Clin Rheumatol DOI 10.1007/s10067-014-2726-8
BRIEF REPORT
Discriminating infectious meningitis versus neuropsychiatric involvement in patients with systemic lupus erythematosus: a single-center experience Jinyun Chen & Xuebing Feng & Hong Wang & Bingzhu Hua & Congzhu Ding & Bujun Liu & Lingyun Sun
Received: 15 January 2014 / Revised: 22 May 2014 / Accepted: 11 June 2014 # Clinical Rheumatology 2014
Abstract The objective of this study is to identify the clinical differences between infectious meningitis and neuropsychiatric systemic lupus erythematosus (NPSLE) in patients with SLE. Clinical manifestations, laboratory test results, and prognoses of 14 SLE patients complicated with various infectious meningitis, hospitalized in the Affiliated Drum Tower Hospital of Nanjing University Medical School in the past 7 years, were reviewed and compared with those of 34 concomitantly treated NPSLE patients. Our study shows that mortality rate was much higher in SLE patients with infectious meningitis than in NPSLE patients. Compared to NPSLE, those with infectious meningitis had lower SLE Disease Activity Index (SLEDAI), but higher doses of corticosteroids 1 month before the occurrence of CNS symptoms. Headache, high fever, and vomiting were more common in patients with infectious meningitis, accompanied with the elevation of C-reactive protein level. Cerebrospinal fluid (CSF) examination showed increased levels of leukocytes and proteins but decreased glucose level in patients with infectious meningitis. We conclude that for SLE patients exhibiting CNS symptoms, high fever, high intake of corticosteroids, and abnormal CSF are important clues for the coexistence of infectious meningitis, especially tuberculous meningitis.
Keywords Central nervous system infection . Neuropsychiatric lupus . Systemic lupus erythematosus J. Chen : X. Feng : H. Wang : B. Hua : C. Ding : B. Liu : L. Sun Department of Rheumatology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China X. Feng (*) : L. Sun (*) Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China e-mail: [email protected] e-mail: [email protected]
Introduction Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease having myriad manifestations, and immune dysregulation plays a central role in its pathogenesis [1]. Despite the improvement of survival rate in SLE patients over the past decades, patients still have higher mortalities compared with the general population, which can be largely attributed to uncontrolled disease activities and, most importantly, various types of severe infections [2]. Although the incidence infectious meningitis in SLE is only 1.4 % [3], an over 40 % death rate in these patients has been reported [4, 5]. In some situation, the manifestations of infectious meningitis are quite similar to that of neuropsychiatric systemic lupus erythematosus (NPSLE), which may hinder the proper diagnosis and treatment, leading to a poor prognosis. Currently, there have been several reports of lupus CNS infection [4, 6–8], yet few of them focused on the differential diagnosis between CNS infection in SLE and NPSLE [8]. To find out the characteristics of SLE patients with infectious meningitis, the data of 14 patients hospitalized in the past 7 years in our center were reviewed and compared to 34 concomitantly treated NPSLE inpatients. This study aims to provide some useful tools for the discrimination of NPSLE and SLE patients with infectious meningitis.
