12Primary Sjögren's syndrome
Section snippets
Sjögren's syndrome
Sjögren's syndrome (SS) is a relatively common systemic autoimmune rheumatic disease, in which lymphocytic infiltration of salivary and lacrimal glands leads to immune-mediated secretory dysfunction. The resulting dryness of the mouth and eyes is termed “sicca syndrome.” SS is referred to as “primary” in patients who do not have an additional systemic rheumatic disease, and “secondary” when immune-mediated sicca syndrome coexists in patients with systemic lupus erythematosus (SLE), scleroderma,
Clinical features of pSS
The clinical and laboratory abnormalities in pSS are listed in Table 3.
Prevalence and incidence
A recent meta-analysis addressed the incidence rate (IR), prevalence rate (PR), gender IR, and age at diagnosis of pSS [48]. The pooled IR of pSS was 6.92 (95% CI 4.98–8.86) per 100,000 person-years at risk. The IRs for females and males were estimated at 12.30 (95% CI 9.07–15.53) and 1.47 (95% CI 0.81–2.12), respectively, resulting in a pooled female-to-male IR ratio of 9.29 (95% CI 6.61–13.04). The overall age of pSS patients at diagnosis was 56 years (95% CI 53–60). Three studies reported
Anti-Ro and anti-La
Antinuclear antibodies (ANAs), rheumatoid factor, and Ro/SSA and La/SSB autoantibodies are key serological findings in pSS, and form part of various criteria for the research classification of disease [57], [58]. ANA are present in the sera of up to 85% [59], and anti-Ro and anti-La autoantibodies are found in 33–74% and 23–52% of patients with pSS, respectively [60]. It is likely that the prevalence of these autoantibodies may be biased upward in some studies, because autoantibody positivity
Histopathology
The principal pathological lesion in pSS is an FLS, predominantly consisting of CD4+ T cells and CD20 + B cells, in the salivary glands, and an analogous lesion may occur in the lacrimal glands. In the absence of pSS-associated serum autoantibodies, a positive labial salivary gland biopsy is a mandatory criterion for classification of pSS [57], ∗[82]. In the majority of pSS patients, the salivary gland inflammatory lesions are fully developed at the time of diagnosis, and remain largely
Pathogenesis
Clinical and laboratory observations have highlighted the central role of the salivary gland epithelial cell (SGEC), and currently it has been suggested that the etiological name of the disease should be “autoimmune epithelitis.” [83] It was initially observed that the characteristic lymphocytic infiltrates were proximal to SGEC, which were subsequently showed to express numerous immunomodulatory molecules, such as cytokines, chemokines, adhesion molecules, MHC molecules, B7 and CD40
SS diagnosis and classification
Classification criteria are used to describe cohorts of patients in the research setting. It is also useful to use these criteria as an aide memoire, guide the diagnosis of pSS in the clinical setting, and differentiate patients from those with other autoimmune diseases or nonautoimmune sicca syndrome. Using the American–European Consensus Group (AECG) classification criteria [82], as described below, although time consuming is a relatively straightforward, one off process, which enables
Anti-Ro/SSA and anti-La/SSB
Anti-Ro/La antibodies are the key immunological markers of pSS; however, their prevalence may vary widely according to the method of detection (ELISA, double immunodiffusion, and Western blot analysis). Anti-Ro60 antibodies are more easily detected using a native antigen (95% vs. 54% using recombinant antigens) [100], and Ro60-transfected cells have improved sensitivity for detection of this low-abundance autoantigen by screening ANA, which may be missed in 5% of cases using the standard
Outcome measures
A challenge in defining the natural history and effective strategies in pSS has been in developing good outcome measures and standardized assessment of disease activity, particularly in those patients with systemic manifestations. Traditional outcome measures included quantitation of sicca symptoms or histopathological changes in biopsied specimens. It was widely recognized, however, that these measures do not strongly correlate to patient-reported outcomes (PROs). More recently, pSS-specific
Dry eyes
Dry eye disease is one of the features that impair quality of life and limit activity most in pSS [119]. A consensus clinical guideline for its management was published in 2015 [119]. Evaluation should include symptoms of both discomfort and visual disturbance, as well as determination of the relative contribution of aqueous production deficiency and evaporative loss of tear volume due to meibomian gland dysfunction, both of which may contribute to dry eyes in SS (both primary and secondary).
Cohort studies: embedding research into clinical practice
There is increasing awareness of the importance of patient cohort studies in medical research. They have a number of applications including determination of the incidence, prevalence, and natural history of disease, causes and risks of disease, and disease complications. Standardized collection of clinical data, disease activity, PRO, and biological samples, including DNA, RNA, and sera, is highly recommended to determine new biological prognostic factors and identify disease activity markers.
Summary
Important advances have been made in the development of classification criteria and disease outcome measures in pSS. Increasingly, we are gaining a better understanding of the pathogenesis of disease and biomarkers that could contribute. In order to better define the natural history, pathogenesis, prognosis, and therapeutic strategies for patients with this multisystem condition, both observational studies and controlled trials are required, using these important tools. With a deeper insight
Disclaimers/sources of funding
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References (141)
- et al.
Clinical and pathological characteristics of Mikulicz's disease (IgG4-related plasmacytic exocrinopathy)
Autoimmun Rev
(2005) - et al.
