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Toxoplasma Infection in Systemic Lupus Erythematosus Mimicking Lupus Cerebritis
Case Report
Toxoplasma Infection in Systemic Lupus Erythematosus Mimicking Lupus Cerebritis DORON Z AMIR, MD; MARY AMAR, MD; GAVRIEL GROISMAN, MD; AND P ALTIEL WEINER,
An opportunistic infection is a known, although underdiagnosed, complication of systemic lupus erythematosus (SLE). A 48-year-old woman with a recent diagnosis of SLE was admitted to the hospital because of a fever, confused state, and convulsive episode. Her symptoms were interpreted as being compatible with lupus cerebritis. Treatment with methylprednisolone resulted in a temporary improvement in the patient's condition. Nevertheless, during the next few weeks, her physical and mental condi-
tion deteriorated, and she died of massive pulmonary emboli. An autopsy revealed no signs of lupus cerebritis; however, disseminated cerebral toxoplasmosis was found. Cerebral toxoplasmosis is a rare complication of SLE that may be misdiagnosed as lupus cerebritis. Mayo Clin Proc. 1999;74:575-578 CNS = central nervous system; CRP = C-reacti ve protein; CSF = cerebrospinall1uid; SLE = systemic lupus erythematosus
O
Pportunistic infections are common in patients with systemic lupus erythematosus (SLE) and are a major cause of death . Opportunistic infections involving the central nervous system (CNS) are uncommon , although CryptocOCCUS, I;1 Nocardia? Listeria.' Neisseria meningitidis? and herpesvirus" have been reported as CNS pathogens. Because brain vasculitis is extremely common in patients with SLE, distinguishing an infection of the CNS from vasculitis can be a diagnostic challenge. In such a case, misdiagnosis may be fatal. We describe a patient with SLE and CNS manifestations that were suspected to be part of the primary disease and were treated as such; however, at autopsy, they were found to be cerebral toxoplasmosis.
increased erythrocyte sedimentation rate, anemia (hemoglobin concentration, 8.9 g/dL), and leukopenia (leukocyte count, 2.5 X 109/L). Results of kidney function tests were normal, and no proteinuria was noted. Antinuclear antibody was positive at a titer of I:160, as was anti-doublestranded DNA. Computed tomography of the brain revealed mild dilatation of the lateral and third ventricle s and small calcifications in the basal ganglia (Figure I). Electroencephalography showed general irregular deceleration. The patient was treated with ciprofloxacin because of a suspected urinary tract infection. The diagnosis of SLE was confirmed on the basis of her having 6 of the 1982 revised criteria for the classification of SLE: malar rash, renal disease with heavy proteinuria, oral ulcers, leukopenia, high antinuclear antibody , and positive anti-double-stranded DNA. 7 Because she was confused and had had a convulsive event, lupus cerebritis was suspected, and the dose of methylprednisolone was increased. She had an uneventful recovery within a few days. A week later, the patient was referred to the hospital after another "convulsive event"; she was in a confused state and had a temperature of 37.8°C. A lumbar puncture was performed. Findings on a cerebrospinal fluid (CSF) examination were normal except for an increased protein level ( ISO mg/dL) and oligoclonal bands ofy-globulin. No bacteria were observed, and CSF cultures were negative. Findings on repeated electroencephalography and computed tomograph y of the brain were normal. Corticosteroid treatment was continued because lupus involvement of the CNS was assumed. During the next 2 weeks, the patient's fever disappeared , but her mental and physical condition deteriorated , with apathy and depression , until she became bedridden .
