Sex differences in comorbidities associated with Sjögren's disease

Abstract

BackgroundLittle is known about the association of comorbidities with sex and age at diagnosis in Sjögren's disease. We tested the hypothesis that sex differences occur in comorbidities in patients with Sjögren's disease.MethodsPatients with Sjögren's disease were identified from 11/1974 to 7/2018 in the Mayo Clinic electronic medical record and assessed for 22 comorbidities according to sex and age at diagnosis.ResultsOf the 13,849 patients identified with Sjögren's disease, 11,969 (86%) were women and 1,880 (14%) men, primarily white (88%) with a sex ratio of 6.4:1 women to men. The mean age at diagnosis was 57 years for women and 59.7 years for men, and 5.6% had a diagnosis of fibromyalgia at Sjögren's diagnosis. Men with Sjögren's disease were more likely than women to be a current or past smoker. The average time to diagnosis of comorbidities after diagnosis of Sjögren's disease was 2.6 years. The top comorbidities in patients with Sjögren's disease were fibromyalgia (25%), depression (21.2%) and pain (16.4%). Comorbidities that occurred more often in women were hypermobile syndromes (31:1), CREST (29:1), migraine (23:1), Ehlers-Danlos syndrome (EDS) (22:1), Raynaud's syndrome (15:1), SLE (13:1), systemic sclerosis (SSc) (13:1), and fibromyalgia (12:1). Women with Sjögren's disease were at increased risk of developing hypermobile syndromes (RR 7.27, CI 1.00–52.71, p = 0.05), EDS (RR 4.43, CI 1.08–18.14, p = 0.039), CREST (RR 4.24, CI 1.56–11.50, p = 0.005), migraine (RR 3.67, CI 2.39–5.62, p < 0.001), fibromyalgia (RR 2.26, CI 1.92–2.66, p < 0.001), Raynaud's syndrome (RR 2.29, CI 1.77–2.96, p < 0.001), SLE (RR 2.13, CI 1.64–2.76, p < 0.001), and SSc (RR 2.05 CI 1.44–2.92; p < 0.001). In contrast, men with Sjögren's were at increased risk for developing myocardial infarction (RR 0.44, CI 0.35–0.55, p < 0.001), atherosclerosis/CAD (RR 0.44, CI 0.39–0.49, p < 0.001), cardiomyopathy (RR 0.63, CI 0.46–0.86, p = 0.003), stroke (RR 0.66 CI 0.51–0.85, p = 0.001), and congestive heart failure (RR 0.70, CI 0.57–0.85, p < 0.001).ConclusionsThe top comorbidities in Sjögren's disease were fibromyalgia, depression, and pain. Women with Sjögren's disease had a higher relative risk of developing fibromyalgia, depression, pain, migraine, hypermobile syndrome, EDS and other rheumatic autoimmune diseases. Men with Sjögren's disease had higher risk of developing cardiovascular diseases.

Pain mechanisms in the transgender individual: a review

“…Consideration of the issues of pain patients ( 241 , 242 ) requires consideration of chromosomal status. Sexual differentiation of pain sensitivity may begin very early in life in humans ( 243 ) and in preclinical models ( 244 ).…”

Impact of sex differences on the clinical presentation, pathogenesis, treatment and prognosis of Sjögren's syndrome

“…Noteworthy, Ro/SSA (Ro52/TRIM21) is also an E3 ubiquitin ligase that plays a key role in host immune defence, signal transduction and cell cycle regulation [20]. More female patients were found to be positive for anti-Ro/SSA than males [9]. However, the comparison of anti-Ro/SSA level in male and female patients is controversial in different studies, with some reporting higher levels of anti-Ro/SSA in female patients with SS than in male patients, but also cohort analyses suggesting higher antibody levels in male patients [5,8].…”

“…Female patients with SS have an increased risk of chronic pain syndromes such as fibromyalgia, migraine, depression, pain and hypermobility syndromes compared to men. In contrast, male patients with SS have a higher risk of cardiovascular disease [9]. Notably, pSS has been reported to cause female genital atrophy and vaginal dryness and thus sexual dysfunction, which may be an important reason why depression is more common in female patients [19].…”

Loss of STIM1 and STIM2 in salivary glands disrupts ANO1 function but does not induce Sjogren’s disease

“…Sjogren's disease (SjD) or Sjogren's syndrome, is a chronic autoimmune disease characterized by the infiltration of T and B cells into salivary and lacrimal glands, and by loss of function of the glands resulting in sicca symptoms including dry mouth (xerostomia) (1, 2). SjD is more prevalent in females and occurs in ~0.5% of the population (3)(4)(5). Disease diagnosis includes the evaluation of ocular and oral dryness, minor salivary gland biopsy and the detection of antibodies such as SS-A and SS-B (6)(7)(8).…”

“…Department of Pharmacology and Physiology, University of Rochester, Rochester, New York, USA 3. Biology Program, Division of Science and Mathematics, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates 4. Department of Pathology, New York University Grossman School of Medicine, New York, New York, USA.…”