Rheumatol Int (2011) 31:555–557 DOI 10.1007/s00296-010-1590-3
SHORT COMMUNICATION
Listeria monocytogenes meningitis in a young woman with systemic lupus erythematosus Ming-Chia Lee • Yao-Kuang Wu • Chun-Hsiung Chen Ta-Wei Wu • Chih-Hsin Lee
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Received: 17 April 2010 / Accepted: 14 July 2010 / Published online: 29 July 2010 Ó Springer-Verlag 2010
Abstract Listeria meningitis, a rare but life-threatening infection in patients with systemic lupus erythematosus, often represents a diagnostic and therapeutic challenge because of its rarity and non-representative manifestations. L. monocytogenes is an intracellular pathogen capable of spreading directly from cell to cell without exposure to the extracellular humoral immune system. With the evolving trend of intense immunosuppressive therapy, patients with SLE usually have abnormal cell-mediated immunity and are susceptible to L. monocytogenes infections. The gastrointestinal tract is usually the portal of entry, and a transient gastroenteritis may precede the full-blown meningitides. Ampicillin and penicillin G are the drugs of choice. For patients who are allergic to penicillin, trimethoprim-sulfamethoxazole is an eligible alternative. Delay in diagnosis and inappropriate antibiotics are detrimental to the outcome. Herein, we report a young woman with systemic lupus erythematosus who developed listeria meningitis. Clinicians are advised to be aware of the clinical presentations of this disease.
Keywords Meningitis Connective tissue disease Septic shock Convulsion Opportunistic infection
Introduction Patients with systemic lupus erythematosus (SLE) have high susceptibility to opportunistic infections due to either disease-related immunologic dysfunction or the immunosuppressive therapies [1, 2]. Infections account for 30–50% morbidity and mortality of patients with SLE [3, 4]. The common sites of infection include lungs, skin, and genitourinary tract [5]. Listeria meningitis, a rare but highly lethal infection in patients with SLE, tends to exhibit non-specific clinical manifestations and may be misdiagnosed as lupus flares. Significant morbidity and mortality are noted unless an accurate diagnosis is made timely, and appropriate therapy is administered as soon as possible [2, 4].
Case report M.-C. Lee T.-W. Wu Department of Pharmacy, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan Y.-K. Wu C.-H. Chen C.-H. Lee (&) Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Taipei Branch, 289, Jianguo Rd., Xindian City, Taipei County 23142, Taiwan e-mail:
[email protected] Y.-K. Wu C.-H. Lee School of Medicine, Tzu Chi University, Hualien, Taiwan C.-H. Lee Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan
A 32-year-old woman, who had history of SLE for 5 years, was receiving hydroxychloroquine, methylprednisolone, and mycophenolate mofetil due to active lupus nephritis. One day prior to admission, she developed spiking fever, watery diarrhea, malaise and non-productive cough. On admission day, blood examinations revealed white blood cells 9,100/lL (N band 7%, N seg 82%); glucose 93 mg/dL; creatinine 5.87 mg/dL; and C-reactive protein 30.53 mg/dL. Methylprednisolone dosage was increased to 20 mg every 8 h for suspected lupus flares, while ceftriaxone 1 g every 12 h was started empirically after obtaining two samples of percutaneous blood for culture.
