Sjogren’s Syndrome with Interstitial Lung Disease

@#Sjogren’s syndrome (SS) is an autoimmune disease affecting exocrine glands with known properties to cause chronic systemic multi-organ disease involvement. It produced the typical features of sicca syndrome, but due to insidious onset of the disease, patient may present with complications of the condition at the initial presentation. We present a case of primary Sjogren’s syndrome (SS) who first presented with pulmonary manifestations and was subsequently diagnosed as Lymphocytic Interstitial Pneumonia (LIP). The patient was extensively investigated and received appropriate treatment modalities.

Puntaje de tinción ocular en pacientes con diagnóstico de síndrome de Sjögren en una institución de salud en Medellín, Colombia / Ocular staining score in patients diagnosed with Sjögren syndrome in a health institution in Medellín, Colombia

RESUMEN Introducción: El síndrome de Sjögren es una enfermedad autoinmune asociada a múltiples factores, tanto genéticos como ambientales, que afecta principalmente a las glándulas salivales y lagrimales con infiltración celular de estas, lo cual causa síntomas secos. Con frecuencia se describe la queratoconjuntivitis sicca y sus complicaciones. Sus criterios clasificatorios han cambiado a lo largo de los años por la diversidad de los órganos implicados y los espectros clínicos de la enfermedad. Hoy se cuenta con parámetros clínicos y paraclínicos para su identificación; uno de estos, el puntaje de tinción ocular ocular staining score (OSS, por sus siglas en inglés), estandarizado a partir de la cohorte SICCA. Objetivo: Describir los hallazgos en la evaluación ocular, el resultado de las pruebas que hacen parte del OSS y las características clínicas de los criterios clasificatorios en pacientes con síndrome de Sjögren en el servicio de consulta externa de reumatología de un hospital universitario en el noroccidente colombiano. Método: Se condujo un estudio observacional, descriptivo y de corte transversal. Se describieron las características de los criterios clasificatorios del síndrome de Sjögren, incluyendo el puntaje de tinción ocular durante un año. Se realizaron las pruebas clínicas y tinciones oculares estandarizadas, evaluando características de la superficie ocular, producción lagrimal y tinciones con verde lisamina y fluoresceína sobre la conjuntiva y la córnea. Según los hallazgos se asignó una puntuación a cada parámetro para evaluar positividad, de acuerdo con el estándar clasificatorio. Las variables cualitativas se expresaron por medio de frecuencias absolutas y relativas y las cuantitativas como mediana y rango intercuartílico (P25-P75), según la distribución de los datos. Se empleó el paquete estadístico Epidat, versión 4.2. Resultados: Se incluyeron 28 pacientes. Los síntomas de ojo seco estuvieron presentes en el 89,2% de ellos; un 96,4% tuvo hallazgos positivos en el examen ocular y el 78,5% alcanzó un puntaje a favor de los criterios clasificatorios en la evaluación del OSS. La mediana del OSS fue 6,14; los anticuerpos anti-Ro fueron positivos en un 57,1%. Conclusión: La evaluación ocular por medio de pruebas objetivas es un método sencillo y reproducible en los pacientes con síndrome de Sjögren. Los índices más afectados fueron aquellos de disminución en la producción lagrimal. Las tinciones oculares no tuvieron una relación directa con la positivad de anticuerpos ni del factor reumatoide.

ABSTRACT Introduction: Sjögren's syndrome is an autoimmune disease associated with multiple genetic and environmental factors. It mainly affects the salivary and lacrimal glands with cellular infiltration leading to dry eye symptoms, with keratoconjunctivitis sicca and its complications often being described. Its classification criteria have changed over the years, due to the diversity in the organs involved and clinical spectrum of the disease. Today, there are clinical and para-clinical parameters for its identification. One of these is the ocular staining score (OSS), standardised from the SICCA cohort. Objective: To describe the findings in the ocular evaluation, the results of the tests of the OSS, and the clinical characteristics of the classification criteria in patients with Sjögren syndrome in the outpatient service of Rheumatology Outpatient Department a university hospital in north-western Colombia. Methods: An observational, descriptive, cross-sectional study was conducted. The characteristics of the Sjögren syndrome classification criteria were described, including the OSS score for one year. Clinical tests and standardised ocular stains were performed, evaluating characteristics of the ocular surface, tearproduction, and lissamine green and fluorescein stains on the conjunctiva and cornea, assigning, according to the findings, a score to each parameter in order to assess positivity according to the classification standard. The qualitative variables were expressed by means of absolute and relative frequencies, and the quantitative ones as the median and interquartile range (P25-P75), according to the distribution of the data. Epidat statistical package, version 4.2, was used. Results: A total of 28 patients were included. Dry eye symptoms were present in 89.2%, 96.4% had positive findings in the eye examination, and 78.5% had a score on the OSS according to the classification criteria. The median OSS was 6.14, and anti-Ro antibodies were positive in 57.1%. Conclusion: Eye evaluation by objective tests is a simple and reproducible method in patients with Sjögren's syndrome. The most affected indices were those of a decrease in tearproduction. The ocular stains did not have a direct relationship with the positivity of antibodies, nor rheumatoid factor.

