Genome-wide association studies (GWAS) revealed regions of linkage that were found on most chromosomes. These studies are useful in identifying the genes that may be responsible for complex diseases such as SLE. Candidate gene loci implicated with SLE include multiple alleles from the HLA region, Fc-gamma receptor, and complement component system. However, association does not prove that a specific form of a gene is responsible for the disease, as there may be other polymorphisms in the region that have a greater association effect. However, because the biological role of most genes are not completely understood, it can be difficult to attribute phenotypic traits to certain genetic polymorphisms. 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. Further complicating our understanding is the association of certain linkages with various ethnic groups.
Inflammation of the heart muscle, usually in the U.S. as a consequence of infections (viruses, esp. coxsackie virus, and occasionally as a consequence of bacterial, protozoan or fungal infections); immunological-rheumatological conditions (e.g., systemic lupus erythematosus, ulcerative colitis, hypersensitivity reactions, or transplant rejection); exposure to chemicals or toxins (e.g., cocaine, doxorubicin, methamphetamine); nutritional or metabolic abnormalities (e.g., thiamine deficiency or hypophosphatemia); or radiation. Myocarditis also is occasionally found in pregnancy and with advanced age. The myocardium is infiltrated by leukocytyes, lymphocytes, and macrophages, leading to inflammation, necrosis of muscle cells, and fibrosis. Inflammatory damage to heart muscle fibers may resolve spontaneously or may cause progressive deterioration of the heart with pericarditis, arrhythmias, chronic dilated cardiomyopathy, and heart failure.
(C) Positive finding of antiphospholipid antibodies based on (1) an abnormal serum level of IgG or IgM anticardiolipin antibodies, (2) a positive test result for lupus anticoagulant using a standard method, or (3) a false-positive serologic test for syphilis known to be positive for =6 months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption tests
Although it is known that chronically low complement levels and functional asplenia may result in a low level of susceptibility to infection, it is not known to what degree. [128, 129] Overall, it is likely that the primary reason patients with SLE die of infections is immunosuppressive medications.Stress-dose steroid protocols should be used in patients who are receiving maintenance corticosteroids when they are admitted with infectious or perioperative stress.
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. In close proximity to TBM, follicular dendritic cells (FDC) are localised in GC, which attach antigen material to their surface and, in contrast to bone marrow-derived DC, neither take it up nor present it via MHC molecules.
Autoantibodies directed against various nuclear antigens including DAutoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren’s syndrome, scleroderma, polymyositis, and mixed connective tissue disease. Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren’s syndrome, scleroderma, polymyositis, and mixed connective tissue disease.
For resistant skin disease, other antimalarial drugs, such as chloroquine (Aralen) or quinacrine, are considered and can be used in combination with hydroxychloroquine. Alternative medications for skin disease include dapsone and retinoic acid (Retin-A). Retin-A is often effective for an uncommon wart-like form of lupus skin disease. For more severe skin disease, immunosuppressive medications are considered as described below.
Steroid medications such as prednisone can also cause significant weight gain and redistribution of fat stores in the body. While taking steroids, your cholesterol, triglyceride, and blood sugar (glucose) levels may increase. For these reasons, it is absolutely essential that you follow a low-fat, low-cholesterol diet. You do not need to cut out all of the foods you love, but concentrate on eating whole grain breads and cereals and lean sources of protein such as chicken and fish. When you need a snack, look to raw vegetables—they are low in sugar and calories and provide the perfect food for “grazing.” Try to eat them without Ranch dressing or vegetable dip, because these items carry lots of fat and calories. If you need something to accompany your vegetables, try lighter dips like hummus. It is also important that you minimize alcohol intake ,because combining alcohol with corticosteroids, Tylenol, warfarin, and other lupus medications could be very harmful to your liver and stomach. For those taking methotrexate, alcohol is never allowed.
Aseptic meningitis is a disease caused by the inflammation of the protective membranes covering the brain and spinal cord known as the meninges. Unlike other forms of meningitis, aseptic meningitis is not caused by infection and cannot be spread person-to-person. Instead it can be caused by lupus, cancers, certain drugs, head injury, and brain surgery, among others. Meningitis is characterized by a sudden onset of fever, headache, and stiff neck. It is often accompanied by other symptoms, such as nausea, vomiting, photophobia (sensitivity to light), and altered mental status (confusion).
A skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Bone strength reflects the integration of two main features: bone density and bone quality. Bone density is expressed as grams of mineral per area or volume and in any given individual is determined by peak bone mass and amount of bone loss. Bone quality refers to architecture, turnover, damage accumulation (e.g., microfractures) and mineralization. A fracture occurs when a failure-inducing force (e.g., trauma) is applied to osteoporotic bone. Thus, osteoporosis is a significant risk factor for fracture, and a distinction between risk factors that affect bone metabolism and risk factors for fracture must be made.
Environment Researchers suspect environmental factors may increase the risk of developing lupus. For example, exposure to sun can cause a lupus rash and some systemic lupus activity, says Stacy Ardoin, MD, a rheumatologist at the Ohio State University Wexner Medical Center in Columbus. Other environmental factors that may contribute to lupus can include some drugs, viral infections, exhaustion, stress, and anything that can cause physical stress to the body (such as surgery, physical harm, injury, pregnancy, or giving birth).
When the kidneys or central nervous systems are affected immunosuppressive drugs such as cyclophosphamide (Cytoxan) and mycophenolate mofetil (CellCept) may be used. These drugs restrain the overactive immune system by blocking production of immune cells. Side effects may include nausea, vomiting, hair loss, bladder problems, decreased fertility, and increased risk of cancer and infection. The risks increase with the length of treatment.
These are used in packaged/processed products and often to fry foods. Cooking at home more and avoiding fast foods, processed meats, and packaged sweets or cheeses can help you decrease your intake. Some people with lupus have a hard time metabolizing saturated fats and should limit sources like cheese, red meat and creamy foods if they causes symptoms to worsen.
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.
Photosensitive systemic lupus erythematosus (SLE) rashes typically occur on the face or extremities, which are sun-exposed regions. Although the interphalangeal spaces are affected, the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints are spared. Photo courtesy of Dr. Erik Stratman, Marshfield Clinic.
Steroids . Steroid creams can be applied directly to rashes. The use of creams is usually safe and effective, especially for mild rashes. The use of steroid creams or tablets in low doses can be effective for mild or moderate features of lupus. Steroids also can be used in higher doses when internal organs are threatened. Unfortunately, high doses also are most likely to produce side effects.
In addition to the oral antimalarial hydroxychloroquine, doctors may prescribe topical steroids for lupus rash. Steroids or antimalarials may also be injected directly into rash lesions. (8) Topical creams containing tacrolimus or pimecrolimus that modulate the skin’s immune response may help manage lupus rash. Oral thalidomide, which affects the immune response, may be prescribed if other therapies don’t work. Doctors may also recommend that people with lupus rash avoid the sun and other ultraviolet light sources and wear sunscreen.
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