One of the factors associated with SLE is vitamin D deficiency. The first mechanism may arise genetically. Research indicates SLE may have a genetic link. SLE does run in families, but no single causal gene has been identified. Instead, multiple genes appear to influence a person's chance of developing lupus when triggered by environmental factors.
While the genetics of SLE are not very well understood, there is growing evidence for the involvement of specific genes in this complex autoimmune disease. Part of the complexity of this disease is due to the effects of both environment and genetics factors that may contribute to its development. Genome-wide association studies GWAS revealed regions of linkage that were found on most chromosomes. Candidate gene loci implicated with SLE include multiple alleles from the HLA region, Fc-gamma receptor , and complement component system. Since SLE is associated with so many genetic regions, it is likely an oligogenic trait, meaning that there are several genes that control susceptibility to the disease.
SLE is regarded as a prototype disease due to the significant overlap in its symptoms with other autoimmune diseases. Drug-induced lupus erythematosus is a generally reversible condition that usually occurs in people being treated for a long-term illness. Drug-induced lupus mimics SLE.
However, symptoms of drug-induced lupus generally disappear once the medication that triggered the episode is stopped. More than 38 medications can cause this condition, the most common of which are procainamide , isoniazid , hydralazine , quinidine , and phenytoin.
Discoid cutaneous lupus is limited to skin symptoms and is diagnosed by biopsy of rash on the face, neck, scalp or arms. One manifestation of SLE is abnormalities in apoptosis , a type of programmed cell death in which aging or damaged cells are neatly disposed of as a part of normal growth or functioning. In SLE, the body's immune system produces antibodies against itself, particularly against proteins in the cell nucleus.
SLE is triggered by environmental factors that are unknown. The immune system must balance between being sensitive enough to protect against infection, and become sensitized to attack the body's own proteins autoimmunity. During an immune reaction to a foreign stimulus, such as bacteria, virus, or allergen, immune cells that would normally be deactivated due to their affinity for self-tissues can be abnormally activated by signaling sequences of antigen-presenting cells.
Thus triggers may include viruses, bacteria, allergens IgE and other hypersensitivity , and can be aggravated by environmental stimulants such as ultraviolet light and certain drug reactions. These stimuli begin a reaction that leads to destruction of other cells in the body and exposure of their DNA, histones , and other proteins, particularly parts of the cell nucleus. The body's sensitized B-lymphocyte cells will now produce antibodies against these nuclear-related proteins.
These antibodies clump into antibody-protein complexes which stick to surfaces and damage blood vessels in critical areas of the body, such as the glomeruli of the kidney; these antibody attacks are the cause of SLE. Researchers are now identifying the individual genes, the proteins they produce, and their role in the immune system. Each protein is a link on the autoimmune chain, and researchers are trying to find drugs to break each of those links. People with SLE have intense polyclonal B-cell activation, with a population shift towards immature B cells. T cells, which regulate B-cell responses and infiltrate target tissues, have defects in signaling, adhesion, co-stimulation, gene transcription, and alternative splicing.
In the complement system low C3 levels are associated with systemic lupus erythematosus [61]. These cells normally engulf B cells that have undergone apoptosis after somatic hypermutation.
Also, uningested apoptotic nuclei can be found outside of TBMs. This material may present a threat to the tolerization of B cells and T cells. Dendritic cells in the germinal center may endocytose such antigenic material and present it to T cells, activating them. Also, apoptotic chromatin and nuclei may attach to the surfaces of follicular dendritic cells and make this material available for activating other B cells that may have randomly acquired self-specificity through somatic hypermutation.
Impaired clearance of dying cells is a potential pathway for the development of this systemic autoimmune disease. This includes deficient phagocytic activity and scant serum components in addition to increased apoptosis. SLE is associated with defects in apoptotic clearance, and the damaging effects caused by apoptotic debris. When apoptotic material is not removed correctly by phagocytes, they are captured instead by antigen-presenting cells, which leads to development of antinuclear antibodies.
Monocytes isolated from whole blood of people with SLE show reduced expression of CD44 surface molecules involved in the uptake of apoptotic cells. Most of the monocytes and tingible body macrophages TBMs , which are found in the germinal centres of lymph nodes , even show a definitely different morphology; they are smaller or scarce and die earlier.
