Evaluation of the Role of the Autonomic Nervous System in Sj(SqrRoot)(Delta)Gren s Syndrome
Condition: Sjogren's Syndrome; Dysautonomia
MeSH terms: Sjogren's Syndrome; Primary Dysautonomias; Autonomic Nervous System Diseases; Syndrome
Study type: Observational

Summary: 
      Background:

      Sj(SqrRoot)(Delta)gren s Syndrome (SS) is an autoimmune disease that affects the glands that
      produce saliva and tears, causing dry eyes and dry mouth.

      Researchers do not know the exact cause of SS, but they believe that it may be caused by
      abnormalities in the autonomic nervous system (ANS) that stimulate these glands.

      Objectives:

      To better understand ANS function in patients with SS.

      To compare information about ANS function in healthy individuals and in patients with SS.

      Eligibility:

      Patients with Sj(SqrRoot)(Delta)gren s Syndrome who are 18 years of age and older, and who
      are not pregnant or breastfeeding.

      Participants will be asked to taper or discontinue the use of certain medications or dietary
      supplements before the ANS testing.

      Participants must be willing to discontinue the use of alcohol and tobacco 24 hours prior to
      testing.

      Design:

      The study will require one inpatient admission and/or outpatient visits to the NIH Clinical
      Center.

      The following tests and procedures will be performed:

        -  Saliva, tear, and sweat production measurements to evaluate the function of glands.

        -  Testing of changes to the cardiovascular system, including blood pressure and blood flow
           testing, and an electrocardiogram designed to evaluate hemodynamic changes controlled by
           the ANS.

        -  Testing of changes to the gastrointestinal system, including a swallowing assessment
           study, barium swallow study, and gastric emptying study designed to evaluate
           gastrointestinal function controlled by the ANS.

        -  Tests to evaluate the ANS function in response to certain drugs (edrophonium, glucagon
           and acetylcholine).

        -  Self-reported questionnaire on ANS function and emotional/psychological well-being.

      Additional procedures and tests may include the following:

        -  Blood samples.

        -  Optional skin biopsy to study sweat glands and nerve supply of the skin.
    

Detailed description: 
      Sj(SqrRoot)(Delta)gren s syndrome (SjS) is a systemic exocrinopathy that affects as high as 5
      percent of the population. It is manifested predominantly as dry eyes, dry mouth, and
      fatigue. The exocrinopathy can be encountered alone (primary SjS) in approximately one half
      of the patients or in the presence of another autoimmune disorder such as rheumatoid
      arthritis, systemic lupus erythematosus, or systemic sclerosis (secondary SjS). The most
      widely accepted classification for SjS is the American-European consensus classification
      criteria for SjS.(Vitali, Bombardieri et al. 2002)

      Current understanding about the pathogenesis of SjS stems from the assumption that the
      autoimmune destruction of the exocrine glands leads to their hypofunction and symptoms of
      dryness. The existing evidence however does not fully support this assumption and cannot
      explain the underlying pathogenic mechanisms of SjS for the following reasons: 1) Discordance
      between severely affected function and abundance of histologically normal and ex vivo
      functional salivary glands; 2) at least 20% of patients have no evidence of systemic
      autoimmunity; 3) Animal models of SjS develop glandular dysfunction long before they develop
      autoimmunity; 4) Dryness and related symptoms respond poorly to immunosuppressive, including
      newer biologics, but fairly well to secretagogues such as pilocarpine. 5) No pathogenic
      antibodies or target epitopes have been identified to date to unify the pathogenesis of the
      syndrome.

      All exocrine glands are innervated by the autonomic nervous system (ANS) and dysautonomia can
      mimic the phenotype of SjS, particularly cardinal manifestations, such as xerostomia and
      xerophthalmia. Thus we hypothesize that ANS dysfunction is central to the pathogenesis of SjS
      and propose to systematically study the ANS function in our cohort of patients with primary
      SjS compared with normative data from age and sex-matched controls. This protocol calls for a
      comprehensive evaluation of autonomic function, using physiological, neuropharmacologic,
      neurochemical, and imaging approaches, to identify consistent distinctive patterns of ANS
      involvement in SjS and thereby improve the diagnosis and understanding of pathophysiologic
      mechanisms of SjS.
    

Time perspective: Prospective
Keywords: Autonomic Nervous System; Sjogren's Syndrome; Pathogenesis; Cholinergic; Parasympathetic; Sjogren Syndrome