The Prevalence and Effects of Sleep Disorders Among Patients With Rheumatological Disorders

The Lancet Rheumatology published an editorial in November of 2022 calling for increased understanding of sleep biology and how sleep disturbances affect people living with rheumatic and autoimmune conditions. The authors highlighted the need for the implementation of programs and policies that emphasize the pivotal importance of sleep across global research and health agendas, stating:

We have all experienced the detrimental effects of a poor night’s sleep, including loss of productivity, changes in mood, and daytime sleepiness. And chronically poor sleep begets poor health. For those with autoimmune rheumatic diseases, sleep deprivation can increase systemic inflammation and pain sensitivity, amplifying the effects of an already overactive immune system.1

Therefore, improving sleep quality is a critical aspect required for the optimal management of rheumatic and autoimmune diseases.

Types of Sleep Disorders Found Among Rheumatology Patients

The third edition of the International Classification of Sleep Disorders divides sleep disorders into 6 categories2:

• Insomnia
• Sleep-disordered breathing, including obstructive sleep apnea (OSA), central sleep apnea (CSA), and obesity hypoventilation syndrome
• Central disorders of hypersomnolence, including narcolepsy
• Circadian rhythm sleep-wake disorders, including environmental factors that are not aligned well with internal circadian timing (shift work or jetlag) and alterations in internal circadian timing due to external environmental factors
• Parasomnias, including nonrapid eye movement (NREM) disorders, such as confusional arousal, sleepwalking, sleep terrors, and sleep-related eating disorders, and rapid eye movement (REM) disorders, such as REM sleep behavior disorder and nightmare disorder
• Sleep-related movement disorders, including restless legs syndrome (RLS)

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[C]hronically poor sleep begets poor health. For those with autoimmune rheumatic diseases, sleep deprivation can increase systemic inflammation and pain sensitivity, amplifying the effects of an already overactive immune system.

Researchers conducted a systematic review and meta-analysis of the literature to assess the prevalence of sleep disturbances among patients diagnosed with ankylosing spondylitis (AS). A total of 18 studies (5840 patients) published between 1999 and 2022 were included in the meta-analysis. Results revealed a 53% pooled prevalence of sleep disorders among patients with AS, including OSA, RLS, and increased NREM during stages I and II, which indicated decreased deep sleep duration. One of the predominant features of AS involves increased night pain, which in turn affects sleep quality and duration.3

Researchers across several studies reported that patients with rheumatoid arthritis (RA) demonstrated increased prevalence of sleep disorders.4,5 In one study assessing sleep disorder prevalence among a large cohort of 4200 patients with RA, 21% had OSA, 31% had RLS, and 43% reported a shortened average sleep duration of less than 6 hours. Nearly two-thirds of the cohort met criteria for at least one sleep disorder.4

In a smaller study including 101 patients with RA, insomnia occurred with a prevalence rate of 63%, RLS with a prevalence rate of 63%, risk for OSA with a prevalence rate of 37%, excessive daytime sleepiness with a prevalence rate of 20%, and sleep disturbances with a prevalence rate of 20%.5

Although the exact etiological mechanism behind narcolepsy is not well understood, scientists postulate that narcolepsy itself may develop due to autoimmune or immune-mediated underpinnings, resulting in selective neural destruction of hypocretin-producing neurons.6,7 Individuals with one autoimmune condition, such as RA, demonstrate a proclivity for developing additional autoimmune diseases.6

Researchers in one study provided evidence that narcolepsy type I co-occurs more frequently among individuals with autoimmune and other immunopathological diseases compared with the general population (odds ratio [OR], 3.17; 95% CI, 1.01-10.07; P =.04). Additionally, these autoimmune or immunopathological conditions increased the risk for more severe forms of cataplexy (OR, 23.6; 95% CI, 5.5-100.1).6

Rapid eye movement sleep behavior disorders and other REM sleep disorders occur more frequently among individuals with neurodegenerative or autoimmune neurological conditions vs individuals with inflammatory arthritis.8 Narcolepsy and excessive daytime sleepiness are also common among those with autoimmune neurologic diseases.9

Insomnia occurs in up to 81% of individuals diagnosed with osteoarthritis (OA), with an association between insomnia symptoms and clinical OA-related pain.10

Bidirectional Relationship Between Sleep Disorders and Rheumatic Diseases

A vicious cycle exists, indicating the bidirectional relationship between sleep disorders and rheumatic diseases. Individuals with these autoimmune rheumatic disorders report increased prevalence of sleep disturbances, while concurrently, sleep disorders increase the risk of developing autoimmune rheumatic disorders.1

Inflammatory Conditions Contribute to Sleep Disorders

Pathological inflammatory processes can disrupt the chemical signaling involved in controlling the homeostatic and circadian processes that regulate sleep. In this way, immune system activity impacts sleep physiology.11 Elevated levels of proinflammatory signaling throughout the central nervous system and periphery occur among autoimmune diseases, influencing disease progression and activity levels.12

