Aspectic meningitis in systemic lupus erythematosus. Report of three cases.

Three patients with aseptic meningitis were subsequently diagnosed as having lupus erythematosus. One patient had a single meningitic episode, another had chronic meningitis, and the third two acute episodes 5 years apart. All 3 patients developed further neurophychiatric manifestations of SLE, leading to death in 1. Aseptic meningitis appears to be an early manifestation of SLE and may herald more serious brain damage. No new cases of aseptic meningitis occurred in this series after initiation of therapy for SLE. In contrast, bacterial meningitis did occur as a late complication of the disease.     

Anti-U1RNP antibody and aseptic meningitis in connective tissue diseases

OBJECTIVE: To investigate the relationship between aseptic meningitis and anti-U1RNP antibody in patients diagnosed with CTD. METHODS: Fourteen patients with aseptic meningitis were selected from among patients with CTDs who had visited our hospital. We analyzed their medical records to clarify the clinical and immunological features of aseptic meningitis. RESULTS: A total of 14 patients with aseptic meningitis were subsequently diagnosed as having either SLE (seven cases), MCTD (four), UCTD (one), overlap syndrome (one), or Sj?gren's syndrome (one). Eight of the 14 patients had received NSAIDs, such as sulindac, naproxen, or loxoprofen, before the onset of aseptic meningitis. CRP levels were increased (mean +/- SD: 7.1 +/- 7.1 mg/dL) and CRP levels (10.4 +/- 7.7) in the drug-induced group were significantly increased (p < 0.01). The anti-U1RNP antibody was found in 13 of the 14 patients. There were no significant differences in cerebrospinal fluid findings between the drug-induced group and the non-drug-induced group. CONCLUSIONS: SLE or MCTD patients with aseptic meningitis tend to have anti-U1RNP antibody.     

Meningitis in Korean patients with systemic lupus erythematosus: analysis of demographics, clinical features and outcomes; experience from affiliated hospitals of the Catholic University of Korea

Meningitis is a rare complication of systemic lupus erythematosus (SLE), potentially leading to a fatal outcome. The demographic, clinical, and laboratory features, and the outcomes of meningitis were evaluated in Korean patients with SLE. In a retrospective medical record review of 1420 SLE patients, 20 patients who had developed septic or aseptic meningitis were identified. In 11 patients, the causative microorganisms were identified ('septic meningitis'), and Cryptococcus neoformans was the major pathogen. The other nine patients were diagnosed with aseptic meningitis. The patients with septic meningitis were older than those with aseptic meningitis (p = 0.025) and displayed mental changes more often (p = 0.005). Leukocyte counts in the cerebrospinal fluid (CSF) were higher (p = 0.044) and the levels of CSF glucose were lower in the septic meningitis group (p = 0.036). Plasma leukocyte counts and neutrophil counts were higher in patients with septic meningitis (p = 0.037 and p = 0.020, respectively). Meningitis was observed in 1.4% of Korean patients with SLE and, in 55% of the meningitis patients, microorganisms were isolated and Cryptococcus neoformans was most commonly identified. Altered mental status, plasma leukocytosis, neutrophilia, and CSF pleocytosis and hypoglycemia were more prominent in patients with septic meningitis.     

Ibuprofen-induced Meningitis in a Male with Systemic Lupus Erythematosus

ABSTRACT. Jensen S, Glud TK, Bacher T, Ersgaard H (Departments of Endocrinology, Clinical Immunology and Anaesthetics, Aalborg Hospital, Aalborg, Denmark). Ibuprofen-induced meningitis in a male with systemic lupus erythematosus. Acta Med Scand 1987; 221:509–11. A 36-year-old male with systemic lupus erythematosus developed aseptic meningitis after in-gestion of ibuprofen. He was unconscious, had a universal rash, high fever and a pathological CSF. Being severely ill he was treated with high doses of corticosteroids and plasmapheresis and recovered within a week. Ibuprofen, a non-steroidal anti-inflammatory drug of the propionic acid group, is frequently used in patients with connective tissue disorders. Within the past eight years a few reports have been published on aseptic meningitis following ingestion of ibuprofen in patients with systemic lupus erythematosus (SLE) (1–5) and mixed connective tissue disease (6–8). All of these patients were women. We report a serious case of aseptic meningitis in a male subject with SLE.     

