Sjogren Syndrome
Sjogren Syndrome is a chronic, systemic autoimmune disorder characterized primarily by lymphocytic infiltration and subsequent destruction of the exocrine glands, notably the salivary and lacrimal glands. This glandular dysfunction results in the hallmark symptoms of xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). The pathogenesis involves a complex interplay of genetic susceptibility, environmental triggers, and aberrant immune responses, particularly the activation of autoreactive T and B lymphocytes, production of autoantibodies (such as anti-SSA/Ro and anti-SSB/La), and cytokine-mediated tissue injury. In addition to exocrine gland involvement, Sjogren Syndrome can manifest with systemic features, including arthralgia, fatigue, interstitial lung disease, renal involvement, and an increased risk of non-Hodgkin lymphoma. The disease significantly impacts quality of life due to persistent mucosal dryness, increased risk of dental caries and oral infections, ocular complications, and systemic manifestations.
Primary Sjogren Syndrome refers to the disease occurring as an isolated autoimmune condition, without association with other systemic autoimmune diseases. Patients present with classic sicca symptoms attributable to exocrine gland dysfunction, and may also exhibit extraglandular manifestations such as arthralgia, fatigue, vasculitis, and neuropathy. Serological findings often include the presence of anti-SSA/Ro and anti-SSB/La antibodies, as well as hypergammaglobulinemia and rheumatoid factor positivity. The diagnosis of primary Sjogren Syndrome is established when no other connective tissue disease is identified.
Secondary Sjogren Syndrome develops in conjunction with another established autoimmune connective tissue disease, most commonly rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis. Patients exhibit the same exocrine gland involvement as in primary disease, but the clinical picture is dominated by features of the underlying primary autoimmune disorder. Diagnosis requires fulfillment of Sjogren Syndrome criteria in the context of a known systemic autoimmune disease, and management often necessitates a coordinated approach to address both Sjogren-related and primary disease manifestations.
Sjogren Syndrome is among the most prevalent systemic autoimmune diseases, with an estimated prevalence ranging from 0.1% to 4.8% in the general population, depending on diagnostic criteria and geographic region. It predominantly affects middle-aged women, with a female-to-male ratio of approximately 9:1. The peak incidence occurs between the fourth and sixth decades of life. While the disease can occur in all ethnicities, certain populations, such as those of Northern European descent, may have higher reported rates. Family clustering and the presence of specific HLA haplotypes (e.g., HLA-DR and HLA-DQ alleles) have been observed, supporting a genetic predisposition. Sjogren Syndrome is associated with increased morbidity due to chronic symptoms, complications such as dental decay and ocular damage, and a heightened risk of lymphoproliferative malignancies, particularly non-Hodgkin lymphoma, with a lifetime risk estimated at 5–10%.
The diagnosis of Sjogren Syndrome is based on a combination of clinical, serological, and histopathological criteria. The most widely used classification is the 2016 ACR/EULAR criteria, which assign weighted scores to objective findings: labial minor salivary gland biopsy showing focal lymphocytic sialadenitis with a focus score ≥1 (3 points), anti-SSA/Ro antibody positivity (3 points), ocular staining score ≥5 or van Bijsterveld score ≥4 (1 point), Schirmer’s test ≤5 mm/5 min (1 point), and unstimulated whole salivary flow rate ≤0.1 mL/min (1 point). A total score of 4 or more is required for classification. Diagnostic evaluation includes detailed history and physical examination, objective tests for dry eyes (Schirmer’s test, ocular surface staining), and dry mouth (sialometry, salivary gland imaging). Serological testing for anti-SSA/Ro and anti-SSB/La antibodies, rheumatoid factor, and antinuclear antibodies is standard. Minor salivary gland biopsy remains the gold standard for histopathological confirmation. Exclusion of other causes of sicca symptoms, such as hepatitis C infection, HIV, sarcoidosis, and anticholinergic medication use, is essential. Additional investigations may be warranted to assess systemic involvement and monitor for complications such as lymphoma.
Cevimeline hydrochloride is an oral muscarinic receptor agonist used to stimulate exocrine gland secretion, particularly enhancing salivary flow in patients with Sjogren Syndrome, thereby providing symptomatic relief from xerostomia. Pilocarpine hydrochloride, another muscarinic agonist, is also administered to increase salivary and lacrimal gland output and is indicated for the management of dry mouth and dry eyes associated with Sjogren Syndrome. Anethole dithiolethione, also known as anethole trithione, is utilized for its sialogogue properties to promote saliva production and alleviate symptoms of oral dryness in affected individuals.
| Structure | Generic Name | CAS Registry Number | Molecular Formula | Molecular Weight |
|---|---|---|---|---|
 | cevimeline hydrochloride (Prop INNM; USAN) | 107233-08-9 (free base, anhydrous) | C10 H17 N O S . Cl H . H2 O | 253.789 |
 | pilocarpine hydrochloride (USAN; BANM) | 54-71-7 | C11 H16 N2 O2 . Cl H | 244.718 |
 | anethole dithiolethione; anethole trithione | 532-11-6 | C10 H8 O S3 | 240.365 |
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