Systemic lupus erythematosus (SLE), also known simply as lupus, is an autoimmune disease in which the body’s immune system mistakenly attacks healthy tissue in many parts of the body.^[1] Symptoms vary between people and may be mild to severe. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face. Often there are periods of illness, called flares, and periods of remission when there are few symptoms.^[1]

The cause is not entirely clear.^[1] It is believed to involve hormonal, environmental, and genetic factors.^[2] Among identical twins, if one is affected there is a 24% chance the other one will be as well.^[1] Female sex hormones, sunlight, smoking, vitamin D deficiency, and certain infections, are also believed to increase the risk.^[2] The mechanism involves an immune response by autoantibodies against a person’s own tissues. These are most commonly anti-nuclear antibodies and they result in inflammation. Diagnosis can be difficult and is based on a combination of symptoms and laboratory tests. There are a number of other kinds of lupus erythematosus including discoid lupus erythematosus, neonatal lupus, and subacute cutaneous lupus erythematosus

Epidemiology

The global rates of SLE are approximately 20-70 per 100,000 people. In females, the rate is highest between 45-64 year of age. The lowest overall rate exists in Iceland and Japan. The highest rates exist in US and France. However, there is no sufficient evidence to conclude that SLE is less common in some countries compared to others, since there is significant environmental variability in these countries. For example, different countries receive different levels of sunlight, and exposure to UV rays affects dermatological symptoms of SLE. Certain studies hypothesize that a genetic connection exists between race and lupus which affects disease prevalence. If this is true, the racial composition of countries affects disease, and will cause the incidence in a country to change as the racial makeup changes. In order to understand if this is true, countries with largely homogenous and racially stable populations should be studied to better understand incidence.^[5] Rates of disease in the developing world are unclear.^[6]

The rate of SLE varies between countries, ethnicity, sex, and changes over time.^[87] In the United States, one estimate of the rate of SLE is 53 per 100,000;^[87] other estimates range from 322,000 to over 1 million.^[88] In Northern Europe the rate is about 40 per 100,000 people.^[89] SLE occurs more frequently and with greater severity among those of non-European descent.^[88] That rate has been found to be as high as 159 per 100,000 among those of Afro-Caribbean descent.^[87] Childhood-onset systemic lupus erythematosus generally presents between the ages of 3 and 15 and is four time more common in girls.^[90]

While the onset and persistence of SLE can show disparities between genders, socioeconomic status also plays a major role. Women with SLE and of lower socioeconomic status have been shown to have higher depression scores, higher body mass index, and more restricted access to medical care than women of higher socioeconomic statuses with the illness. People with SLE had more self-reported anxiety and depression scores if they were from a lower socioeconomic status.^[91]

Ethnicity

There are assertions that race affects the rate of SLE. However, a 2010 review of studies which correlate race and SLE identified several sources of systematic and methodological error, indicating that the connection between race and SLE may be spurious.^[92] For example, studies show that social support is a modulating factor which buffers against SLE-related damage and maintains physiological functionality.^[92] Studies have not been conducted to determine whether people of different racial backgrounds receive differing levels of social support.^[92] If there is a difference, this could act as a confounding variable in studies correlating race and SLE. Another caveat to note when examining studies about SLE is that symptoms are often self-reported. This process introduces additional sources of methodological error. Studies have shown that self-reported data is affected by more than just the patients experience with the disease- social support, the level of helplessness, and abnormal illness-related behaviors also factor into a self-assessment. Additionally, other factors like the degree of social support which a person receives, socioeconomic status, health insurance, and access to care can contribute to an individual’s disease progression.^[92][93] It is important to note that racial differences in lupus progression have not been found in studies that control for the socioeconomic status [SES] of participants.^[92][94] Studies that control for the SES of its participants have found that non-white people have more abrupt disease onset compared to white people and that their disease progresses more quickly. Non-white patients often report more hematological, serosal, neurological, and renal symptoms. However, the severity of symptoms and mortality are both similar in white and non-white patients. Studies that report different rates of disease progression in late-stage SLE are most likely reflecting differences in socioeconomic status and the corresponding access to care.^[92] The people who receive medical care often have accrued less disease-related damage and are less likely to be below the poverty line.^[94] Additional studies have found that education, marital status, occupation, and income create a social context which contributes to disease progression.^[92]

Sex

SLE, like many autoimmune diseases, affects females more frequently than males, at a rate of about 9 to 1.^[3][87] The X chromosome carries immunological related genes, which can mutate and contribute to the onset of SLE. The Y chromosome has no identified mutations associated with autoimmune disease.^[95]

Hormonal mechanisms could explain the increased incidence of SLE in females. The onset of SLE could be attributed to the elevated hydroxylation of estrogen and the abnormally decreased levels of androgens in females. In addition, differences in GnRH signalling have also shown to contribute to the onset of SLE. While females are more likely to relapse than males, the intensity of these relapses is the same for both sexes.^[96]

In addition to hormonal mechanisms, specific genetic influences found on the X chromosome may also contribute to the development of SLE. Studies indicate that the X chromosome can determine the levels of sex hormones. A study has shown an association between Klinefelter syndrome and SLE. XXY males with SLE have an abnormal X-Y translocation resulting in the partial triplication of the PAR1 gene region.

Keeping Your Immune System Healthy

How do you keep the immune system active and healthy? All the books say essentially the same thing— simply by living well. And “living well” involves common sense practices such as eating a healthful diet, getting enough sleep, exercising, drinking alcohol only in moderation, and avoiding stress. A few additional tips for keeping the immune system healthy include:

• Avoid or prevent exposure to environmental toxins such as mercury, poisons and heavy metals.
• Avoid taking unnecessary drugs.
• Understand that diet can influence your immune system, and choose your foods wisely.
• Have sex. Sexual activity has been found to be good for the immune system because it activates the hormones that are regulated by the act of having sex and helps maintain a healthy hormone balance.

References

• The Immune System Cure by Lorna R. Vanderhaeghe and Patrick J.D. Bouic, PhD, Penguin Books; Ontario, Canada; 1999.
• Living Well with Autoimmune Disease by Mary J. Shomon, Harper Collins; New York, NY; 2002.
• Women and Autoimmune Disease by Robert G. Lahita, MD, PhD, ReganBooks; New York, NY; 2004.
• “DHEA for Lupus” by Kay Shaver, PharmD; Pharmacist’s Letter/ Prescriber’s Letter, 2000.
• “Treatment of Multiple Sclerosis with the Pregnancy Hormone Estriol” by Nancy L. Sicotte, MD, et al; Ann Neurol, 2002.
• “Progesterone Synthesis and Myelin Formation by Schwann Cells” by Herbert L. Koenig, PhD, et al; Science, 1995.
• “Hormonal Pattern in Women Affected by Rheumatoid Arthritis” by Rossella Valentino, MD, et al; J Endocrinol Invest, 1993.
• “Intraarticular Progesterone: Effects of a Local Treatment for Rheumatoid Arthritis” by Miguel Cuchacovich, MD, et al; J Rheumatol, 1988.
• “Menopause, Sex Hormones and the Immune System” by Sarit Aschkenazi, MD, et al; Menopause Management, March/April 2000.