The history of SLE can be divided into three periods: classical, neoclassical, and modern. In each period, research and documentation advanced the understanding and diagnosis of SLE, leading to its classification as an autoimmune disease in 1851, 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.[105]
A substance that blocks a type of enzyme called a kinase. Human cells have many different kinases, and they help control important functions, such as cell signaling, metabolism, division, and survival. Certain kinases are more active in some types of cancer cells and blocking them may help keep the cancer cells from growing. Kinase inhibitors may also block the growth of new blood vessels that tumors need to grow.

Not necessarily. The antinuclear antibody (ANA) test is positive in most people who have lupus, but it also may be positive in many people who are healthy or have another autoimmune disease. Therefore, a positive ANA test alone is not adequate for the diagnosis of lupus. There must be at least three additional clinical features from the list of 11 features for the diagnosis to be made.

The discovery of the LE cell led to further research and this resulted in more definitive tests for lupus. Building on the knowledge that those with SLE had auto-antibodies that would attach themselves to the nuclei of normal cells, causing the immune system to send white blood cells to fight off these "invaders", a test was developed to look for the anti-nuclear antibody (ANA) rather than the LE cell specifically. This ANA test was easier to perform and led not only to a definitive diagnosis of lupus but also many other related diseases. This discovery led to the understanding of what are now known as autoimmune diseases.[119]

It also is known that some women with systemic lupus erythematosus can experience worsening of their symptoms prior to their menstrual periods. This phenomenon, together with the female predominance of systemic lupus erythematosus, suggests that female hormones play an important role in the expression of SLE. This hormonal relationship is an active area of ongoing study by scientists.

The most commonly sought medical attention is for joint pain, with the small joints of the hand and wrist usually affected, although all joints are at risk. More than 90 percent of those affected will experience joint or muscle pain at some time during the course of their illness.[16] Unlike rheumatoid arthritis, lupus arthritis is less disabling and usually does not cause severe destruction of the joints. Fewer than ten percent of people with lupus arthritis will develop deformities of the hands and feet.[16] People with SLE are at particular risk of developing osteoarticular tuberculosis.[17]
Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an ‘overarching’ treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.
The rate of SLE varies between countries, ethnicity, and sex, and changes over time.[95] In the United States, one estimate of the rate of SLE is 53 per 100,000;[95] other estimates range from 322,000 to over 1 million.[96] In Northern Europe the rate is about 40 per 100,000 people.[97] SLE occurs more frequently and with greater severity among those of non-European descent.[96] That rate has been found to be as high as 159 per 100,000 among those of Afro-Caribbean descent.[95] Childhood-onset systemic lupus erythematosus generally presents between the ages of 3 and 15 and is four times more common in girls.[98]
At least half of people with lupus experience fatigue. (4) Fatigue may be brought on by the disease itself or from associated depression, anxiety, lack of exercise, and problems with sleep. ( 5) Because people with lupus need to avoid sun exposure, they may have low levels of vitamin D, which can contribute to fatigue. Lupus treatments may also play a role.
SLE is undoubtedly a potentially serious illness with involvement of numerous organ systems. However, it is important to recognize that most people with SLE lead full, active, and healthy lives. Periodic increases in disease activity (flares) can usually be managed by varying medications. Since ultraviolet light can precipitate and worsen flares, people with systemic lupus should avoid sun exposure. Sunscreens and clothing covering the extremities can be helpful. Abruptly stopping medications, especially corticosteroids, can also cause flares and should be avoided. People with SLE are at increased risk of infections as SLE-related complications, especially if they are taking corticosteroids or immunosuppressive medications. Therefore, any unexpected fever should be reported to medical professionals and evaluated.
Studies from around the world have documented a higher prevalence of vitamin D insufficiency and deficiency in patients with SLE, compared with the general population, especially in conjunction with obesity. [108, 152, 153, 154, 155, 110] Studies from Australia, [152] France, [155] the Mediterranean region, [109] and Taiwan [154] —but not from Mexico [153] —have shown an association between serum vitamin D levels and SLE disease activity.
According to the Lupus Foundation of America, approximately 1.5 million people in the U.S. have lupus. People of African, Asian, and Native American descent are more likely to develop lupus than are Caucasians. Although it can occur in both men and women, 90% of people diagnosed with the disease are women. Women of childbearing age (14 to 45 years old) are most often affected and as many as 1 in 250 people may develop lupus.
Blood and urine tests. The antinuclear antibody (ANA) test can show if your immune system is more likely to make the autoantibodies of lupus. Most people with lupus test positive for ANA. But, a positive ANA does not always mean you have lupus. If you test positive for ANA, your doctor will likely order more tests for antibodies that are specific to systemic lupus erythematosus (SLE).
There is no permanent cure for SLE. The goal of treatment is to relieve symptoms and protect organs by decreasing inflammation and/or the level of autoimmune activity in the body. The precise treatment is decided on an individual basis. Many people with mild symptoms may need no treatment or only intermittent courses of anti-inflammatory medications. Those with more serious illness involving damage to internal organ(s) may require high doses of corticosteroids in combination with other medications that suppress the body's immune system.
In patients with SLE, the risk of developing cardiovascular disease (CVD) is at least twice that in the general population, and over half of patients have 3 or more CVD risk factors.3,4 “Following a heart-healthy diet that is rich in fruits, vegetables, whole grains, lean protein, and fatty fish and limiting saturated and trans fats can actually help reduce the risk of heart disease,” Gibofsky told Rheumatology Advisor.
The panel suggests SOC alone over adding other immunosuppressant (IS) in adult patients with SLE with MSK manifestations (weak recommendation based on low certainty of the evidence). It suggests also adding either MTX, LFN, belimumab or ABT to those failing to respond to SOC (weak recommendation based on low to moderate certainty of the evidence). Cost and availability may favour MTX (table 1).

