HOME

TheInfoList



OR:

Lupus, technically known as systemic lupus erythematosus (SLE), is an
autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
in which the body's
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common symptoms include painful and swollen joints,
fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
,
chest pain Chest pain is pain or discomfort in the chest, typically the front of the chest. It may be described as sharp, dull, pressure, heaviness or squeezing. Associated symptoms may include pain in the shoulder, arm, upper abdomen, or jaw, along with n ...
,
hair loss Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarri ...
,
mouth ulcer A mouth ulcer (aphtha) is an ulcer that occurs on the mucous membrane of the oral cavity. Mouth ulcers are very common, occurring in association with many diseases and by many different mechanisms, but usually there is no serious underlying cause ...
s,
swollen lymph node Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cl ...
s, feeling tired, and a red
rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...
which is most commonly on the face. Often there are periods of illness, called
flares A flare, also sometimes called a fusée, fusee, or bengala in some Latin-speaking countries, is a type of pyrotechnic that produces a bright light or intense heat without an explosion. Flares are used for distress signaling, illumination, o ...
, and periods of remission during which there are few symptoms. The cause of SLE is not clear. It is thought to involve a mixture of
genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
combined with
environmental factor An environmental factor, ecological factor or eco factor is any factor, abiotic or biotic, that influences living organisms. Abiotic factors include ambient temperature, amount of sunlight, and pH of the water soil in which an organism lives. Bi ...
s. Among
identical twins Twins are two offspring produced by the same pregnancy.MedicineNet > Definition of TwinLast Editorial Review: 19 June 2000 Twins can be either ''monozygotic'' ('identical'), meaning that they develop from one zygote, which splits and forms two em ...
, if one is affected there is a 24% chance the other one will also develop the disease.
Female sex hormones Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects ar ...
, sunlight, smoking,
vitamin D deficiency Vitamin D deficiency or hypovitaminosis D is a vitamin D level that is below normal. It most commonly occurs in people when they have inadequate exposure to sunlight, particularly sunlight with adequate ultraviolet B rays (UVB). Vitamin D defic ...
, and certain infections are also believed to increase a person's risk. The mechanism involves an immune response by
autoantibodies An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. Pr ...
against a person's own tissues. These are most commonly
anti-nuclear antibodies Antinuclear antibodies (ANAs, also known as antinuclear factor or ANF) are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human prot ...
and they result in
inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
. Diagnosis can be difficult and is based on a combination of symptoms and laboratory tests. There are a number of other kinds of
lupus erythematosus Lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blo ...
including
discoid lupus erythematosus Discoid lupus erythematosus is the most common type of chronic cutaneous lupus (CCLE), an autoimmune skin condition on the lupus erythematosus spectrum of illnesses. It presents with red, painful, inflamed and coin-shaped patches of skin with a sc ...
,
neonatal lupus Neonatal lupus erythematosus is an autoimmune disease in an infant born to a mother with anti-Ro/SSA and with or without anti-La/SSB antibodies. The disease most commonly presents with a rash resembling subacute cutaneous lupus erythematosus and c ...
, and
subacute cutaneous lupus erythematosus Subacute cutaneous lupus erythematosus is a clinically distinct subset of cases of lupus erythematosus that is most often present in white women aged 15 to 40, consisting of skin lesions that are scaly and evolve as ''poly-cyclic annular'' les ...
. There is no cure for SLE, but there are experimental and symptomatic treatments. Treatments may include
NSAID Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
s,
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
s,
immunosuppressants Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified into ...
,
hydroxychloroquine Hydroxychloroquine, sold under the brand name Plaquenil among others, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine. Other uses include treatment of rheumatoid arthritis, lupus, an ...
, and
methotrexate Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...
. Although corticosteroids are rapidly effective, long-term use results in side effects.
Alternative medicine Alternative medicine is any practice that aims to achieve the healing effects of medicine despite lacking biological plausibility, testability, repeatability, or evidence from clinical trials. Complementary medicine (CM), complementary and alt ...
has not been shown to affect the disease. Life expectancy is lower among people with SLE, but with modern treatment, 80-90% of patients can have a normal life span. SLE significantly increases the risk of
cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
with this being the most common cause of death. While women with lupus have higher risk pregnancies, most are successful. Rate of SLE varies between countries from 20 to 70 per 100,000. Women of childbearing age are affected about nine times more often than men. While it most commonly begins between the ages of 15 and 45, a wide range of ages can be affected. Those of
African African or Africans may refer to: * Anything from or pertaining to the continent of Africa: ** People who are native to Africa, descendants of natives of Africa, or individuals who trace their ancestry to indigenous inhabitants of Africa *** Ethn ...
,
Caribbean The Caribbean (, ) ( es, El Caribe; french: la Caraïbe; ht, Karayib; nl, De Caraïben) is a region of the Americas that consists of the Caribbean Sea, its islands (some surrounded by the Caribbean Sea and some bordering both the Caribbean Se ...
, and
Chinese Chinese can refer to: * Something related to China * Chinese people, people of Chinese nationality, citizenship, and/or ethnicity **''Zhonghua minzu'', the supra-ethnic concept of the Chinese nation ** List of ethnic groups in China, people of va ...
descent are at higher risk than those of
European descent White is a racialized classification of people and a skin color specifier, generally used for people of European origin, although the definition can vary depending on context, nationality, and point of view. Description of populations as " ...
. Rates of disease in the developing world are unclear. Lupus is Latin for "wolf": the disease was so-named in the 13th century as the rash was thought to appear like a wolf's bite.