Ecografía de la glándula salival mayor en pacientes con síndrome seco: descripción de una cohorte colombiana, reporte preliminar / Major salivary gland ultrasound in patients with dry syndrome: Description of a Colombian cohort, and a preliminary report

RESUMEN Introducción: El síndrome de Sjögren (SS) es una enfermedad autoinmune que afecta a las glándulas exocrinas condicionando síndrome seco. Los criterios diagnósticos se basan en pruebas serológicas, oftalmológicas, histopatológicas y flujo salival. Se ha propuesto el uso de la ecografía glandular salival como prueba diagnóstica. Escasos estudios se han realizado en Latinoamérica. Objetivo: Describir las alteraciones ecográficas en las glándulas salivales en una población colombiana que asiste al servicio de reumatología con síntomas secos. Materiales y métodos: Estudio de corte transversal; análisis preliminar de 50 pacientes que asisten por consulta externa (agosto de 2019 a enero de 2020). Evaluación sociodemográfica y clínica a través de cuestionario estructurado, pruebas paraclínicas y oftalmológicas, biopsia de glándula salival menor y valoración ecográfica de las glándulas salivales mayores (puntuación 0-6 basada en De Vita). Análisis univariado y bivariado (Chi-cuadrado y prueba de Fischer). Resultados: El 94% de la población eran mujeres y el 38% tenían SS. El promedio de edad fue de 55,9 ± 9,6 arios. La proporción de pacientes con ecografía positiva para el SS y diagnóstico por criterios del SS es mayor respecto a los pacientes con ecografía negativa (p< 0,0001). Los pacientes con ecografía positiva presentaron mayor proporción de anti-La (p = 0,002), ANA (p = 0,008), anti-Ro (p< 0,0001), linfopenia (p = 0,007), xerostomía objetiva (p = 0,019) y subjetiva (p = 0,041). Conclusiones: La ecografía podría considerarse una herramienta útil en el diagnóstico del SS, dado que los pacientes que presentan alteraciones ecográficas glandulares tienen una mayor proporción de perfil inmunológico positivo (anti-Ro, ANA, anti-La) y su positividad se encuentra asociada al SS por criterios. Se requieren nuevos estudios para evaluar las características operativas de la prueba.

ABSTRACT Introduction: Sjögren's syndrome (SS) is an autoimmune disease affecting the exocrine glands causing dry syndrome. The diagnostic criteria are based on serological, ophthalmological, histopathological, and salivary flow tests. The use of salivary gland ultrasound has been proposed as a diagnostic test. Few studies have been carried out in Latin America. Objective: To describe the ultrasound patterns in the salivary glands in the Colombian population seen in the Rheumatology Department due to dry symptoms. Materials and methods: Cross-sectional study; a preliminary analysis was performed on 50 patients attending the Outpatient Clinic (August-January 2020). A sociodemographic and clinical evaluation was made using a questionnaire. Paraclinical and ophthalmological tests, minor salivary gland biopsy, and ultrasound assessment of the major salivary glands (De Vita score 0-6) were the main items to evaluate. Univariate and bivariate analyses (Chi-squared, Fischer test) were performed. Results: Most (94%) of the population were women, and 38% had SS. The mean age was 55.9±9.6 years old. The proportion of patients with positive ultrasound for SS and a diagnosis using SS criteria was higher compared to patients with negative ultrasound (p<.0001). Patients with positive ultrasound had a higher proportion of anti-La (p=.002), ANAS (p=.008), anti-Ro (p<.0001), lymphopenia (p=.007), and objective and subjective xerostomia (p=.019 and p=.041, respectively). Conclusions: Ultrasound assessment could be considered a useful tool in the diagnosis of SS, since more patients presenting with glandular ultrasound abnormalities have a higher positive immunological profile (anti-Ro, ANAS, anti-La) and their positivity is associated with SS criteria. New studies are required to evaluate the operational characteristics of the test.

