Increased Risk of Subarachnoid Hemorrhage in Patients With Systemic Lupus Erythematosus: A Nationwide Population-Based Study YU-SHENG CHANG, 1 CHIA-JEN LIU, 2 WEI-SHENG CHEN, 3 CHIEN-CHIH LAI, 3 SHU-HUNG WANG, 3 TZENG-JI CHEN, 3 CHENG-HWAI TZENG, 3 CHANG-YOUH TSAI, 3 AND SHUU-JIUN WANG 3 Objective. A relatively common occurrence of spontaneous subarachnoid hemorrhage (SAH) in patients with systemic lupus erythematosus (SLE) has been noted; however, the subsequent studies were conflicting. This nationwide population- based study aimed to evaluate the risk of SAH in patients with SLE. Methods. We identified 16,967 SLE patients from the Taiwan National Health Insurance (NHI) database between 2000 and 2006, and compared the incidence rate of SAH with 16,967 randomly selected age- and sex-matched non-SLE subjects. A Cox multivariable proportional hazards model was used to evaluate the risk factors of SAH in the SLE cohort. Results. The SLE cohort had a higher risk of SAH, with an incidence rate ratio of 4.84 (P < 0.001). Despite a younger age, the mortality rate after SAH was significantly higher in the SLE cohort compared to all of the non-SLE SAH patients identified from the 1 million NHI beneficiaries (60.0% versus 38.9%; P  0.007). Age (hazard ratio [HR] 1.03, 95% confidence interval [95% CI] 1.01–1.05), platelet transfusion (HR 2.75, 95% CI 1.46 –5.17), red blood cell transfusion (HR 7.11, 95% CI 2.81–17.97), and a mean daily steroid dose >10 mg of prednisolone or equivalent (HR 4.36, 95% CI 2.19 – 8.68) were independent risk factors for the new onset of SAH. Conclusion. This study demonstrated that SAH is a rare but associated complication of SLE with a high mortality rate. Other than age, higher mean daily steroid use and a history of platelet or red blood cell transfusion were associated with the occurrence of SAH in patients with SLE. INTRODUCTION Systemic lupus erythematosus (SLE) is a systemic auto- immune disease affecting mainly women of childbearing age. The clinical manifestations spare no particular organ, but vary between individuals (1). Neuropsychiatric events, one of the major complications of SLE, occur in 30 – 40% of patients and warrant aggressive management (2). Among various neuropsychiatric manifestations, cerebrovascular diseases account for considerable morbidity and mortality (3). In contrast to ischemic stroke, where the increased risk and associated mechanisms in SLE patients are well stud- ied, subarachnoid hemorrhage (SAH) is much less well understood (3– 8). Spontaneous SAH due to an aneurysm rupture usually occurs between ages 40 and 60 years, with a slightly higher incidence in women. The major clinical symptom is the sudden onset of a severe headache, i.e., a “thunderclap headache,” in 97% of patients. The mortality and morbidity rate of SAH is high (9,10). Due to the ex- tremely low incidence of SAH, studying the risk of SAH in patients with SLE is difficult and the results are easily influenced by selection bias. Two studies reported a rela- Supported in part by the Taiwan National Science Coun- cil (grants 100-2314-B-010-019-MY2 and 100-2314-B-010- 018-MY3); the Taipei Veterans General Hospital (grants VGHUST101-G7-1-1, V101C-106, and V101E7-003); National Science Council support for the Center for Dynamical Bio- markers and Translational Medicine, National Central Uni- versity, Taiwan (NSC grant 100-2911-I-008-001); the Brain Research Center, National Yang-Ming University; and a grant from the Ministry of Education, Aim for the Top Uni- versity Plan. 1 Yu-Sheng Chang, MD: Shuang Ho Hospital, Taipei Med- ical University, New Taipei City, and National Yang-Ming University, Taipei, Taiwan; 2 Chia-Jen Liu, MD: National Yang-Ming University and Taipei Veterans General Hospi- tal, Taipei, and National Yang-Ming University Hospital, Yilan, Taiwan; 3 Wei-Sheng Chen, MD, Chien-Chih Lai, MD, Shu-Hung Wang, MD, Tzeng-Ji Chen, PhD, Cheng-Hwai Tzeng, MD, Chang-Youh Tsai, PhD, Shuu-Jiun Wang, MD: Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan. Drs. Chang and Liu contributed equally to this work. Address correspondence to Shuu-Jiun Wang, MD, Depart- ment of Neurology, Neurological Institute, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, Taipei, Taiwan, 112. E-mail: sjwang@vghtpe.gov.tw. Submitted for publication April 28, 2012; accepted in revised form August 27, 2012. Arthritis Care & Research Vol. 65, No. 4, April 2013, pp 601– 606 DOI 10.1002/acr.21846 © 2013, American College of Rheumatology ORIGINAL ARTICLE 601