This may be a part of the puzzle around EDS, intercranial hypertension, and the surprisingly high incidence of autoimmune problems in our population.
Idiopathic intracranial hypertension (IIH; also called pseudotumor cerebri [PTC] or benign intracranial hypertension) is surprisingly common in patients with systemic lupus erythematosus (SLE) and should be considered when working up SLE patients who have intractable headache, according to a report by Ji-Min Kim, MD, and colleagues published online February 2 in Lupus.
The retrospective study, which was conducted at The Catholic University of Korea College of Medicine in Seoul, consisted of a chart review of 1084 patients with SLE, 47 of whom had undergone cerebrospinal fluid (CSF) studies because of intractable headache, and eight of whom were then diagnosed as having IIH.
Dr. Kim told Medscape Medical News that "17% of the lupus patients with intractable headache with CSF studies had IIH. Rheumatologists (or physicians) have thought that lupus patients with IIH are very rare, so if the physicians met a lupus patient with headache, they tended not to consider IIH as a possible cause. The fact that none of these lupus patients with IIH were obese was an additional finding."
IIH, the clinical syndrome of increased intracranial pressure in the absence of space-occupying lesions, or ventriculomegaly, is usually seen "as severe headache in obese women of childbearing age, [and] may result in severe ophthalmologic complications," the authors write.
Among the SLE patients who had undergone CSF studies, all IIH cases were in women 14 to 32 years of age, and none were obese. The most common presenting symptoms were headache, nausea, vomiting, and blurred vision, and all of the IIH patients had an SLE disease activity index score of six or higher at admission.
All eight patients were treated with more than one mg/kg per day of intravenous (IV) steroids (methylprednisolone or dexamethasone). Two received IV cyclophosphamide pulse therapy, three received acetazolamide, and seven received IV mannitol. All recovered with no residual ophthalmologic complications. Dr. Kim recommends considering steroids as first-line therapy.
"If lupus patients have nausea and blurred vision with severe headache, physicians should start the workup for IIH," Dr. Kim advised. "Headache caused by IIH is usually unresponsive to any analgesics or narcotics. The diagnosis may be suspected on the basis of history and examination."
"However, lupus patients often present atypical symptoms and signs," Dr. Kim pointed out. "To confirm the diagnosis, [and to exclude] alternative causes, several investigations are required, such as neuroimaging (usually with computed tomography or magnetic resonance imaging), cerebrospinal fluid examination, and examination of the retinas."
Five of eight IIH patients did not have papilledema; the researchers suspect that this might have slowed the diagnosis of IIH. Dr. Kim said that "papilledema is not essential to diagnose IIH. Clinical features, including typical symptoms associated with increased intracranial pressure, increased CSF opening pressure with normal composition, and normal findings of brain imaging, are sufficient to diagnose IIH. Moreover, slight edema of the optic disc may not be detected if using the direct ophthalmoscope, as is usually done in the emergency room."
Data Convincing, But Relationship Tenuous
Alon Hershko, MD, PhD, from the Department of Medicine at Meir Medical Center, Kfar Saba, Israel, reviewed the study for Medscape Medical News. Dr. Hershko and colleagues previously reported their 26-year experience with IIH related to SLE (Semin Arthritis Rheum. 2008; 38: 110-115).
"I was delighted to see that their data strongly support what we published in 2008 (so much so that the concluding words in both works are very similar). I think that their data are convincing and clearly presented," he said.
"In our work, we found an effect of ethnic background on the susceptibility to develop IIH, which is not reported by Kim et al. This difference may be due to the fact that the Korean population is more homogeneous in terms of ethnicity," Dr. Hershko explained.
"I believe that in light of the available data, IIH is likely in SLE patients with intractable headaches, and lumbar puncture should therefore be considered. Corticosteroids are reasonable, especially if the patient presents other indications for this treatment (e.g., renal disease). Acetazolamide might also be beneficial," said Dr. Hershko. However, he cautioned that "these recommendations are based on clinical experience rather than on solid evidence."
Neuro-ophthalmologist Deborah I. Friedman, MD, professor of neurology and neurotherapeutics and of ophthalmology at the University of Texas Southwestern Medical Center in Dallas, also reviewed the study for Medscape Medical News.
She said that the relation between SLE and PTC has always been a bit tenuous, and is hesitant to call this condition IIH in the presence of SLE.
"Lupus ends up on lists of 'associated conditions' with PTC/IIH, although there have never been any good studies proving it. Note that there is also a postulated relationship between lupus and migraine, so this seems as though patients with lupus frequently have headaches," Dr. Friedman explained. "This is a retrospective study and likely did not capture all of the patients with lupus and chronic headache, but looked only at the ones who had a lumbar puncture. So the 17% number in the chronic headache group is likely an overestimation," she noted.
Dr. Friedman also pointed out that most patients with active lupus are treated with corticosteroids, and that withdrawal of corticosteroids is associated with intracranial hypertension. "Thus, treatment of their intracranial hypertension with corticosteroids is not recommended unless the high-pressure syndrome is felt to be a direct consequence of lupus," she said.
Finally, Dr. Friedman questioned whether four of the eight patients truly had PTC/IIH, because the elevation of pressure was not significantly high and they did not have papilledema. "I would only workup for PTC if papilledema was present in the setting of other typical symptoms.
In general, it is hard to make anything of IIH studies that don't involve an ophthalmologist or neuro-ophthalmologist. A slightly elevated pressure doesn't really confirm the diagnosis, especially when no papilledema is present," Dr. Friedman said.
Dr. Kim, Dr. Hershko, and Dr. Friedman have disclosed no relevant financial relationships.
Lupus. Published online February 2, 2012. Abstract
Janis C. Kelly • Medscape Medical News © 2012 WebMD, LLC