Lupus erythematosus describes a collection of autoimmune diseases with several varying symptoms that may affect different body systems. Lupus erythematosus may present as a systemic disease or in a cutaneous form known as incomplete lupus erythematosus. Lupus may also be more extensively categorized into several subtypes. The most common and most severe form is systemic lupus erythematosus (SLE). Lupus may be difficult to diagnose because of its signs and symptoms often mimicking other illnesses. People born with a higher likelihood of developing lupus may be triggered by infections, drugs, or sunlight. No cure for lupus exists but there are ways to help treat and mange symptoms.
Lupus has four main forms which include systemic, discoid, drug-induced, and neonatal. Incomplete lupus erythematosus may be further sub-categorized into several types: acute cutaneous erythematosus, and subacute cutaneous lupus erythematosus. Discoid lupus erythematosus can be further sub-categorized to include childhood discoid lupus erythematosus, generalized discoid lupus erythematosus, localized discoid lupus erythematosus, chilblain lupus, lupus erythematosus-lichen planus overlap syndrome, lupus erythematosus panniculitis, tumid lupus, verrucous lupus, cutaneous lupus mucinosis.
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Systemic lupus erythematosus (SLE) has varying degrees of severity from mild to severe affecting multiple body systems such as the heart, kidneys, muscles, and bones. Symptoms may include painful, swollen joints, fevers, chest pain, mouth ulcers, hair loss, swollen and tender lymph nodes, fatigue, and red rash known as a “butterfly rash” across the face (1). It is also known as “the great imitator” as it often mimics and may be mistaken for other illnesses. Common early and chronic complaints include malaise, joint pains and muscle pains, fever, and fatigue. Systemic lupus has episodes of more severe illness, called flares. There are also periods of improvement of the disease with few symptoms, called remission (1).
Systemic lupus erythematosus has no clear cause for systemic lupus but it is believed to be a combination of genetic factors and environmental factors. Genetically identical twins have an increased 24% chance of being affected if one of the twins if affected (2). Sunlight, smoking, vitamin D deficiency, female sex hormones, and infections are also believed to increase risk of developing systemic lupus erythematosus.
Systemic lupus erythematosus has a higher incidence rate among females, different symptoms than males, and have higher incidence of flares compared to males (3). Low white blood cell count, arthritis, psychiatric symptoms, and Raynaud’s phenomenon tend to be found in females. Males have a higher likelihood of having seizures, serositis, skin problems, kidney disease, and peripheral neuropathy.
About 70% of people diagnosed with lupus have accompanying skin symptoms. These include the cutaneous categories of lupus such as chronic (discoid) lupus erythematosus, subacute and acute cutaneous lupus erythematosus (4). Discoid lupus may display red, thick, scaly patches on skin. Acute cutaneous lupus includes a rash, with some having the classic malar rash known as the butterfly rash displayed across the face. The malar rash occurs in about 30-60% of people with systemic lupus erythematosus. Other accompanying cutaneous symptoms include hair loss, mouth, and nasal ulcer, and lesions on skin.
One of the most common complaints is joint pain, especially of the hands and wrist, though all joints may be affected. About 90% of people with systemic lupus will experience muscle and join pain, known as lupus arthritis. Lupus arthritis differs from rheumatoid arthritis as it does not severely destroy joints and is less disabling to the person. There may be association between rheumatoid arthritis and systemic lupus as suggested by …(?). Systemic lupus has also been correlated with an increased risk of bone fractures in young females suffering from condition.
Anemia, a decrease in red blood cells circulating the blood stream, is common in systemic lupus and develops in approximately 50% of the cases. It is unclear if low white blood cells and low platelets may be due to the disease or a side effect of treatment of lupus but there seems to be association with antiphospholipid syndrome (?). Antiphospholipid syndrome is an autoimmune clotting disorder that promotes thrombus formation in veins and arteries among other complications (?). Other complications associated with antiphospholipid syndrome include a prolonged partial thromboplastin time which inhibits clot formation and may prolong bleeding time.
Systemic lupus erythematosus may also affect the heart by causing pericarditis, which is an inflammation of the outer membrane surrounding the heart. It may also cause myocarditis, which is inflammation of the heart muscle. It has also been found to cause endocarditis, specific to lupus called Libman-Sacks endocarditis, which is inflammation of the inner lining of the heart not caused by infection.