Diagnóstico diferencial dentro del espectro del síndrome de Sjögren / Differential diagnosis within the spectrum of Sjögren's syndrome

RESUMEN El síndrome de Sjögren es una enfermedad autoinmune sistémica caracterizada clínicamente por ojo y boca secos, acompañados de manifestaciones extraglandulares como edema de glándulas submandibulares y parotidomegalia. La prevalencia varía en diferentes estudios epidemiológicos del 5 al 30%, dependiendo de la población estudiada. La xeroftalmia es más común en mujeres y su frecuencia incrementa con la edad. Cuando evaluamos un paciente con síndrome de Sjögren, debemos tener en cuenta diagnósticos diferenciales que pueden simular esta patología, como causas locales, sistémicas que incluyen metabólicas, infecciosas, medicamentosas, infiltrativas y malignas. Es necesario el estudio de otras causas para decidir si la terapia dirigida puede ser benéfica y evitar riesgos de eventos adversos en pacientes con síndrome sicca no autoinmune. Se realizó una revisión narrativa sobre los diagnósticos diferenciales en el espectro de paciente con síndrome seco a través de búsqueda de la literatura en las bases de datos PubMed y Google Scholar.

ABSTRACT Sjögren's syndrome is a systemic autoimmune disease clinically characterised by dry eye and mouth accompanied by extra-glandular manifestations such as oedema of the sub-mandibular glands and parotidomegaly. The prevalence of dry eye varies from 5% to 30% in different epidemiological studies, depending on the studied population. Xerophthalmia is more common in women and its frequency increases with age. When evaluating a patient with Sjogrens syndrome, differential diagnoses with disease that can simulate this pathology must be taken into account, such as local, systemic causes that include metabolic, infectious, medicinal, infiltrative, and malignancy. The study of other causes is necessary to decide whether targeted therapy can be beneficial and avoid risks of adverse events in patients with non-autoimmune sicca syndrome. A narrative review was conducted on the differential diagnoses in the spectrum of patients with 'dry syndrome' using a literature search in the PubMed and Google Scholar databases.

Questions as regards the recognition of elderly-onset primary Sjögren's syndrome: Where we are and where we would rather be / Preguntas sobre el reconocimiento del síndrome de Sjögren primario con inicio en la edad avanzada: ¿dónde estamos y dónde preferiríamos estar?

ABSTRACT Several epidemiological studies have suggested that the prevalence of the onset of primary Sjögren's Syndrome in the elderly (EOpSS) is significantly higher (between five to eight times) than in other age groups. However, when a literature review was performed, the number of patients with EOpSS was much lower than epidemiologically expected. An evaluation was performed on Sjögren (sicca) syndrome, including immunological markers, labial salivary glands biopsy, and some extra-glandular manifestations. These could be confounding factors in the elderly patients, much more so than in other age groups, and lead to a misdiagnosis of EOpSS. This article presents a review of the most common difficulties that may be present in the recognition of EOpSS, and highlights the lack of elderly patient-centred studies as the most important unmet need.

RESUMEN Varios estudios epidemiológicos han sugerido que la prevalencia del síndrome de Sjögren primario (SSp) en la población de edad avanzada (Elderly-Onset primary Sjögren's Syndrome [EOpSS], según la clasificación inglés) es considerablemente mayor (entre 5 y 8 veces) que en grupos de edad diferente. Sin embargo, una revisión sistemática de la literatura mostró que el número de pacientes con EOpSS era mucho menor de lo que se esperaba epidemiológicamente. La evaluación del síndrome de sicca, los marcadores inmunológicos, la biopsia de las glándulas salivales labiales y algunas manifestaciones extraglandulares podrían convertirse en factores de confusión en pacientes de edad avanzada mucho más frecuentemente que en personas de otros grupos de edad, lo que favorecería un diagnóstico erróneo del EOpSS. En este artículo se revisan las principales dificultades que pueden afectar al reconocimiento del EOpSS, destacando la falta de estudios centrados en el paciente anciano como la necesidad insatisfecha más importante.

