Given the frequent link between sleep disorders and associated rheumatologic conditions, and the possible need for diagnostic referrals, this author discusses some of the common findings as well as helpful diagnostic tests that can be preformed at sleep laboratories.

Although we spend about a third of our lives sleeping, we give very little thought to what happens during the “dark hours” of sleep and how it can affect our patients, their medical problems and their treatment. Why we sleep is still pretty much a mystery but what happens during sleep is slowly being revealed through modern research techniques and the dedication of specialists in the new and emerging field of sleep medicine.

Over the past two decades in particular, we have made amazing strides in elucidating the physiology of sleep and defining a host of sleep disorders with which health care providers should become familiar. Some of these sleep disorders are particularly common in rheumatologic conditions (see “A Guide To Possible Causes Of Daytime Sleepiness” above) and may be easy for clinicians to diagnose and treat.



These rheumatologic conditions may have certain manifestations, which clinicians need to identify as sleep-associated problems even if the symptoms may confound those that one sees with rheumatologic disorders. Indeed, tiredness is the major complaint of those with significant organic sleep disorders. Being tired all the time is also an especially common complaint of patients with rheumatoid arthritis and fibromyalgia.

Understanding The Relationship Between Rheumatologic Conditions And Sleep Disorders
The first task in recognizing sleep disorders is being able to distinguish between someone who is feeling tired and someone who is suffering from fatigue. If the patient can easily fall asleep or doze off unintentionally during waking hours, this is known as excessive daytime sleepiness (EDS) or hypersomnia, and signals a sleep disorder.

However, if the patient does not have a propensity to fall asleep yet feels physically tired with an active mind, this is fatigue. Those with fatigue may or may not have a sleep disorder but the symptom of fatigue is especially common and is often overbearing in those with fibromyalgia and rheumatoid arthritis (RA).1,2

There is a dynamic and complex relationship between rheumatologic conditions and sleep disorders. Chronic pain at night will disturb sleep and is a common cause of sleep-maintenance insomnia. In part, this is due to medication effects wearing off during the night. In addition, sleep deprivation (especially rapid eye movement (REM) sleep loss) as well as sleep disruption from sleep disorders and pain may actually lower the pain threshold. This in turn renders patients hyperalgesic and increases their suffering. Disruption of deep (delta or slow-wave) sleep may result in musculoskeletal pain and tenderness.3,4

Accordingly, let us take a closer look at some of the causes of excessive daytime sleepiness as well as some organic causes of insomnia and non-refreshing sleep. Having a strong awareness of these disorders, which are often associated with rheumatologic conditions, can go a long way toward facilitating accurate diagnosis and appropriate referral to a sleep medicine specialist.

Making The Referral For Polysomnography: What You Should Know
The most important test that can be done in a sleep laboratory is polysomnography, which means “writing down many things during sleep.” For people with a normal sleep/wake schedule (circadian rhythm), this test is done at night by polysomnographic technologists who continuously monitor the patient.

Some of the important things to monitor are the electroencephalogram (EEG), eye movements and chin muscle tone via electromyography (EMG). These enable the technologist and sleep specialist to determine when the patient is asleep and what stage of sleep the patient is in. This is essential to validate an adequate sleep study because it enables one to determine adequate sleep time and adequate REM sleep time. Without these determinations, the polysomnography could wind up being a “false negative” study.



Other parameters that sleep specialists routinely monitor during polysomnography include airflow, breathing effort and electrocardiogram (EKG). In addition, other monitoring areas include oxygen saturation, end-tidal CO2 and muscle tone. Sleep specialists monitor all of these with the help of a microphone to detect movement activity and breathing sounds as well as snoring, etc. Sometimes, they will also measure esophageal pH in order to evaluate sleep-related gastroesophageal reflux.

These specialists monitor airflow via nasal pressure, oral and nasal temperature (via thermistors), and/or expired CO2. Serving as an auxiliary airflow monitor is a microphone that records the sounds of breathing.
Absence of airflow for more than 10 seconds in an adult (or two respiratory cycles in children) is referred to as apnea, which means the person is not breathing. The sleep specialists score apneas when they are accompanied by oxygen desaturation, EEG arousal or bradycardia in children. In this case, bradycardia is a 25 percent decrease in heart rate.

A 50 percent reduction in airflow for more than 10 seconds is called hypopnea, which is low breath. Hypopneas are scored when low breath is accompanied by oxygen desaturation. If the abnormal breathing causes an EEG arousal but no oxygen desaturation, the patient has a respiratory effort-related arousal (RERA). One may see this in cases of upper airway resistance syndrome (UARS) in which there is an exaggerated effort to breathe through a narrow airway. This causes sleep disruption that results in daytime sleepiness. Utilizing impedance plethysmography, piezocrystal belts and/or intercostal EMG, sleep specialists can measure and detect abdominal and chest wall excursion, thus documenting respiratory effort to distinguish obstructive from central apnea during polysomnography.

