Systemic Lupus Erythematosus

Abstract
Systemic Lupus Erythematosus (SLE) is a systemic rheumatic autoimmune disease that affects multiple organ systems. The exact cause or causes of (SLE) is unknown, however genetic factors, gender, ethnic origin, and environmental factors have all been implicated in its development. Earlier diagnosis and more effective treatment options have significantly improved survival rates and life quality. Medical and pharmacologic treatment is usually tailored to the specific symptoms or organ systems that are involved due to its unpredictability and range of manifestations. Systemic Lupus Erythematosus affects primarily women of childbearing age and mostly in Asian, African American, and Hispanic populations. Treatment options include steroids, antimalarial drugs, and immunosuppressive agents. This overview will examine the etiology and effects of Lupus, how it impacts fertility and pregnancy in women, and life quality and expectancy. Various treatment options and alternative treatment methods will be discussed; considerations for employment and rehabilitation will be reviewed, as well as the future of therapeutic approaches.

Systemic Lupus Erythematosus
Introduction
The name “Lupus” is Latin for wolf and may have first been used to describe the lesions that resembled the bite marks and scratches made by a wolf's attack. The term “Lupus Erythematosus” was first introduced by physicians in the nineteenth century to describe skin lesions. Over one hundred years later it was realized that this disease does not only affect the skin, but it is systemic. Systemic Lupus Erythematosus is a severe chronic rheumatic inflammatory autoimmune disease that can affect any organ or system in the body at any time. For unknown reasons, the body’s immune system which normally serves to protect the body from bacteria, viruses, and other foreign invaders, instead turns on the body. It produces antibodies that attack its very own systems. It can include the joints, skin, kidneys, brain, heart, blood vessels, and lungs. In the brain and nervous system, it can cause numbness, tingling, vision disturbances, headaches, seizures, personality changes, and an array of neuropsychiatric disorders. In the digestive tract it may cause abdominal pains, nausea, and vomiting. A person may experience abnormal heart rhythms (arrhythmias) in the heart. The lungs may cough up blood or a person may have difficulty breathing. SLE affecting the skin can cause patchy skin color, rashes, lesions, or fingers that change color or turn bluish when they become cold. This is referred to as Raynaud's phenomenon. Sometimes people have only display skin symptoms, and this is called discoid lupus. Symptoms vary from person to person, and may come and go at different times affecting different parts. Most individuals with SLE have joint pain and swelling, and some will develop arthritis. The joints of the fingers, hands, wrists, and knees are most often affected, because SLE causes inflammation in the connective tissues of the body. Other symptoms that are common include swollen lymph nodes and chest pain when breathing deeply. Symptoms will depend on which part of the body is being affected.

Symptoms, Prevalence, and Etiology SLE has many serological and systemic manifestations. Antinuclear factors (AFA) or antinuclear antibodies (ANA’s) are autoantibodies produced by the immune system that attack the body's own tissues and cause inflammation. These antibodies that are directed against one's own tissues are referred to as autoantibodies. Symptoms of the disease include fever, fatigue, weight loss, muscle and or joint pain, Raynaud’s phenomenon, photosensitivity, fever, oral, nasal and skin ulcers, skin rashes, lesions which can affect the scalp, face, or any other part of the body. It may cause chronic fatigue, kidney problems, heart problems, and affect the central nervous system. SLE spares no organ. Living with SLE, and treating the disease can be complicated by its multiple exacerbations and remissions, changes in body appearance, cognitive impairments, as well as various neuropsychiatric disorders. Symptoms vary greatly, and no patients experience this disease in the exact same way. SLE is up to ten times more common in women than in men, particularly during their childbearing years. This also happens to be at the prime of most working careers. Systemic lupus Erythematosus (SLE) is associated with significant mortality and morbidity, and has a huge impact on the well-being of individuals who have the disease. SLE has been reported in six continents (South America, North America, Europe, Asia, Australia, and Africa). The disease is rare in Africa, but is common in African descendants around the globe (Guillermo, Alarcon, Scofield, Reinlib, Cooper, 2008). The disease occurs around the globe, but it is particularly common in people of Asian origin, and in Europe and North America. Patients from an African or Asian background living in industrialized places appear to have the highest prevalence of SLE (Tiffin, Ademayo, Okpechi, 2013). Prevalence is also high among Hispanics. Genetics, hormones, vaccines, certain drugs, toxins, and environmental factors are all areas of current consideration and research. However as treatment outcomes improve, there is still no proven cure, and SLE can cause death; the leading cause being from cardiovascular disease due to accelerated atherosclerosis. Statistics show that survival for people with SLE in Europe, Canada, and the United States, has risen to approximately 95% at five years, 90% at 10 years, and 78% at 20 years (Fauchi, 2005). To receive a diagnosis of lupus, four out of the eleven common signs of the disease set forth by The American College of Rheumatology must be present. There are several different tests used to diagnose the presence of SLE. These might include antibody tests, including the antinuclear antibody (ANA) panel, chest x-rays, urinalysis, and kidney biopsy, and a complete blood count (CBC).