In 2007, the European League Against Rheumatism (EULAR) released recommendations for the treatment of SLE. [61] In patients with SLE without major organ manifestations, glucocorticoids and antimalarial agents may be beneficial. [61] NSAIDs may be used for short periods in patients at low risk for complications from these drugs. Consider immunosuppressive agents (eg, azathioprine, mycophenolate mofetil, methotrexate) in refractory cases or when steroid doses cannot be reduced to levels for long-term use. [106]
Steroids or prednisone and related derivatives of cortisone. Steroid creams can be directly applied to rashes. The use of creams is usually safe and effective, especially for mild rashes. The use of steroid creams or pills in low doses can be effective for mild or moderate features of lupus. Steroids can also be used in higher doses when internal organs are threatened. Unfortunately, high doses are also most likely to produce side effects.
Immunoglobulins are formed by light and heavy (depending on molecular weight) chains of polypeptides made up of about 100 amino acids. These chains determine the structure of antigen-binding sites and, therefore, the specificity of the antibody to one antigen. The five types of immunoglobulins (IgA, IgD, IgE, IgG, IgM) account for approximately 30% of all plasma proteins. Antibodies are one of the three classes of globulins (plasma proteins) in the blood that contribute to maintaining colloidal oncotic pressure.
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Peripheral neuropathy describes damage to the peripheral nervous system, the vast communications network that transmits information from the brain and spinal cord (the central nervous system) to every other part of the body. Peripheral nerves also send sensory information back to the brain and spinal cord, such as a message that the feet are cold or a finger is burned. Damage to the peripheral nervous system interferes with these vital connections. Like static on a telephone line, peripheral neuropathy distorts and sometimes interrupts messages between the brain and the rest of the body.
Systemic sclerosis (SSc): Similar symptoms between SSc and lupus are reflux and Raynaud's disease (when your fingers turn blue or white with cold). One difference between SSc and lupus is that anti-double-stranded DNA (dsDNA) and anti-Smith (Sm) antibodies, which are linked to lupus, don't usually occur in SSc. Another differentiator is that people with SSc often have antibodies to an antigen called Scl-70 (topoisomerase I) or antibodies to centromere proteins.
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.
Research is indicating benefits of rituximab (Rituxan) in treating lupus. Rituximab is an intravenously infused antibody that suppresses a particular white blood cell, the B cell, by decreasing their number in the circulation. B cells have been found to play a central role in lupus activity, and when they are suppressed, the disease tends toward remission. This may particularly helpful for people with kidney disease.
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.
With the vast amount of misinformation available online, Gibofsky often sees patients who went on restrictive diets that are purported to reduce lupus symptoms, which they may have read about on the internet or heard about from a neighbor. “Upon further discussion, I find that they do not actually feel better on the diet and, in fact, they have multiple nutritional deficiencies that could actually be the reason behind their worsening symptoms,” she said.
Lupus is a serious disease that can affect anyone. It is most often diagnosed in young women, between the ages of 15 and 44. While the cause is not known, lupus is an autoimmune disease – in which your immune system attacks healthy cells by mistake – that can potentially damage many parts of the body. There is no known cure for lupus, though effective treatments are available.
I believe that we should ALL benefit from regularly working on stress relief! Take care of yourself by adopting stress-relieving strategies, such as exercise, meditation, yoga, art, or whatever works for you. The key is to choose something that you will enjoy and stick with. I personally use a heart rhythm pacer called InnerBalance, an app that coaches you to breathe in line with your heartbeat. Even giving yourself five minutes to sit quietly with a fragrant cup of herbal tea (caffeine-free, of course!) can work wonders for your adrenal glands.
SLE is undoubtedly a potentially serious illness with involvement of numerous organ systems. However, it is important to recognize that most people with SLE lead full, active, and healthy lives. Periodic increases in disease activity (flares) can usually be managed by varying medications. Since ultraviolet light can precipitate and worsen flares, people with systemic lupus should avoid sun exposure. Sunscreens and clothing covering the extremities can be helpful. Abruptly stopping medications, especially corticosteroids, can also cause flares and should be avoided. People with SLE are at increased risk of infections as SLE-related complications, especially if they are taking corticosteroids or immunosuppressive medications. Therefore, any unexpected fever should be reported to medical professionals and evaluated.
An inflammatory response (inflammation) occurs when tissues are injured by bacteria, trauma, toxins, heat, or any other cause. The damaged cells release chemicals including histamine, bradykinin, and prostaglandins. These chemicals cause blood vessels to leak fluid into the tissues, causing swelling. This helps isolate the foreign substance from further contact with body tissues.
Why the test is used: Anti-Ro is found in anywhere from 24% to 60% of lupus patients. It's also found in 70% of people with another autoimmune disorder called Sjögren's syndrome. Anti-La is found in 35% of people with Sjögren's syndrome. For this reason, their presence may be useful in diagnosing one of these disorders. Both antibodies are associated with neonatal lupus, a rare but potentially serious problem in newborns. In pregnant women, a positive Anti-Ro(SSA) or Anti-La(SSB) warns doctors of the need to monitor the unborn baby.