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On day 4 after admission, she developed oliguria and showed signs of confusion. Severe azotemia and metabolic acidosis were noticed. During emergency dialysis, she experienced a general tonic-clonic convulsion and collapsed. She was supported with mechanical ventilation and transferred to the intensive care unit. Due to status epilepticus, intravenous phenytoin and continuous midazolam infusion were administered. Cerebrospinal fluid (CSF) examination revealed pleocytosis (391 cells/lL) and high protein content (552.3 mg/dL), glucose (301 mg/dL), and lactic dehydrogenase (2037 IU/L) levels. The Gram stain and acid fast stain of the CSF were negative. Brain magnetic resonance imaging revealed acute hydrocephalus with tonsillar hernia. A neurosurgeon was consulted, but the families declined the emergency surgical decompression. Culture of blood and CSF samples grew Listeria monocytogenes on day 5 and day 7, respectively. Ceftriaxone was replaced with intravenous ampicillin two grams every 8 h and gentamicin 100 mg once daily. CSF was negative for cytomegalovirus, herpes simplex virus 1 IgM, and cryptococcal antigen. On day 14 and 19, higher protein content (1771.5 and 4502 mg/dL, respectively), lower glucose (10 and 93 mg/dL, respectively), and extremely high lactic dehydrogenase (41545 and 1913 IU/L, respectively) levels were disclosed in successive CSF studies. She remained in deep coma and developed multiorgan failure and died on day 34 after admission. CSF cultures for fungus and mycobacteria were negative.
Discussion The presentations of central nervous system (CNS) infections among patients with SLE are often atypical and indistinguishable from those of lupus CNS involvement. The clinical features of SLE patients with CNS infection include fever, febrile gastroenteritis, headache, and anorexia, while neck stiffness, coma, and seizures are less common [2, 6, 7]. The most important risk factors include pregnancy, glucocorticoid therapy, old age, and other co-existing immunocompromising conditions [2, 4, 6, 8–10]. Among patients with acute bacterial meningitis, CSF analysis usually demonstrates pleocytosis, ranging from 100% polymorphonuclear cells to 100% mononuclear cells while the protein concentration is moderately elevated (mean 168 mg/dL), and the CSF glucose concentration is usually below 34 mg/dL [11, 12]. However, as reported in this study, a high CSF glucose level does not exclude the possibility of listeria meningitis. Because of the rarity and non-representative manifestations, timely diagnosis of listeria meningitis in patients with SLE is usually confounded by other prevailing differential diagnoses [2, 4]. Since the gastrointestinal tract is usually the portal of entry for
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L. monocytogenes, a transient gastroenteritis may precede the full-blown meningitides and can be an important clue for correct diagnosis and appropriate empirical antibiotics. L. monocytogenes is an intracellular pathogen capable of spreading directly from cell to cell without exposure to the extracellular humoral immune system [13]. Immune response to infection with L. monocytogenes is predominantly cell mediated. CD4 T cell dysfunction is a major predisposing factor for L. monocytogenes infections [14]. With the evolving trend of intense immunosuppressive therapy, patients with SLE usually have abnormal cellmediated immunity and are susceptible to L. monocytogenes infections. In a study from Taiwan, among 17 SLE patients with CNS infection, Cryptococcus neoformans was identified in 10 patients (59%), L. monocytogenes in 4 (23%), Enterobacter aerogenes in one (6%), and Streptococcus pneumoniae in 2 (12%) [4]. In another retrospective study that enrolled 38 SLE patients with CNS infections, Mycobacterium tuberculosis was identified in 19 patients (50%), Cryptococcus neoformans in 12 patients (31.6%) and L. monocytogenes in 3 patients (7.9%) [2]. For treating L. monocytogenes infection, ampicillin and penicillin G are the drugs of choice [15]. Ampicillin and penicillin G have extended in vitro bactericidal activity at concentrations attainable in the CSF [15]. Combination therapy with gentamicin, a bactericidal agent, showed synergic effects and is recommended in treating listeria CNS infections, endocarditis, and infections in immunocompromised patients, such as patients with SLE [11, 16, 17]. Trimethoprim-sulfamethoxazole, a bactericidal agent against L. monocytogenes that attains adequate levels in serum and CSF, is an eligible alternative and has elucidated clinical efficacy in treating listeria meningitis for patients allergic to penicillin [18, 19]. Antibiotics treatment for listeria meningitis in immunocompromised patients is advised to be extended to four to eight weeks [11, 15]. In conclusion, Listeria monocytogenes, though uncommon, is potentially fatal and could be the cause of infection and ampicillin, and gentamicin should be included in the empirical antibiotic therapy for SLE patients with suspected CNS infection. Conflict of interest
None.
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