5 mg weekly, pyrimethamine 50 mg and sulphadiazine 5 g daily was given on suspicion of an SLE pericarditis. The patient was transferred to the Department of Infectious Diseases, Rigshospitalet,where gradual decrease of prednisolone were started after 1 week. T. gondii IgG antibodies were 150 with the dye test and 1 : l O with IFAT in the pericardial fluid; toxoplasma parasites were later detected in inoculated mice, which died less than 6 weeks after inoculation. During the 7 weeks of treatment the patient's heart symptoms gradually resolved. The clinical condition deteriorated again 2 months later. The patient had rising toxoplasma titres, for which 4 weeks of treatment with pyrimethamine-sulphadiazine was given. The condition of the patient improved clinically as well as paraclinically. The ECG and X-ray of the chest findings normalized and the lymphocyte subpopulation ratio also reverted to normal. The toxoplasma antibodies titres declined gradually and SLE symptoms as well as ANA antibodies subsided (Table 1). The patient is now back at work and has been followed in the out-patient clinic for 9 months.
Discussion The present patient had arthritic symptoms, CNS affection, high ANA antibodies, anti-DNA antibodies, decreased ratio of T-helper/T-suppressor lymphocytes, thus having more than four of the 11 SLE criteria (l), besides which the patient later developed pericarditis. Pericarditis is the most common cardiac involvement in SLE (5) and has been found in up to 80% of autopsies (5). Therefore, the pericarditis of the present case would
Table 1. Decrease In antinuclear and toxoplasma antibodies during and after treatment in a patient with SLE and toxoplasmlc perlcardltls. Months
1
2
3
6
8
11
15
Antinuclear antibody titres ANA 1280 320 N/A N/A 16 80 40 ANA GS IgG N/A 2048 2048 1024 512 1024 0 ANA GS Compl N/A 1024 1024 256 256 0 0 ANA ON Cornpl N/A N/A 256 16 32 32 N/A qntinuclear antibodies (ANA), granulocyte-specific (GS), organ-non-specific (ON), Complement binding (Compl) N/A not available. Toxoplasma antibody titres IFAT IgG 156256 31 250 31 250 31250 31250 6250 31250 ELSA IgG 143 157 164 153 156 98 106 Dye test 6250 1250 6250 N/A 6250 1250 6250 CF 1:4 1:8 1:2 1:2 N/A 1:2 1:2 Indirect immunofluorescenceantibody test (IFAT), enzyme-linked immunosorbent assay (IIF ELISA), Sabin-Feldrnandye test (Dye), and complement fixation antibody test (CF). N/A not available. Treatment periods Pyrimethamine Sulphadiazine Leucovorin Prednisolone 'Low dose; "increased dose.
I*
**
**
Downloaded by [University of Western Ontario] at 03:34 30 March 2016
Toxoplasma Pericarditis in SLE Patient probably have been attributed to the SLE, had not the pericardial fluid been inoculated into mice with the subsequent growth of T. gondii. Fewer than 20 cases have been described with T. gondii pericarditis (6-15) and few without subsequent myocarditis (7,8, 10, 15), which is the most common presentation of cardiac toxoplasmosis (6-8, 12, 13, 16). Toxoplasmosis affecting the heart may not be suspected ante-mortem (18) and, when found, the diagnosis has been based on serological findings only in 90% of the cases (6, 12-15). The diagnosis may be particularly difficult when the patient has simultaneous rheumatic-mimicking disease, and may be further complicated if the serological results are insecure: false positive IgG and IgM anti-toxoplasma