Inflammation causes increased production of chemical substances, including nitric oxide, prostaglandins, and cytokines. Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α ) and interleukin-1 beta (IL-1β), interact with the circadian system, affecting sleep regulation.13 Tumor necrosis factor-alpha levels affect inflammatory processes, immune functioning, cognition, mood, fatigue, and cell survival, proliferation, and differentiation.14 Dysregulated homeostatic cytokine expression, which occurs in autoimmune and rheumatic diseases, contributes to the development of sleep disorders among this patient population. Loss of sleep, in turn, increases the activity of proinflammatory cytokines which worsens sleep disturbances, resulting in a self-perpetuating cycle.12

Increases in chronic rheumatic disease activity — reflective of these higher levels of inflammation — are independently correlated with deterioration of several sleep domain measures. In a cohort study comparing patients diagnosed with RA and primary OA, researchers analyzed 6 sleep domains, including sleep adequacy, sleep disturbance, somnolence, snoring, sleep quantity, and awakening due to shortness of breath or headache.13 Level of disease activity was the only factor to influence all 6 domains of sleep, although mood disorders and obesity also affected several sleep parameters. All sleep domains were altered among patients with RA, whereas only somnolence and sleep disturbance were the most impaired domains among those with OA.14

Sleep Disorders Increase Risk for Autoimmune and Inflammatory Conditions

On the other hand, sleep disorders can increase the risk of developing inflammatory,11 neurodegenerative,11 and autoimmune conditions.15 Inconsistent sleep increases inflammatory biomarker levels, including c-reactive protein, interleukin-6, and fibrinogen levels, especially among women.16 Compared against people in the general population without sleep disorders, nonapnea sleep disorders increased the overall risk for occurrence of autoimmune conditions (adjusted hazard ratio [aHR], 1.47; 95% CI, 1.41-1.53), including RA, AS, systemic lupus erythematosus, and Sjögren syndrome (SS). Similarly, OSA increased the overall risk for incident autoimmune conditions (aHR, 1.95; 95% CI, 1.66-2.27), including RA, SS, and Behçet disease.15,17

Studies have shown that sleep deprivation increases IL-1β and TNF-α expression, along with other proinflammatory proteins, in the cortex and other brain regions, as well as the peripheral tissues and circulation.11 The increased concentrations of proinflammatory cytokines due to sleep deprivation may explain the increased prevalence of inflammatory rheumatic and autoimmune conditions among those with sleep disorders.

How Sleep Disorders Affect Sleep Quality

Sleep disorders affect the quality of sleep by increasing the time spent awake, decreasing the time spent asleep, decreasing sleep efficiency, and increasing sleep onset latency.15 Pain caused by musculoskeletal inflammatory processes10 or involuntary RLS movements may prevent individuals from falling or staying asleep.18

Even during sleep, individuals with OSA may experience complete or partial collapse of the airway, resulting in decreased oxygen saturation or waking up. Obstructive sleep apnea leads to fragmented and nonrestorative sleep.19 Individuals with CSA exhibit a lack of drive to breathe during sleep, resulting in decreased ventilation and oxygenation. Central sleep apnea is associated with excessive daytime sleepiness and frequent awakening during sleep.20

Outcome Measures Used to Assess Sleep Quality in People With Rheumatic Diseases

Patients with RA scored lower for sleep adequacy and higher for snoring according to measurements of sleep quality using the Medical Outcome Study Sleep Scale (MOS-SS).21 In addition to the MOS-SS, other outcome measures that can assess sleep quality among individuals with rheumatic diseases include the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the Patient Reported Outcome Measurement Information System sleep disturbance and sleep related impairment instruments, the Insomnia Severity Index, the Athens Insomnia Scale, and the Berlin Questionnaire for those with OSA.22

Effects of Sleep Disorders on Daily Living and Treatment Efficacies

Not only do sleep disorders affect sleep quality, they impact general health, mood, quality of life, and safety.2 People experiencing excessive daytime sleepiness, extreme fatigue, or narcolepsy may be at increased risk for accidents when driving.23

In one study, 46.6% of 330 patients with axial spondyloarthritis and psoriatic arthritis with positive measurements of poor sleep or abnormal sleep behaviors reported decreased satisfaction with overall health, increased depressive symptoms, and reduced quality of life.24

Sleep may also impact the efficacy of certain interventions among the rheumatic disease population. For example, perioperative insomnia trajectories were significantly correlated with postoperative outcomes among individuals with knee OA who underwent total knee arthroplasty. Patients with persistent levels of preoperative insomnia demonstrated worse postoperative pain, physical functioning, and insomnia.25

Why Improving Sleep Matters for People With Rheumatic Diseases

Sleep is a fundamental human need. Restorative sleep allows the body to repair and replace depleted cellular components needed for metabolism and biological functioning during the day.26 Sleep also enables the brain to reorganize and recharge, allowing for removal of toxic byproducts that have built up during the day.27 Quality sleep is also imperative for proper immune function.1

A clear link has been established between poor sleep and the incidence of rheumatic, neurodegenerative, and autoimmune conditions. Conversely, people with these conditions also demonstrate increased prevalence of sleep disorders, indicating a bidirectionality between inflammatory conditions and sleep disorders.

Routine assessment of sleep dysfunction among people with rheumatic diseases and prescription of interventions that are effective for improving sleep quality can affect overall patient outcomes, quality of life, and disease progression/activity levels. While sleep should become a priority for everyone, improving sleep quality has a particularly meaningful impact on people living with rheumatic and autoimmune diseases.

This article originally appeared on Rheumatology Advisor