□
CASE REPORT
□
Cerebral Toxoplasmosis in a Patient on Methotrexate and Infliximab for Rheumatoid Arthritis Swaroopa Pulivarthi 1, Rwoof A. Reshi 2, Carl T. McGary 3 and Murali Krishna Gurram 4
Abstract Cerebral toxoplasmosis is a rare disease predominantly found in immunocompromised hosts. However, cerebral toxoplasmosis has not been frequently described in association with the use of immunosuppressive medications. We herein report a case of cerebral toxoplasmosis in a 76-year-old Caucasian woman on methotrexate and infliximab for rheumatoid arthritis. The patient presented with right facial droop, slurred speech and difficulty walking. In addition to receiving methotrexate and infliximab and owning a cat, she had no other obvious risk factors. Imaging studies were not conclusive; however, brain biopsy confirmed the diagnosis. Serology was positive for anti-toxoplasma immunoglobulin G. Cerebral toxoplasmosis should be included in the differential diagnosis of patients under immunosuppressive medication who present with neurological manifestations. Key words: cerebral toxoplasmosis, rheumatoid arthritis, immunosuppressive medications (Intern Med 54: 1433-1436, 2015) (DOI: 10.2169/internalmedicine.54.3977)
Introduction Toxoplasmosis is usually the result of the reactivation of latent infection by Toxoplasma gondii in patients with immune suppression, such as that due to acquired immunodeficiency syndrome (AIDS), organ transplantation, hematopoietic stem cell transplantation, or cancer chemotherapy (1, 2). The difficulty in making the clinical diagnosis of cerebral toxoplasmosis is attributed to the lack of pathognomonic clinical or radiological features (1). In immunocompetent asymptomatic individuals, latent infection has been reported to be associated with psychiatric diseases, such as schizophrenia, inferring its subtle neurological effects (1). We herein describe a patient diagnosed with cerebral toxoplasmosis following treatment with methotrexate and infliximab for rheumatoid arthritis (RA).
Case Report A 76-year-old Caucasian woman presented to the emergency room with right facial droop, slurred speech and diffi-
culty walking. She had noticed progressively worsening right-sided weakness, slurred speech and right facial droop for one week. Two days prior to presentation, she had been noted to be forgetful and experienced difficulty in finding words. Her past medical history included diabetes mellitus, hypertension, RA, chronic kidney disease and chronic stable thrombocytopenia. While her family history was noncontributory, she had a pet cat of unknown age and duration. She was receiving chronic treatment with high-dose methotrexate (17.5 mg once every week), which had been tapered to 2.5 mg per week. She was also receiving infliximab (Remicade; 7.5 mg/kg every 6-8 weeks), with the last infusion being six weeks before presentation. On a neurological examination, all cranial nerves were intact, with the exception of right central facial palsy. Her motor strength was 5/5 in the left extremities and 4/5 in the right extremities, with normal tone and sensation. She exhibited dysmetria and moderate hyperreflexia on the right side. A complete blood count revealed thrombocytopenia, with a platelet count of 94,000/μL, white blood cell count of 5,000/μL, hemoglobin level of 11.4 g/dL and mean corpuscular volume of 91fL. Blood chemistry showed an albumin
１
Research Department, HealthEast Care System, USA, ２Department of Neurology, University of Minnesota, USA, ３Department of Pathology, HealthEast Care System, USA and ４Department of Internal Medicine, HealthEast Care System, USA Received for publication August 25, 2014; Accepted for publication October 5, 2014 Correspondence to Dr. Murali Krishna Gurram, [email protected]
1433
Intern Med 54: 1433-1436, 2015
DOI: 10.2169/internalmedicine.54.3977
rologically stable and was discharged to the transitional care unit.