Evolution of diagnostic criteria for Sjögren′s Syndrome / 口腔疾病防治

@#Sjögren′s syndrome lacks a single and objective diagnostic index, and its diagnosis often requires comprehensive analysis according to classification criteria. With increasing research and a deepening understanding of the disease, the classification criteria are constantly being adjusted and revised. The sensitivity and specificity of the diagnosis have gradually improved, which has the value of diagnostic criteria largely. Since 1965, more than ten diagnostic criterias for Sjögren′s syndrome have been published. After debate and experience, international criteria with wide applicability have gradually replaced regional criteria. In the evolution of the diagnostic criteria, the diagnostic rules and evaluation methods have become more concise and unified. Techniques with poor specificity and operative difficulty, which are not easy to popularize or apply in the clinic, have gradually been eliminated. A diagnostic system based on an objective examination and subjective symptoms has gradually formed, and lip gland biopsy and serum autoantibody sampling have demonstrated great diagnostic value. The optimization of diagnostic rules makes the diagnosis of this disease more efficient and scientific. This paper reviews the characteristics of and differences in diagnostic criteria for Sjögren′s syndrome and analyzes the internal logic of the evolution of different diagnostic criteria in light of development in research on the disease with the hope of benefitting the diagnosis, treatment and related research of Sjögren′s syndrome.

Sjögren's syndrome and sicca symptoms in patients with systemic sclerosis / Síndrome de Sjögren y síntomas de sicca en pacientes con esclerosis sistémica

Introduction: Several autoimmune diseases can be accompanied by dysfunction of the salivary glands, regardless of the presence or absence of association with Sjögren's syndrome (SS). A recent study by Maeshima and colleagues found salivary hyposecretion in 58.3% of patients with various connective tissue diseases, particularly systemic sclerosis (SSc). Objective: To determine the prevalence of SS and Sicca symptoms in patients with SSc. Assess whether the presence of SS in patients with SSc causes worsening of the disease. Methods: 69 SSc patients periodically monitored in the rheumatology clinic at NHU/UFMS composed the study. All patients were questioned about sicca symptoms and clinical features. We evaluated the RF levels, ANA, anti-Ro/La. Results and discussion: 69 SSc patients were enrolled in the study, with average age of 51.2 years, 98.3% females and 50% caucasian. Sicca symptoms were present in 48 patients (69.5%) with SSc; 43/69 patients (62.3%) with dry mouth and 46/69 patients (66.7%) with dry eye. Sicca symptoms were observed in patients with limited and diffuse form of the disease. The antinuclear antibody positivity was 95% and the rheumatoid factor (RF) was observed in 14 patients (23.3%). Anti-Ro (SSA) antibodies were detected in 11 patients (15.9%) and anti-La (SSB) in 6 patients (8.7%) in this study. Only 16 patients (23.2%) had true SS, according to the American-European Consensus Group on Classification Criteria for Sjögren's syndrome. The findings in the study corroborate data found in literature. Conclusion: This study confirms that Sicca symptoms are found in a large number of patients with SSc. Sjögren prevalence was observed in 23.2% of the SSc patients, including patients with limited and diffuse cutaneous subtype of disease. Key words: Sicca syndrome, Sjögren's syndrome, overlap, autoantibodies, systemic sclerosis

Introducción: Varias enfermedades autoinmunes pueden ir acompañadas de disfunción de las glándulas salivales, independientemente de la presencia o ausencia de asociación con el síndrome de Sjögren (SS). Un estudio reciente de Maeshima y sus colegas hallaron hiposecreción salival en el 58,3% de los pacientes con diversas enfermedades del tejido conectivo, particularmente la esclerosis sistémica (SSc). Objetivo: Determinar la prevalencia de los síntomas de SS y sicca en pacientes con SSc. Evaluar si la presencia de SS en pacientes con SSc provoca empeoramiento de la enfermedad. Métodos: 69 pacientes SSc periódicamente monitorizados en la clínica de reumatología en NHU/UFMS formaron parte del estudio. Todos los pacientes fueron interrogados acerca de síntomas sicca y características clínicas. Se evaluaron los niveles de FR, FAN, anti-Ro/La. Resultados y discusión: Se incluyeron 69 pacientes SSc en el estudio, con edad promedio de 51,2 años, 98,3% mujeres y 50% caucásicos. Los síntomas de Sicca estuvieron presentes en 48 pacientes (69,5%) con SSc; 43/69 pacientes (62,3%) con boca seca y 46/69 pacientes (66,7%) con ojo seco. Síntomas sicca se observaron en pacientes con forma limitada y difusa de la enfermedad. La positividad del anticuerpo antinuclear fue del 95% y el factor reumatoideo se observó en 14 pacientes (23,3%). Anticuerpos Anti-Ro (SSA) se detectaron en 11 pacientes (15,9%) y anti-La (SSB) en 6 pacientes (8,7%) en este estudio. Sólo 16 pacientes (23,2%) tenían verdaderas SS, según el Grupo de Consenso Americano-Europeo sobre los criterios de clasificación para el síndrome de Sjögren. Los hallazgos del estudio corroboran los datos encontrados en la literatura. Conclusión: Este estudio confirma que los síntomas sicca se encuentran en un gran número de pacientes con SSc. Se observó una prevalencia de Sjögren en el 23,2% de los pacientes con esclerodermia, incluyendo pacientes con subtipo cutáneo limitado y difuso