Patients and methods Patients Data of SLE patients complicated with various infectious meningitis and NPSLE patients that were admitted to the Affiliated Drum Tower Hospital of Nanjing University
Clin Rheumatol
Medical School from 2005 to 2013 were collected. All patients satisfied the revised American College of Rheumatology (ACR) criteria for SLE [9], and their disease activity on admission was measured using the SLE Disease Activity Index (SLEDAI) through charts review [10]. Accumulated damage related to SLE was calculated using the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI) [11]. NPSLE was defined as SLE having at least one of the following CNS manifestations: (1) seizure, (2) cerebral vascular accident (CVA), (3) cognitive dysfunction, (4) psychosis, (5) acute confusional state, and (6) refractory headache, with the exclusion of uremia, hypertensive encephalopathy, infection, and corticosteroid induction. Those with CNS thrombotic vasculopathy due to antiphospholipid syndrome were excluded. Infectious meningitis was diagnosed according to the patient’s clinical manifestations, cerebrospinal fluid (CSF) examination results, pathogen tests, and responses to anti-infective treatment. Among the patients, nine were identified as tuberculosis meningitis, three purulent meningitis, and two cryptococcal meningitis. Variables The following variables were included in the analysis: demographic data, medication before disease onset, major clinical manifestations (fever, vomit, headache, seizure, acute confusion, CVA, cognitive dysfunction, and psychosis), laboratory data [blood routine, urine routine, 24-h urine protein, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin, globulin, and anti-double-stranded DNA (dsDNA)], CSF examination results, and radiologic data of CNS. In this study, fever was defined as a temperature (T) of >37.5 °C lasting for at least 1 day, and high fever as T>39.0 °C. Headache was defined according to ACR definition of lupus headache [10]. Abnormal radiologic findings were defined as having ischemia, infarction, or demyelination in MRI or CT scan. Average equivalent dose to prednisone in the previous month before admission and concomitantly used immunosuppressive agents (including cyclophosphamide and mycophenolate mofetil) were documented as well. Statistical analysis Data processing and statistical analyses were performed using GraphPad Prism (version 5.01). The Student’s t test was applied for unpaired, continuous variables when variances were equal, and if variances were significantly different, Mann-Whitney test was applied. Fisher’s exact test was applied when frequencies were compared. Cox regression analysis was performed to find out possible risk factors associated with mortality. All probabilities were two-tailed, and a p value less than 0.05 was considered statistically significant.
Results Patients with infectious meningitis had low disease activity and organ damage but took high dosage of corticosteroids Fourteen SLE patients complicated with various infectious meningitis (11 females) and 34 NPSLE patients (32 females) were included for analysis. There were no differences in gender, age, or lupus disease duration between SLE patients with infectious meningitis (hereinafter referred to as infection group) and those having NPSLE (Table 1). Most of the patients with CNS tuberculosis infections (66.7 %) had extracerebral lesions, five with miliary tuberculosis of the lungs, and one with tuberculous pleuritis. Compared to NPSLE patients, SLE patients with infectious meningitis had lower SLEDAI scores (5.9±1.1 vs. 16.8±1.1, p
BRIEF REPORT
Discriminating infectious meningitis versus neuropsychiatric involvement in patients with systemic lupus erythematosus: a single-center experience Jinyun Chen & Xuebing Feng & Hong Wang & Bingzhu Hua & Congzhu Ding & Bujun Liu & Lingyun Sun
Received: 15 January 2014 / Revised: 22 May 2014 / Accepted: 11 June 2014 # Clinical Rheumatology 2014
Abstract The objective of this study is to identify the clinical differences between infectious meningitis and neuropsychiatric systemic lupus erythematosus (NPSLE) in patients with SLE. Clinical manifestations, laboratory test results, and prognoses of 14 SLE patients complicated with various infectious meningitis, hospitalized in the Affiliated Drum Tower Hospital of Nanjing University Medical School in the past 7 years, were reviewed and compared with those of 34 concomitantly treated NPSLE patients. Our study shows that mortality rate was much higher in SLE patients with infectious meningitis than in NPSLE patients. Compared to NPSLE, those with infectious meningitis had lower SLE Disease Activity Index (SLEDAI), but higher doses of corticosteroids 1 month before the occurrence of CNS symptoms. Headache, high fever, and vomiting were more common in patients with infectious meningitis, accompanied with the elevation of C-reactive protein level. Cerebrospinal fluid (CSF) examination showed increased levels of leukocytes and proteins but decreased glucose level in patients with infectious meningitis. We conclude that for SLE patients exhibiting CNS symptoms, high fever, high intake of corticosteroids, and abnormal CSF are important clues for the coexistence of infectious meningitis, especially tuberculous meningitis.