Discussion
Figure 1. CT head demonstrated extensive vasogenic edema involving the left cerebrum and an ill-defined area of decreased attenuation near the posterior aspect of the left putamen. There was a mass effect on the left lateral ventricle, with approximately 0.4 cm of subfalcine herniation to the right (arrow).
level of 2.7 g/dL, creatinine level of 1.06 mg/dL, International Normalized Ratio (INR) of 1.17, glucose level of 145 mg/mL, glycosylated hemoglobin level of 6.7 %, aspartate aminotransferase (AST) level of 40 IU/L and alanine aminotransferase (ALT) level of 16 IU/L. Head CT (Fig. 1) demonstrated extensive vasogenic edema involving the left cerebrum and an ill-defined area of decreased attenuation near the posterior aspect of the left putamen. In addition, there was a mass effect on the left lateral ventricle, with an approximate 0.4-cm shift to the right. MRI of the brain without (Fig. 2A) and with (Fig. 2B) contrast, as well as a coronal section (Fig. 2C) and flair image (Fig. 2D), demonstrated a 2.9-cm irregular lesion centered in the left putamen with thin peripheral enhancement and a number of smaller punctate cortical enhancing lesions involving the brain parenchyma. The patient was started on treatment with dexamethasone and levetiracetam. A lumbar puncture was not performed due to the significant amount of edema and mass effect. CT scans of the chest, abdomen and pelvis were negative for primary malignancy, and a bone scan of the whole body revealed no evidence of primary or metastatic disease. A left thalamic stereotactic brain biopsy was performed for tissue diagnosis. The pathological examination (squash preparation) showed extensive necrosis and inflammation with lymphocytes and plasma cells, consistent with the presence of an abscess, with an encysted organism (trophozoites) indicating toxoplasmosis (Fig. 3). The tissue sections were stained with GMS silver stain and found to be negative for fungi. HIV antigen and antibody screening was negative. Toxoplasma immunoglobulin M was negative (900 IU/mL). Due to the patient’s sulfa allergy, she was started on therapy with once daily pyrimethamine (75 mg), clindamycin (600 mg) and leucovorin (25 mg). After the procedure, she remained neu-
Toxoplasma gondii is a ubiquitous obligate intracellular protozoan that causes latent infection in 30% of the world’s population (1). In most infected individuals, the organism remains dormant, and clinical reactivation is often associated with host immunosuppression. The usual presentation in immunosuppressed patients includes meningoencephalitis, pneumonitis and disseminated infection (1). Focal neurological deficits are also common in immunocompromised patients (3). In a retrospective review of 85 AIDS patients with cerebral toxoplasmosis (4), the most frequent clinical manifestations were headache (89%), hemiparesis (88%), fever (54%) and seizures (45%). As expected, patients with cortical lesions were found to be at greater risk of seizures than those with white matter disease (4). Ten (8.5%) patients did not present with any focal neurological signs (4). Meanwhile, the oculomotor nerve (66%) was the most frequently involved cranial nerve among the 14% of patients with cranial nerve deficits (4). The Centers for Disease Control and Prevention (CDC) has proposed four criteria for establishing the diagnosis of cerebral toxoplasmosis, including the proper clinical setting, consistent findings on imaging, positive serological studies and a therapeutic response to treatment (5). Of late, the use of immunosuppressive medications, such as adalimumab, rituximab, etc., has increased significantly. A Cochrane database systematic review was carried out in 2011 to compare the rates of serious adverse events, including tuberculosis reactivation, in all tumor necrosis factor (TNF) blocker trials published to date (6). Tuberculosis reactivation exhibited an odds ratio of 4.68 with a 95 CI of 1.18-18.60 (6). Although toxoplasmosis was not compared in this review, to the best of our knowledge, only a few cases of toxoplasmosis associated with immunosuppressive agents have been reported. Nardone et al. reported the development of cerebral toxoplasmosis in a patient on adalimumab for RA (7). In addition, Lassoued et al., who documented two cases of toxoplasmic chorioretinitis following anti-TNF alpha treatment (with adalimumab, infliximab and etanercept) for RA, suggested measuring the toxoplasma antibody titer prior to the initiation of anti-TNF alpha therapy (8). Cerebral toxoplasmosis associated with immunosuppression medications have also been reported by Safa G. (9) and Nakamura T. (10). Young et al. reported a case of cerebral toxoplasmosis in a patient receiving multiple immunosuppressive medications, including methotrexate, infliximab, prednisone and leflunomide, for RA (11). Methotrexate obviously causes immunosuppression; however, there is only one reported case of toxoplasmosis associated with the use of methotrexate in an otherwise immunocompetent patient. Horiuchi et al. reported this association in a 60-year-old woman with a history of RA who had
1434
Intern Med 54: 1433-1436, 2015
DOI: 10.2169/internalmedicine.54.3977
Figure 2. MRI of the brain without (2A) and with contrast (2B), as well as a coronal section (2C) and flair image (2D), demonstrated a 2.9-cm irregular lesion (red arrow) centered in the left putamen with thin peripheral enhancement and a number of smaller punctate cortical enhancing lesions involving the brain parenchyma, mostly in cortical locations, suggesting metastases.