Blood clots are more common in people with lupus. Clots often occur in the legs (called deep venous thrombosis or DVT) and lungs (called pulmonary embolus or PE) and occasionally in the brain (stroke). Blood clots that develop in lupus patients may be associated with the production of antiphospholipid (APL) antibodies. These antibodies are abnormal proteins that may increase the tendency of the blood to clot. Blood can be tested for these antibodies.

Neutrophils, 55% to 70% of all leukocytes, are the most numerous phagocytic cells and are a primary effector cell in inflammation. Eosinophils, 1% to 3% of total leukocytes, destroy parasites and are involved in allergic reactions. Basophils, less than 1% of all leukocytes, contain granules of histamine and heparin and are part of the inflammatory response to injury. Monocytes, 3% to 8% of all leukocytes, become macrophages and phagocytize pathogens and damaged cells, esp. in the tissue fluid. Lymphocytes, 20% to 35% of all leukocytes, have several functions: recognizing foreign antigens, producing antibodies, suppressing the immune response to prevent excess tissue damage, and becoming memory cells.
Most all studies (such as the paleo and anti-inflammatory diets), are fairly in line with their recommendations. Funny enough, these dietary recommendations are for the general populous as well! So it’s not just people with lupus who should be re-aligning dietary thinking.  However, as lupus is an inflammatory disease, it only makes sense that eating an anti-inflammatory diet, one rich in vitamins, iron, antioxidants and fish, also including the following suggestions, would be prudent.
Vasculitis, antiphospholipid antibodies, and renal failure are commonly found in patients with lupus; these conditions greatly increase the risk of developing pulmonary emboli. The diagnosis in a patient with shortness of breath, hemoptysis, and pleuritic chest pain is commonly made with ventilation-perfusion scans or computed tomography (CT) angiography. The CT angiogram demonstrates a filling defect in the left anterior segmental artery (arrow).
Nutrients that are important for managing lupus, such as fiber and antioxidants, seem to have the most beneficial effects when consumed from real food rather than from supplements.  What type of foods are included in a lupus diet? These include healthy fats, plenty of fresh veggies and fruits, and probiotic foods. Considering the fact that lupus can increase your risk for other chronic health problems (for example, women with lupus have a five- to tenfold higher risk for heart disease than the general population!), a nutrient-rich lupus diet can have far-reaching protective effects.