fluorescent-antibodies have been described in patients with ANA antibodies (1 7-19). Symptomatic toxoplasmosis can be caused by both newly acquired infection and reactivation and, especially in the immunologically suppressed, the T. gondii parasite most frequently invades the cerebrum, skeleton or heart muscles (20). Toxoplasma antibodies are found in onethird of the Danish population as a sign of early unrecognized infection (21). Specific IgM antibodies are normally present in primary acute toxoplasmosis, whereas in secondary toxoplasmosis (reactivation), high IgG antibodies are characteristic (2, 3, 22). Magid (22) reported increased toxoplasma IgG antibody in a small group of SLE patients, but no increase in the frequency of IgM antibodies as found in polymyositis-dermatomyositis. Our patient had active disease with a negative IgM test and a high stable IgG titre indicating reactivation although primary infection with loss of IgM antibodies cannot be ruled out. Steroids are believed to cause reactivation in toxoplasmosis (12), but this patient had not been treated with corticosteroids before the serious symptoms of tOXOplaSmosis appeared. Early death in SLE is mostly caused by infections (23, 24); opportunistic infections in particular have been found in steroid-treated SLE patients (23,24). Toxoplasma and polymyositis are linked (22,25-29) and improvements have been reported following treatment for toxoplasmosis in polymyositis (26, 28), but not in SLE. In the present case, however, the SLE-related symptoms disappeared after prolonged and repeated treatment. In SLE, prolonged treatment may be recommended as in other immunodeficient patients. Several reports describe relapses in toxoplasmosis (11, 12, 30), presumably caused by breakdown of tissue cysts that are normally not eradicated by chemotherapy, therefore repeated treatment may be needed (12). The chemotherapy eradicates the trophozoites that cause the symptoms in toxoplasmosis. In the present case SLErelated symptoms as well as ANA antibodies disappeared after prolonged treatment of toxoplasmosis. The decrease in ANA antibodies following toxoplasmosis therapy in the present case is remarkable and has not been described previously. Whether the SLE-like syndrome in this case was actually precipitated by toxoplasmosis may be a subject for discussion. It may be valuable to screen patients with SLE for toxoplasmosis and further elucidate the possible etiological role of toxoplasmosis in SLE.
339
References 1. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ et al. The 1982 revised criteria for the classification of systemic lupus erythematosus.Arthritis Rheum 1982; 25: 1271-7. 2. Brooks RG, McCabe RE, Remington JS. Role of serology in the diagnosis of toxoplasmic lymphadenopathy. Rev lnfect Dis 1987; 9: 1055-62. 3. Welch PC, Masur H,Jones TC, Remington JS. Serologic diagnosis of acute lymphadenopathic toxoplasrnosis. J lnfect Dis 1980; 142: 256-64. 4. Remington JS, Desmonts G. Toxoplasmosis. In: Remington JS, Klein JO, eds. lnfectious diseases of the fetus and newborn infant. Philadelphia: W B Saunders, 1983: 143-263. 5. Hart HH. Ethnic difference in the prevalence of systemic lupus erythematosus.Ann Rheum Dis 1983; 42: 529-32. 6. Hakkila, J, Frick HM, Halonen PI. Pericarditis and rnyocarditis caused by toxoplasma: report of a case and review of the literature. Am Heart J 1958; 55: 758-5. 