Figure 3. Squash preparation slides showed extensive necrosis and inflammation with lymphocytes and plasma cells, consistent with an abscess, and an encysted organism (trophozoites-arrow), indicating toxoplasmosis.
been on treatment with methotrexate and prednisolone for 20 years prior to presentation (12). She exhibited multiple brain lesions involving the bilateral globus pallidus, right
thalamus and left dentate nucleus of the cerebellum (12). CT images usually reveal either hypodense lesions with ring enhancement or nodular enhancing lesions (13). T2-
1435
Intern Med 54: 1433-1436, 2015
DOI: 10.2169/internalmedicine.54.3977
weighted MRI images show multiple basal ganglia lesions with high-intensity signals or the “eccentric target sign,” a small nodule in a ring-enhancing lesion, or the “concentric target sign,” with concentric alternating zones of hypo- and hyper-intensity (13, 14). If the diagnosis is in doubt, a biopsy is recommended, particularly to rule out other CNS pathologies (15). The most frequent therapy for cerebral toxoplasmosis is pyrimethamine and sulfadiazine along with folinic acid to reduce hematological complications associated with pyrimethamine (13). Other alternative drugs used for the treatment of cerebral toxoplasmosis include clarithromycin and pyrimethamine, sulfamethoxazole and trimethoprim, and clindamycin and pyrimethamine for patients allergic to sulfa drugs (13). The most common duration of therapy is six weeks (13). Cerebral toxoplasmosis was successfully treated with intravenous clindamycin (600 mg thrice daily) for three weeks in a 30-year-old AIDS patient with a history of sulfonamide allergy, with symptomatic improvement noted within two days and resolution of the lesion on repeat head CT at three weeks (16). Cerebral toxoplasmosis should be considered in the differential diagnosis of patients receiving immunosuppressive medications, such as methotrexate, rituximab, adalimumab and infliximab, who present with neurological manifestations. Although there is no evidence for testing patients for toxoplasmosis prior to treatment or primary prophylaxis if positive, this strategy may be considered on a case-by-case basis weighing the risks and benefits carefully. Knowledge of the patient’s seropositive status aids close monitoring and the ability to provide early treatment, if necessary. Further data are needed regarding the risks and benefits of pretesting and primary prophylaxis for this potentially life-threatening disease. The authors state that they have no Conflict of Interest (COI).
