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ARTICLES: J. de Seze, D. Devos, G. Castelnovo, P. Labauge, S. Dubucquoi, T. Stojkovic, D. Ferriby, and P. Vermersch The prevalence of Sjögren syndrome in patients with primary progressive multiple sclerosis Neurology 2001; 57: 1359-1363 [Abstract] [Full text] [PDF]

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Reply to Dr. Fox's Letter to the Editor

Jerome de Seze   (20 December 2001)

The prevalence of Sjögren syndrome in patients with primary progressive multiple sclerosis

Robert J Fox   (20 December 2001)

Reply to Dr. Fox's Letter to the Editor 20 December 2001
Jerome de Seze Hopital R. Salengro Lillie France Send Correspondence to journal: Re: Reply to Dr. Fox's Letter to the Editor j-deseze{at}chru-lille.fr Jerome de Seze	We thank Dr. Fox for the interest he has shown in our paper and for his comments. [1] Dr. Fox suggested that we should have excluded patients 7 and 9. Regarding patient 7, we agree that a positive Schirmer test after the age of 60 years should be treated with caution, in line with the recommendations of Vitali et al. [2] but, since the upper age limit for PPMS proposed by Thompson et al. is 65 years, [4] we included patients between the ages of 25 and 65. We do not, however, agree that there were grounds for excluding patient 9 since the inclusion criteria for our study were those of Thompson et al. [4] When these criteria were applied, patient 9 had possible PPMS and did not meet any of the exclusion criteria. Possible PPMS is rare in the spectrum of PPMS and can reasonably be excluded from therapeutic trials. However, had we excluded this patient we would have introduced a selection bias. It should be emphasized that the only patient with possible PPMS in our series had criteria for SS. This is why we stated that possible MS should be considered rather as "probably not MS". We agree that our study raises a number of questions, most notably whether to consider SS as being associated with MS (SS as secondary SS) or primary SS as being a disease mimicking PPMS. At the end of our manuscript we emphasize that we are not yet able to answer this question. However, in previous studies MS was never considered as a disease potentially inducing secondary SS. This is why we used the criteria for primary SS rather than those for secondary SS. Had we applied the criteria for secondary SS, [2] two of our patients would have been excluded and five others included, thereby increasing the proportion of PPMS cases associated with SS to 21.6% (13 of the 60 patients). In our routine experience (unpublished data), SS is rarely associated with relapsing–remitting or secondary progressive MS. Therefore, we considered the possibility that SS may mimic PPMS to be more likely than that of MS inducing secondary SS, but this is of course debatable. In reply to the comment on autonomic dysfunction, we previously demonstrated a frequency of around 50% but this abnormality was also frequent in relapsing–remitting and secondary progressive MS. [3] Lastly, we do not consider MS to be on the same level as the other autoimmune diseases usually associated with SS. We have no definite proof of B-cell implication in MS, unlike lupus erythematosus, sclerodermia, myasthenia gravis or rheumatoid arthritis, in which antigenic targets have been clearly defined. References: [1] de Seze J, Devos D, Castelnovo G, et al. The prevalence of Sjogren syndrome in patients with primary progressive multiple sclerosis. Neurology 2001;57:1359-1363. [2] Vitali C, Bombardieri S, Moutsopoulos HM, et al. Assessment of the European classification criteria for Sjogren's syndrome in a series of clinically defined cases: results classification criteria for Sjogren's syndrome in a series of clinically defined cases: results of a prospective multicentre study. The European Study Group on Diagnostic Criteria for Sjogren's Syndrome. Ann Rheum Dis 1996;55(2):116-121. [3] de Seze J, Stojkovic T, Gauvrit JY, et al. Autonomic dysfunction in multiple sclerosis: cervical spinal cord atrophy correlates. J Neurol 2001;248(4):297-303. [4] Thompson AJ, Montalban X, Barkhof F, et al. Diagnostic criteria for primary progressive multiple sclerosis: a position paper. Ann Neurol 2000;47:831-835
The prevalence of Sjögren syndrome in patients with primary progressive multiple sclerosis 20 December 2001
Robert J Fox Cleveland Clinic Foundation Cleveland OH Send Correspondence to journal: Re: The prevalence of Sjögren syndrome in patients with primary progressive multiple sclerosis foxr{at}ccf.org Robert J Fox	de Seze et al.[1] provide an important addition to our understanding of Sjorgren syndrome (SS) and primary progressive multiple sclerosis (PPMS), but several aspects of the report need comment. Two of the ten patients with SS and PPMS should have been excluded. Patient 7 was age 64, and according the European classification criteria used in this study,[2] the Shirmer test is not applicable over age 60. Without this test, the patient would not meet criteria for SS. Patient 9 had "possible PPMS," with normal brain and spine MRI and normal CSF. Patients with only "possible PPMS" are excluded from most studies of PPMS, and should have been excluded here, too. To my knowledge, the autonomic testing employed by the European criteria has not been evaluated in patients with MS or other myelopathies. Using different autonomic tests, the same authors have reported autonomic dysfunction in 56% of MS patients,[3] so an abnormal Shirmer test in 28% and abnormal scintigraphy in 40% of PPMS patients is not unexpected. Many autoimmune disorders are associated with SS (so-called secondary SS). Importantly, the European criteria for secondary SS is different from that for primary SS, presumably because of a high rate of false- positive SS classifications with primary SS criteria. For example, secondary SS criteria do not include SS A/SS B antibodies, since there is a high incidence of these antibodies in many autoimmune disorders, including MS. Given the purported autoimmune etiology of MS, it is unclear why primary SS criteria were used instead of secondary SS criteria. It would be of interest to know how many of the eight study subjects with SS and PPMS would fulfill secondary SS criteria. The authors dismiss the possibility that SS associated with PPMS could be secondary SS because of different brain MRI features between their patients with and without SS. Several autoimmune disorders have a different clinical course depending upon the presence of secondary SS, so different MRI characteristics between the two groups is not surprising. Indeed, other measured disease characteristics were similar between the two groups, which suggest that groups were more similar than different. Finally, the accompanying editorial [4] suggests that SS needs to be excluded before making a diagnosis of PPMS. Such an exclusion is not done with other autoimmune disorders and SS, so compelling evidence is needed before doing so with MS. References: [1] de Seze J, Devos D, Castelnovo G, et al. The prevalence of Sjogren syndrome in patients with primary progressive multiple sclerosis. Neurology 2001;57:1359-1363. [2] Vitali C, Bombardieri S, Moutsopoulos HM, et al. Assessment of the European classification criteria for Sjogren's syndrome in a series of clinically defined cases: results of a prospective multicentre study. The European Study Group on Diagnostic Criteria for Sjogren's Syndrome. Ann Rheum Dis 1996;55(2):116-121. [3] de Seze J, Stojkovic T, Gauvrit JY, et al. Autonomic dysfunction in multiple sclerosis: cervical spinal cord atrophy correlates. J Neurol 2001;248(4):297-303. [4] Giovannoni G, Thorpe J. Is it multiple sclerosis or not? Neurology 2001;57:1357-1358.