REPORT OFCASE A 48-year-old woman was referred to the hospital in January 1996 because of a high fever, confused state, and convulsive episode. At age 40 years, she had undergone a subtotal thyroidectomy because of a multinodular goiter. A month before the current hospitalization, she had been hospitalized elsewhere for peripheral edema, and nephrotic syndrome was diagnosed. Histologic findings were consistent with membranou s glomerulonephritis, a manifestation of SLE. Methylprednisolone, 60 mg/d, was begun. On admission to our hospital, the patient had a fever (39.3°q, a resting pulse rate of 100/min, a few oral ulcers, and a facial butterfly rash. Initial assessment revealed an From the Department of Medicine A (D.Z., p.w. ) and Institute of Pathology (M.A., G.G.), Hillel Yaffe Medical Center, Hadera, Israel. Dr Zamir is now with Barzilai Medical Center, Ashkelon, Israel. Individual reprints of this article are not available. Address correspondence to Doron Zamir, MD, Herzel 33, Hadera 38421, Israel. Mayo Clin Proc . 1999;74:575-578
MD
575
© 1999 Mayo Foundation / or Medical Education and Research
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
576
Toxoplasma Infection Mimicking Lupus Cerebritis
Figure I. Computed tomographic scan of the brain of a 48-yearold woman, demonstrating calcifications in the basal ganglia.
Deep venous thrombosis developed in her left thigh, and she underwent complete anticoagulation. However, acute respiratory failure occurred and led to her sudden death.
PATHOLOGIC FINDINGS Pathologic examination revealed a massive pulmonary embolism that probably caused our patient's death. Although membranous glomerulonephritis was found , no signs of lupus cerebritis were detected. Sections of the brain disclosed numerous necroinflammatory foci within the basal ganglia and cerebral gray matter. These foci were remarkable for the presence of microcy stic structures that were 18 to 40 11m in diameter. The cysts were filled with minute round basophilic structures consistent with bradyzoites of Toxoplasma (Figure 2). Plasma cells and lymphocytes were observed surrounding the cysts, inflammatory cells, and macrophages. Blood vessels showed perivascular lymphoid infiltration, endothelial swelling, and thrombosis. Immunohistochemical staining for Toxoplasma was positive in the cysts, an outcome confirming the histological diagnosis (Figure 3). DISCUSSION Toxoplasma gondii infection is a common disease worldwide. Acute infection in an immunocompetent host is usually asymptomatic.
Mayo Clin Proc, June 1999, Vol 74
The 3 major pathologic pattern s of cerebral toxopla smosis are diffuse encephalopathy with or without seizures, meningoencephalitis, and singular or large progre ssive mass lesions.t Increased protein and increased IgG levels in the CSF, as in our patient, are the most common abnormalities in toxoplasmosis of the CNS. In the current case, the 2 nonspecific clues for toxoplasmosis were calcifications in the basal ganglia and a positive serum C-reactive protein (CRP).1 Basal ganglia calcifications (Figure 1) could lead to suspected toxoplasmosis."!" Other causes of basal ganglia calcifications include cytomegalovirus, rubella, herpes simplex, hypoparathyroidism, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, Cockayne syndrome, Wilson disease, Fahr syndrome, anoxia, lead poisoning, carbon monoxide poisoning , and familial and idiopathic causes." In toxopla smosis, a contrast-enhanced computed tomographic scan usually shows solitary or multiple ring-enhancing lesion s with peripheral edema, II a pattern not found in our patient. Healed lesions show focal areas of malacia, which may calcify." The absence of any other lesions in the brain of our patient suggests that the calcifications were benign and were not related to toxoplasmosis. A quantitative serum CRP determination, probably with a finding of high levels, could be a clue for such a superinfection. Such CRP detection in serum during an acute phase of CNS infection is diagnostically important because a CRP increase suggests a purulent process" and may be used for determining optimal duration of antibiotic treatment of meningitis." However, CRP levels in CSF are much more accurate. Stearman and Southgate" reported that a CRP concentration of 100 ng/mL had a sensitivity of 87% for bacterial meningitis. The diagnosis of SLE was based on the 1982 revised criteria for the classification of SLE7of which our patient had 6. CNS disease in SLE may be expressed either by organic psychosis or by seizures. IS Seizures are usually of the grand mal type, but chorea, petit mal seizures, jacksonian epilepsy , and temporal lobe seizures may also occur, usually during the beginning of the acute stage . Organic syndromes are characterized by impairment of orientation and perception , loss of ability to calculate, memory loss, and psychosis. Our patient had general convulsions and signs of organic brain disease , both typical manifestations of lupus cerebritis; thus, we assumed that she had lupus cerebritis. In a study involving 37 patients with neural lupus, Feinglass et aP6 detected CSF abnormalities in 32% of cases of neuropsychiatric illness . Demonstration of tachyzoites in tissue sections or smears of body fluids establishes the diagnosis of acute Toxoplasma infection. I? Detecting tachyzoites in stained tissue sections is often
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Toxoplasma Infection Mimicking Lupus Cerebritis
Mayo Clin Proc, June 1999, Vol 74
577
Figure 2. Brain tissue showing inflammatory cells and several cystsfilled withToxoplasma (hematoxylin-eosin, original magnification x400).