References
2. Hakko E, Ozkan HA, Karaman K, et al. Analysis of cerebral toxoplasmosis in a series of 170 allogeneic hematopoietic stem cell transplant patients. Transpl Infect Dis 15: 575-580, 2013. 3. Silva LA, Vieira RA, Serafini LN, et al. Toxoplasmosis of the central nervous system in a patient without immunosuppression: case report. Rev Soc Bras Med Trop 34: 487-490, 2001 (in Portuguese, Abstract in English). 4. Correia Cda C, Melo HR, Costa VM, et al. Features to validate cerebral toxoplasmosis. Rev Soc Bras Med Trop 46: 373-376, 2013. 5. Centers for Disease Control. 1993 revised classification system for HIV infection and expanded surveillance case definition for IDS among adolescents and adults. MMWR recomm Reo 41: 1-19, 1992. 6. Singh JA, Wells GA, Christensen R, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database System Review 16: CD008794, 2001. 7. Nardone R, Zuccoli G, Brigo F, et al. Cerebral toxoplasmosis following adalimumab treatment in rheumatoid arthritis. Rheumatology (oxford) 53: 284, 2014. 8. Lassoued S, Zabraniecki L, Marin F, et al. Toxoplasmosis chorioretinitis and antitumor necrosis factor in rheumatoid arthritis. Semin Arthritis Rheum 36: 262-263, 2007. 9. Safa G, Darrieux L. Cerebral toxoplasmosis after rituximab therapy. JAMA Intern Med 173: 924-926, 2013. 10. Nakamura T, Shimizu Y, Toi S, et al. Toxoplasmosis involving the rostral medulla oblongata bilaterally in a non-HIV patient. Clin Neurol Neurosurg 115: 1561-1563, 2013. 11. Young JD, McGwire BS. Infliximab and reactivation of cerebral toxoplasmosis. N Engl J Med 352: 1530-1531, 2005. 12. Horiuchi K, Yabe I, Tajima Y, et al. Case of toxoplasma encephalopathy with specific MRI findings, diagnosed by IgG avidity index and nested PCR. Rinsho Shinkeigaku 50: 252-256, 2010 (in Japanese, Abstract in English). 13. Pereira-Chioccola VL, Vidal JE, Su C. Toxoplasma gondii infection and cerebral toxoplasmosis in HIV-infected patients. Future Microbiol 4: 1363-1379, 2009. 14. Mahadevan A, Ramalingaiah AH, Parthasarathy S, et al. Neuropathological correlate of the “concentric target sign” in MRI of HIVassociated cerebral toxoplasmosis. J Magn Reson Imaging 38: 488-495, 2013. 15. Nimir AR, Osman E, Ibrahim IA, Saliem AM. Is it toxoplasma encephalitis, HIV encephalopathy or brain tuberculoma? BMJ Case Rep (Epub ahead of print). 16. Madi D, Achappa B, Rao S, et al. Successful treatment of cerebral toxoplasmosis with clindamycin: a case report. Oman Med J 27: 411-412, 2012.
1. Halonen SK, Weiss LM. Toxoplasmosis. Handb Clin Neurol 14: 125-145, 2013.
Ⓒ 2015 The Japanese Society of Internal Medicine http://www.naika.or.jp/imonline/index.html
1436
CASE REPORT
□
Cerebral Toxoplasmosis in a Patient on Methotrexate and Infliximab for Rheumatoid Arthritis Swaroopa Pulivarthi 1, Rwoof A. Reshi 2, Carl T. McGary 3 and Murali Krishna Gurram 4
Abstract Cerebral toxoplasmosis is a rare disease predominantly found in immunocompromised hosts. However, cerebral toxoplasmosis has not been frequently described in association with the use of immunosuppressive medications. We herein report a case of cerebral toxoplasmosis in a 76-year-old Caucasian woman on methotrexate and infliximab for rheumatoid arthritis. The patient presented with right facial droop, slurred speech and difficulty walking. In addition to receiving methotrexate and infliximab and owning a cat, she had no other obvious risk factors. Imaging studies were not conclusive; however, brain biopsy confirmed the diagnosis. Serology was positive for anti-toxoplasma immunoglobulin G. Cerebral toxoplasmosis should be included in the differential diagnosis of patients under immunosuppressive medication who present with neurological manifestations. Key words: cerebral toxoplasmosis, rheumatoid arthritis, immunosuppressive medications (Intern Med 54: 1433-1436, 2015) (DOI: 10.2169/internalmedicine.54.3977)
Introduction Toxoplasmosis is usually the result of the reactivation of latent infection by Toxoplasma gondii in patients with immune suppression, such as that due to acquired immunodeficiency syndrome (AIDS), organ transplantation, hematopoietic stem cell transplantation, or cancer chemotherapy (1, 2). The difficulty in making the clinical diagnosis of cerebral toxoplasmosis is attributed to the lack of pathognomonic clinical or radiological features (1). In immunocompetent asymptomatic individuals, latent infection has been reported to be associated with psychiatric diseases, such as schizophrenia, inferring its subtle neurological effects (1). We herein describe a patient diagnosed with cerebral toxoplasmosis following treatment with methotrexate and infliximab for rheumatoid arthritis (RA).
