Of the major autoimmune connective tissue diseases, Sjören’s syndrome (SS) is perhaps the least well understood. Both primary and secondary forms of SS occur, but their phenotypes are not well defined. No less than 10 sets of diagnostic/classification criteria for SS have been applied since 1965 (1–11), but none have been universally adopted or accepted by the American College of Rheumatology. These criteria have often identified patients with similar clinical features, but not necessarily with a common disease process. There is scant longitudinal data on SS. The absence of recognized classification criteria contributes to delays in diagnosis for individual patients and hampers research into SS due to small sample sizes and heterogeneously diagnosed patient populations.
To address these issues, the ongoing Sjören’s International Collaborative Clinical Alliance (SICCA) was funded under a US National Institutes of Health contract beginning in 2003. The SICCA project has the goals of 1) designing and implementing an international SS registry for collecting and storing clinical data and biospecimens; 2) developing standardized classification/diagnostic criteria for SS that are universally applicable; and 3) providing these resources for future studies of SS funded by the NIH or comparable agencies.
SICCA is an ongoing longitudinal multi-site observational study that is developing and studying a large and growing cohort of uniformly evaluated individuals from ethnically diverse populations to achieve these goals. SICCA participants must be at least 21 years of age and have: a complaint of dry eyes or dry mouth or a previous suspicion or diagnosis of SS or elevated serum ANA, RF, SS-A, or SS-B or bilateral parotid enlargement in a clinical setting of SS, or a recent increase in dental caries, or have diagnoses of rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and thus have secondary SS. We enroll individuals using broad criteria to create a cohort reflecting a wide range of symptoms, from possible early SS to well established disease. However, to avoid circular reasoning in developing a new definition of SS, no diagnostic labels are used at study entry even for participants previously diagnosed with primary SS.
SICCA recruits participants using announcements in patient support group publications and public media, and from patients referred by intramural and extramural practices or clinics having populations meeting these enrollment criteria, Enrollment began in fall 2004 at six international SICCA Research Groups that recruit, enroll and examine participants, and collect and ship biospecimens to the central repository in San Francisco. The Groups are located at University of Buenos Aires and German Hospitals, Buenos Aires, Argentina; Peking Union Medical College Hospital, Beijing, China; Copenhagen University Hospital Glostrup, Denmark; Kanazawa Medical University, Japan; Kings College London, UK; and University of California, San Francisco, USA.
All SICCA groups use the same protocol-directed methods to provide uniform evaluations and record data from ocular, oral and rheumatologic examinations and biospecimen collections. The latter include serum, DNA, whole and parotid saliva, tears, conjunctival cells, frozen and paraffin-embedded labial salivary gland (LSG) biopsy specimens, peripheral blood mononuclear cells and plasma from all participants and DNA from blood-related controls. SICCA participants, who have any objective measures of salivary hypofunction, ocular dryness, any amount of focal lymphocytic infiltration in their LSG biopsy specimen, or positive anti SS-A/-B (95.3% of the cohort so far) at their baseline examination, are being recalled two years later to repeat all examinations and specimen collections. Participants with no positive objective tests are not recalled. This group may serve as controls in future analyses. SICCA clinical questionnaires, data collection forms, and protocols for clinical examination and specimen collection are available for review from the SICCA website <http://sicca.ucsf.edu>