• John G. Hanly MD, FRCP(C),

    1. Queen Elizabeth II Health Sciences Centre, and Dalhousie University, Halifax, Nova Scotia, Canada
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  • for the Systemic Lupus International Collaborating Clinics

We thank Dr. Mitsikostas and colleagues for their helpful comments on our study and for drawing our attention to their own contributions to the study of headache in patients with systemic lupus erythematosus (SLE), some of which we cited. The meta-analysis of headache in SLE that they performed is a landmark paper in the field ([1]). Their prospective, controlled study over 12 months comparing patients with SLE, patients with multiple sclerosis (MS), and matched healthy controls ([2]) indicated a similar prevalence of migraine in the 3 groups (21%, 23%, and 22%, respectively) and a higher prevalence of chronic tension-type headache in both patients with SLE and patients with MS compared with healthy controls (12.5%, 8.3%, and 1.4%, respectively). Overall, these studies and our own study indicate that patients with SLE are not more likely to experience severe isolated headache, including migraine, compared with disease controls and healthy controls. The lack of association between isolated headaches, global SLE disease activity, and lupus autoantibodies further undermines the previously held belief that such headaches are among the primary manifestations of neuropsychiatric SLE. Despite these findings, it should be acknowledged that the occurrence of headache in patients with SLE, regardless of attribution, impacts negatively on patient self-reported health-related quality of life ([2]).

The findings of these previous studies raise several important issues, some of which were highlighted in an editorial by Dr. Lockshin ([3]), which accompanied publication of our study. For example, what are the optimal diagnostic and treatment strategies to deal with headache in patients with SLE? In the spirit and tradition of multidisciplinary models of care for other manifestations of SLE (e.g., nephritis), the management of headache may require input from non-rheumatologic disciplines such as neurology, psychology, and pain management. The potential benefits of this approach are emphasized by the frequent co-occurrence of other neuropsychiatric manifestations, including mood disorders ([2]), with headache. Second, how should isolated headache be accommodated in the formal assessment of disease activity in patients with SLE, using current disease activity instruments? This issue is more complex and likely to be more challenging to address.

Table 1 summarizes headache variables and their definitions in 4 of the most frequently used SLE disease activity instruments ([4]). As acknowledged in our recent study and as reported by other investigators ([5]), headache may be part of a broader neuropsychiatric manifestation of primary SLE such as aseptic meningitis, seizures, or cerebrovascular events. Although such presentations are acknowledged in 2 of the 4 instruments, the occurrence of isolated severe headache, which includes migraine and “lupus headache,” is also described. The recent studies shed doubt on the association of such headaches with SLE ([2]) and also indicate substantial inconsistency in the recognition and reporting of lupus headache in particular. Thus, although any change to these validated measures would require careful revalidation, it is timely to review the inclusion of isolated headache in disease activity measures and to consider either defining them more accurately or completely removing them from the instruments.

Table 1. Headache variable definitions in SLEDAI, SLAM, BILAG, and ECLAM*
Instrument (ref.)Variable nameDefinition
  1. SLAM-R = Systemic Lupus Activity Measure-Revised; BILAG = British Isles Lupus Assessment Group; ECLAM = European Consensus Lupus Activity Measure; SELENA−SLEDAI = Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); CSF = cerebral spinal fluid; CNS = central nervous system.
SLEDAI 2000 ([6]) and SELENA−SLEDAI ([7])Lupus headacheSevere, persistent headache; may be migrainous but must be nonresponsive to narcotic analgesia
SLAM ([8])HeadacheIncluding migraine equivalents
SLAM-RHeadacheIncluding migraine equivalents and aseptic meningitis
BILAG 2004 ([9])Aseptic meningitisAll of the following criteria: acute/subacute onset, headache, fever, abnormal CSF (increased protein and/or lymphocyte predominance) but negative cultures; preferably photophobia, neck stiffness, and meningeal irritation should be present as well but are not essential for diagnosis; exclude CNS/meningeal infection, intracranial hemorrhage
 Severe lupus headache (unremitting)Disabling headache unresponsive to narcotic analgesia and lasting ≥3 days; exclude intracranial space−occupying lesion and CNS infection
 Headache from intracranial hypertensionExclude cerebral sinus thrombosis
ECLAM ([5])Headache/migraineRecently developed, persistent, or recurrent; poorly responsive to the most commonly used drugs, but partially or totally responsive to corticosteroids