Primary Sjögren's syndrome (pSS) is a chronic, systemic, autoimmune disease that mainly affects the exocrine glands. From the clinical point of view, the most characteristic signs are dry mouth (xerostomia) and dry eyes (xerophthalmia). However, the clinical and serological spectra are wide and heterogeneous and—at onset or as it progresses—cytopenias, hypergammaglobulinemia or hypocomplementemia can develop, as can a number of extraglandular manifestations involving joints, lungs, kidneys, the nervous system, and the lymphatic system in the form of lymphoma. These extraglandular manifestations will mark the prognosis of the disease.1 The histological study of the glands reveals a lymphoplasmacytic infiltrate that leads to the destruction of acini and the ductal epithelial cells. Primary Sjögren's syndrome is considered a true autoimmune epithelitis,2 and is characterized by the production of certain autoantibodies, such as anti-Ro and anti-La, among others.

Primary Sjögren's syndrome can be found anywhere in the world. Over the years, the application of a variety of classification criteria has largely impeded the interpretation of the results of different studies. Its incidence in the general population differs according to sex, age and race. A recent meta-analysis, published in 2015,3 reported an estimated incidence of pSS of 6.92 per 100,000 population/year (95% confidence interval [CI], 4.98–8.86).

The same meta-analysis found a prevalence of pSS in the general population of 60.82 per 100,000 population (95% CI, 43.69–77.94); a subanalysis of that study estimated the prevalence of pSS, when classified exclusively on the basis of European/United States consensus criteria, at 73.57 cases per 100,000 population (95% CI, 37.51–109.63).

Primary Sjögren's syndrome is of growing interest in the scientific community and is estimated to be the second most widespread rheumatic disease. The lack of clear symptoms, especially in the early stages, and the clinical heterogeneity result in a considerable delay in the diagnosis. The disease occurs more frequently in women, with an estimated prevalence of 116.72 cases per 100,000 women (95% CI, 70.39–163.05) and 5.53 per 100,000 men (95% CI, 2.49–15.62), with a ratio of women to men of 10.72 (95% CI, 7.35–15.62).3 It occurs most frequently between the fourth and fifth decades of life, although it can develop at any age. In European cohorts, we find that 6% of the patients with pSS in the Italian population are diagnosed after the age of 65 years4 and that 15% of the pSS patients in the Spanish population are over 70 years of age when diagnosed.5 Primary Sjögren's syndrome is rare in children, with only 81 cases reported between 2000 and 2010; the age at diagnosis ranges between 4 and 16 years, with a mean age of 9.84 years and a ratio of girls to boys of 5:1.6

The GEMESS group reported their findings in a Spanish multicenter cohort in 2008.5 It involved 1010 patients who met the 1993 European criteria.7 This registry was established in 2005 and included incident and prevalent cases recorded between 1994 and 2007. Of the 1010 patients recruited, 707 also met the 2002 classification criteria of the American-European Consensus Group.8

The availability of a new homogeneous cohort of pSS patients in Spain will enable us to further our understanding of this complex and heterogeneous disease, update the epidemiological and clinical characteristics of pSS in our setting and improve the evaluation of certain outcome measures such as damage, comorbidity and the level of activity. It will also make it possible to compare subgroups of patients according to age, sex or serological profile, among other variables. There is lack of data on the diagnostic and therapeutic management of pSS in Spain, the percentage of patients with disease that is refractory to treatment, or the extent to which certain therapies are being employed. Thus, knowledge of these aspects would facilitate the standardized utilization of different tools for the diagnosis and evaluation of this disease, which would result in a greater uniformity of the clinical management of pSS in our population.

For this purpose, the Spanish Society of Rheumatology (SER [Sociedad Española de Reumatología]) has promoted its first registry of pSS patients (SJÖGREN'S-SER), an initiative of its working group on systemic autoimmune diseases (SAD-SER), with the methodological support and supervision of the SER research unit (RU-SER). SJÖGREN'S-SER is a descriptive, multicenter study of pSS patients who meet the consensus classification criteria of 2002.8 The 1-year cross-sectional phase, during which the patients were enrolled, has been completed. In this special article, we describe the objectives, design and methodology of SJÖGREN'S-SER, and some of the basic descriptive results as well as the strengths and weaknesses of the registry.

SJÖGREN'S-SER is a Spanish retrospective multicenter registry of pSS patients who meet the American-European classification criteria of 20028 being treated in Spanish rheumatology outpatient clinics. The data were obtained from the review of medical records and from interviews between physicians and patients, and were collected using an electronic format.

Thirty-three Spanish centers participated (Table 1). A total of 437 patients were included. The sociodemographic characteristics of the patients are shown in Table 2.

The 115 patients who declined the invitation to participate in the study had a mean age of 62.25±16.63 years. The majority were women and 3.48% were men. The minimum questionnaire completed by these 115 patients revealed no significant differences with respect to the group of participants.