7. Jones TC, Kean BH, Klmball AC. Pericarditis associated with toxoplasrnosis. Ann Intern Med 1965; 62: 786-90. 8. Theologides A, Kennedy BJ. Toxoplasmic myocarditis and pericarditis. Am J Med 1969; 47: 167-74. 9. Nagaratnam N, Stephen SJ. Chronic constrictive pericarditis associated with toxoplasmosis. Br Heart J 1973; 868-70. 10. Mirada A, RubiBs-Prat J, Cerdh E, Foz M. Pericarditis associated to acquired toxoplasmosis in a child. Cardiology 1976; 61 : 303-6. 1 1 . McCabe R, Brooks RG, Dorfman RE, Remington JS. Clinical spectrum in 107 cases of toxoplasmic lymphadenopathy. Rev lnfect Dis 1987; 9: 754-74. 12. Leak D, Meghjl M. Toxoplasrnic infection in cardiac disease. Am J Cardioll979; 43: 841 -9. 13. Cunningham T. Pancarditis in acute toxoplasmosis. Am J Clin Patholl982; 78: 403-5. 14. Sagristh-Sauleda J, Permanyer-Miralda G, JusteSanchez S et el. Huge chronic pericardial effusion caused by Toxoplasrnagondii. Circulation 1982; 66: 895-7. 15. Collarl F, Glupzlnski Y, Cogan E. Schmerber J. Acute pericarditis of toxoplasmic origin. J lnfect 1983; 7: 82-3. 1 6. Siball’c D, Djurkovl’c-Djakovi’c 0. Role of toxoplasmosis in the aetiology of some cardiac diseases: an immunobiological investigation. J Clin Pathol 1986; 39: 204-7. 17. Araujo FG, Barnett EV, Gentry LO, Remington JS. Faisepositive anti-toxoplasrna fluorescent-antibody tests in patients with antinuclear antibodies. Appl Microbiol 1971 ; 22: 270-5. 18. Desmonts G, Naot V, Remington JS. Immunoglobulin M-immunosorbent agglutination assay for diagnosis of infectious diseases: diagnosis of acute congenital and acquired toxoplasma infections. J Clin Microbiol 1981 ; 14: 486-91. 19. Wilcox MH, Powell RJ, Pugh SF, Balfour AH. Toxoplasmosis and systemic lupus erythematosis. Ann Rheum Dis 1990; 49: 254-7. 20. Beattie CP. The ecology of toxoplasmose. Ecol Dis 1982; 1: 13. 21. Vennervald BJ. Human toksopiasmose. Ugeskr Laeger 1990; 15: 1068-70. 22. Magid SK, Kagen LJ. Serologic evidence for acute toxoplasmosis in polymyositis-dermatornyositis. Increased frequency of specific anti-toxoplasma IgM antibodies. Am J Med 1983; 75: 31 3-20. 23. Rosner S, Glnzler EM, Diamond HS et al. A multicenter study of outcome in systemic lupus erythematosus. II Causes of death. Arthritis Rheum 1982; 25: 61 2-17. 24. Ridiey MG, Long PJ, Hughes GRV. Survival in systemic lupus erythematosus. Br J Hap Med 1988, March; 237-41.
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25. Greenlee JE, Johnson WD, Campa JF,et al. Adult toxoplasmosis presenting as polymyositis and cerebellar ataxia. Ann lntem Med 1975;82 367-71. 26. Samuel8 BS, Reltschel RL. Polymyositis and toxoplasmosis. J A M 1976;235: 60-1. 27. Behan WMH, Behan PO, Draper IT, Williams H. Does toxoplasma cause polymyositis? Report of a case of polymyositis associated with toxoplasmosis and a critical review of the literature. Acra Neuropafholl983;61: 246-52.
28. Adam8 EM, Hafer GR, Carnes M, Wiesner JK, Graziano FY. The development of polymyositisin a patient with toxo-
plasmosis: clinical and pathologic findings and review of literature. Clin Exp Rheumat 1984;2 205-8. 29. Schrater HM, Sarnat HB, Matheson DS, Seland TP. Juvenile dermatomyositis induced by toxoplasmosis. J Child Neurol 1987;2: 101-4. 30. Norrby, R, Eilald T. Recurrent toxoplasmosis. Scand J lnfect Dis 1976;8: 275-6.
