Background/Purpose: Headache is common in SLE patients and in the general population. We examined the frequency, characteristics and attribution of headaches in a large, prospective, inception cohort of SLE patients and determined the association with global disease activity and health related quality of life.

Methods: An international network of 31 academic medical centers enrolled patients within 15 months of SLE diagnosis. Assessments occurred annually for up to 10 years for headache (5 types) and other neuropsychiatric (NP) events as per the ACR case definitions for 19 NP syndromes. Additional data were demographic and clinical variables, SLE global disease activity (SLEDAI-2K), SLICC/ACR damage index (SDI) and self-report mental (MCS) and physical (PCS) component summary scores of the SF-36. Statistical analyses of time to first headache (all headaches and migraine only) were based on Cox’s proportional hazards model. SF-36 scores were examined by linear regression models with generalized estimating equations to account for within patient correlation.

Results: Of the 1732 enrolled patients 89% were female with the following racial/ethnic distribution: Caucasian (48%), African (16%), Asian (16%), Hispanic (16%) and other (4%). At enrollment the mean (± SD) age was 34.6 ± 13.4 years, disease duration was 5.6 ± 4.8 months and followup was 3.8 ± 3.1 years. Mean SLEDAI-2K at enrollment was 4.0 ± 5.3 and SDI was 0.32 ± 0.78. Within the enrollment window (6 months pre-diagnosis up to the enrollment visit) the proportion of patients with headache was 17.8% subdivided into: migraine (55.2%), tension (35.1%), intractable non-specific (6.5%), cluster (2.4%) and intracranial hypertension (0.9%). The estimated proportion of patients ever reporting a headache increased to 57% after 10 years (Kaplan-Meier estimate) with similar subset distribution. Only 2% of patients in 0.6% of assessments had “lupus headache” in SLEDAI-2K scores over the study. Headache was associated with other NP events as indicated by Hazard Ratio (HR) estimates (95% CI) for: aseptic meningitis 3.8 (1.2, 12.0), autonomic disorder 13.3 (3.3, 53.6), cerebrovascular disease 2.3 (1.5, 3.6), anxiety disorder 2.2 (1.5, 3.2) and mood disorder 2.1 (1.6, 2.7). Headache increased with rising SLEDAI-2K (excluding “lupus headache” variable). The estimated risk for any 5 unit increase in SLEDAI-2K corresponded to an HR (CI) of 1.13 (1.03, 1.23). The mean (SD) SF-36 MCS scores were lower in patients with headache compared to patients without headache (mean ± SD: 42.5 ± 12.2 vs 47.8 ± 11.3; p < 0.001) as were PCS scores (38.0 ± 11.0 vs 42.6 ± 11.4; p < 0.001). Comparable results were found in all analyses when migraine was examined separately. All associations with headache and migraine alone remained significant after adjustment for gender, race/ethnicity, geographic location and age at diagnosis.

Conclusion: Headaches, particularly migraine and tension types, occur frequently among SLE patients and are associated with other types of NP events. Although the majority of headaches are not attributable to active lupus, they are associated with higher global SLE disease activity and lower self-reported health-related quality of life.