隱球菌性腦膜炎在紅斑性狼瘡患者之臨床表現與實驗室特徵

Clinical and laboratory characteristics of cryptococcal meningitis in patients with systemic lupus erythematosus

目的：紅斑性狼瘡患者較容易得到伺機性感染。隱球菌腦膜炎患者，因無典型的腦膜炎症狀，患病初期可能被忽略。若延遲診斷或沒有適當的抗真菌治療，往往引起高死亡率。本研究的目的在探討11位紅斑性狼瘡患者合併隱球菌腦膜炎的臨床表徵，實驗室及血清學檢驗之特徵。方法：2036位符合SLE 診斷之台中榮總住院病患中，共有11位病患確定診斷為隱球菌腦膜炎，以回溯病例分析方式分析其臨床表現與實驗室特徵。結果：11位病患當中，10（90.9%）位病患有發燒，7（63.9%）位病患有頭痛的症狀，但只有2（18.2%）位病患出現腦脊髓膜刺激症狀（meningeal sign）。所有的病患有淋巴球低下（lymphopenia）之現象，只有33%的病患發炎指數（CRP）升高。45% 的病患腦脊髓液之白血球數目幾近正常（<10/mm3）。腦脊髓液中隱球菌抗原陽性率可高達100%，高於印地安墨染色與腦脊髓液培養。結論：紅斑性狼瘡併有淋巴球低下患者患者，若有不明原因發燒合併頭痛，應考慮是否有罹患隱球菌腦膜炎之可能。並且隱球菌抗原之檢測有助於早期診斷隱球菌腦膜炎。

Objective: Patients with systemic lupus erythematosus (SLE) are prone to develop opportunistic infections. Cryptococcal infection, particularly meningitis, frequently develops insidiously and is associated with high mortality if there is delayed diagnosis or inappropriate antifungal therapy. The aim of this study was to describe the clinical, laboratory and serological features of 11 SLE patients with cryptococcal meningitis. Methods: In total, 2036 patients, who fulfilled the diagnosis criteria for SLE, were hospitalized in Taichung Veterans General Hospital. Eleven patients were diagnosed as cryptococcal meningitis according to cerebrospinal fl uid (CSF) analysis. Results: Of the 11 patients, 10 (90.9%) patients had fever, 7 (63.9%) patients had headache, but only 2 (18.2%) patients had meningeal signs. At the time of investigation, all patients were in lymphopenic status, only 33% (3/9) of patients had elevated levels of serum C-reactive protein, and 45% (5/11) of patients had a low leukocyte count (<10/mm3) in CSF. The mean value of CSF protein was 95 mg/dL. Eighty-percent (8/10) of patients had elevated IgG index in CSF, while 83.3% (5/6) of patients had positive oligoclonal band. The positive rate for the latex agglutination test for cryptococcal antigen was 100% in CSF. The India ink stain was 81.8% positive and Cryptococcus neoformans was obtained in 81.8% of CSF cultures. All patients underwent corticosteroid treatment and most patients received immunosuppressants including cyclophosphamide, hydroxychloroquine, and azathioprine. The most common clinical manifestations of cryptococcal meningitis in our SLE patients were fever and headache; however, meningeal signs were rare. Lymphopenia seems to be a risk factor for cryptococcal meningitis. Conclusion: The clinical presentation of cryptococcal meningitis in SLE patients is non-specifi c and the cell count in CSF may be normal. Cryptococcal meningitis should be taken in mind in SLE patients under lymphopenic status with fever of headache.