Figure 3. Immunohistochemical staining for Toxoplasma shows strong reactivity within parasitic cysts (immunoperoxidase stain, original magnification x400).
difficult." Fluorescent antibody staining may be a useful, although nonspecific, method. IS The peroxidase-antiperoxidase technique with the use of antisera to Toxoplasma has proved to be both sensitive and specific in revealing the organism in the CNS. IS Other methods for detecting Toxoplasma in body fluids or tissues include enzyme-linked immunosorbent assay, fluorescein-labeled monoclonal antibodies to Toxoplasma for touch preparations of specimens and rapid electron microscopy, polymerase chain reaction examination, and Wright-Giemsastained slides of sediment of CSF or smears of biopsy tissue. In the immunocompromised host, toxoplasmosis is an important cause of morbidity and mortality." Few reports of toxoplasmosis complicating SLE have been reported in the medical literature, and this emphasizes the difficulty in establishing the diagnosis. Noel and associates" found high titers of Toxoplasma antibodies to be more common in patients with SLE than in healthy control subjects, and therefore test results should be interpreted carefully. Wechsler and colleagues" described 4 cases of toxoplasmosis in patients with SLE. They also emphasized the diagnostic problems and recommended serologic analysis for toxoplasmosis before initiation of and during treatment with corticosteroids. Deleze et aF2 described toxoplasmosis of the brain that resembled lupus cerebritis and thus created a diagnostic challenge in a patient with SLE.
primary symptoms are typical for SLE: psychosis and general convulsions. Nonetheless, a CNS infection must always be considered. Because laboratory diagnosis of lupus cerebritis is difficult and computed tomography is frequently nonspecific, other methods such as lumbar puncture should be performed when CNS symptoms are present. Magnetic resonance imaging is the most sensitive radiographic technique to detect changes of SLE and may be helpful in diagnosing lupus cerebritis. Both lumbar puncture and magnetic resonance imaging, however, may fail to identify CNS infection in a patient with SLE. Because the clinical manifestations of Toxoplasma infection may be protean and nonspecific, it must be carefully considered in the differential diagnosis of lupus cerebritis. Either histological diagnosis or serologic tests for demonstration of Toxoplasma antigen or specific antibody in both blood and CSF should be performed when lupus cerebritis does not abate with conventional immunosuppressive therapy.
CONCLUSION The diagnosis of CNS infection in SLE may be difficult. A patient with SLE and neurologic manifestations is naturally suspected to have lupus cerebritis, especially when the
REFERENCES 1.
2. 3. 4. 5.
Mok CC, Lau CS, Yuen KY. Cryptococcal meningitis presenting concurrently with systemic lupus erythematosus. Clin Exp Rheumatol. 1998;16:169-171. Huang J-L, Chou M-L, Hung I-J, Hsieh K-H. Multiple cryptococcal brain abscesses in systemic lupus erythematosus [letter]. Br J Rheumatol. 1996;35:1334-1335. Mok CC, Lau CS, Poon SP. Ptimary nocardial meningitis in systemic lupus erythematosus. Br J Rheumatol. 1995;34:178-181. Kraus A, Cabral AR, Sifuentes-Osornio J, Alarcon-Segovia D. Listeriosis in patients with connective tissue diseases. J Rheumatol. 1994;21:635-638. Fijen CA, Kuijper EJ, Tjia HG, Daha MR, Dankert J. Complement deficiency predisposes for meningitis due to nongroupable meningococci and Neisseria-related bacteria. Clin Infect Dis. 1994;18: 780-784.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
578
6.