Case Report A 76-year-old Caucasian woman presented to the emergency room with right facial droop, slurred speech and diffi-
culty walking. She had noticed progressively worsening right-sided weakness, slurred speech and right facial droop for one week. Two days prior to presentation, she had been noted to be forgetful and experienced difficulty in finding words. Her past medical history included diabetes mellitus, hypertension, RA, chronic kidney disease and chronic stable thrombocytopenia. While her family history was noncontributory, she had a pet cat of unknown age and duration. She was receiving chronic treatment with high-dose methotrexate (17.5 mg once every week), which had been tapered to 2.5 mg per week. She was also receiving infliximab (Remicade; 7.5 mg/kg every 6-8 weeks), with the last infusion being six weeks before presentation. On a neurological examination, all cranial nerves were intact, with the exception of right central facial palsy. Her motor strength was 5/5 in the left extremities and 4/5 in the right extremities, with normal tone and sensation. She exhibited dysmetria and moderate hyperreflexia on the right side. A complete blood count revealed thrombocytopenia, with a platelet count of 94,000/μL, white blood cell count of 5,000/μL, hemoglobin level of 11.4 g/dL and mean corpuscular volume of 91fL. Blood chemistry showed an albumin
１
Research Department, HealthEast Care System, USA, ２Department of Neurology, University of Minnesota, USA, ３Department of Pathology, HealthEast Care System, USA and ４Department of Internal Medicine, HealthEast Care System, USA Received for publication August 25, 2014; Accepted for publication October 5, 2014 Correspondence to Dr. Murali Krishna Gurram, [email protected]
1433
Intern Med 54: 1433-1436, 2015
DOI: 10.2169/internalmedicine.54.3977
rologically stable and was discharged to the transitional care unit.
Discussion
Figure 1. CT head demonstrated extensive vasogenic edema involving the left cerebrum and an ill-defined area of decreased attenuation near the posterior aspect of the left putamen. There was a mass effect on the left lateral ventricle, with approximately 0.4 cm of subfalcine herniation to the right (arrow).
level of 2.7 g/dL, creatinine level of 1.06 mg/dL, International Normalized Ratio (INR) of 1.17, glucose level of 145 mg/mL, glycosylated hemoglobin level of 6.7 %, aspartate aminotransferase (AST) level of 40 IU/L and alanine aminotransferase (ALT) level of 16 IU/L. Head CT (Fig. 1) demonstrated extensive vasogenic edema involving the left cerebrum and an ill-defined area of decreased attenuation near the posterior aspect of the left putamen. In addition, there was a mass effect on the left lateral ventricle, with an approximate 0.4-cm shift to the right. MRI of the brain without (Fig. 2A) and with (Fig. 2B) contrast, as well as a coronal section (Fig. 2C) and flair image (Fig. 2D), demonstrated a 2.9-cm irregular lesion centered in the left putamen with thin peripheral enhancement and a number of smaller punctate cortical enhancing lesions involving the brain parenchyma. The patient was started on treatment with dexamethasone and levetiracetam. A lumbar puncture was not performed due to the significant amount of edema and mass effect. CT scans of the chest, abdomen and pelvis were negative for primary malignancy, and a bone scan of the whole body revealed no evidence of primary or metastatic disease. A left thalamic stereotactic brain biopsy was performed for tissue diagnosis. The pathological examination (squash preparation) showed extensive necrosis and inflammation with lymphocytes and plasma cells, consistent with the presence of an abscess, with an encysted organism (trophozoites) indicating toxoplasmosis (Fig. 3). The tissue sections were stained with GMS silver stain and found to be negative for fungi. HIV antigen and antibody screening was negative. Toxoplasma immunoglobulin M was negative (900 IU/mL). Due to the patient’s sulfa allergy, she was started on therapy with once daily pyrimethamine (75 mg), clindamycin (600 mg) and leucovorin (25 mg). After the procedure, she remained neu-
Toxoplasma gondii is a ubiquitous obligate intracellular protozoan that causes latent infection in 30% of the world’s population (1). In most infected individuals, the organism remains dormant, and clinical reactivation is often associated with host immunosuppression. The usual presentation in immunosuppressed patients includes meningoencephalitis, pneumonitis and disseminated infection (1). Focal neurological deficits are also common in immunocompromised patients (3). In a retrospective review of 85 AIDS patients with cerebral toxoplasmosis (4), the most frequent clinical manifestations were headache (89%), hemiparesis (88%), fever (54%) and seizures (45%). As expected, patients with cortical lesions were found to be at greater risk of seizures than those with white matter disease (4). Ten (8.5%) patients did not present with any focal neurological signs (4). Meanwhile, the