Serum components like complement factors, CRP , and some glycoproteins are, furthermore, decisively important for an efficiently operating phagocytosis. With SLE, these components are often missing, diminished, or inefficient. Recent research has found an association between certain people with lupus especially those with lupus nephritis and an impairment in degrading neutrophil extracellular traps NETs. The clearance of early apoptotic cells is an important function in multicellular organisms. It leads to a progression of the apoptosis process and finally to secondary necrosis of the cells if this ability is disturbed.
Necrotic cells release nuclear fragments as potential autoantigens , as well as internal danger signals, inducing maturation of dendritic cells DCs , since they have lost their membranes' integrity. Increased appearance of apoptotic cells also stimulates inefficient clearance. That leads to maturation of DCs and also to the presentation of intracellular antigens of late apoptotic or secondary necrotic cells, via MHC molecules. Autoimmunity possibly results by the extended exposure to nuclear and intracellular autoantigens derived from late apoptotic and secondary necrotic cells.
B and T cell tolerance for apoptotic cells is abrogated, and the lymphocytes get activated by these autoantigens; inflammation and the production of autoantibodies by plasma cells is initiated. A clearance deficiency in the skin for apoptotic cells has also been observed in people with cutaneous lupus erythematosus CLE. In healthy conditions, apoptotic lymphocytes are removed in germinal centers GC by specialized phagocytes, the tingible body macrophages TBM , which is why no free apoptotic and potential autoantigenic material can be seen.
In some people with SLE, accumulation of apoptotic debris can be observed in GC because of an ineffective clearance of apoptotic cells. Autoreactive B cells can accidentally emerge during somatic hypermutation and migrate into the germinal center light zone. Autoreactive B cells, maturated coincidentally, normally do not receive survival signals by antigen planted on follicular dendritic cells and perish by apoptosis.
In the case of clearance deficiency, apoptotic nuclear debris accumulates in the light zone of GC and gets attached to FDC. This serves as a germinal centre survival signal for autoreactive B-cells. After migration into the mantle zone, autoreactive B cells require further survival signals from autoreactive helper T cells, which promote the maturation of autoantibody-producing plasma cells and B memory cells. In the presence of autoreactive T cells, a chronic autoimmune disease may be the consequence.
Antibody binding subsequently spread to other epitopes. The similarity and cross-reactivity between the initial targets of nRNP and Sm autoantibodies identifies a likely commonality in cause and a focal point for intermolecular epitope spreading. Elevated expression of HMGB1 was found in the sera of people and mice with systemic lupus erythematosus, high mobility group box 1 HMGB1 is a nuclear protein participating in chromatin architecture and transcriptional regulation.
Recently, there is increasing evidence HMGB1 contributes to the pathogenesis of chronic inflammatory and autoimmune diseases due to its inflammatory and immune stimulating properties. Several techniques are used to detect ANAs. Clinically the most widely used method is indirect immunofluorescence IF. The pattern of fluorescence suggests the type of antibody present in the people's serum.
Direct immunofluorescence can detect deposits of immunoglobulins and complement proteins in the people's skin. When skin not exposed to the sun is tested, a positive direct IF the so-called lupus band test is an evidence of systemic lupus erythematosus. ANA screening yields positive results in many connective tissue disorders and other autoimmune diseases, and may occur in normal individuals. Subtypes of antinuclear antibodies include anti-Smith and anti-double stranded DNA dsDNA antibodies which are linked to SLE and anti-histone antibodies which are linked to drug-induced lupus.
Other tests routinely performed in suspected SLE are complement system levels low levels suggest consumption by the immune system , electrolytes and kidney function disturbed if the kidney is involved , liver enzymes , and complete blood count. Because of this, the LE cell test is now performed only rarely and is mostly of historical significance. The criteria, however, were established mainly for use in scientific research including use in randomized controlled trials which require higher confidence levels, so many people with SLE may not pass the full criteria.
The American College of Rheumatology ACR established eleven criteria in , [72] which were revised in [73] as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individuals and do not do well in that capacity. For the purpose of identifying people for clinical studies, a person has SLE if any 4 out of 11 symptoms are present simultaneously or serially on two separate occasions. Other than the ACR criteria, people with lupus may also have: Some people, especially those with antiphospholipid syndrome , may have SLE without four of the above criteria, and also SLE may present with features other than those listed in the criteria.