When an apnea is accompanied by respiratory effort, the patient has an obstructive apnea. When there is no effort or attempt to breath, the patient has a central apnea. The most common form of sleep-disorder breathing is obstructive sleep apnea, which clinicians may see as often as asthma if they look for it. Central sleep apnea, on the other hand, is not as common and is sometimes associated with a central nervous system (CNS) disorder.

Cheyne-Stokes breathing is a specific type of central sleep apnea, which is characterized by gradually decreasing effort, central apnea and gradually increasing effort in a crescendo-decrescendo pattern. It is seen in heart failure and in CNS disease such as a stroke.

What MSLT And MWT Tests Can Reveal
In addition to polysomnography, there are two other types of studies that sleep specialists can perform in the sleep laboratory. The Multiple Sleep Latency Test (MSLT) is a series of five 20-minute daytime naps, which are usually done at 8 a.m., 10 a.m., 12 p.m., 2 p.m. and 4 p.m. During these naps, sleep specialists monitor EEG, eye movements and chin EMG in the sleep laboratory. The patient is also kept under video surveillance to ensure he or she does not sleep between the naps. The specialist conducts the MSLT after nocturnal polysomnography (NPSG), which allows them to verify that the patient has had an adequate amount of sleep with adequate REM sleep and no disruption (e.g. sleep apnea). Patients also have a urine test for drugs that may cause sleepiness or wakefulness.

The time it takes to fall asleep is called the sleep latency and the average sleep latency for the five naps, or MSLT score, is an objective measurement of daytime sleepiness. If the patient enters REM sleep (characteristic of narcolepsy), sleep specialists will note this as well.

An active EEG (see above) with rapid eye movements but absent of muscle tone is known as REM sleep. The low muscle tone in REM sleep makes this a particularly vulnerable time for sleep-disorder breathing, such as obstructive sleep apnea, to occur.

The MSLT is the definitive test for the diagnosis of narcolepsy, post-traumatic hypersomnia and idiopathic CNS hypersomnia.

The Maintenance of Wakefulness Test (MWT) is similar to the MSLT but this test is conducted with the patient in a semi-erect position in a dark room. The patient must try to stay awake for periods of 20, 30 or 40 minutes at a time during the day. The MWT is an objective measure of the ability to stay awake. This test is commonly used to certify the ability of pilots to fly or commercial drivers to drive trucks or buses. Patients also undergo a urine drug screen in conjunction with this test but it does not have to be preceded by a NPSG.

A Guide To Differentiating Between REM Sleep, Non-REM Sleep And Alpha-Delta Sleep
An active EEG with rapid eye movements but absent of muscle tone is known as REM sleep. This is the stage of sleep in which we do our normal dreaming but we are ordinarily paralyzed to keep from acting out our dreams. The low muscle tone in REM sleep makes this a particularly vulnerable time for sleep-disorder breathing, such as obstructive sleep apnea, to occur. Without the presence of REM sleep, the study is not considered valid.

There are four stage of non-REM sleep and each stage has a different EEG pattern. The deepest stages of sleep are characterized by an EEG pattern with very large (>75 mV), slow (1/2 to 2 cycles/second) delta (d) waves. When there are > 30 percent delta waves, the patient has Stage 3 non-REM sleep. Greater than 50 percent delta waves constitutes Stage 4 non-REM sleep. These two stages (3 and 4) are often lumped together as delta sleep or slow wave sleep (SWS) since they are physiologically similar. Stage 4 represents the deepest sleep, a sleep in which it is difficult to arouse the patient and a stage in which some events (parasomnias) like sleepwalking and night terrors occur.

There are some conditions of sleep in which large, slow delta waves of deep sleep are riddled with alpha waves of wakefulness (see above). This alpha-delta sleep is associated with a sensation of non-restorative or non-refreshing sleep. This occurs with particular frequency in patients with chronic fatigue, fibromyalgia or rheumatoid arthritis.

There are some conditions of sleep in which these large, slow delta waves of deep sleep are riddled with alpha (a) waves of wakefulness. These alpha waves are characteristic of the drowsy waking state and should not occur during deep delta sleep. When this occurs, it is called alpha-delta sleep and is associated with a sensation of non-restorative or non-refreshing sleep. This occurs with particular frequency in patients with chronic fatigue and especially in patients with fibromyalgia. However, one may also see this frequently among patients with rheumatoid arthritis.5-7

Patients with alpha-delta sleep are not necessarily sleepy but they are tired and fatigued. When alpha-delta sleep is severe, patients can also suffer from hypersomnolence.8,9 Patients with alpha-delta sleep may improve with low doses of antidepressants such as amitriptyline (10 mg hs), trazodone, fluoxetine and venlafaxine. Researchers have also reported significant improvement with the use of sodium oxybate (gamma hydroxybutyrate or GHB).10

Is There A High Incidence Of RLS and PLMD With Rheumatologic Conditions?
Fibromyalgia is associated with a high incidence of three sleep disorders: alpha-delta sleep, restless legs syndrome (RLS) and periodic limb movement disorder (PLMD). About 5 to 10 percent of chronic sleep-onset insomnia may be related to RLS, which is common among those with systemic sclerosis, Sjögren’s syndrome or fibromyalgia. Restless legs syndrome is an unrelenting urge to move one’s legs with unpleasant sensations, which can be difficult to describe. This usually occurs when the patient’s legs are at rest or inactivity. The patient experiences relief once there is movement in his or her legs. This syndrome is usually worse in the evening.