ISSN: 0785-3890 (Print) 1365-2060 (Online) Journal homepage: http://www.tandfonline.com/loi/iann20
Toxoplasma Pericarditis Mimicking Systemic Lupus Erythematosus.: Diagnostic and Treatment Difficulties in One Patient Kirsten K. Lyngberg, Birgitte J. Vennervald, Ib C. Bygbjerg, Troels Mørk Hansen & Ole Østergaard Thomsen To cite this article: Kirsten K. Lyngberg, Birgitte J. Vennervald, Ib C. Bygbjerg, Troels Mørk Hansen & Ole Østergaard Thomsen (1992) Toxoplasma Pericarditis Mimicking Systemic Lupus Erythematosus.: Diagnostic and Treatment Difficulties in One Patient, Annals of Medicine, 24:5, 337-340, DOI: 10.3109/07853899209147833 To link to this article: http://dx.doi.org/10.3109/07853899209147833
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 11
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=iann20 Download by: [University of Western Ontario]
Date: 30 March 2016, At: 03:34
Toxoplasma Pericarditis Mimicking Systemic Lupus Erythematosus. Diagnostic and Treatment Difficulties in One Patient Kirsten K. Lyngberg’, Birgitte J. Vennervald2,Ib C. Bygbjerg3,Troels Mark Hansen4 and Ole 0stergaard Thomsen4
Downloaded by [University of Western Ontario] at 03:34 30 March 2016
A life-threatening T. gondii pericarditis developed in a patient with symptoms corre-
sponding to systemic lupus erythematosus (SLE) with high concentrations of antinuclear antibodies and lymphadenopathy. The diagnosis would have been SLE-associated serositis, had not perlcardial fluid been inoculated into mice, because pericarditis is frequently seen in SLE and false positive toxoplasma seroreactions may occur in ANA positive patients. High IgG T. gondii antibodies without increased IgM antibodies indicated reactivation rather than primary infection. Prolonged high-dose treatment with pyrimethamine-sulphadiazine was needed. Interestingly, the patient‘s SLE symptoms, including high ANA antibodies, declined to an unexpected remission after treatment for toxoplasmosis. This may not be mere coincidence, but may point to a causative role of toxoplasmosis in some cases of SLE. Key words: toxoplasmosis; systemic lupus erythematosus; antinuclear antibodies; toxoplasma antibodies; pericarditis. (Annals of Medlcine 24: 337-340,1992)
Introduction The clinical manifestations in toxoplasmosis and systemic lupus erythematosus (SLE) are interchangeable, being lymphadenopathy, low grade fever, and vague symptoms such as weakness, arthralgia and weight loss. Symptomatic toxoplasmosis can be caused by both newly acquired infection and reactivation. Muscular symptoms may precede the diagnosis of SLE and toxoplasmosis. In order to classify SLE four criteria out of 11 are needed (American Rheumatism Association’s (ARA) 1982 revised criteria)(1 ). In toxoplasmosis the antibody production usually leads to the diagnosis, but it may be difficult with a disease lasting several months where no IgM antibodies are found and the IgG titre are still high after earlier Toxoplasma gondii (T. gondio infection (2, 3). The present case story describes a verified toxoplasmatic pericarditis in a patient with SLE symptoms and antibodies, where treatment induced an
From the ‘Department of Clinical Chemistry, Herlev Hospital, University of Copenhagen; ‘Department of Toxoplasmosis, Statens Serurninstitut, Copenhagen; 3Department of Infectious Diseases. Rigshospitalet, University of Copenhagen; and 4Division of Rheurnatology, Medical Department C, Herlev Hospital, University of Copenhagen, Denmark. Address and reprint requests: K. K. Lyngberg, M.D., Division of Rheurnatology, Medical Dept. C, Herlev Hospital, DK-2730 Herlev, Denmark. Received: March 3, 1992; revision accepted May 21, 1992.
unexpectedly positive result not only to the serious pericarditis but also regarding SLE.