Signs and symptoms

SLE is one of several diseases known as "
the great imitator The Great Imitator (also the Great Masquerader) is a phrase used for medical conditions that feature nonspecific symptoms and may be confused with a number of other diseases.J.C. Segen. The Dictionary of Modern Medicine'. CRC Press; 1992. . p. 265. ...
" because it often mimics or is mistaken for other illnesses. SLE is a classical item in
differential diagnosis In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that p ...
, because SLE symptoms vary widely and come and go unpredictably. Diagnosis can thus be elusive, with some people having unexplained symptoms of SLE for years. Common initial and chronic complaints include
fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
,
malaise As a medical term, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. The word has existed in French since at least the 12th century. The term is often used ...
, joint pains,
muscle pains Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likel ...
, and
fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
. Because these symptoms are so often seen in association with other diseases, these signs and symptoms are not part of the diagnostic criteria for SLE. When occurring in conjunction with other signs and symptoms, however, they are considered suggestive. While SLE can occur in both males and females, it is found far more often in women, and the symptoms associated with each sex are different. Females tend to have a greater number of
relapse In internal medicine, relapse or recidivism is a recurrence of a past (typically medical) condition. For example, multiple sclerosis and malaria often exhibit peaks of activity and sometimes very long periods of dormancy, followed by relapse or r ...
s, a low white blood cell count, more
arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...
,
Raynaud's phenomenon Raynaud syndrome, also known as Raynaud's phenomenon, eponymously named after the physician Auguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862, is a medical condition in which the spasm of small arteries cau ...
, and
psychiatric symptoms A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...
. Males tend to have more
seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...
s,
kidney disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can ...
,
serositis Serositis refers to inflammation of the serous tissues of the body, the tissues lining the lungs (pleura), heart (pericardium), and the inner lining of the abdomen (peritoneum) and organs within. It is commonly found with fat wrapping or creeping ...
(inflammation of tissues lining the lungs and heart), skin problems, and
peripheral neuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
.


Skin

As many as 70% of people with lupus have some skin symptoms. The three main categories of lesions are chronic cutaneous (discoid) lupus, subacute cutaneous lupus, and acute cutaneous lupus. People with
discoid lupus Discoid lupus erythematosus is the most common type of chronic cutaneous lupus (CCLE), an Autoimmune disease, autoimmune skin condition on the lupus erythematosus spectrum of illnesses. It presents with red, painful, inflamed and coin-shaped patch ...
may exhibit thick, red scaly patches on the skin. Similarly, subacute cutaneous lupus manifests as red, scaly patches of skin but with distinct edges. Acute cutaneous lupus manifests as a rash. Some have the classic
malar rash A malar rash (from Latin ‘jaw, cheek-bone’), also called butterfly rash, is a medical sign consisting of a characteristic form of facial rash. It is often seen in lupus erythematosus. More rarely, it is also seen in other diseases, such as pel ...
(commonly known as the ''butterfly rash'') associated with the disease. This rash occurs in 30 to 60% of people with SLE.
Hair loss Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarri ...
,
mouth In animal anatomy, the mouth, also known as the oral cavity, or in Latin cavum oris, is the opening through which many animals take in food and issue vocal sounds. It is also the cavity lying at the upper end of the alimentary canal, bounded on ...
and nasal ulcers, and lesions on the skin are other possible manifestations.