Trimethoprim-sulfamethoxasole induced meningitis in systemic lupus erythematosus.

Most reports of drug induced meningitis in systemic lupus erythematosus (SLE) have implicated ibuprofen. We describe a 46-year-old woman with SLE who developed aseptic meningitis abruptly after ingesting trimethoprim-sulfamethoxasole (TMP-SMX). This patient had received TMP-SMX twice before; each was associated with increasingly severe reactions, whose relationship with the use of TMP-SMX became apparent only in retrospect. A history of medication use should be sought in all patients with meningitis who have an underlying autoimmune disorder.     

Recurrent aseptic meningitis followed by transverse myelitis as a presentation of systemic lupus erythematosus

Recurrent aseptic meningitis as a manifestation of systemic lupus erythematosus (SLE) has most often been reported as an adverse reaction to the use of nonsteroidal antiinflammatory drugs. We present a case of recurrent aseptic meningitis and transverse myelitis as the initial manifestation of SLE.     

Méningite aseptique sévère induite par la rifampicine

We report the first case of acute drug-induced aseptic meningitis (DIAM) due to rifampin in a young female with systemic lupus erythematosus (SLE). DIAM is uncommon and its diagnosis is often difficult. This type of drug hypersensitivity is more frequently observed in patients with a history of auto-immune disease, particularly SLE. The major categories of causative agents are: nonsteroidal anti-inflammatory drugs, antimicrobials, intravenous immunoglobulins and biotherapies.     

Herpes simplex virus type 2 and acute aseptic meningitis. Clinical features of cases with isolation of herpes simplex virus from cerebrospinal fluids.

Herpes simplex virus (HSV) was recovered from the cerebrospinal fluids (CSF) of 10 patients with acute aseptic meningitis. HSV type 1 was isolated from the CSF of a 6-month-old boy. The other 9 HSV isolates from CSF were from adults in the age-group 15 to 29 years; 7 of these isolates were available for typing and were identified as HSV type 2. In a further 9 patients with acute aseptic meningitis and belonging to the same age-group a HSV infection was suggested by a significant titre rise in complement-fixing antibodies against HSV. The clinical features of the 10 patients with HSV isolation from CSF are presented. The 6-month-old boy with HSV type 1 had an acute benign aseptic meningitis. Seven of the 9 adults with HSV isolation from CSF (type 2 in all isolates available for typing) had an acute uncomplicated aseptic meningitis, one patient (with type 2 isolated) had an acute meningoencephalitis and one (isolate untyped) an acute meningomyelitis.     

St Louis encephalitis in Ohio, September 1975: clinical and EEG studies in 16 cases.

In 1975, during the largest epidemic of St Louis encephalitis (SLE) in the United States, 416 cases were diagnosed in Ohio. Persons who were admitted to two Columbus (Ohio) hospitals with suspected acute viral CNS infection were prospectively studied to define the virologic and clinical aspects of SLE. Sixteen cases of SLE were diagnosed serologically. Fifteen patients had signs of encephalitis and one had aseptic meningitis. Six patients had the syndrome of inappropriate antidiuretic hormone secretion. Other frequent findings included moderate peripheral leukocytosis and CSF pleocytosis, with mild elevation of CSF protein levels but normal glucose levels. Severe neurologic sequelae were infrequent. The EEG proved valuable in diagnosis and prognosis. Results of brain scans were normal. Virus in CSF or urine was not demonstrated, nor was viral antigen in CSF or urine sediments. Specific antibody was found in the sera and CSF of all patients who were tested, but interferon was not detected.     

