A possible novel mechanism of opportunistic infection in systemic lupus erythematosus, based on a case of toxoplasmic encephalopathy

N. Seta, T. Shimizu1, M. Nawata, R. Wada2, K. Mori1, I. Sekigawa, N. Iida, M. Maeda1 and H. Hashimoto3

Department of Medicine,
1 Department of Neurosurgery and
2 Department of Pathology, Juntendo University Izu-Nagaoka Hospital, 1129 Nagaoka, Izu-Nagaoka-cho, Tagata-gun, Shizuoka 410-2295 and
3 Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113, Japan

SIR, Opportunistic infection is common in patients with systemic lupus erythematosus (SLE). In some patients, it is difficult to distinguish between the effect of infection and exacerbation of SLE because both can produce similar symptoms [1]. Toxoplasma infection (toxoplasmosis) is generally benign in healthy persons, with a tendency to chronic latency. However, activation of toxoplasmosis in patients with human immunodeficiency virus (HIV) infection or organ transplantation may have serious consequences. There have been many reports of toxoplasmosis in SLE patients, with conditions such as cerebritis and pericarditis mimicking SLE manifestations [24]. In addition, seropositivity for Toxoplasma gondii is more common among SLE patients than control individuals [57].

In September 1999, a 24-yr-old woman was admitted to our hospital with fever, arthralgia, lymphopenia and proteinuria (3 g/day). She also showed several immune abnormalities [antinuclear antibody (ANA) >x1280, normal (n) <x40; anti-DNA antibody >400 IU/ml, n <10.0; CH50 15.1 U/ml, n=30–40]. The CRP level was 1.3 mg/dl (n<0.3) and the ESR was 80 mm/h. SLE was diagnosed and prednisolone therapy was started from 60 mg/day. This was effective for her SLE-related symptoms and laboratory abnormalities. There were no abnormalities on her brain computed tomography (CT) at admission. After discharge, the steroid dose was gradually tapered to 12.5 mg/day. In September 2000, she was re-admitted to hospital with a right homonymous hemianopsia, transient unconsciousness, and right hemiparesis. Brain CT revealed a giant mass in the left cerebral hemisphere (Fig. 1aGo). On admission, exacerbation of SLE was not suggested by immunologic findings (anti-DNA antibody <2.0 IU/ml, CH50 40.2 U/ml). Her CRP level and ESR were 16.3 mg/dl and 101 mm/h, respectively. Serum IgG antibodies, but not IgM antibodies, for Toxoplasma were positive (IgG 1200 IU/ml, n<5; IgM 0.1 IU/ml, n<0.7), while HIV infection was negative. The tumour was removed and the histological examination revealed an inflammatory mass with necrosis and infiltration of lymphocytes (mainly B cells) and histiocytes (Fig. 1bGo). The lesion was positive for antibodies to T. gondii p30 antigen (Fig. 1cGo). She was diagnosed as having toxoplasmic encephalopathy, probably due to recurrence of chronic latent infection, and was treated with anti-Toxoplasma agents (sulphamonomethoxine and sulphadoxine-pyrimethamine). The steroid dose was increased to 60 mg/day in order to prevent an increase of intracranial pressure though her SLE activity was stable. Her symptoms subsequently improved, so anti-Toxoplasma agents were stopped and her steroid dose was tapered to 40 mg/day. She is now being followed as an outpatient without further exacerbation of SLE and/or toxoplasmosis.



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FIG. 1. (a) CT findings. An arrow indicates the toxoplasmic tumour. (b) Haematoxylin–eosin and (c) anti-Toxoplasma antibody stainings of the inflammatory cerebral tumour (original magnification x200)

 

In our patient, toxoplasmosis occurred when her SLE activity and steroid dosage were relatively low. Similarly, a previous case of toxoplasmic encephalitis also occurred when SLE was inactive [3]. Furthermore, it has been reported that a high titre of Toxoplasma antibody is not correlated with any of the parameters used to monitor SLE, including ANA and anti-DNA antibody, or with the prior treatment [5, 6]. Recent evidence about the relationship between opportunistic infections and HIV infection is interesting with regard to these issues. Several reports have indicated that an increase of CD4+ T cells following intensive antiretroviral therapy (HAART) can induce the development of symptoms related to opportunistic infection such as retinitis in certain HIV-infected patients and that steroids may be effective for suppressing such symptoms [8, 9]. This may result from normalization of the immune response by a recovery of memory CD4+ T-cell numbers and activity against opportunistic pathogens. The CD4+/CD8+ T-cell ratio (CD4/CD8 ratio) generally decreases in patients with SLE as compared with normal individuals and the ratio increases with amelioration of the disease [10]. Although the ratio in our patient was decreased at the onset of SLE (CD4/CD8 ratio 0.13, n=0.6–2.9), it was higher when toxoplasmosis occurred (0.44), reflecting the lower activity of SLE. The importance of immunosuppressive therapy, including steroids, has been noted with regard to the induction of SLE-mediated opportunistic infection [1]. In addition, the findings obtained in HIV-infected patients treated with HAART indicate that normalization of immunity in patients who have inactive SLE and are receiving relatively low doses of steroids and/or immunosuppressants may contribute to the manifestation of opportunistic infections, as the immune system of SLE patients may originally show hyper-responsiveness to non-self as well as self-antigens [11]. A similar course to that observed in our toxoplasmosis patient seems to empirically occur in SLE patients with other opportunistic infections such as cytomegalovirus infection [12]. Investigation of similar cases, especially SLE patients showing a severe decrease of the CD4/CD8 ratio like our patient, is required to clarify this novel concept of the relationship between SLE and opportunistic infections.

Notes

Correspondence to: I. Sekigawa. Back

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Accepted 13 March 2002





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