Systemic lupus erythematosus can also cause pleurisy, which is inflammation of the pleurae. Further complications pertaining to lungs can include pneumonitis, pulmonary hypertension, pulmonary hemorrhage or emboli, and/or chronic interstitial lung disease.
In some people diagnosed with systemic lupus, there may be minimal kidney damage involvement. In those with lupus nephritis, there may be renal impairment leading to end-stage (5) kidney failure. This is preventable with early diagnosis and management of lupus. Lupus nephritis is a type of glomerulonephritis, which causes inflammation of the glomeruli by immune complex deposits along the glomerular basement membrane (6).
Systemic lupus can affect the central and peripheral nervous system, possibly resulting in neuropsychiatric syndromes. The term NPSLE is used to describe diagnoses of neuropsychiatric syndromes along with system lupus. One of the most common neurological disorder of system lupus are headaches. Other common symptoms are mood disorder, cognitive dysfunction, seizures, cerebrovascular disease, anxiety, depression, psychosis, and in extreme personality disorders. Rare symptoms include Guillain-Barre syndrome, aseptic meningitis, movement disorder, myasthenia gravis, plexopathy, and cranial neuropathy. A critical feature of system lupus is the damaging effects on epithelial cells of the blood-brain barrier, making the brain vulnerable.
Another common organ involvement are the eyes. Up to one-third of those diagnosed with systemic lupus have dry eye syndrome, and Sjogren’s syndrome. Retinopathy, ischemic optic neuropathy, secondary angle-closure glaucoma, and retinal detachment may also be a symptom. Eye involvement may be further complicated by treatments used for systemic lupus (7).
Systemic lupus erythematosus causes an increased fetal death rate and spontaneous abortion, with an average live-birth rate of 72% (?). Pregnancy complications worsen when there is a systemic lupus flare during pregnancy. Infants born from a mother with systemic lupus may be born with neonatal lupus. Neonatal lupus neonates usually present with rashes and lesions, similar to subacute cutaneous lupus erythematosus, and at times with further abnormalities involving the heart conduction or hepatosplenomegaly (?). Neonatal lupus is commonly self-limiting and benign.
Causes
The causes of systemic lupus erythematosus has a genetic susceptibility and environmental triggers. Systemic lupus tends to run in families but a specific gene has not been attributed to causing systemic lupus. Several genes appear to contribute to susceptibility when triggered by an environmental trigger to develop lupus. Susceptibility appears to possibly be population-specific with genetic studies showing a rate greater than 66% heritability (?). Genetically identical twins where one twin was affected with lupus, had a rate greater than 35% of susceptibility to also develop lupus compared to fraternal twins with a rate of 2-5% (?).
Drug-induced lupus erythematosus is another category of lupus that is a reversible condition. Drug-induced lupus occurs in people being treated for chronic illnesses, mimicking systemic lupus erythematosus. There are more than thirty-eight medications that can trigger drug-induced lupus with chronic use. Most commonly include isoniazid, procainamide, hydralazine, quinidine, and phenytoin. The symptoms of drug-induced lupus usually stop once the medications are discontinued. Approximately 5% of people diagnosed with drug-induced lupus erythematosus develop to system lupus erythematosus (?).
Diagnosis
Many physicians follow the diagnosis criteria of the American College of Rheumatology classification criteria not intended for individual diagnosis. This is a more rigorous classification criteria established primarily for scientific research and controlled trails that require stringent definitions. There are other diagnostic criteria meant for individual diagnosis that may be used. There are eleven established symptoms of the American College of Rheumatology classification, which a person must meet 4 out of 11 symptoms to be able to participate in studies pertaining to systemic lupus. These 11 symptoms include malar rash, discoid rash, serositis (pleurisy, or pericarditis), oral ulcers, arthritis, photosensitivity, hematologic disorder (anemia, leukopenia, lymphopenia), renal disorders, anti-nuclear antibody test, immunologic disorder, neurologic disorder (seizures, psychosis).
The main serologic diagnostic testing for system lupus erythematosus is the antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (anti-ENA). Many techniques are available to test for ANA’s but most used is the indirect immunofluorescence (IF) method. Using this method, the lupus band test is interpreted as evidence of systemic lupus erythematosus (8). Antinuclear antibody testing include anti-double-stranded DNA (dsDNA) antibodies which have been linked to system lupus. ANA also includes anti-histone antibodies which have been linked to drug-induced lupus erythematosus. Anti-dsDNA antibodies are very specific for systemic lupus, present in up to 70% of systemic lupus cases.
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