Faculty Bibliography

BACKGROUND:Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disorder that increases the risk of developing cardiovascular disease. There is accumulating evidence that the RA disease state accelerates the formation of atherosclerotic plaques. Treatments for RA improve joint symptomatology and may reduce inflammation, but consideration of their effects on the cardiovascular system is generally low priority. OBJECTIVE:Since cardiovascular disease is the leading cause of mortality in RA patients, the impact of RA therapies on atherosclerosis is an area in need of attention and the focus of this review. RESULTS:The drugs used to treat RA may be analgesics, conventional disease-modifying anti-rheumatic drugs, and/or biologics, including antibodies against the cytokine tumor necrosis factor-α. Pain relievers such as non-selective non-steroidal anti-inflammatory drugs and cyclooxygenase inhibitors may adversely affect lipid metabolism and cyclooxygenase inhibitors have been associated with increased adverse cardiovascular events, such as myocardial infarction and stroke. Methotrexate, the anchor disease-modifying anti-rheumatic drug in RA treatment, has multiple atheroprotective advantages and is often combined with other therapies. Biologic inhibitors of tumor necrosis factor-α may be beneficial in preventing cardiovascular disease because tumor necrosis factor-α promotes initiation and progression of atherosclerosis. However, some studies show a worsening of the lipid profile in RA with blockade of this cytokine, leading to higher total cholesterol and triglycerides. CONCLUSION/CONCLUSIONS:Greater understanding of the pharmacologic activity of RA treatments on the atherosclerotic process may lead to improved care, addressing both damage to the joints and damage to the heart.

Background. Management guidelines for Sjogren's patients remain a major unmet need, particularly for potentially severe extraglandular (systemic) manifestations. To meet this patient and clinician need, the Sjogren's Syndrome Foundation (SSF) launched a major initiative to develop Clinical Practice Guidelines for Sjogren's in 2012. Goals include: improving quality and consistency of care, creating guidance documents for US clinicians, obtaining broad acceptance of guidelines by key professional and government organizations, educating payers and identifying gaps in evidence to spur much needed research. Following 4 recent publications by the SSF on initial Clinical Practice Guidelines under the rheumatology/systemic, oral, and ocular topics, Phase 2 is now well underway. This phase aims to comprehensively collate scientific evidence and expert opinion on the management of pulmonary manifestations of Sjogren's. Methods. Guideline members developed a rigorous and transparent process based on American College of Rheumatology quality of care standards and protocols developed by other professional organizations such as the American Society of Clinical Oncology. A unique aspect of these guidelines is the inclusion of multiple specialists. The Pulmonary Topic Review Group (TRG) includes an equal number of rheumatologists and pulmonologists as well as an oncologist with expertise in Sjogren's. The process involved drafting and ranking clinical questions, defining the literature search and study criteria, and outcome measures to be addressed a priori to execution of the search. Members then identified eligible abstracts, and a minimum of 2 TRG members extracted data into tables, which included study characteristics and evidence and quality assessment. Recommendations will be drafted and finalized via a Delphi-type consensus process involving more than 30 medical specialists. Results. Areas of pulmonary coverage were outlined and include screening and diagnosis; upper airway disease (xerostomia, dysphagia, laryngopharyngeal reflux, vocal cord, obstructive sleep apnea); lower airway disease (xerotrachea, bronchiectasis, bronchiolitis, obstructive lung diseases including COPD and asthma); interstitial lung disease; lymphoproliferative disease (including bronchus- associated lymphoid tissue lymphoma/ non- Hodgkin lymphoma, amyloid, and nodular lymphoid hyperplasia); vascular lung disease; lung transplant; and peri-operative and other non-medication management. Almost 200 informational and clinical questions were drafted. Conclusions. Clinically relevant questions for the development of Clinical Practice Guidelines for pulmonary manifestations in Sjogren's were developed by multi-specialty teams of Sjogren's experts across the U.S. Literature searches, data extraction, and recommendation development are underway. Recommendations will utilize evidence in Sjogren's when available and evidence from closely related diseases and expert opinion when little to no evidence in Sjogren's is available. Areas for future research will be delineated with a focus on patient-perceived areas of unmet need