Case Story A 61-year old woman was referred to the department of rheumatology after 8 months of unsuccessful treatment with non-steroidal anti-inflammatory drugs and sulphasalarin for a suspected sero-negative rheumatoid arthritis. The previous symptoms and signs were synovitis of the right knee, bursitis olecranii, stiffness of the fingers and general weakness. At admission the complaints were: restlessness, general malaise, muscular pain, decreased appetite and weight loss. Physical examination revealed tender extremities, no joint effusions, slight generalized lymphadenopathy and a low grade fever. Abnormal laboratory analyses were: haemoglobin 5.4 (7-1 0) mmol/l, serum albumine 342 (550-760) pnolll, IgG 23.8 (5.8-14) g/l. ESR, thrombocytes count, and serum lactic-dehydrogenase were slightly elevated. X-ray examinations of the thorax and colon, gastro- and sigmoidoscopy, intravenous urography, ultrasound examination of the abdomen, and echocardiography at admission were all normal. A CTscan of the brain showed signs of a small nonspecific infarct. Non-specific slight alterations were found in both bone marrow and in an axillary lymph node biopsy. Serum-autoantibodies determined by indirect immunofluorescence (IIF) showed the following titres: antinuclear antibodies (ANA) on in vitfo cultured human fibroblasts (organ-non-specific (ON))1280, ANA on
Downloaded by [University of Western Ontario] at 03:34 30 March 2016
338
Lyngberg
Vennervald
Bygbjerg
Hep-2 cells 1280, and anti-double-stranded DNA antibodies 10. The ratio of T-helper/T-suppressor lymphocytes was decreased to 0.57 (normally > 1.00). Granulocyte-specific (GS) IgG titre and complementbinding granulocyte-specific (GS compl) ANA decreased during the disease period (Table 1). Autoantibodies were all negative to cytoplasmic and cytoskeletal cell components such as nucleoproteins (anti-ENA), nuclear ribonucleoprotein (anti-RNP), and SM-antigen (anti-SM). Furthermore, IgM rheumatoid factor, anti-cardiolipin antibodies IgG and IgM, direct Coombs' test, tuberculin skin test (Mantoux), and antibodies to Borrelia, human immunodeficiency virus (HIV), and cytomegalo virus (CMV) were also negative. Reactivated toxoplasmosis was suspected when finding very high IgG antibody titre against toxoplasma, and normal IgM antibody titre using the indirect immunofluorescence antibody test (IFAT), the Sabin-Feldman dyetest (dye-test), the enzyme-linked immunosorbent assay (ELISA) and the complement fixation test (CF) (4) (Table 1). Pyrimethamine, 50 mg initially and later 25 mg daily, sulphadiazine, 1.5 g initially and later 0.5.9 daily, and leucovorin 7.5 mg once weekly were given for 3 weeks. One week after completing this treatment the patient was readmitted with increasing symptoms, including a weight loss of 5 kg, dyspnoea and psychosomatic reactions. Clinical examination revealed a pericardial rub and ECG changes as found with pericarditis. Initially the patient refused further examinations and treatment, but a few days later she developed a serious right-sided cardiac tamponade with low arterial blood pressure. X-ray examination showed an enlarged heart, and ECG disclosed general ST segment elevation and low voltage. Echocardiography showed signs of severe exudative pericarditis but normal valves and myocardium, and in particular no hypokinetic areas were seen. At pericardial centesis 340 ml of fluid was aspirated. The following day
Hansen
Thomsen
another 250 ml was aspirated during pericardial catheter insertion. The pericardial fluid showed marked polymorphonuclear leucocytosis, but bacterial culture was negative. Treatment with prednisolone 40 mg twice daily, leucovorin 7.5 mg weekly, pyrimethamine 50 mg and sulphadiazine 5 g daily was given on suspicion of an SLE pericarditis. The patient was transferred to the Department of Infectious Diseases, Rigshospitalet,where gradual decrease of prednisolone were started after 1 week. T. gondii IgG antibodies were 150 with the dye test and 1 : l O with IFAT in the pericardial fluid; toxoplasma parasites were later detected in inoculated mice, which died less than 6 weeks after inoculation. During the 7 weeks of treatment the patient's heart symptoms gradually resolved. The clinical condition deteriorated again 2 months later. The patient had rising toxoplasma titres, for which 4 weeks of treatment with pyrimethamine-sulphadiazine was given. The condition of the patient improved clinically as well as paraclinically. The ECG and X-ray of the chest findings normalized and the lymphocyte subpopulation ratio also reverted to normal. The toxoplasma antibodies titres declined gradually and SLE symptoms as well as ANA antibodies subsided (Table 1). The patient is now back at work and has been followed in the out-patient clinic for 9 months.