Central nervous system disease in systemic lupus erythematosus: Therapy and prognosis

The effect of corticosteroid therapy in 28 patients with 52 episodes of neuropsychiatric disease in systemic lupus erythematosus (SLE) was evaluated. Categories of organic central nervous system disease were seizures (eight patients), organic brain syndromes (nine patients), aseptic meningitis (four patients) and a variety of focal neurologic findings (seven patients). Fourteen patients had 15 episodes of functional psychosis without other evidence of neurologic disease.Although there was a general correlation between clinical and serologic evidence of active SLE and the development of organic neurologic disease, there was no evidence that therapy with very large doses of corticosteroids was beneficial. Of the deaths in this series, two were due to probable active SLE involving the central nervous system whereas five were attributable to complications of therapy. The long-term morbidity, likewise, was high in the patients who received large doses of corticosteroids. In all, 12 patients had major complications of corticosteroid therapy.Functional psychosis was usually precipitated by corticosteroid therapy and responded to a reduction in steroid dosage and administration of psychotropic drugs.     

Clinical predictors of bacterial versus aseptic meningitis in childhood.

STUDY OBJECTIVE: To assess the reliability of meningeal signs and other physical findings in predicting bacterial and aseptic meningitis at various ages. DESIGN: Children requiring lumbar puncture were evaluated prospectively for meningeal signs and other physical parameters before lumbar puncture. SETTING: Emergency department of Children's Hospital of Wisconsin. PARTICIPANTS: One hundred seventy-two children, aged 1 week to 17 years, with meningitis (53 bacterial and 119 aseptic). MEASUREMENTS AND MAIN RESULTS: Nuchal rigidity was present in 27% of infants aged 0 to 6 months with bacterial meningitis versus 95% of patients 19 months or older (P = .0001). Three percent of infants 0 to 6 months old with aseptic meningitis had nuchal rigidity versus 79% of patients 19 months or older (P = .0005). Seventy-two percent of infants 12 months of age or younger with bacterial meningitis has at least one positive meningeal sign versus 17% of infants with aseptic meningitis (P = .0001). Eighty-five percent of children older than 12 months with meningitis had at least one positive meningeal sign, 93% with bacterial meningitis, and 82% with aseptic meningitis. CONCLUSION: Despite a lack of meningeal signs, a high index of suspicion for meningitis is essential when evaluating the febrile infant 12 months of age or younger.     

Creatine kinase in the serum of patients with acute infections of the central nervous system

Serum creatine kinase was assessed in 94 consecutive patients without convulsions admitted to hospital due to suspicion of infection of the central nervous system. No reliable discrimination between patients with aseptic and those with bacterial meningitis was obtained. Patients with bacterial meningitis and brain oedema, as well as patients with encephalitis, had significantly higher values (P less than 0.01) than patients with meningism, aseptic meningitis and bacterial meningitis without cerebral oedema. Very high values, above 2500 U/1, were encountered in only the most severe cases of bacterial meningitis. The highest serum CK value found in patients with encephalitis was 725 U/l. Reference values for control patients with meningism were 16-269 U/1. In a subset of 9 patients creatine kinase isoenzyme analysis was performed. In all cases only muscle type (MM) isoenzyme was found.     

Comparison between cerebrospinal fluid concentrations of glucose, total protein, chloride, lactate, and total amino acids for the differential diagnosis of patients with meningitis

The purpose of this study was to compare the ability of cerebrospinal fluid (CSF) concentrations of glucose, protein, chloride, lactate, and total amino acids, as well as CSF/blood glucose ratio to distinguish bacterial meningitis from aseptic meningitis. 56 patients with proven bacterial meningitis, 102 patients with aseptic meningitis, and 108 controls were investigated. On admission CSF lactate determination was the most sensitive and the most efficient test to distinguish bacterial meningitis from aseptic meningitis. In patients with bacterial meningitis reexamined after 24-48 h of treatment with antibiotics and compared with patients with aseptic meningitis also reexamined 24-48 h after admission determination of CSF total amino acids was the most sensitive and efficient test.     

