Headache is a common symptom among patients with systemic lupus erythematosus, but analysis of data from a large inception cohort found no evidence that it was a discrete neuropsychiatric manifestation of the disease.
While headache was reported by 17.8% of patients at the time of enrollment into the cohort, only 1.5% had "lupus headache" using the criteria of "severe, persistent, and nonresponsive" to treatment, even with narcotic analgesics, according to John G. Hanly, MD, of Dalhousie University in Halifax, Nova Scotia, and colleagues.
Rather, headache appeared to be a harbinger of other neuropsychiatric manifestations, including cerebrovascular disease (RR 2.29, 95% CI 1.17-6.15, P=0.019) and polyneuropathy (RR 3.25, 95% CI 1.45-7.26, P=0.004), the researchers reported online in Arthritis & Rheumatism.
In an accompanying editorial, Michael D. Lockshin, MD, of Weill-Cornell Medical College in New York City noted that, in his experience, severe, persistent, and nonresponsive headaches in patients with lupus are often quickly followed by serious complications such as cerebral edema and seizures.
"In fact, new, severe, persistent headache should trigger immediate evaluation for these other findings rather than be treated as an isolated symptom by itself," Lockshin stated.
Whether headache should be considered a specific disease-related entity in lupus has long been controversial, with some studies reporting a high frequency but other reports, including a meta-analysis, finding no greater prevalence than in the general population.
Nonetheless, in 1999, the American College of Rheumatology (ACR) defined 19 separate neuropsychiatric syndromes associated with systemic lupus erythematosus (SLE), including aseptic meningitis, polyneuropathy, seizures, cognitive dysfunction, and headache.
In addition, the SLE Disease Activity Index 2000 (SLEDAI-2K) not only includes headache as a disease-related entity, but weights it very strongly, with a score of 8 points. In comparison, arthritis is given 4 points and anti-DNA antibodies only receive 2 points.
To address this controversy, Hanly and colleagues from the Systemic Lupus International Collaborating Clinics (SLICC) network conducted a study of 1,732 patients recruited from 30 sites between October 1999 and September 2011.
Almost 90% of patients were women, mean age was 35, and mean disease duration at the time of enrollment was 5.6 months.
Disease activity at enrollment was moderate, there was little organ damage, and the medications used were typical, including steroids, anti-malarials, and immunosuppressants.
Among the 308 patients who reported headache, the specific types were migraine in 61% and tension in 39%. Additional small numbers were classified as intractable nonspecific or cluster headaches and intracranial hypertension. In only 26 of the patients was "lupus headache" specified on the SLEDAI-2K.
Overall, 55.1% of the headaches resolved, including all but one of those classified as lupus headache.
Headache did influence quality of life, the researchers noted. On the mental and physical components of the Short Form-36 questionnaire, respectively, patients with headache had lower scores (42.5 versus 47.8 and 38 versus 42.6, P<0.001 for both).
"This emphasizes the clinical impact of headache, regardless of etiology, on SLE patients," Handy and colleagues noted.
There was no association between onset of headache and autoantibodies including lupus anticoagulant and IgG anticardiolipin, either in univariate or multivariate analyses.
Whether or not headache is considered a specific lupus-related entity has therapeutic implications, Hanly and colleagues observed.
"For example, if headache is a primary manifestation of nervous system lupus in an individual patient, it is logical to introduce or intensify lupus-specific therapies with potential short- and long-term consequences, including drug toxicity," they wrote.
Lockshin echoed that observation in his editorial.
"All clinicians know that it is very tempting to treat an unexplained symptom in a lupus patient with a high-dose corticosteroid or other immunosuppressive agent on the assumption that the symptom indicates lupus activity," Lockshin commented.
Further arguing against headache as being specific to lupus is the fact that no mechanism has been identified, although it's possible that "our early twenty-first century tools are insufficient to the task of describing why or how headache occurs," Lockshin conceded.
Including headache as a measure of disease activity also has implications for research, pointed out Chaim Putterman, MD, of Albert Einstein College of Medicine in New York.
"In lupus clinical trials you need to have a certain degree of activity to say that the patient is eligible for the treatment you are offering. And, in fact, with the way lupus headache has been classified and scored, being very heavily weighted, just having a headache in and of itself might be sufficient to include a patient in a clinical trial," Putterman explained.
For example, in the current study, the authors noted that among patients whose disease activity scores included 8 points for lupus headache, the mean SLEDAI-2K score was 14.6, but this fell to 7.2 if headache was omitted as a variable.
In any case, including headache as a criterion in the disease activity score "no longer seems to serve a useful purpose. It is time for it to be discarded -- completely split off, so to speak -- from SLEDAI-2K," editorialist Lockshin argued.
Limitations of the study included the lack of a healthy control group and inconsistency in the use of investigations such as neuroimaging.
The lead author has received financial support from the Canadian Institutes of Health Research.
His co-authors reported receiving support from the U.K. Medical Research Council, the Korean Ministry for Health and Welfare, Lupus U.K., the Wellcome Trust, the National Institutes of Health, the Singer Family Fund for Lupus Research, Arthritis Research U.K., the Danish Rheumatism Association, the Novo Nordisk Foundation, and the Basque government.
- Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Arthritis & RheumatismSource Reference: Hanly JG, et al "Headache in systemic lupus erythematosus: results from a prospective, international inception cohort" Arthritis Rheum 2013; DOI: 10.1002/art.38106.
Arthritis & RheumatismSource Reference: Lockshin M "Splitting headache (off)" Arthritis Rheum 2013; DOI: 10.1002/art.38108.