Living with SLE The Americans with Disabilities Act has a general definition of what a disability is and each person must meet certain criteria. Therefore, some people with SLE will have a disability under the ADA and others will not. According to the ADA, a person is defined as having a disability if he or she has physical or mental impairments that substantially limits one or more of their life activities, if they have a record of such impairment, or are regarded as having an impairment. Because of the variations of severity and different manifestations of SLE, no single patient experiences the disease exactly the same way. Aside from its physical symptoms, lupus can affect almost every aspect of the patient’s life. Socially, a patient may become isolated due to changes in appearance either from medications or effects from the disease itself. Although SLE does not cause some of the joint deformities characteristic of other rheumatic diseases, hair loss, skin rashes, and the long term use of steroid medication can dramatically alter physical appearance, leading to lack of confidence, depression, and feelings of stigmatization, and isolation. The majority of SLE patients have some form of neuropsychiatric disorder and cognitive dysfunction caused by the inflammatory nature of SLE and its effects on the central nervous system. (80% to 90%) of SLE patients have some neuropsychiatric manifestation, the most common being depression at (50% to 60%); headache (50%-60%); and cognitive dysfunction (30%-50%). Other manifestations include anxiety, confusion, stroke, and psychosis (Gulinelo, Wen, Putterman 2012). Mood disorders and anxiety that are common in SLE may represent neuropsychiatric manifestations or they may be the consequence of stress, and the results of negative life events (Merry, Borba, Hatch, et al 2007). Problems can arise from the disorder itself, bothersome side effects of the disease or medications, drug abuse or misuse, management of daily routines, trying to maintain employment, financial strain, family obligations, as well as family planning. As is the case with other chronic illnesses, marital distress, separation, and divorce are not uncommon in the lives of people with SLE.

Fertility Most patients with Lupus are women, which can raise questions about family planning, fertility, and the role of motherhood. Fertility in women with SLE is fairly comparable to that of the normal population when patients have a mild disease; however, the pregnancy rate has been known to drop once SLE has been diagnosed. Several factors may contribute to this. Disease related causes for infertility include primary ovarian failure, also known as premature ovarian failure, menstrual disturbances ranging from amenorrhea to menorrhagia, and cervical vaginal inflammation and other infections that are secondary to SLE, as women with the disease may be more susceptible to sexually transmitted diseases. Stress in the relationships of patients with their partners due to the effects of their own mental well-being and self-esteem, or loss of libido or sexual function in women are some reasons to consider. Reduced libido and impotence are also a factor for some men affected by Lupus. For women, some of the drugs used to treat the disease can reduce fertility, and high doses of steroids such as prednisone can stop menstrual periods completely. Most lupus patients have normal fertility and can conceive a child, although it is recommended that the patient be in remission at least six months before trying. Pregnancy has been documented to trigger a flare (a measurable increase in disease activity). When a mother has SLE, aggravation or exacerbation of the disease has been estimated to occur in about 20-30% pregnancies (Smyth, 2010). There is an increased rate of fetal death in utero and spontaneous abortion (miscarriage). Overall, the live-birth rate in SLE patient has been estimated to be about 72%. (Smyth, 2010). The outcome of pregnancy appears to be worse in SLE patients whose disease flares up during the course of pregnancy (Cortez, Hernandez, 2010). One of the greatest concerns is premature birth. About half of mothers with lupus deliver before full-term (40 weeks). Careful monitoring throughout pregnancy can lower risks associate with miscarriage and premature births. Children born to mothers who have SLE may have a higher risk of autism spectrum disorders than children born to healthy mothers, although the overall risk is small according to the results of a study reported at the American College of Rheumatology Annual Scientific Meeting. Autism spectrum disorders (ASD’s) are a group of developmental disabilities that can cause communication, behavioral, and social challenges. (1.4 percent vs. 0.6 percent, respectively). Researchers also observed that children born to mothers with SLE were diagnosed with ASD earlier in life. This research builds on experimental studies in animals, showing that autoantibodies and cytokines (proteins and chemicals that play important roles in the immune systems of women with lupus) could alter fetal brain development and induce behavioral irregularities in offspring. Other factors may contribute to increased risk of autism that may not be readily apparent, and as this was a preliminary study, more research needs to be conducted. Most births are healthy, but