7. 8. 9. 10. 11.
12.
13. 14. 15.
Toxoplasma Infection Mimicking Lupus Cerebritis
Feinman MC, Friedberg MA, Schwartz JC, et al. Central nervous system herpesvirus infection in systemic lupus erythematosus: diagnosis by endoretinal biopsy. J Rheumatol. 1993;20:10581061. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25:1271-1277. Remington J, Desmonts G. Toxoplasmosis. In: Remington JS, Klein JO, eds. Infectious Diseases ofthe Fetus and Newborn Infant. 3rd ed. Philadelphia, Pa: WB Saunders Co; 1990:89-95. Castillo M. Neuroradiology Companion: Methods, Guidelines, and Imaging Fundamentals. Philadelphia, Pa: JB Lippincott; 1995:144. Chapman S, Nakielny R. Aids to Radiological Differential Diagnosis. 3rd ed. London, England: WB Saunders Co; 1995:407-408. Post MJ, Chan JC, Hensley GT, Hoffman TA, Moskowitz LB, Lippmann S. Toxoplasma encephalitis in Haitian adults with acquired immunodeficiency syndrome: a clinical-pathologic-Cf correlation. AiR Am J Roentgenol. 1983;140:861-868. Przyjalkowski W, Lipowski D, Kolasa T, Issa E, Janeczko J. Creactive protein (CRP) and its significance in purulent meningitis [published correction appears in Neurol Neurochir Pol. 1996;30: 177]. Neurol Neurochir Pol. 1995;29:687-693. Nouira S, Elatrous S, Mustapha R, et al. C-reactive protein in bacterial meningitis in adults. Presse Med. 1993;22:153-156. Stearman M, Southgate HJ. The use of cytokine and C-reactive protein measurements in cerebrospinal fluid during acute infective meningitis. Ann Clin Biochem. 1994;31:255-261. Rothfield NF. Systemic lupus erythematosis: clinical aspects and treatment. In: McCarty DJ, Koopman WJ, eds. Arthritis and
Mayo Clin Proc, June 1999, Vol 74
16.
17.
18. 19.
20. 21.
22.
Allied Conditions: A Textbook of Rheumatology. Vol 2. 12th ed. Philadelphia, Pa: Lea & Febiger; 1993:1155-1177. Feinglass EJ, Arnett FC, Dorsch CA, Zizic TM, Stevens MB. Neuropsychiatric manifestations of systemic lupus erythematosus: diagnosis, clinical spectrum, and relationship to other features of the disease. Medicine (Baltimore). 1976;55:323-339. Beaman MH, McCabeRE, Wong S-Y, Remington JS. Toxoplasma gondii. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. Vol 2. 4th ed. New York, NY: Churchill Livingstone; 1995:24552475. Frenkel JK, Piekarski G. The demonstration of toxoplasma and other organisms by immunofluorescence: a pitfall [editorial]. J Infect Dis. 1978;138:265-266. Conley FK, Jenkins KA, Remington JS. Toxoplasma gondii infection of the central nervous system: use of the peroxidase-antiperoxidase method to demonstrate toxoplasma in formalin fixed, paraffin embedded tissue sections. Hum Pathol. 1981;12:690-698. Noel I, Balfour AH, Wilcox MH. Toxoplasma infection and systemic lupus erythematosus: analysis of the serological response by immunoblotting. J Clin Pathol. 1993;46:628-632. Wechsler B, Le Thi Huong Du, Vignes B, Piette JC, Chomette G, Godeau P. Toxoplasmosis and lupus: a review of the literature apropos of 4 cases [in French]. Ann Med Interne (Paris). 1986;137: 324-330. Deleze M, Mintz G, del Carmen Mejia M. Toxoplasma gondii encephalitis in systemic lupus erythematosus: a neglected cause of treatable nervous system infection. J Rheumatol. 1985;12:994996.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Toxoplasma Infection in Systemic Lupus Erythematosus Mimicking Lupus Cerebritis DORON Z AMIR, MD; MARY AMAR, MD; GAVRIEL GROISMAN, MD; AND P ALTIEL WEINER,