oculomotor nerve (66%) was the most frequently involved cranial nerve among the 14% of patients with cranial nerve deficits (4). The Centers for Disease Control and Prevention (CDC) has proposed four criteria for establishing the diagnosis of cerebral toxoplasmosis, including the proper clinical setting, consistent findings on imaging, positive serological studies and a therapeutic response to treatment (5). Of late, the use of immunosuppressive medications, such as adalimumab, rituximab, etc., has increased significantly. A Cochrane database systematic review was carried out in 2011 to compare the rates of serious adverse events, including tuberculosis reactivation, in all tumor necrosis factor (TNF) blocker trials published to date (6). Tuberculosis reactivation exhibited an odds ratio of 4.68 with a 95 CI of 1.18-18.60 (6). Although toxoplasmosis was not compared in this review, to the best of our knowledge, only a few cases of toxoplasmosis associated with immunosuppressive agents have been reported. Nardone et al. reported the development of cerebral toxoplasmosis in a patient on adalimumab for RA (7). In addition, Lassoued et al., who documented two cases of toxoplasmic chorioretinitis following anti-TNF alpha treatment (with adalimumab, infliximab and etanercept) for RA, suggested measuring the toxoplasma antibody titer prior to the initiation of anti-TNF alpha therapy (8). Cerebral toxoplasmosis associated with immunosuppression medications have also been reported by Safa G. (9) and Nakamura T. (10). Young et al. reported a case of cerebral toxoplasmosis in a patient receiving multiple immunosuppressive medications, including methotrexate, infliximab, prednisone and leflunomide, for RA (11). Methotrexate obviously causes immunosuppression; however, there is only one reported case of toxoplasmosis associated with the use of methotrexate in an otherwise immunocompetent patient. Horiuchi et al. reported this association in a 60-year-old woman with a history of RA who had
1434
Intern Med 54: 1433-1436, 2015
DOI: 10.2169/internalmedicine.54.3977
Figure 2. MRI of the brain without (2A) and with contrast (2B), as well as a coronal section (2C) and flair image (2D), demonstrated a 2.9-cm irregular lesion (red arrow) centered in the left putamen with thin peripheral enhancement and a number of smaller punctate cortical enhancing lesions involving the brain parenchyma, mostly in cortical locations, suggesting metastases.
Figure 3. Squash preparation slides showed extensive necrosis and inflammation with lymphocytes and plasma cells, consistent with an abscess, and an encysted organism (trophozoites-arrow), indicating toxoplasmosis.
been on treatment with methotrexate and prednisolone for 20 years prior to presentation (12). She exhibited multiple brain lesions involving the bilateral globus pallidus, right
thalamus and left dentate nucleus of the cerebellum (12). CT images usually reveal either hypodense lesions with ring enhancement or nodular enhancing lesions (13). T2-
1435
Intern Med 54: 1433-1436, 2015
DOI: 10.2169/internalmedicine.54.3977
weighted MRI images show multiple basal ganglia lesions with high-intensity signals or the “eccentric target sign,” a small nodule in a ring-enhancing lesion, or the “concentric target sign,” with concentric alternating zones of hypo- and hyper-intensity (13, 14). If the diagnosis is in doubt, a biopsy is recommended, particularly to rule out other CNS pathologies (15). The most frequent therapy for cerebral toxoplasmosis is pyrimethamine and sulfadiazine along with folinic acid to reduce hematological complications associated with pyrimethamine (13). Other alternative drugs used for the treatment of cerebral toxoplasmosis include clarithromycin and pyrimethamine, sulfamethoxazole and trimethoprim, and clindamycin and pyrimethamine for patients allergic to sulfa drugs (13). The most common duration of therapy is six weeks (13). Cerebral toxoplasmosis was successfully treated with intravenous clindamycin (600 mg thrice daily) for three weeks in a 30-year-old AIDS patient with a history of sulfonamide allergy, with symptomatic improvement noted within two days and resolution of the lesion on repeat head CT at three weeks (16). Cerebral toxoplasmosis should be considered in the differential diagnosis of patients receiving immunosuppressive medications, such as methotrexate, rituximab, adalimumab and infliximab, who present with neurological manifestations. Although there is no evidence for testing patients for toxoplasmosis prior to treatment or primary prophylaxis if positive, this strategy may be considered on a case-by-case basis weighing the risks and benefits carefully. Knowledge of the patient’s seropositive status aids close monitoring and the ability to provide early treatment, if necessary. Further data are needed regarding the risks and benefits of pretesting and primary prophylaxis for this potentially life-threatening disease. The authors state that they have no Conflict of Interest (COI).