Periodic limb movement disorder is characterized by repetitive cramping and movements of the limbs during sleep with transient arousals. Clinicians see this more frequently among patients who have rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It can be a cause of sleep maintenance insomnia or excessive daytime sleepiness. The patient is usually unaware of the limb movements unless he or she is informed by a spouse or bed partner.

Methylxanthines (i.e. caffeine), selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, along with uremia and metabolic abnormalities, may cause RLS and PLMD. The most common metabolic disturbance is iron deficiency and iron supplementation is recommended if the ferritin level is less than 50.
The drugs of choice for both RLS and PLMD are ropinirole (0.25 to 4 mg) and pramipexole (0.125 to 0.5 mg), which patients should take 30 minutes before bedtime. One may diagnose RLS via the patient history alone but polysomnography is necessary for the diagnosis of PLMD. Most patients with RLS will also have PLMD but not the reverse.

What About Obstructive Sleep Apnea And Central Sleep Apnea?
The most common sleep disorder causing excessive daytime sleepiness is obstructive sleep apnea (OSA). This is caused by the collapse of the upper airway during sleep (sometimes only during REM sleep) when the muscle tone is physiologically diminished. The blocked airway causes hypoxemia until the patient reaches a hypoxic threshold. This provokes a transient arousal and brief change in neuronal output to upper airway muscles to open the airway. There is always some anatomic predisposing factor (i.e. large tonsils, small jaw, obesity, etc.) and there is often loud snoring. This is a particular problem among patients with rheumatoid arthritis due to acquired retroganthia and micrognathia.

While symptomatic OSA is found in 2 percent of women and 4 percent of men, it can be seen in 70 percent of those with destruction of the temporomandibular joint from RA. Clinicians should also be aware that the use of infliximab (Remicade, Centocor) can make OSA worse. 11

The treatment of choice for most patients with OSA is continuous positive airway pressure (CPAP), a treatment that is utilized with titration of pressure in the sleep laboratory to eliminate all apneas and snoring. However, when it comes to patients with retronathia or micrognathia, clinicians may want to refer these patients for surgical mandibular advancement and hyoid suspension or a mandibular-advancing oral appliance, which can be made for the individual patient by an oral surgeon or dentist.

Central sleep apnea (CSA) is a less common form of sleep apnea that clinicians may see among patients with RA. This is cessation of breathing caused by failure of the brain to initiate breathing. In this case, the cause is brainstem compression due to vertical luxation of the odontoid process.

Both OSA and CSA need to be diagnosed in the sleep laboratory with polysomnography.

Other Pertinent Pearls About Sleep Disorders And Rheumatologic Conditions
While sleep disorders appear to be most frequent with fibromyalgia and RA, they are frequently overlooked problems with many of the rheumatologic disorders.

Those with SLE are prone to poor sleep quality, OSA and PLMD.12 Systemic sclerosis patients have a high rate of sleep-related gastroesophageal reflux and aspiration during sleep. In order to make this diagnosis for patients with scleroderma, it is recommended to include esophageal pH monitoring with the polysomnography. These patients also have a very high prevalence of PLMD (48 percent) and RLS (22 percent) in addition to sleep-related GERD, and may present with insomnia or hypersomnia.13

Patients with ankylosing spondylitis have very frequent complaints of insomnia (41 percent), both sleep-onset and sleep-maintenance forms of insomnia, as well as daytime fatigue. One may note obstructive sleep apnea in 12 percent of ankylosing spondylitis patients.14 Insomnia is also the major complaint in Sjögren’s syndrome.

The most common sleep disorder causing excessive daytime sleepiness is obstructive sleep apnea (OSA).

When sleep-onset insomnia is present, 24 percent is due to RLS and 45 percent is due to muscle tension.15 One may also detect alpha-delta sleep with these patients.

There are two major sleep problems in those with dermatomyositis/polymyositis: nocturnal hypoventilation and aspiration during sleep. These patients should have end-tidal carbon dioxide (PetCO2) monitored during polysomnography if they are evaluated in the sleep laboratory in order to detect significant hypoventilation during sleep.

In Conclusion
Sleep disorders, ranging from restless legs syndrome (RLS) and insomnia to obstructive sleep apnea and hypersomnolence, are commonly associated with rheumatologic conditions. Understanding some of the signs and symptoms of these disorders as well as having an awareness of key diagnostic tests that can be conducted in sleep laboratories may facilitate improved diagnosis and timely referrals.