An opportunistic infection is a known, although underdiagnosed, complication of systemic lupus erythematosus (SLE). A 48-year-old woman with a recent diagnosis of SLE was admitted to the hospital because of a fever, confused state, and convulsive episode. Her symptoms were interpreted as being compatible with lupus cerebritis. Treatment with methylprednisolone resulted in a temporary improvement in the patient's condition. Nevertheless, during the next few weeks, her physical and mental condi-
tion deteriorated, and she died of massive pulmonary emboli. An autopsy revealed no signs of lupus cerebritis; however, disseminated cerebral toxoplasmosis was found. Cerebral toxoplasmosis is a rare complication of SLE that may be misdiagnosed as lupus cerebritis. Mayo Clin Proc. 1999;74:575-578 CNS = central nervous system; CRP = C-reacti ve protein; CSF = cerebrospinall1uid; SLE = systemic lupus erythematosus
O
Pportunistic infections are common in patients with systemic lupus erythematosus (SLE) and are a major cause of death . Opportunistic infections involving the central nervous system (CNS) are uncommon , although CryptocOCCUS, I;1 Nocardia? Listeria.' Neisseria meningitidis? and herpesvirus" have been reported as CNS pathogens. Because brain vasculitis is extremely common in patients with SLE, distinguishing an infection of the CNS from vasculitis can be a diagnostic challenge. In such a case, misdiagnosis may be fatal. We describe a patient with SLE and CNS manifestations that were suspected to be part of the primary disease and were treated as such; however, at autopsy, they were found to be cerebral toxoplasmosis.
increased erythrocyte sedimentation rate, anemia (hemoglobin concentration, 8.9 g/dL), and leukopenia (leukocyte count, 2.5 X 109/L). Results of kidney function tests were normal, and no proteinuria was noted. Antinuclear antibody was positive at a titer of I:160, as was anti-doublestranded DNA. Computed tomography of the brain revealed mild dilatation of the lateral and third ventricle s and small calcifications in the basal ganglia (Figure I). Electroencephalography showed general irregular deceleration. The patient was treated with ciprofloxacin because of a suspected urinary tract infection. The diagnosis of SLE was confirmed on the basis of her having 6 of the 1982 revised criteria for the classification of SLE: malar rash, renal disease with heavy proteinuria, oral ulcers, leukopenia, high antinuclear antibody , and positive anti-double-stranded DNA. 7 Because she was confused and had had a convulsive event, lupus cerebritis was suspected, and the dose of methylprednisolone was increased. She had an uneventful recovery within a few days. A week later, the patient was referred to the hospital after another "convulsive event"; she was in a confused state and had a temperature of 37.8°C. A lumbar puncture was performed. Findings on a cerebrospinal fluid (CSF) examination were normal except for an increased protein level ( ISO mg/dL) and oligoclonal bands ofy-globulin. No bacteria were observed, and CSF cultures were negative. Findings on repeated electroencephalography and computed tomograph y of the brain were normal. Corticosteroid treatment was continued because lupus involvement of the CNS was assumed. During the next 2 weeks, the patient's fever disappeared , but her mental and physical condition deteriorated , with apathy and depression , until she became bedridden .