approximately one third of babies born to women with SLE will contract neonatal lupus. However, this is not SLE and it usually disappears within the first month. After neonatal lupus, the child should grow up healthy, having no adverse effects later on in life. According to studies of mothers with chronic diseases, being a parent is one of the most important roles in women’s lives (Poole, Rymek, Mendelson, 2012). Consequently, this role is also a major source of stress. Mothers with chronic fatigue may be too tired to participate in many normal family and social activities with their children, and everyday family life. Photosensitivity may significantly limit time spent playing outside or engaging in outdoor activities. Life concepts and expectations sometimes cannot be filled, and the future has to be re-evaluated and re-planned in ways that a mother or family never expected, or do not resemble personal or societal expectations. All of these factors combined can lead to greater feelings of guilt depression and stigma. Though SLE is often thought of as a women’s health issue, men as well are affected, and while nearly 90% of lupus patients are in fact women between the ages of fifteen to forty-five, men should not discount both the potential of getting lupus and the seriousness with which the disease presents. Symptoms that are prevalent in women but seem to be more common in men include pleurisy (inflammation of the sac around the lungs), renal disease, discoid lupus, hemolytic anemia (from the destruction of red blood cells), lupus anticoagulant (can promote abnormal blood clotting) and seizures (Petri, 2008). While those differences may exist, lupus’ similarities in men and women, especially with regard to symptom manifestations, are many. For example, discoid lupus while more common in males, manifests the same in both sexes, appearing as lesions. Why the disease affects so many more women than men is one of the questions scientists are trying to research and explain. Multiple sex hormones may be involved in the pathogenesis of SLE, estrogen with women and androgen with men. Both these hormones are produced in both sexes, and are not exclusive to either males or females. It is possible that estrogen may encourage the development of autoimmune disorders, and that androgens may offer some protection. The higher levels of estrogen in women could be one reason why the disease is more prevalent in females, and the low levels of androgen in men are thought to connect to the development of SLE in males, but this is still unclear. In males with lupus, lower testosterone levels and higher estrogen levels have been reported as well. With women who have SLE, there are lower levels of both testosterone and the mild androgen Dehydroepiandrosterone (DHEA). In both men and women, it is the major product of the adrenal glands and can be converted to both testosterone and estradiol (Petri, 2008)

Treatment and Complementary Alternative Medicine SLE is incurable, and it can be fatal, but today with the advances in medicine it is very treatable. Sixty years ago, many or most people diagnosed with SLE might have lived fewer than five years, but today, over 90% can survive over ten years. Many live relatively normal productive lives with few symptoms. At present, 80-90% of people with SLE live normal lifespans. Despite that, evidence suggests that the quality of life for most individuals with SLE remains poor compared to that of the general population, and worse than that of individuals with other chronic diseases (Rosario, Seguro, Vasconcelos, Shoenfeld, 2013). Outcomes are typically worse for men than for women, but if the symptoms of SLE are present after the age of sixty, then the disease tends to run a more benign course. Early mortality is likely due to organ failure or serious infections that may manifest from lack of immunity, but these can be altered if diagnosis is early enough and proper treatment interventions are made. The mortality risk is much higher when compared to that of the normal population in the late stages, which can be attributed to cardiovascular disease from accelerated atherosclerosis, which is the leading cause of death for people with SLE (Martin, 2007). Since no known cure exists for SLE, the goal of most current treatments is to control symptoms. SLE is most often treated with immunosuppressive drugs that inhibit or prevent activity of the immune system. One negative and common side-effect of many immunosuppressive drugs is immunodeficiency, resulting in increased susceptibility to infections and risk of cancer. Corticosteroids are drugs that reduce inflammation in various tissues of the body. These drugs are strong, and used to treat many of the symptoms of lupus that result from inflammation. Cyclophosphamide, a very powerful drug, is usually the last resort of medication when the body is not responding to corticosteroids. It also suppresses the immune system but it is most commonly known for treating cancers and its side effects are much more severe. Other symptoms of SLE that involve the heart, lungs, kidneys, and other organs often require treatment from appropriate specialists. Mild forms of the disease can be treated with NSAIDs, such as Ibuprofen or Naproxen for joint symptoms. Corticosteroid creams for skin rashes and antimalarial drugs such as hydroxychloroquine