Keywords Central nervous system infection . Neuropsychiatric lupus . Systemic lupus erythematosus J. Chen : X. Feng : H. Wang : B. Hua : C. Ding : B. Liu : L. Sun Department of Rheumatology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China X. Feng (*) : L. Sun (*) Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China e-mail: [email protected] e-mail: [email protected]
Introduction Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease having myriad manifestations, and immune dysregulation plays a central role in its pathogenesis [1]. Despite the improvement of survival rate in SLE patients over the past decades, patients still have higher mortalities compared with the general population, which can be largely attributed to uncontrolled disease activities and, most importantly, various types of severe infections [2]. Although the incidence infectious meningitis in SLE is only 1.4 % [3], an over 40 % death rate in these patients has been reported [4, 5]. In some situation, the manifestations of infectious meningitis are quite similar to that of neuropsychiatric systemic lupus erythematosus (NPSLE), which may hinder the proper diagnosis and treatment, leading to a poor prognosis. Currently, there have been several reports of lupus CNS infection [4, 6–8], yet few of them focused on the differential diagnosis between CNS infection in SLE and NPSLE [8]. To find out the characteristics of SLE patients with infectious meningitis, the data of 14 patients hospitalized in the past 7 years in our center were reviewed and compared to 34 concomitantly treated NPSLE inpatients. This study aims to provide some useful tools for the discrimination of NPSLE and SLE patients with infectious meningitis.
Patients and methods Patients Data of SLE patients complicated with various infectious meningitis and NPSLE patients that were admitted to the Affiliated Drum Tower Hospital of Nanjing University
Clin Rheumatol
Medical School from 2005 to 2013 were collected. All patients satisfied the revised American College of Rheumatology (ACR) criteria for SLE [9], and their disease activity on admission was measured using the SLE Disease Activity Index (SLEDAI) through charts review [10]. Accumulated damage related to SLE was calculated using the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI) [11]. NPSLE was defined as SLE having at least one of the following CNS manifestations: (1) seizure, (2) cerebral vascular accident (CVA), (3) cognitive dysfunction, (4) psychosis, (5) acute confusional state, and (6) refractory headache, with the exclusion of uremia, hypertensive encephalopathy, infection, and corticosteroid induction. Those with CNS thrombotic vasculopathy due to antiphospholipid syndrome were excluded. Infectious meningitis was diagnosed according to the patient’s clinical manifestations, cerebrospinal fluid (CSF) examination results, pathogen tests, and responses to anti-infective treatment. Among the patients, nine were identified as tuberculosis meningitis, three purulent meningitis, and two cryptococcal meningitis. Variables The following variables were included in the analysis: demographic data, medication before disease onset, major clinical manifestations (fever, vomit, headache, seizure, acute confusion, CVA, cognitive dysfunction, and psychosis), laboratory data [blood routine, urine routine, 24-h urine protein, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin, globulin, and anti-double-stranded DNA (dsDNA)], CSF examination results, and radiologic data of CNS. In this study, fever was defined as a temperature (T) of >37.5 °C lasting for at least 1 day, and high fever as T>39.0 °C. Headache was defined according to ACR definition of lupus headache [10]. Abnormal radiologic findings were defined as having ischemia, infarction, or demyelination in MRI or CT scan. Average equivalent dose to prednisone in the previous month before admission and concomitantly used immunosuppressive agents (including cyclophosphamide and mycophenolate mofetil) were documented as well. Statistical analysis Data processing and statistical analyses were performed using GraphPad Prism (version 5.01). The Student’s t test was applied for unpaired, continuous variables when variances were equal, and if variances were significantly different, Mann-Whitney test was applied. Fisher’s exact test was applied when frequencies were compared. Cox regression analysis was performed to find out possible risk factors associated with mortality. All probabilities were two-tailed, and a p value less than 0.05 was considered statistically significant.
Results Patients with infectious meningitis had low disease activity and organ damage but took high dosage of corticosteroids Fourteen SLE patients complicated with various infectious meningitis (11 females) and 34 NPSLE patients (32 females) were included for analysis. There were no differences in gender, age, or lupus disease duration between SLE patients with infectious meningitis (hereinafter referred to as infection group) and those having NPSLE (Table 1). Most of the patients with CNS tuberculosis infections (66.7 %) had extracerebral lesions, five with miliary tuberculosis of the lungs, and one with tuberculous pleuritis. Compared to NPSLE patients, SLE patients with infectious meningitis had lower SLEDAI scores (5.9±1.1 vs. 16.8±1.1, p