Discussion The present patient had arthritic symptoms, CNS affection, high ANA antibodies, anti-DNA antibodies, decreased ratio of T-helper/T-suppressor lymphocytes, thus having more than four of the 11 SLE criteria (l), besides which the patient later developed pericarditis. Pericarditis is the most common cardiac involvement in SLE (5) and has been found in up to 80% of autopsies (5). Therefore, the pericarditis of the present case would
Table 1. Decrease In antinuclear and toxoplasma antibodies during and after treatment in a patient with SLE and toxoplasmlc perlcardltls. Months
1
2
3
6
8
11
15
Antinuclear antibody titres ANA 1280 320 N/A N/A 16 80 40 ANA GS IgG N/A 2048 2048 1024 512 1024 0 ANA GS Compl N/A 1024 1024 256 256 0 0 ANA ON Cornpl N/A N/A 256 16 32 32 N/A qntinuclear antibodies (ANA), granulocyte-specific (GS), organ-non-specific (ON), Complement binding (Compl) N/A not available. Toxoplasma antibody titres IFAT IgG 156256 31 250 31 250 31250 31250 6250 31250 ELSA IgG 143 157 164 153 156 98 106 Dye test 6250 1250 6250 N/A 6250 1250 6250 CF 1:4 1:8 1:2 1:2 N/A 1:2 1:2 Indirect immunofluorescenceantibody test (IFAT), enzyme-linked immunosorbent assay (IIF ELISA), Sabin-Feldrnandye test (Dye), and complement fixation antibody test (CF). N/A not available. Treatment periods Pyrimethamine Sulphadiazine Leucovorin Prednisolone 'Low dose; "increased dose.
I*
**
**
Downloaded by [University of Western Ontario] at 03:34 30 March 2016
Toxoplasma Pericarditis in SLE Patient probably have been attributed to the SLE, had not the pericardial fluid been inoculated into mice with the subsequent growth of T. gondii. Fewer than 20 cases have been described with T. gondii pericarditis (6-15) and few without subsequent myocarditis (7,8, 10, 15), which is the most common presentation of cardiac toxoplasmosis (6-8, 12, 13, 16). Toxoplasmosis affecting the heart may not be suspected ante-mortem (18) and, when found, the diagnosis has been based on serological findings only in 90% of the cases (6, 12-15). The diagnosis may be particularly difficult when the patient has simultaneous rheumatic-mimicking disease, and may be further complicated if the serological results are insecure: false positive IgG and IgM anti-toxoplasma fluorescent-antibodies have been described in patients with ANA antibodies (1 7-19). Symptomatic toxoplasmosis can be caused by both newly acquired infection and reactivation and, especially in the immunologically suppressed, the T. gondii parasite most frequently invades the cerebrum, skeleton or heart muscles (20). Toxoplasma antibodies are found in onethird of the Danish population as a sign of early unrecognized infection (21). Specific IgM antibodies are normally present in primary acute toxoplasmosis, whereas in secondary toxoplasmosis (reactivation), high IgG antibodies are characteristic (2, 3, 22). Magid (22) reported increased toxoplasma IgG antibody in a small group of SLE patients, but no increase in the frequency of IgM antibodies as found in polymyositis-dermatomyositis. Our patient had active disease with a negative IgM test and a high stable IgG titre indicating reactivation although primary infection with loss of IgM antibodies cannot be ruled out. Steroids are believed to cause reactivation in toxoplasmosis (12), but this patient had not been treated with corticosteroids before the serious symptoms of tOXOplaSmosis appeared. Early death in SLE is mostly caused by infections (23, 24); opportunistic infections in particular have been found in steroid-treated SLE patients (23,24). Toxoplasma and polymyositis are linked (22,25-29) and improvements have been reported following treatment for toxoplasmosis in polymyositis (26, 28), but not in SLE. In the present case, however, the SLE-related symptoms disappeared after prolonged and repeated treatment. In SLE, prolonged treatment may be recommended as in other immunodeficient patients. Several reports describe relapses in toxoplasmosis (11, 12, 30), presumably caused by breakdown of tissue cysts that are normally not eradicated by chemotherapy, therefore repeated treatment may be needed (12). The chemotherapy eradicates the trophozoites that cause the symptoms in toxoplasmosis. In the present case SLErelated symptoms as well as ANA antibodies disappeared after prolonged treatment of toxoplasmosis. The decrease in ANA antibodies following toxoplasmosis therapy in the present case is remarkable and has not been described previously. Whether the SLE-like syndrome in this case was actually precipitated by toxoplasmosis may be a subject for discussion. It may be valuable to screen patients with SLE for toxoplasmosis and further elucidate the possible etiological role of toxoplasmosis in SLE.
339
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