are used to control skin rashes, and they may also help relieve muscle and joint pain, fatigue, and fever that are not controlled with other medications. Aside from medication, it is recommended that people diagnosed with SLE wear protective clothing, sunglasses, and sunscreen when in the sun. They should have tests to screen for osteoporosis, get preventative heart care, and keep up with immunizations. Individualized physical exercise programs and energy conservation techniques can reduce fatigue in people who have lupus. Because of photosensitivity, most SLE patients are deficient in vitamin D. This is an important factor to consider because 80% of vitamin D is synthesized in the skin upon exposure to UVB radiation. It is essential for maintaining homeostasis of calcium and bone mineral content (Pike, 2010). In fact, vitamin deficiency has been implicated as an environmental trigger for the development of a number of auto immune diseases, including SLE (Gatenby, Lucas, Swaminathason, 2013). There is also increasing evidence that vitamin D status is linked to cardiovascular disease, which may compound the risk for SLE patients who are already susceptible. The use of glucocorticoids also interferes with vitamin catabolism, so those using them may need a higher dosage to receive any therapeutic effect; however, there is no specific recommendation for dosage in SLE patients. Avoidance of sunlight, renal insufficiency, obesity, and medication use such as glucocorticoids are all risk factors for vitamin D deficiency in patients with SLE. A number of studies have shown that low levels in SLE patients are associated with more active disease, and complications such as osteoporosis, atherosclerosis and fatigue. Vitamin D deficiency may be an important factor that influences the long term morbidity and survival of SLE. The American College of Rheumatology recommends an intake of 800-1000 IU daily and there is strong evidence that vitamin D exhibits a wide range of beneficial and regulatory actions within the immune system. Randomized controlled trials of vitamin D therapy in patients with SLE are ongoing. Over the last two decades the treatment of autoimmune diseases has entered the era of targeted therapies. Unfortunately, the treatment of SLE has not evolved as much. Medications with high toxicity such as cyclophosphamide and high dose prednisone remain the mainstay of treatment if patients present with involvement of major organs such as the kidney, the central nervous system, or blood. (Vasileios, C., Kyttaris,, 2013) It is estimated that over 50 % of patients with SLE have utilized complementary and alternative medicine (CAM) treatments to reduce symptoms and manage their health. However, there are relatively few randomized controlled trials of CAM for SLE. (Greco, Nakajima, Manzi, 2013 ).The recent trials of CAM treatments for SLE indicate that supplements such as vitamin D, Omega 3 fatty acids, N-acetyl cysteine and turmeric show some promise for reducing SLE disease activity (Kamen, 2008). Curcumin is the most active component in the spice turmeric. Turmeric can inhibit tumor growth, inflammatory cytokine production, and inflammatory bowel disease, and curcumin can lower cholesterol and enhance wound healing. DHEA is an adrenal steroid hormone that tends to be reduced in SLE. There has been longstanding interest in dehydroepiandrosterone (DHEA) supplementation for improving SLE disease activity and protecting against the negative effects of steroids. The results of studies are mixed. Although the evidence base for acupuncture’s effects on pain in rheumatic conditions is growing, to date few studies have examined acupuncture’s utility in patients with SLE. In addition, mind-body methods such as cognitive behavioral therapy and other counseling interventions may improve mood and quality of life in individuals with chronic illness and SLE. Mind–body interventions for SLE may be focused on reducing pain, stress, anxiety, and fatigue, and consist of skills training in physiologic relaxation, meditation, problem-solving, and assertive communication skills and identifying and modifying distorted or unhelpful thinking styles. These interventions may be delivered individually, in groups, or to couples. Yoga, tai-chi, and chiropractic manipulation and massage have not been studied in SLE, and trials of acupuncture for SLE are limited. There are few studies on Mind–body medicine, and CAM interventions have thus far been mainly in the area of psychological and psychoeducational treatments and the evidence is positive for their impact on psychosocial consequences of living with a chronic, painful, and unpredictable illness such as SLE (Greco, et. al. 2013). Support groups and counseling can help with the emotional issues involved with this chronic disease. New technologies, ideas, and concepts are bringing interest and insights into what factors may predispose people to lupus. As new data is analyzed, new models are tested and avenues are being discovered that lead to identification of new diagnostic tools and therapies. New technologies allow for the study of how genes interact with each other and with the environment to cause SLE. Exploration of gene-environment interactions advances, and more improved methods in exposure assessment are being integrated into studies with genetic data.

