Recommendations from the Brazilian society of rheumatology for the diagnosis of Sjögren’s syndrome (Part I): glandular manifestations (systematic review)

Abstract

Background: Primary Sjögren's syndrome (pSS) is a systemic immune-mediated disease whose main characteristic is exocrine gland inflammation and, subsequent reduction in tear and saliva production. A delayed diagnosis is common due to the nonspecific clinical manifestations of disease. The aim of the present study was to develop recommendations for the diagnosis of glandular manifestations of pSS based on evidence and expert opinion. Main body of the abstract: We conducted a systematic literature review to retrieve the best evidence available on the accuracy of diagnostic tests for pSS. We also held two in-person meetings with experts (rheumatologists, pathologists, ophthalmologists and dentists) to establish their level of agreement using the Delphi method. Ultimately, we generated 18 recommendations that aim to facilitate the diagnosis of the glandular manifestations of pSS. Conclusion: The diagnosis of glandular manifestations of pSS is complex and multidisciplinary. It requires specific knowledge in the field of ophthalmology, immunology, pathology and imaging, making it compulsory for the rheumatologist to work with professionals from these different areas in order to improve accuracy and early diagnosis. Glandular dysfunction tests, ANA, RF, Anti-Ro, protein electrophoresis, urinalysis, blood count, C-Reactive protein, complement, testing for syphilis and viruses (HCV, HIV) and SGUS should be investigated when dryness or systemic manifestation are present. Minor salivary gland biopsy is recommended for all anti-Ro negative or incomplete criteria cases.

Current State of Knowledge on Primary Sjögren’s Syndrome, an Autoimmune Exocrinopathy

“…ANA is positive in 70% of pSS patients, usually with a fine speckled fluorescence [ 273 ]. Anti-Ro/SSA and/or anti-La/SSB autoantibodies are identified in 50–90% and 25–60% of patients, respectively [ 274 ]. It should be borne in mind that the Hep-2 cells do not sufficiently express Ro/SSA antigen, explaining the fact that 10% of patients anti-Ro/SSA-positive in ELISA have negative ANA in IF on HEp-2 cells [ 274 ].…”

“…Anti-Ro/SSA and/or anti-La/SSB autoantibodies are identified in 50–90% and 25–60% of patients, respectively [ 274 ]. It should be borne in mind that the Hep-2 cells do not sufficiently express Ro/SSA antigen, explaining the fact that 10% of patients anti-Ro/SSA-positive in ELISA have negative ANA in IF on HEp-2 cells [ 274 ]. Therefore, in case of suspicion of pSS, it is necessary to request the anti-Ro/SSA antibodies identification by ELISA, even in the presence of a negative ANA IF screening.…”

“…Two types of anti-Ro/SSA autoantibodies can be differentiated: anti-Ro52 and anti-Ro60 [ 272 ]. Anti-Ro52/SSA have no specific ANA fluorescence staining pattern (might even exhibit a cytoplasmic pattern [ 274 ]), is precipitin negative and is not detected by ELISAs based on natural SSA/Ro. Ro52+ Ro60+ patients are likely to have pSS while Ro52+ Ro60- patients are not [ 275 ].…”

Accuracy of minor salivary gland biopsy in the diagnosis of Sjögren syndrome

“…Focal lymphocytic infi ltration (FLS) occurs in all organs affected by Sjögren syndrome and is associated with diverse clinical manifestations of the disease. To date, the salivary glands have been the most thoroughly studied among the organs affected by Sjögren syndrome (25).…”

Síndrome de Sjögren en un adolescente. Caso Clínico

“…-Los anticuerpos anti-La del paciente fueron negativos. En la literatura médica se reportan frecuencias de hallazgos positivos con un promedio de 63% para los anti-Ro (los cuales fueron positivos y tienen más especificidad en la enfermedad) y menos del 51% para los anti-La 5,9,18 . -Flujo salival sin estimular menor o igual a 0,1ml/min; éste no se llevó a cabo en nuestro paciente, pero de haber sido positivo, apenas sumaría un punto, dejando por fuera el diagnóstico.…”