Any problem with managing of your lupus diet must be consulted to your doctor so that he can refer you to a registered dietician who can create a diet that will best suit your nutrition requirements. But one should remember that there are no difficult rules when planning a diet for a lupus patient like yourself. You should just be always aware foods that usually trigger your lupus symptoms. A lupus diet plan shall effectively help you control the symptoms of lupus as well as improve your general well being.
EULAR recommendations for the management of SLE with neuropsychiatric manifestations support the evaluation and treatment of these symptoms in the same way as they are evaluated and treated in patients without SLE; if symptoms persist, management of these symptoms as an extension of SLE should be considered. [83, 61] For example, in patients with neuropsychiatric manifestations that may have an inflammatory etiology, immunosuppressive agents may be considered. [61]
A person suffering from systemic lupus erythematosus SLE  is not required to take a certain lupus diet. The most appropriate way of being well is still to have a healthy and balanced diet. Good nutrition is a very important ingredient in a general lupus treatment plan. Some vitamins and foods may be helpful for lupus patients. But there are also some foods that may cause lupus flares which make lupus symptoms very evident or active.
Avoid calcium supplements, however, which Johns Hopkins researchers have found to potentially increase the risk of heart damage and arterial plaque buildup. “Due to the risk of accelerated atherosclerosis in lupus, we no longer recommend calcium supplementation and encourage a diet rich in calcium instead,” noted George Stojan, MD, a rheumatologist and assistant professor of medicine at Johns Hopkins.
Limitations of the test: Like CRP, the ESR is not specific to lupus. Because there are many causes for a positive result, including infection, the test is not diagnostic for lupus. Nor can it distinguish a lupus flare from an infection. Also, the level doesn't directly correlate with lupus disease activity. So it isn't necessarily useful for monitoring disease activity.
People with SLE have intense polyclonal B-cell activation, with a population shift towards immature B cells. Memory B cells with increased CD27+/IgD—are less susceptible to immunosuppression. CD27-/IgD- memory B cells are associated with increased disease activity and renal lupus. T cells, which regulate B-cell responses and infiltrate target tissues, have defects in signaling, adhesion, co-stimulation, gene transcription, and alternative splicing. The cytokines B-lymphocyte stimulator (BLys), interleukin 6, interleukin 17, interleukin 18, type I interferons, and tumor necrosis factor α (TNFα) are involved in the inflammatory process and are potential therapeutic targets.[4][60][61]
Gene regulation is the process of turning genes on and off. During early development, cells begin to take on specific functions. Gene regulation ensures that the appropriate genes are expressed at the proper times. Gene regulation can also help an organism respond to its environment. Gene regulation is accomplished by a variety of mechanisms including chemically modifying genes and using regulatory proteins to turn genes on or off.
Although no one symptom qualifies someone as having lupus, certain clinical techniques can be used to narrow down the diagnosis. For example, a test for antinuclear antibodies (ANAs) in the blood is probably the first tool a physician will use. A positive ANA test does not necessarily mean that someone has lupus; in fact, one out of five normal women has a positive ANA. However, a negative ANA test greatly reduces the suspicion.
Vasculitis, antiphospholipid antibodies, and renal failure are commonly found in patients with lupus; these conditions greatly increase the risk of developing pulmonary emboli. The diagnosis in a patient with shortness of breath, hemoptysis, and pleuritic chest pain is commonly made with ventilation-perfusion scans or computed tomography (CT) angiography. The CT angiogram demonstrates a filling defect in the left anterior segmental artery (arrow).
However, three placebo-controlled studies, including the Exploratory Phase II/III SLE Evaluation of Rituximab [EXPLORER] trial and the Lupus Nephritis Assessment with Rituximab [LUNAR] trial, [124, 125] failed to show an overall significant response. Despite the negative results in these trials, rituximab continues to be used to treat patients with severe SLE disease that is refractory to standard therapy.