REPORT OFCASE A 48-year-old woman was referred to the hospital in January 1996 because of a high fever, confused state, and convulsive episode. At age 40 years, she had undergone a subtotal thyroidectomy because of a multinodular goiter. A month before the current hospitalization, she had been hospitalized elsewhere for peripheral edema, and nephrotic syndrome was diagnosed. Histologic findings were consistent with membranou s glomerulonephritis, a manifestation of SLE. Methylprednisolone, 60 mg/d, was begun. On admission to our hospital, the patient had a fever (39.3°q, a resting pulse rate of 100/min, a few oral ulcers, and a facial butterfly rash. Initial assessment revealed an From the Department of Medicine A (D.Z., p.w. ) and Institute of Pathology (M.A., G.G.), Hillel Yaffe Medical Center, Hadera, Israel. Dr Zamir is now with Barzilai Medical Center, Ashkelon, Israel. Individual reprints of this article are not available. Address correspondence to Doron Zamir, MD, Herzel 33, Hadera 38421, Israel. Mayo Clin Proc . 1999;74:575-578
MD
575
© 1999 Mayo Foundation / or Medical Education and Research
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
576
Toxoplasma Infection Mimicking Lupus Cerebritis
Figure I. Computed tomographic scan of the brain of a 48-yearold woman, demonstrating calcifications in the basal ganglia.
Deep venous thrombosis developed in her left thigh, and she underwent complete anticoagulation. However, acute respiratory failure occurred and led to her sudden death.
PATHOLOGIC FINDINGS Pathologic examination revealed a massive pulmonary embolism that probably caused our patient's death. Although membranous glomerulonephritis was found , no signs of lupus cerebritis were detected. Sections of the brain disclosed numerous necroinflammatory foci within the basal ganglia and cerebral gray matter. These foci were remarkable for the presence of microcy stic structures that were 18 to 40 11m in diameter. The cysts were filled with minute round basophilic structures consistent with bradyzoites of Toxoplasma (Figure 2). Plasma cells and lymphocytes were observed surrounding the cysts, inflammatory cells, and macrophages. Blood vessels showed perivascular lymphoid infiltration, endothelial swelling, and thrombosis. Immunohistochemical staining for Toxoplasma was positive in the cysts, an outcome confirming the histological diagnosis (Figure 3). DISCUSSION Toxoplasma gondii infection is a common disease worldwide. Acute infection in an immunocompetent host is usually asymptomatic.
Mayo Clin Proc, June 1999, Vol 74
The 3 major pathologic pattern s of cerebral toxopla smosis are diffuse encephalopathy with or without seizures, meningoencephalitis, and singular or large progre ssive mass lesions.t Increased protein and increased IgG levels in the CSF, as in our patient, are the most common abnormalities in toxoplasmosis of the CNS. In the current case, the 2 nonspecific clues for toxoplasmosis were calcifications in the basal ganglia and a positive serum C-reactive protein (CRP).1 Basal ganglia calcifications (Figure 1) could lead to suspected toxoplasmosis."!" Other causes of basal ganglia calcifications include cytomegalovirus, rubella, herpes simplex, hypoparathyroidism, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, Cockayne syndrome, Wilson disease, Fahr syndrome, anoxia, lead poisoning, carbon monoxide poisoning , and familial and idiopathic causes." In toxopla smosis, a contrast-enhanced computed tomographic scan usually shows solitary or multiple ring-enhancing lesion s with peripheral edema, II a pattern not found in our patient. Healed lesions show focal areas of malacia, which may calcify." The absence of any other lesions in the brain of our patient suggests that the calcifications were benign and were not related to toxoplasmosis. A quantitative serum CRP determination, probably with a finding of high levels, could be a clue for such a superinfection. Such CRP detection in serum during an acute phase of CNS infection is diagnostically important because a CRP increase suggests a purulent process" and may be used for determining optimal duration of antibiotic treatment of meningitis." However, CRP levels in CSF are much more accurate. Stearman and Southgate" reported that a CRP concentration of 100 ng/mL had a sensitivity of 87% for bacterial meningitis. The diagnosis of SLE was based on the 1982 revised criteria for the classification of SLE7of which our patient had 6. CNS disease in SLE may be expressed either by organic psychosis or by seizures. IS Seizures are usually of the grand mal type, but chorea, petit mal seizures, jacksonian epilepsy , and temporal lobe seizures may also occur, usually during the beginning of the acute stage . Organic syndromes are characterized by impairment of orientation and perception , loss of ability to calculate, memory loss, and psychosis. Our patient had general convulsions and signs of organic brain disease , both typical manifestations of lupus cerebritis; thus, we assumed that she had lupus cerebritis. In a study involving 37 patients with neural lupus, Feinglass et aP6 detected CSF abnormalities in 32% of cases of neuropsychiatric illness . Demonstration of tachyzoites in tissue sections or smears of body fluids establishes the diagnosis of acute Toxoplasma infection. I? Detecting tachyzoites in stained tissue sections is often
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Toxoplasma Infection Mimicking Lupus Cerebritis
Mayo Clin Proc, June 1999, Vol 74
577
Figure 2. Brain tissue showing inflammatory cells and several cystsfilled withToxoplasma (hematoxylin-eosin, original magnification x400).