Aseptic necrosis presenting as wrist pain in sle

Aseptic necrosis of the wrist in systemic lupus erythematosus (SLE) is not rare. In 156 patients with SLE, aseptic necrosis occurred in 11 patients, of whom 3 (27%) had wrist involvement. Onset of pain was insidious and the symptoms were thought to be related to synovitis due to SLE. An average of 11 months elapsed before aseptic necrosis was correctly diagnosed. An awareness of this possibility is important in the management of any patient with SLE who complains of wrist pain.     

Determination of interleukin-2 (IL-2) and soluble IL-2 receptors (S-IL-2R) in serum and cerebrospinal fluid does not discriminate purulent and aseptic meningitis

Elevated levels of soluble interleukin-2 receptors (S-IL-2R) but not interleukin-2 (IL-2) activity were found in sera from patients with aseptic meningitis, purulent meningitis, and meningism. Elevated levels of S-IL-2R in serum was also observed in 4/4 patients with bacterial pneumonia and 2/2 patients with infectious mononucleosis. The inflammation of the meninges was only reflected by an increase in S-IL-2R in cerebrospinal fluid (CSF) in 1/14 patients with aseptic meningitis and 3/10 patients with purulent meningitis. Further, IL-2 activity was only demonstrated in CSF from 2 patients with aseptic meningitis and 3 patients with purulent meningitis. In conclusion, neither S-IL-2R nor IL-2 in serum or CSF seem to have any value in the diagnosis of or discrimination between purulent meningitis and aseptic meningitis. Further, the elevation of S-IL-2R in serum is not specific for infections primarily fought by cytotoxic T-lymphocytes such as viral infections, but seems merely to reflect an unspecific activation of the immune system.     

Aseptic necrosis and glucocorticosteroids in systemic lupus erythematosus: a reevaluation

To reassess predisposing factors in patients with systemic lupus erythematosus (SLE) who develop aseptic necrosis of bone, we studied 172 patients with SLE seen at our institution between 1975 and 1987 followed for longer than 1 year. Twenty-eight (16.3%) of these patients developed clinically apparent aseptic necrosis. In 12 of these 28 the continuous glucocorticosteroid dose was known. These 12 patients were compared to 15 controls with SLE followed for a minimum of 4.5 years for whom continuous glucocorticosteroid dosage was also known. We were unable to find any significant differences between patients with aseptic necrosis and controls in prevalence of specific lupus organ system involvement, Raynaud's phenomenon, or abnormal serological or hematological variables. Overall disease activity at the time of maximal glucocorticosteroid dosage did not differ significantly between the 2 groups but was slightly greater at the time SLE was diagnosed in the group with aseptic necrosis. Glucocorticosteroid intake during the first 1.5 years after diagnosis of SLE and during the third year after diagnosis was significantly greater for the patients with aseptic necrosis than for the control patients, as was glucocorticosteroid intake during the maximal 1, 3 and 6 months of therapy. We conclude that glucocorticosteroid intake is the major factor predisposing to aseptic necrosis in patients with SLE.     

Characteristics of meningitis caused by Ibuprofen: report of 2 cases with recurrent episodes and review of the literature