Recursive partitioning has been used to identify more parsimonious criteria. Other alternative criteria have been suggested, e. Thomas' Hospital "alternative" criteria in The treatment of SLE involves preventing flares and reducing their severity and duration when they occur. Treatment can include corticosteroids and anti-malarial drugs.
Certain types of lupus nephritis such as diffuse proliferative glomerulonephritis require intermittent cytotoxic drugs. These drugs include cyclophosphamide and mycophenolate. Hydroxychloroquine was approved by the FDA for lupus in In November , an FDA advisory panel recommended approving belimumab Benlysta as a treatment for the pain and flare-ups common in lupus. The drug was approved by the FDA in March Due to the variety of symptoms and organ system involvement with SLE, its severity in an individual must be assessed in order to successfully treat SLE.
Mild or remittent disease may, sometimes, be safely left untreated. If required, nonsteroidal anti-inflammatory drugs and antimalarials may be used. Medications such as prednisone , mycophenolic acid and tacrolimus have been used in the past. Disease-modifying antirheumatic drugs DMARDs are used preventively to reduce the incidence of flares, the progress of the disease, and the need for steroid use; when flares occur, they are treated with corticosteroids.
DMARDs commonly in use are antimalarials such as hydroxychloroquine and immunosuppressants e. Hydroxychloroquine is an FDA-approved antimalarial used for constitutional, cutaneous, and articular manifestations. Hydroxychloroquine has relatively few side effects, and there is evidence that it improves survival among people who have SLE. Mycophenolic acid is also used for treatment of lupus nephritis, but it is not FDA-approved for this indication, and FDA is investigating reports that it may be associated with birth defects when used by pregnant women. In more severe cases, medications that modulate the immune system primarily corticosteroids and immunosuppressants are used to control the disease and prevent recurrence of symptoms known as flares.
Depending on the dosage, people who require steroids may develop Cushing's syndrome , symptoms of which may include obesity , puffy round face, diabetes mellitus , increased appetite, difficulty sleeping and osteoporosis. These may subside if and when the large initial dosage is reduced, but long-term use of even low doses can cause elevated blood pressure and cataracts.
Numerous new immunosuppressive drugs are being actively tested for SLE. Rather than suppressing the immune system nonspecifically, as corticosteroids do, they target the responses of individual [types of] immune cells. Some of these drugs are already FDA-approved for treatment of rheumatoid arthritis. Since a large percentage of people with SLE have varying amounts of chronic pain , stronger prescription analgesics painkillers may be used if over-the-counter drugs mainly nonsteroidal anti-inflammatory drugs do not provide effective relief.
Potent NSAIDs such as indomethacin and diclofenac are relatively contraindicated for people with SLE because they increase the risk of kidney failure and heart failure. Pain is typically treated with opioids , varying in potency based on the severity of symptoms. When opioids are used for prolonged periods, drug tolerance, chemical dependency, and addiction may occur. Opiate addiction is not typically a concern since the condition is not likely to ever completely disappear.
Thus, lifelong treatment with opioids is fairly common for chronic pain symptoms, accompanied by periodic titration that is typical of any long-term opioid regimen. Intravenous immunoglobulins may be used to control SLE with organ involvement, or vasculitis. It is believed that they reduce antibody production or promote the clearance of immune complexes from the body, even though their mechanism of action is not well understood.
Avoiding sunlight in SLE is critical, since sunlight is known to exacerbate skin manifestations of the disease. Avoiding activities which induce fatigue is also important, since those with SLE fatigue easily and it can debilitating. These two problems can lead to people becoming housebound for long periods of time. Drugs unrelated to SLE should be prescribed only when known not to exacerbate the disease.
Occupational exposure to silica , pesticides , and mercury can also worsen the disease. In this form of the disease the cause is very different from lupus: If this disorder is suspected in people, brain scans are usually required for early detection. These scans can show localized areas of the brain where blood supply has not been adequate. The treatment plan for these people requires anticoagulation.
Often, low-dose aspirin is prescribed for this purpose, although for cases involving thrombosis anticoagulants such as warfarin are used. While most infants born to mothers who have SLE are healthy, pregnant mothers with SLE should remain under medical care until delivery. Neonatal lupus is rare, but identification of mothers at highest risk for complications allows for prompt treatment before or after birth.