Figure 3. Immunohistochemical staining for Toxoplasma shows strong reactivity within parasitic cysts (immunoperoxidase stain, original magnification x400).
difficult." Fluorescent antibody staining may be a useful, although nonspecific, method. IS The peroxidase-antiperoxidase technique with the use of antisera to Toxoplasma has proved to be both sensitive and specific in revealing the organism in the CNS. IS Other methods for detecting Toxoplasma in body fluids or tissues include enzyme-linked immunosorbent assay, fluorescein-labeled monoclonal antibodies to Toxoplasma for touch preparations of specimens and rapid electron microscopy, polymerase chain reaction examination, and Wright-Giemsastained slides of sediment of CSF or smears of biopsy tissue. In the immunocompromised host, toxoplasmosis is an important cause of morbidity and mortality." Few reports of toxoplasmosis complicating SLE have been reported in the medical literature, and this emphasizes the difficulty in establishing the diagnosis. Noel and associates" found high titers of Toxoplasma antibodies to be more common in patients with SLE than in healthy control subjects, and therefore test results should be interpreted carefully. Wechsler and colleagues" described 4 cases of toxoplasmosis in patients with SLE. They also emphasized the diagnostic problems and recommended serologic analysis for toxoplasmosis before initiation of and during treatment with corticosteroids. Deleze et aF2 described toxoplasmosis of the brain that resembled lupus cerebritis and thus created a diagnostic challenge in a patient with SLE.
primary symptoms are typical for SLE: psychosis and general convulsions. Nonetheless, a CNS infection must always be considered. Because laboratory diagnosis of lupus cerebritis is difficult and computed tomography is frequently nonspecific, other methods such as lumbar puncture should be performed when CNS symptoms are present. Magnetic resonance imaging is the most sensitive radiographic technique to detect changes of SLE and may be helpful in diagnosing lupus cerebritis. Both lumbar puncture and magnetic resonance imaging, however, may fail to identify CNS infection in a patient with SLE. Because the clinical manifestations of Toxoplasma infection may be protean and nonspecific, it must be carefully considered in the differential diagnosis of lupus cerebritis. Either histological diagnosis or serologic tests for demonstration of Toxoplasma antigen or specific antibody in both blood and CSF should be performed when lupus cerebritis does not abate with conventional immunosuppressive therapy.
CONCLUSION The diagnosis of CNS infection in SLE may be difficult. A patient with SLE and neurologic manifestations is naturally suspected to have lupus cerebritis, especially when the
REFERENCES 1.
2. 3. 4. 5.
Mok CC, Lau CS, Yuen KY. Cryptococcal meningitis presenting concurrently with systemic lupus erythematosus. Clin Exp Rheumatol. 1998;16:169-171. Huang J-L, Chou M-L, Hung I-J, Hsieh K-H. Multiple cryptococcal brain abscesses in systemic lupus erythematosus [letter]. Br J Rheumatol. 1996;35:1334-1335. Mok CC, Lau CS, Poon SP. Ptimary nocardial meningitis in systemic lupus erythematosus. Br J Rheumatol. 1995;34:178-181. Kraus A, Cabral AR, Sifuentes-Osornio J, Alarcon-Segovia D. Listeriosis in patients with connective tissue diseases. J Rheumatol. 1994;21:635-638. Fijen CA, Kuijper EJ, Tjia HG, Daha MR, Dankert J. Complement deficiency predisposes for meningitis due to nongroupable meningococci and Neisseria-related bacteria. Clin Infect Dis. 1994;18: 780-784.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
578
6.