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.[10][56][57]
More serious organ involvement with inflammation occurs in the brain, liver, and kidneys. White blood cells can be decreased in SLE (referred to as leukopenia or leucopenia). Also, low blood-clotting factors called platelets (thrombocytopenia) can be caused by lupus. Leukopenia can increase the risk of infection, and thrombocytopenia can increase the risk of bleeding. Low red blood cell counts (hemolytic anemia) can occur.
The panel judged the observed reduction in pregnancy loss with the addition of heparin to LDA as a large benefit. This intervention was not associated with significant harms. The addition of GCs or intravenous Ig to heparin plus LDA was associated with large harms (significant increase in premature delivery) without relevant benefits. Regarding heparin administration, the panel considered the reduction in pregnancy loss with low molecular weight heparin (LMWH) in comparison with unfractionated heparin (UFH) as a large benefit without significant adverse effects. No additional benefits were observed with LMWH-enoxaparin 80 mg compared with 40 mg.
The aim of this review is to provide an up-to-date overview of treatment approaches for systemic lupus erythematosus (SLE), highlighting the multiplicity and heterogeneity of clinical symptoms that underlie therapeutic decisions. Discussion will focus on the spectrum of currently available therapies, their mechanisms and associated side-effects. Finally, recent developments with biologic treatments including rituximab, epratuzumab, tumor necrosis factor (TNF) inhibitors, and belimumab, will be discussed.
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.[1] 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.[1] Often there are periods of illness, called flares, and periods of remission during which there are few symptoms.[1]
Heart and Lungs. Heart and lung involvement often is caused by inflammation of the covering of the heart (pericardium) and lungs (pleura). When these structures become inflamed, patients may develop chest pain, irregular heartbeat, and accumulation of fluid around the lungs (pleuritis or pleurisy) and heart (pericarditis). The heart valves and the lung itself can also be affected by lupus, resulting in shortness of breath.
Rheumatologists may not discuss the topic of nutrition with their patients, which is “mainly due to the complex nature of the disease, and doctors often do not have time to discuss diet when there are so many other topics to cover,” Gibofsky explained. “Many rheumatologists will admit that diet is not their area of expertise and will instead refer their patient[s] to meet with a registered dietitian (RD) who can better help with these questions.”

Acute cutaneous LE typically presents in the third decade of life and is frequently associated with active SLE. There are localized and generalized forms of ACLE. The localized form is the frequently described malar, or “butterfly” rash, which refers to erythema that occurs over both cheeks, extends over the nasal bridge, and spares the nasolabial folds. These lesions are classically transient, sun-induced, and non-scarring, although dyspigmentation can occur. Patients may initially mistake this rash for a sunburn, and only seek medical attention when it persists for several days. A fine surface scale and/or edema may be associated with the erythema. Malar rashes have been reported to be present in up to 52% of SLE patients at the time of diagnosis, with clinical activity of the rash paralleling that of the systemic disease. This rash can be confused with acne rosacea and seborrheic dermatitis, however the former is associated with the formation of papules and pustules, and the latter occurs within the nasolabial folds.

This gene encodes a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats. Alternative promoter use and alternative splicing result in multiple transcript variants, and a 30-nt indel polymorphism (SNP rs60344245) can result in loss of a 10-aa segment.

The NIH: National Institute of Arthritis and Musculoskeletal and Skin Diseases (2014) suggests that the symptoms may vary dependent on the type of lupus and the person. Symptoms tend to ‘come and go’, ‘flare’ from mild to severe intensity, and new symptoms of lupus can arise at any stage (NIH, 2014). Better Health Channel (n. d.) state that lupus may even become life-threatening, for example, should it damage major organs such as the kidneys or brain.

Lupus News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

Over half of the people with SLE develop a characteristic red, flat facial rash over the bridge of their nose. Because of its shape, it is frequently referred to as the "butterfly rash" of SLE. The rash is painless and does not itch. The facial rash, along with inflammation in other organs, can be precipitated or worsened by exposure to sunlight, a condition called photosensitivity. This photosensitivity can be accompanied by worsening of inflammation throughout the body, called a "flare" of the disease.

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