Background. Standardization of the diagnosis and treatment of neurologic manifestations of Sjogren's remains an unmet clinical need. A multi-disciplinary task force of rheumatologists, neurologists and other specialists has been formed to develop consensus recommendations concerning the neurological features of the disease. Methods. Guidelines members in rheumatology and neurology were organized into central (CNS) and peripheral nervous system (PNS) Topic Review Groups (TRGs). Additional specialists include neuro-ophthalmology, vasculitis, psychiatry, neuro-psychology, and sleep medicine. The initial guidelines development process is based on American College of Rheumatology and American Society of Clinical Oncology procedures, including drafting and ranking of clinical questions, defining literature search parameters and determining outcome measures to be addressed prior to the literature review. Members then will identify eligible abstracts and a minimum of 2 TRG members extract data on evidence and study quality. Recommendations will be drafted and finalized via the Delphi method. The American Academy of Neurology appointed representatives to both TRGs. Results. PNS coverage areas were based upon both the neuro-anatomic localization to the motor, sensory and autonomic nerves and the etiology involving demyelinating, axonal and antibody-based pathologies. These include cranial neuropathies; axonal or sensory motor or sensory neuropathies; small fiber neuropathies (length-dependent or non-length dependent); ataxic sensory neuropathies/large fiber ganglionopathies; mononeuritis multiplex/multiple mononeuropathies; and autonomic neuropathies. CNS coverage areas were based upon the clinical syndromes involving encephalopathies, seizures, strokes, and myelopathies and etiologies including demyelinating and vasculopathic pathology. Included are vasculitis; optic neuritis; vestibular/auditory, olfactory, taste; autoimmune encephalitis; myelitis or other demyelinating syndromes; psychiatric (anxiety, depression, psychosis); cognitive dysfunction; and impaired sleep. Conclusions. The initial clinically relevant questions for Clinical Practice Guidelines for neurological manifestations in Sjogren's were developed by multi-specialty teams of Sjogren's experts across the U.S. Literature searches, data extraction, and recommendations for the diagnosis and treatment of neurological manifestations of Sjogren's are based on published studies related to Sjogren's or related diseases. When results of clinical investigation are not available, consensus expert opinion will be used as an initial step to standardize management and treatment

Background. Oral complications in Sjogren's can lead to painful oral infection/ lesions/irritation, rampant caries and loss of teeth, in addition to difficulty eating and talking, which compromise the quality of life of patients with Sjogren's. There is a clear unmet need for managing the lack of saliva and its consequences in Sjogren's. The Sjogren's Syndrome Foundation (SSF) launched a major initiative to address this need in 2012, and clinical practice guidelines for caries prevention were published in 2016 in the Journal of the American Dental Association (JADA) and included in the Rheumatic Diseases Clinics of North America. Phase 2 oral guidelines are now well underway and include coverage of mucosal management and treatment and use of secretagogues in Sjogren's. Guidelines on caries restoration and management and parotid gland swelling also will be developed. Methods. Guidelines members developed a rigorous and transparent process based on standards set by the American Dental Association, American College of Rheumatology and American Society of Clinical Oncology. The methodology utilizes a Delphi-type consensus process and includes drafting clinical questions and defining literature search parameters and study criteria a priori to execution of the search. Eligible abstracts then are identified, and a minimum of 2 guidelines members extract the data on study characteristics, evidence and quality assessment. Recommendations will be drafted and finalized with input from at least 30 oral healthcare professionals who were not involved in the guidelines development. Results. The Mucosal Management and Treatment Topic Review Group (TRG) drafted clinical questions for its outline covering oral symptoms of mucosal pain and/or inflammation in Sjogren's, including prevalence and identification of oral cancer. Prevention and management of burning mouth; oral candidiasis; lichenoid reactions or hypersensitivity-induced mucositis; and oral trauma associated with oral dryness were discussed. The Secretagogues TRG's clinical questions explore whether studies have demonstrated that sialogogues improve salivary flow and composition; reduce the occurrence of candida, other oral infections and burning mouth; and translate to better outcomes for the incidence of caries, periodontal disease, taste disturbance; hoarseness, chronic cough, and subjective and objective dryness and discomfort. Conclusions. Initial clinically relevant questions for Clinical Practice Guidelines for oral mucosal management and use of secretagogues for dry mouth in Sjogren's were established by Sjogren's experts across the U.S. Literature searches, data extraction, and recommendation development is underway. Recommendations utilize evidence from Sjogren's studies when available and expert opinion when little to no evidence in Sjogren's literature is available. Areas for future research will be delineated with a focus on patient-perceived areas of unmet need

OBJECTIVES/OBJECTIVE:To analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögren's syndrome (SjS) at diagnosis. METHODS:The Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Multivariable logistic regression analyses were performed. RESULTS:We included 7748 women (93%) and 562 men (7%), with a mean age at diagnosis of primary SjS of 53 years. Ethnicity data were available for 7884 patients (95%): 6174 patients (78%) were white, 1066 patients (14%) were Asian, 393 patients (5%) were Hispanic, 104 patients (1%) were black/African-American and 147 patients (2%) were of other ethnicities. SjS was diagnosed a mean of 7 years earlier in black/African-American compared with white patients; the female-to-male ratio was highest in Asian patients (27:1) and lowest in black/African-American patients (7:1); the prevalence of sicca symptoms was lowest in Asian patients; a higher frequency of positive salivary biopsy was found in Hispanic and white patients. A north-south gradient was found with respect to a lower frequency of ocular involvement in northern countries for dry eyes and abnormal ocular tests in Europe (OR 0.46 and 0.44, respectively) and Asia (OR 0.18 and 0.49, respectively) compared with southern countries. Higher frequencies of antinuclear antibodies (ANAs) were reported in northern countries in America (OR=1.48) and Asia (OR=3.80) while, in Europe, northern countries had lowest frequencies of ANAs (OR=0.67) and Ro/La (OR=0.69). CONCLUSIONS:This study provides the first evidence of a strong influence of geolocation and ethnicity on the phenotype of primary SjS at diagnosis.