Ibuprofen is a common nonsteroidal antiinflammatory drug that is the most frequent cause of aseptic meningitis induced by drugs. The incidence of this type of aseptic meningitis is increasing, mainly among patients with underlying autoimmune connective tissue disorder, but also among healthy people. We report 2 patients with recurrent meningitis caused by ibuprofen mimicking bacterial meningitis: the first patient a woman with dermatomyositis and the second patient a previously healthy woman who developed autoimmune thyroiditis a few months later. We then review 71 episodes of ibuprofen-related meningitis in 36 patients reported in the literature. Twenty-two patients (61%) presented with an autoimmune connective tissue disorder, mainly systemic lupus erythematosus, and 22 (61%) had recurrent episodes. Most episodes consisted of an acute meningeal syndrome with a predominance of neutrophils in cerebrospinal fluid (CSF) in 72.2% of episodes and elevated protein in the CSF, so the clinical presentation of this type of aseptic meningitis may be quite similar to that of acute bacterial meningitis. CSF glucose levels are usually normal, which may help to differentiate between these 2 types of meningitis. In some cases the clinical presentation is that of meningoencephalitis with neurologic focal deficits. Although based on the close relation between the administration of ibuprofen and the onset of symptoms, especially if previous episodes have occurred, the diagnosis of ibuprofen-induced aseptic meningitis is a diagnosis by exclusion. If the clinical picture is compatible with bacterial meningitis, empirical antibiotic therapy must be administered until negativity of cultures and other microbiologic tests is determined. Rechallenge to ibuprofen reproduces the symptoms and confirms the diagnosis, but is usually not advised. Whatever the clinical presentation, physicians must consider the possibility of ibuprofen-related meningitis or meningoencephalitis in patients taking ibuprofen, especially if they are suffering from an autoimmune connective tissue disorder. On the other hand, we think it would be appropriate to screen for autoimmune disease in previously healthy patients diagnosed with ibuprofen-related meningitis or meningoencephalitis. Finally, we propose that meningitis due to ibuprofen be included in the list of causes of recurrent aseptic meningitis.     

Kikuchi-Fujimoto disease: an unusual association with acute renal failure

Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis of unknown etiopathogenesis, is a self-limited disease which frequently appears as feverish lymphadenomegaly, thus creating the need for differential diagnosis with lymphoma, systemic lupus erythematosus (SLE), infectious mononucleosis, cat-scratch disease, and toxoplasmosis with lymphonodal impairment. However, there are cases in which it may evolve with complications such as aseptic meningitis, cerebellar ataxia, and aseptic myocarditis. We are presenting a case of a 24-year-old man who had an initial picture of arthralgia, evening fever and adenomegaly. Kikuchi disease was diagnosed through lymph node biopsy with immunohistochemistry and evolves with severe systemic manifestations, such as pericarditis with cardiac tamponade, pneumonitis, hepatitis, and acute kidney failure - the latter has not been reported in literature yet. There was significant improvement of the clinical picture with prednisone.     

Nonsteroidal anti-inflammatory drugs in systemic lupus erythematosus

Up to 80% of patients with systemic lupus erythematosus (SLE) are treated with nonsteroidal anti-inflammatory drugs (NSAID) for musculoskeletal symptoms, serositis and headache. This survey reviews the literature on non-selective and selective inhibitors of cyclooxygenases, with an emphasis on the efficacy and safety profile reported in SLE patients. No lupus-specific data on gastro-intestinal side effects of NSAID exist. Both non-selective Cox inhibitors and selective Cox-2 inhibitors induce renal side effects, including sodium retention and reduction of the glomerular filtration rate. Lupus nephritis is a risk factor for NSAID-induced acute renal failure, but not for rare idiosyncratic toxic renal reactions to NSAID. In refractory nephrotic syndrome, NSAID have been used successfully. Cutaneous and allergic reactions to NSAID are increased in SLE patients as well as hepatotoxic effects, particularly with high dose aspirin. Whereas a variety of central nervous system side effects of NSAID are probably no more common in SLE patients than others, aseptic meningitis has been reported more frequently. Ovulation and pregnancy can be adversely affected by Cox inhibitors. The antiplatelet effect of aspirin and non-selective Cox inhibitors has a therapeutic potential in patients with antiphospholipid syndrome (APS). In summary, treatment of SLE with NSAID requires awareness for the increased frequency of some side effects and close monitoring of toxicity.