In addition, SLE can flare up during pregnancy, and proper treatment can maintain the health of the mother longer. Women pregnant and known to have anti-Ro SSA or anti-La antibodies SSB often have echocardiograms during the 16th and 30th weeks of pregnancy to monitor the health of the heart and surrounding vasculature. Contraception and other reliable forms of pregnancy prevention is routinely advised for women with SLE, since getting pregnant during active disease was found to be harmful.
Lupus nephritis was the most common manifestation. No cure is available for SLE but there are many treatments for the disease. In the s, most people diagnosed with SLE lived fewer than five years. Prognosis is typically worse for men and children than for women; however, if symptoms are present after age 60, the disease tends to run a more benign course. Early mortality, within 5 years, is due to organ failure or overwhelming infections, both of which can be altered by early diagnosis and treatment.
The mortality risk is fivefold when compared to the normal population in the late stages, which can be attributed to cardiovascular disease from accelerated atherosclerosis, the leading cause of death for people with SLE.
Steroids should be used at the lowest dose for the shortest possible period, and other drugs that can reduce symptoms should be used whenever possible. The global rates of SLE are approximately 20—70 per , people. In females, the rate is highest between 45 and 64 years of age. The lowest overall rate exists in Iceland and Japan.
The highest rates exist in the 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. The rate of SLE varies between countries, ethnicity, and sex, and changes over time. 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. There are assertions that race affects the rate of SLE. However, a 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.
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. 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. SLE, like many autoimmune diseases, affects females more frequently than males, at a rate of about 9 to 1. The Y chromosome has no identified mutations associated with autoimmune disease. 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.
While females are more likely to relapse than males, the intensity of these relapses is the same for both sexes. In addition to hormonal mechanisms, specific genetic influences found on the X chromosome may also contribute to the development of SLE.
In more severe cases, medications that modulate the immune system primarily corticosteroids and immunosuppressants are used to control the disease and prevent recurrence of symptoms known as flares. The lupus band test in systemic lupus erythematosus patients. Numerous new immunosuppressive drugs are being actively tested for SLE. Similarly, subacute cutaneous lupus manifests as red, scaly patches of skin but with distinct edges. Retrieved 18 April Pityriasis simplex capillitii Cradle cap. SLE may cause pericarditis —inflammation of the outer lining surrounding the heart, myocarditis —inflammation of the heart muscle, or endocarditis —inflammation of the inner lining of the heart.
Studies indicate that the X chromosome can determine the levels of sex hormones. A study has shown an association between Klinefelter syndrome and SLE. Whether the increase is due to better diagnosis or to increasing frequency of the disease is unknown. The history of SLE can be divided into three periods: In each period, research and documentation advanced the understanding and diagnosis of SLE, leading to its classification as an autoimmune disease in , and to the various diagnostic options and treatments now available to people with SLE.
The advances made by medical science in the diagnosis and treatment of SLE have dramatically improved the life expectancy of a person diagnosed with SLE. There are several explanations ventured for the term lupus erythematosus. The classical period began when the disease was first recognized in the Middle Ages. The term lupus is attributed to 12th-century Italian physician Rogerius Frugard , who used it to describe ulcerating sores on the legs of people. The neoclassical period began in when the skin disease which is now known as discoid lupus was documented by the French physician, Pierre Cazenave.
Cazenave termed the illness lupus and added the word erythematosus to distinguish this disease from other illnesses that affected the skin except they were infectious. He was one of the first to document that lupus affected adults from adolescence into the early thirties and that the facial rash is its most distinguishing feature. Research and documentation of the disease continued in the neoclassical period with the work of Ferdinand von Hebra and his son-in-law, Moritz Kaposi.
They documented the physical effects of lupus as well as some insights into the possibility that the disease caused internal trauma. One-Straw Revolutionary Larry Korn. The Enigma Andrew Hodges. Life on Air Sir David Attenborough. Emergency Doctor Edward Ziegler. The Science Book DK. Lab Girl Hope Jahren. A Life Underwater Charlie Veron. Gifted Hands Ben Carson. Walden Henry David Thoreau.
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