References
2. Hakko E, Ozkan HA, Karaman K, et al. Analysis of cerebral toxoplasmosis in a series of 170 allogeneic hematopoietic stem cell transplant patients. Transpl Infect Dis 15: 575-580, 2013. 3. Silva LA, Vieira RA, Serafini LN, et al. Toxoplasmosis of the central nervous system in a patient without immunosuppression: case report. Rev Soc Bras Med Trop 34: 487-490, 2001 (in Portuguese, Abstract in English). 4. Correia Cda C, Melo HR, Costa VM, et al. Features to validate cerebral toxoplasmosis. Rev Soc Bras Med Trop 46: 373-376, 2013. 5. Centers for Disease Control. 1993 revised classification system for HIV infection and expanded surveillance case definition for IDS among adolescents and adults. MMWR recomm Reo 41: 1-19, 1992. 6. Singh JA, Wells GA, Christensen R, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database System Review 16: CD008794, 2001. 7. Nardone R, Zuccoli G, Brigo F, et al. Cerebral toxoplasmosis following adalimumab treatment in rheumatoid arthritis. Rheumatology (oxford) 53: 284, 2014. 8. Lassoued S, Zabraniecki L, Marin F, et al. Toxoplasmosis chorioretinitis and antitumor necrosis factor in rheumatoid arthritis. Semin Arthritis Rheum 36: 262-263, 2007. 9. Safa G, Darrieux L. Cerebral toxoplasmosis after rituximab therapy. JAMA Intern Med 173: 924-926, 2013. 10. Nakamura T, Shimizu Y, Toi S, et al. Toxoplasmosis involving the rostral medulla oblongata bilaterally in a non-HIV patient. Clin Neurol Neurosurg 115: 1561-1563, 2013. 11. Young JD, McGwire BS. Infliximab and reactivation of cerebral toxoplasmosis. N Engl J Med 352: 1530-1531, 2005. 12. Horiuchi K, Yabe I, Tajima Y, et al. Case of toxoplasma encephalopathy with specific MRI findings, diagnosed by IgG avidity index and nested PCR. Rinsho Shinkeigaku 50: 252-256, 2010 (in Japanese, Abstract in English). 13. Pereira-Chioccola VL, Vidal JE, Su C. Toxoplasma gondii infection and cerebral toxoplasmosis in HIV-infected patients. Future Microbiol 4: 1363-1379, 2009. 14. Mahadevan A, Ramalingaiah AH, Parthasarathy S, et al. Neuropathological correlate of the “concentric target sign” in MRI of HIVassociated cerebral toxoplasmosis. J Magn Reson Imaging 38: 488-495, 2013. 15. Nimir AR, Osman E, Ibrahim IA, Saliem AM. Is it toxoplasma encephalitis, HIV encephalopathy or brain tuberculoma? BMJ Case Rep (Epub ahead of print). 16. Madi D, Achappa B, Rao S, et al. Successful treatment of cerebral toxoplasmosis with clindamycin: a case report. Oman Med J 27: 411-412, 2012.
1. Halonen SK, Weiss LM. Toxoplasmosis. Handb Clin Neurol 14: 125-145, 2013.
Ⓒ 2015 The Japanese Society of Internal Medicine http://www.naika.or.jp/imonline/index.html
1436