Clinical and Serological Features of Sjogren Syndrome in Patients with Rheumatoid Arthritis.

Background: It is uncertain whether the Sjogren Syndrome (SS) associated with Rheumatoid Arthritis (RA) represents a clinical entity similar to primary SS (pSS) or merely a manifestation in the clinical spectrum of RA. In the present study, we sought to determine the clinic and serologic features of SS associated with RA in comparison to the RA features using well defined SS classification criteria. Methods: RA patients successively referred for a biologic infusion were questioned on oral and ocular dryness. Schirmer’s test and unstimulated salivary flow were performed in each patient. Patients with subjective oral or ocular dryness and/or 1 abnormal objective test underwent a minor salivary gland biopsy. The diagnosis of secondary SS was based on the criteria of European- American consensus group criteria for SS. Clinical and biological parameters of SS and RA (with measure of disease activity and health status of RA, search for Raynaud’s phenomenon, anti-CCP, RF anti-SSA-positivity and beta2-microglobulin level) were then compared between patients with/without sSS. Results: Among the 76 patients prospectively assessed, 11(14.1%) fulfilled the European- American consensus group criteria for secondary SS. Median age and RA disease duration were similar in patients with sSS as in patients with RA only (63.0 v 59.2, p=0;33; 18.2 vs 13.9, p= 0.12). Median DAS28-ESR and HAQ were not significantly different between patients with sSS and patient with RA only (4.0 vs 4.1, p= 0.8; 0.84 vs 0.81, p=0.7). Patients with sSS had more frequently a Raynaud’s phenomenon (27.2 vs 1.5%, p=0.01). RF and anti-CCP-positivity were similar in the 2 groups. The prevalence of anti-SSA antibodies was comparable in the 2 groups (p=1). Median beta2-microglobulin levels were higher in sSS than RA only (2.4 vs 1.9 mg/l, p= 0.02). Conclusion: 14% of patients with RA had secondary SS in the present study. Conversely to previous reports, secondary SS did not modify the clinical and biologic pattern of RA.

Dynamic Salivary Gland Scintigraphy in Clinical Sicca Syndrome: Comparison with Static images / 대한핵의학회잡지

PURPOSE: In this study, we compared the quantitative characteristics of dynamic salivary gland scintigraphy with static scintigraphy in patients with clinical sicca syndrome using Tc-99m pertechnetate. MATERIALS AND METHODS: Fifty-two parotid glands and 52 submandibular glands out of 26 patients with clinical sicca syndrome were studied by dynamic and static salivary gland scintigraphy. Ten normal volunteers were also studied as a control group for comparison of scintigraphic parameters. Ten minutes after injection of 370 MBq Tc-99m pertechnetate, we obtained pre-stimulus static images for a few minutes. Then dynamic salivary gland scintigraphy with lemon juice stimulation was performed for 20 minutes. Finally we obtained post-stimulus static images after dynamic images. On dynamic study, functional parameters such as uptake rate, secretion rate and re-uptake rate were calculated. The results of dynamic study and static images were compared. RESULTS: On dynamic study, we could obtain functional parameters of salivary glands successfully. On dynamic study, 22 parotid glands and 22 submandibular glands out of each of 52 glands are abnormal. The static images demonstrated somewhat different results, of which reasons we could assume via dynamic study. CONCLUSION: Dynamic salivary gland scintigraphy using Tc-99m perechnetate were more functional than static images and might be useful in the assessment of the functional change of the salivary gland in patients with clinical sicca syndrome.