Sleep disordered breathing in patients with primary Sjogren's syndrome: a group controlled study
Sleep Med
(2012) - et al.
Peripheral neuropathies in Sjogren's syndrome: a critical update on clinical features and pathogenetic mechanisms
J Autoimmun
(2012) - et al.
B-cell activating factor genetic variants in lymphomagenesis associated with primary Sjogren's syndrome
J Autoimmun
(2014) - et al.
Incidence of physician-diagnosed primary Sjogren syndrome in residents of Olmsted County, Minnesota
Mayo Clin Proc
(2001) Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology
Adv Immunol
(1989)- et al.
Latest update on the Ro/SS-A autoantibody system
Autoimmun Rev
(2009) - et al.
The meaning of anti-Ro and anti-La antibodies in primary Sjogren's syndrome
Autoimmun Rev
(2011) - et al.
B cell apotopes of the 60-kDa Ro/SSA and La/SSB autoantigens
J Autoimmun
(2008) - et al.
The accuracy of the anti-alpha-fodrin antibody test for diagnosis of Sjogren's syndrome: a meta-analysis
Clin Biochem
(2013)
Novel autoantibodies in Sjogren's syndrome
Clin Immunol
A novel cell-based assay for inhibitory anti-muscarinic type 3 receptor antibodies in primary Sjogren's syndrome
J Immunol Methods
Subgroups of Sjogren syndrome patients according to serological profiles
J Autoimmun
A comprehensive review of autoantibodies in primary Sjogren's syndrome: clinical phenotypes and regulatory mechanisms
J Autoimmun
HLA and Sjogren's syndrome susceptibility. A meta-analysis of worldwide studies
Autoimmun Rev
Relation of systemic autoantibodies to the number of extraglandular manifestations in primary Sjogren's Syndrome: a retrospective analysis of 65 patients in the Netherlands
Semin Arthritis Rheum
Sjogren's syndrome: where do we stand, and where shall we go?
J Autoimmun
A simplified quantitative method for assessing keratoconjunctivitis sicca from the Sjogren's Syndrome International Registry
Am J Ophthalmol
Early diagnosis of primary Sjogren's syndrome: EULAR-SS task force clinical recommendations
Expert Rev Clin Immunol
The impact of primary Sjogren's syndrome on female sexual function
Rheumatol Oxf
Systemic involvement in primary Sjogren's syndrome evaluated by the EULAR-SS disease activity index: analysis of 921 Spanish patients (GEAS-SS Registry)
Rheumatol Oxf
Unusual presentation of Sjogren syndrome
South Med J
Recurrent parotitis as a presentation of primary pediatric Sjogren syndrome
Pediatrics
A child with primary Sjogren syndrome and a review of the literature
Clin Pediatr (Phila)
A retrospective study of long-term outcomes in 152 patients with primary Sjogren's syndrome: 25-year experience
Clin Med
EULAR Sjogren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren's syndrome
Ann Rheum Dis
Primary Sjogren's syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients
Rheumatol Oxf
One year in review 2015: Sjogren's syndrome
Clin Exp Rheumatol
Primary Sjogren syndrome
BMJ
Primary Sjogren's syndrome: cognitive symptoms, mood, and cognitive performance
Acta Neurol Scand
Sleepiness or fatigue? Can we detect treatable causes of tiredness in primary Sjogren's syndrome?
Rheumatol Oxf
Fatigue and depression predict physician visits and work disability in women with primary Sjogren's syndrome: results from a cohort study
Rheumatol Oxf
Mild autonomic dysfunction in primary Sjogren's syndrome: a controlled study
Arthritis Res Ther
Autonomic symptoms are common and are associated with overall symptom burden and disease activity in primary Sjogren's syndrome
Ann Rheum Dis
EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjogren's syndrome
Ann Rheum Dis
Upper airway surface tension but not upper airway collapsibility is elevated in primary Sjogren's syndrome
Sleep
Pain severity and neuropathic pain symptoms in primary Sjogren's syndrome: a comparison study of seropositive and seronegative Sjogren's syndrome patients
Arthritis Care Res Hob
Lower prevalence of extra-glandular manifestations and anti-SSB antibodies in patients with primary Sjogren's syndrome and widespread pain: evidence for a relatively benign subset
Clin Exp Rheumatol
Characterization of systemic disease in primary Sjogren's syndrome: EULAR-SS task force recommendations for articular, cutaneous, pulmonary and renal involvements
Rheumatol Oxf
Cutaneous vasculitis in primary Sjogren syndrome: classification and clinical significance of 52 patients
Medicine
Pulmonary manifestations of Sjogren's syndrome
Curr Allergy Asthma Rep
Sjogren syndrome-associated small fiber neuropathy: characterization from a prospective series of 40 cases
Medicine
White matter abnormalities in primary Sjogren syndrome
QJM
Renal involvement in primary Sjogren's syndrome
Rheumatol Oxf
Increased severity of lower urinary tract symptoms and daytime somnolence in primary Sjogren's syndrome
J Rheumatol
Sjögren’s syndrome
Thrombotic thrombocytopenic purpura as an initial presentation of primary Sjogren's syndrome
Clin Rheumatol
The clinical spectrum of autoimmune congenital heart block
Nat Rev Rheumatol
Disease progression in mothers of children enrolled in the research registry for neonatal lupus
Ann Rheum Dis
French cohort study of 141 cases of autoimmune congenital heart block
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