Cultural, Vocational, and Other Considerations The complexity of SLE demands long-term and multiple-approach treatments. There is a need for comprehensive information and educational support to promote self-care, positive adjustment, and treatment adherence. Those living with SLE are at risk of feeling depression, anxiety, and an array of emotional and physical disturbances. The highest general cause of self-reported depressive and anxious feelings was change in appearance, and limitations in physical abilities due to SLE (primarily from muscle and joint pain). Patients with SLE worry about the possible side effects of medications such as developing infections, weight gain and hair loss, cushingoid features (moon face), dependence on drugs, and their teratogenicity (capacity for birth defects).These are huge concerns for women. The higher the sense of control over the disease, the less likely people are to feel anxious and depressed. African-American and Hispanic SLE patients reported a higher level of unmet psychological needs due to SLE than did their other ethnic counterparts. Comprehensive assessments, screening, patient education, and individualized plans, can produce better outcomes for the client with SLE. Physicians and counselors across the disciplines should be prepared to make referrals as needed to specifically meet each client’s needs. Degrees of limitation varies vary among individuals. Patients should be advised about the benefits and potential side effects of medications, alternative therapies, treatment advances, and research about SLE. Effective communication about diagnosis and course of the disease, involvement in treatment decision making, and proper communication with clinicians can promote and improve the capacity for individuals to cope with a diagnosis of SLE. Addressing patient concerns about medications, including treatment costs, side effects, and facilitating their involvement in treatment decision making, can promote adherence to treatments, satisfaction, and improved health outcomes. SLE is debilitating and patients must often live with unpredictable and pervasive pain, fatigue, multi-organ damage, physical limitations, stigmatization, and psychosocial challenges. The complexity of SLE demands long-term, multifaceted, and individualized care. Psychosocial support, education, self-care interventions, self-advocacy, and health management in patients with SLE is needed. This is likely to contribute to improved health and better outcomes. Because of the damages to both body and mind, areas that rehabilitation should pay attention to are: socioeconomic factors, medical factors, mental health, family support, coping styles, and culture. When counseling a client with SLE, cultural and societal roles should always be taken into consideration by the therapist. Although minimal studies exist on suicide rates, one study has found that the rate of suicidal ideation in SLE patients in China is higher than in other countries. According to this study, 34.4% of 285 SLE patients had suicidal ideation. Factors that contribute to the risk of suicidal ideation include social and cultural domains, physical and psychological health, heavy financial burden, low levels of familial function, and poor coping skills (Xie et. al., 2012). Another study conducted in Japan found that 8.4 of 84 females with SLE had suicidal ideation. High steroid usage correlated with those statistics. (Ishikura et.al., 2001). Another study of 85 patients with SLE in Iran which was focusing on depression found that 10.5 of their patients had suicidal ideation. (Zakeri et al., 2011). Currently, there is little data to be found in the United States or Europe on this type of specific study. Vocationally some people with Lupus may need modifications or accommodations to remain productive in work environments. Sometimes a change of pace or work environment is necessary, other times no changes are necessary. Counselors should be prepared to provide employers with educational resources or training regarding the effects of Lupus. Some simple job accommodations include allowing for longer breaks, providing written instructions, allowing flexible work hours and periodic rests, providing memory aids such as schedulers and organizers, providing more structure, and reducing job stress by allowing a self-paced workload. Maintaining an appropriate temperature is important or allowing the employee to work from home on very hot or cold days. Other supports may include implementing an ergonomic workstation and reducing physical excursion. Arm supports, writing grips or aids, and replacing florescent lights with full spectrum or natural lighting are all low cost accommodations that can provide comfort and help employees with SLE be more productive in the workplace It is also very important for employees with SLE to be protected from dust, smoke, odor, and fumes or toxins in the environment.

Conclusion Generally, the outlook for people with SLE is improving with the development of more accurate tests and treatments. New advancements are being made in medicine, and quality of life and lifespan is improved. With a multidisciplinary individualized treatment plan that treats the person as a whole, and takes into consideration the psychological, social, and cultural dynamics of this disease, it is possible for most individuals living with SLE to live fruitful and productive long lives. Several biological agents are currently being tested in clinical trials. New concepts about the environment give hope to scientists and patients that new discoveries will be made, and that these will transform the lives of those living with this chronic disease, but unfortunately today the cause and the cure still remain unknown.
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