7. 8. 9. 10. 11.
12.
13. 14. 15.
Toxoplasma Infection Mimicking Lupus Cerebritis
Feinman MC, Friedberg MA, Schwartz JC, et al. Central nervous system herpesvirus infection in systemic lupus erythematosus: diagnosis by endoretinal biopsy. J Rheumatol. 1993;20:10581061. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25:1271-1277. Remington J, Desmonts G. Toxoplasmosis. In: Remington JS, Klein JO, eds. Infectious Diseases ofthe Fetus and Newborn Infant. 3rd ed. Philadelphia, Pa: WB Saunders Co; 1990:89-95. Castillo M. Neuroradiology Companion: Methods, Guidelines, and Imaging Fundamentals. Philadelphia, Pa: JB Lippincott; 1995:144. Chapman S, Nakielny R. Aids to Radiological Differential Diagnosis. 3rd ed. London, England: WB Saunders Co; 1995:407-408. Post MJ, Chan JC, Hensley GT, Hoffman TA, Moskowitz LB, Lippmann S. Toxoplasma encephalitis in Haitian adults with acquired immunodeficiency syndrome: a clinical-pathologic-Cf correlation. AiR Am J Roentgenol. 1983;140:861-868. Przyjalkowski W, Lipowski D, Kolasa T, Issa E, Janeczko J. Creactive protein (CRP) and its significance in purulent meningitis [published correction appears in Neurol Neurochir Pol. 1996;30: 177]. Neurol Neurochir Pol. 1995;29:687-693. Nouira S, Elatrous S, Mustapha R, et al. C-reactive protein in bacterial meningitis in adults. Presse Med. 1993;22:153-156. Stearman M, Southgate HJ. The use of cytokine and C-reactive protein measurements in cerebrospinal fluid during acute infective meningitis. Ann Clin Biochem. 1994;31:255-261. Rothfield NF. Systemic lupus erythematosis: clinical aspects and treatment. In: McCarty DJ, Koopman WJ, eds. Arthritis and
Mayo Clin Proc, June 1999, Vol 74
16.
17.
18. 19.
20. 21.
22.
Allied Conditions: A Textbook of Rheumatology. Vol 2. 12th ed. Philadelphia, Pa: Lea & Febiger; 1993:1155-1177. Feinglass EJ, Arnett FC, Dorsch CA, Zizic TM, Stevens MB. Neuropsychiatric manifestations of systemic lupus erythematosus: diagnosis, clinical spectrum, and relationship to other features of the disease. Medicine (Baltimore). 1976;55:323-339. Beaman MH, McCabeRE, Wong S-Y, Remington JS. Toxoplasma gondii. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. Vol 2. 4th ed. New York, NY: Churchill Livingstone; 1995:24552475. Frenkel JK, Piekarski G. The demonstration of toxoplasma and other organisms by immunofluorescence: a pitfall [editorial]. J Infect Dis. 1978;138:265-266. Conley FK, Jenkins KA, Remington JS. Toxoplasma gondii infection of the central nervous system: use of the peroxidase-antiperoxidase method to demonstrate toxoplasma in formalin fixed, paraffin embedded tissue sections. Hum Pathol. 1981;12:690-698. Noel I, Balfour AH, Wilcox MH. Toxoplasma infection and systemic lupus erythematosus: analysis of the serological response by immunoblotting. J Clin Pathol. 1993;46:628-632. Wechsler B, Le Thi Huong Du, Vignes B, Piette JC, Chomette G, Godeau P. Toxoplasmosis and lupus: a review of the literature apropos of 4 cases [in French]. Ann Med Interne (Paris). 1986;137: 324-330. Deleze M, Mintz G, del Carmen Mejia M. Toxoplasma gondii encephalitis in systemic lupus erythematosus: a neglected cause of treatable nervous system infection. J Rheumatol. 1985;12:994996.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.