Fatigue that is often severe, persistent and disabling is a common problem for lupus patients. A sense of exhaustion which interferes with normal functioning is an experience that affects as many as 70% of people with lupus. We all appreciate that illness of many types is associated with extreme tiredness. Fatigue is frequently the first symptom of common illnesses such as viral infection.
Distressingly, in lupus, often the tiredness persists even when the disease is “under control,” a fact that has led many researchers to conclude that disease activity has little or nothing to do with the cause of the fatigue. Yet paradoxically, many patients report that the first symptom of a flare is a worsening or relapse of fatigue. Despite extensive research, many questions remain about the biology of fatigue.
One of the reasons that progress in understanding abnormal fatigue has been slow is that fatigue, like pain, is complex and subjective and therefore a challenge for researchers to describe and measure. Fatigue has physical (needing to rest, weakness), emotional (decreased interest, low motivation) and cognitive aspects (for example: problems with concentration). The physical and emotional impact of fatigue is not the same for each individual and can be present to varying degrees in the same person at different times. Also, the words used to describe fatigue such as tiredness, sleepiness, and exhaustion mean different things to different people.
Clearly, fatigue is very challenging problem and multiple factors potentially contribute. Not surprisingly poor sleep is a major factor. Two thirds of patients with SLE report poor sleep quality. Low mood, pain, lack of exercise and medications all contribute to the high prevalence of fatigue in autoimmune disorders. A comprehensive evaluation to address each one of these issues is a good place to start in turning the fatigue problem into a symptom that is manageable and not disabling.
Fatigue, Depression and Sleep Disorder
Both fatigue and pain are strongly associated with depression in patients with autoimmune disorders including SLE. Depression is particularly frequent in the first year after lupus is diagnosed when medications and inflammatory processes, as well as the challenges of coping with a serious unpredictable illness, can be overwhelming. People with depression typically experience decreased energy along with changes in appetite, memory problems, slow thinking, difficulty with attention, feelings of sadness and loss, and pessimistic thoughts.
Medication to treat depression is often very helpful in treating both the low mood and accompanying changes in appetite, energy and sleep. When daytime tiredness persists even in the absence of depression, poor sleep quality is often a major factor. Sleep disturbance can also be related to many different problems. When pain interferes with sleep, whether the cause is nerve damage, joint inflammation or fibromyalgia , appropriate treatment of the underlying cause is essential.
Sorting out the Cause
Fatigue that follows even minimal activity is frequently associated with deconditioning. Whether decreased physical fitness is the cause or the result of abnormal fatigue, a conditioning exercise program designed to gradually improve fitness is safe and effective in treating fatigue in SLE. Depression is often associated with fatigue that is present throughout the day and is not relieved by sleep or rest. The fatigue is typically severe in the morning, which is also the case when fibromyalgia is present. In fibromyalgia sufferers, patients are likely to awaken feeling unrefreshed, tired or exhausted.
As many as 20% of SLE patients are also experiencing the symptoms of fibromyalgia: widespread muscle pain that is not associated with tissue damage and diffuse tenderness. Because the pain in fibromyalgia is thought to be due to abnormal sensory pain processing, treatment with anti-inflammatory and narcotic analgesics is usually not effective, whereas pain medications that act specifically on pain pathways that are dysregulated may be beneficial. If treatment of depression or fibromyalgia is not helpful in improving poor sleep quality, a formal evaluation to determine whether there is a specific sleep disorder interfering with normal sleep patterns, such as obstructed airway or restless leg syndrome, can be useful. Delay in falling asleep can also be helped by exercising early in the day, avoiding alcoholic beverages after dinner and a establishing a relaxing gradual process of winding down before bedtime.
Unraveling the mystery of fatigue: the way forward
More effective treatments for fatigue are likely to be linked to the discovery of novel lupus biomarkers. Biomarkers can be any one of several types of measurable quantities that reflect the biology of a disease process and relate to the mechanism of the disease. Research is this area has been very exciting. A good example is the discovery that up-regulation of the interferon gene pathway is characteristic of lupus and Sjogren’s syndrome as well as several other autoimmune disorders.
The interferon gene signature is a fingerprint for severe SLE that is more likely to be detected in patients with serious organ involvement (especially kidney and brain) and when disease is very active. Within the central nervous system, inflammatory molecules regulated by interferon play a role in causing symptoms that we associate with illness including decreased appetite, fatigue and abnormal sleep as well as depression. Other potential biomarkers for fatigue include genetic fingerprints (DNA and RNA messages within cells that are identifiable with modern technologies of molecular biology) and imaging techniques, such as nonconventional protocols for high resolution brain magnetic resonance imaging.
So far, while the results are preliminary and require further study, there are some clues that suggest that disruption in normal signaling between brain cells involved in monitoring stress and pain may contribute to fatigue in individuals with autoimmune disease. Another line of recent research suggests that increased oxidative stress and possibly mitochondrial dysfunction could play a role in causing fatigue in lupus as well as fibromyalgia and chronic fatigue syndrome. Future studies combining both high resolution brain imaging and molecular techniques capable of measuring abnormal proteins could provide answers to the mystery of the origin of fatigue. New insights into the two-way relationships between the immune system and the brain will shed more light on the origin of abnormal pain and fatigue. In the meantime a model that takes into account the complex physical and psychological aspects is the starting point for tailor-made therapeutic help.
You can learn more about fatigue on lupus.org.
Dr. Barbara Segal
Hennepin County Medical Center