The data concerning the prevalence in the registry cohort of the 6 criteria that comprise the American-European classification appear in Table 3. The table includes information on the numbers and percentages of patients who responded affirmatively to each of the 14 items encompassed in the 6 criteria, as well as the median of items recorded for these individuals, which was 5 (interquartile range: 4–5). Clinical criteria were those most often reported. The Schirmer I test was performed in 402 patients; it was indicative of disease in 85% (371 of 402). Unstimulated salivary flow rate was measured in 133 patients, representing 30% of the individuals in the cohort; the results were abnormal in 89%. Rose Bengal staining was used in 144 patients, 81% of whom had evidence of disease. Salivary gland scintigraphy was carried out in more than half the participants (253 of 437), with results indicative of disease in 87%. Minor salivary gland biopsy was carried out in 193 patients, 44% of the patients in the cohort; the histological criteria for disease were met in 69% of the cases in which this study was performed. In all, 93% of the patients tested positive for anti-Ro and 67% for anti-La at some point in the course of the disease (Table 3).

A total of 119 patients (27%) met the new classification criteria issued in 2012 by the Sjögren's International Collaborative Clinical Alliance Cohort-American College of Rheumatology (SICCA-ACR).11Table 4 shows the prevalence of each item in this cohort. The criteria that were most frequently met (86.47% of the patients) were serological findings (anti-Ro or anti-La antibodies or RF+ and ANA ≥1/320). Staining with lissamine green and with fluorescein was carried out in 38 and 56 patients, respectively; thus, the total ocular staining score (OSS)12 was not determined in 416 patients, more than 94% of the cohort.

The Spanish SJÖGREN'S-SER registry was designed for the purpose of characterizing a representative cohort of patients with pSS in Spain, in the routine clinical practice setting, in order to analyze the magnitude and distribution of the clinical signs, the biological features, the activity and cumulative damage of the disease, the associated comorbidity and the therapeutic management with and without drug treatment in the Spanish population. This will enable us to build on and update our understanding of this disease and plan strategies to be implemented in the early diagnosis, follow-up and management of the patients. This would not only benefit these individuals, but would facilitate strategic health planning, which is the responsibility of both primary care specialists and rheumatologists.

The participating patients are presently being followed up in the participating departments, a circumstance that reflects real-world routine clinical practice in pSS in Spain. The purpose of this cross-sectional study is to address certain well-defined objectives. We established the mandatory collection of certain variables for the database, most of which have standardized definitions, as they are used in validated damage and activity indices. The SJÖGREN'S-SER will make it possible to analyze subgroups according to age, clinical characteristics or biological features, will provide information on cardiovascular risk in pSS patients in the Spanish population and will outline the therapeutic management of pSS patients in Spain. Thus, this registry is an important knowledge instrument that will enable the multicenter study of pSS, either with the data stored in a database or the collection of data on additional variables in new lines of research.

The SJÖGREN'S-SER recruited a total of 437 patients who meet American-European classification criteria and are being treated in Spanish rheumatology departments. The demographic profile of a patient included in this cohort is similar to that of other series: a Caucasian woman over 50 years of age.5 The delay between the onset of the first symptoms and diagnosis is considerable, the median age at the time of the first symptom being 47 years and the median age at diagnosis being 50 years. The great majority of the patients presented with oral and ocular sicca syndrome. The Schirmer test was the technique of choice for the evaluation of ocular dryness in most of the patients. Despite its being a simple and readily available technique, unstimulated salivary flow rate was measured much less frequently than salivary gland scintigraphy in the evaluation of dry mouth (30% and 50%, respectively). In all, 69% of the minor salivary gland biopsies met the histological classification criteria for pSS. The majority of the patients enrolled in this cohort are serologically positive. Classical rose Bengal staining was performed in only 1 third of the patients. Staining with lissamine green and fluorescein was carried out in 9% and 13% of the patients, respectively. For this reason, the results of the OSS were not determined in over 94% of the participants. This circumstance is probably related to the recent introduction of these stains as classification criteria in the new 2012 criteria, and this may explain the low percentage of patients who met the SICCA-ACR criteria.

One of the strengths of our study lies in the fact that all the centers with specialized care in rheumatology of the SAD-SER group were invited to participate. These centers are not expected to have a selection bias, since none of them receive pSS patients referred from other institutions. They simply are centers in which there is a higher probability that the professionals perform a complete follow-up of the patients because of their interest in autoimmune diseases. Although no secondary care centers were included, it can be expected that a sufficiently representative proportion of the patients with pSS in Spain has been attended to at some point at the tertiary care level, either because of complications or in regard to some specific problem.

The extensive representation of the different Spanish autonomous communities among the participating centers and the large number of centers collaborating in the project will enable us to better adjust our basic knowledge of pSS to the particular features of our patient population.

One limitation of our study is the retrospective collection of the clinical characteristics and analytical data of the patients at the time of their inclusion in the study. This could pose certain problems such as the absence of control of the quality of the information, measurement errors that can result in a bias in the magnitude of the associations, difficulties in establishing the moment at which a given event occurred or problems related to the collection of data for important confounding variables.

Another limitation of the study is that it will only be representative of pSS patients attended to in rheumatology departments. Thus, there could be an overrepresentation of bone and joint and systemic autoimmune manifestations, as well as an underrepresentation of severe ocular involvement, among other signs.

The SJÖGREN'S-SER is a registry of pSS patients in Spain that is in the process of examining and analyzing a current, homogeneous, multicenter cohort. It has collected detailed and reliable information on the clinical signs, biological features, activity and damage of the disease, associated comorbidity and management with and without drug treatment.

The Spanish Society of Rheumatology (SER).

The authors declare they have no conflicts of interest.