Muscles and bones

The most commonly sought medical attention is for
joint pain Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication. According to MeSH, ...
, 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.Joint and Muscle Pain
Lupus Foundation of America
Unlike
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
, 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. People with SLE are at particular risk of developing osteoarticular
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
. A possible association between
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
and SLE has been suggested, and SLE may be associated with an increased risk of
bone fracture A bone fracture (abbreviated FRX or Fx, Fx, or #) is a medical condition in which there is a partial or complete break in the continuity of any bone in the body. In more severe cases, the bone may be broken into several fragments, known as a '' ...
s in relatively young women.


Blood

Anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
is common in children with SLE and develops in about 50% of cases. Low platelet count (
thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...
) and low white blood cell count (
leukopenia Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of inf ...
) may be due to the disease or a side effect of pharmacological treatment. People with SLE may have an association with
antiphospholipid antibody syndrome Antiphospholipid syndrome, or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy- ...
(a thrombotic disorder), wherein autoantibodies to phospholipids are present in their serum. Abnormalities associated with antiphospholipid antibody syndrome include a paradoxical prolonged
partial thromboplastin time The partial thromboplastin time (PTT), also known as the activated partial thromboplastin time (aPTT or APTT), is a blood test that characterizes coagulation of the blood. A historical name for this measure is the kaolin-cephalin clotting time ( ...
(which usually occurs in hemorrhagic disorders) and a positive test for antiphospholipid antibodies; the combination of such findings have earned the term "
lupus anticoagulant Lupus anticoagulant is an immunoglobulin that binds to phospholipids and proteins associated with the cell membrane. Its name is a partial misnomer, as it is actually a prothrombotic antibody ''in vivo''. Lupus anticoagulant in living systems cause ...
-positive". Another autoantibody finding in SLE is the
anti-cardiolipin antibody Anti-cardiolipin antibodies (ACA) are antibodies often directed against cardiolipin and found in several diseases, including syphilis, antiphospholipid syndrome, livedoid vasculitis, vertebrobasilar insufficiency, Behçet's syndrome, idiopathic sp ...
, which can cause a false positive test for
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...
.


Heart

SLE may cause
pericarditis Pericarditis is inflammation of the pericardium, the fibrous sac surrounding the heart. Symptoms typically include sudden onset of sharp chest pain, which may also be felt in the shoulders, neck, or back. The pain is typically less severe when sit ...
—inflammation of the outer lining surrounding the heart,
myocarditis Myocarditis, also known as inflammatory cardiomyopathy, is an acquired cardiomyopathy due to inflammation of the heart muscle. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The ...
—inflammation of the heart muscle, or
endocarditis Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the ...
—inflammation of the inner lining of the heart. The endocarditis of SLE is non-infectious, and is also called
Libman–Sacks endocarditis Libman–Sacks endocarditis is a form of non-bacterial endocarditis that is seen in association with systemic lupus erythematosus, antiphospholipid syndrome, and malignancies. It is one of the most common cardiac manifestations of lupus (the most ...
. It involves either the
mitral valve The mitral valve (), also known as the bicuspid valve or left atrioventricular valve, is one of the four heart valves. It has two cusps or flaps and lies between the left atrium and the left ventricle of the heart. The heart valves are all one-w ...
or the
tricuspid valve The tricuspid valve, or right atrioventricular valve, is on the right dorsal side of the mammalian heart, at the superior portion of the right ventricle. The function of the valve is to allow blood to flow from the right atrium to the right vent ...
.
Atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...
also occurs more often and advances more rapidly than in the general population. Steroids are sometimes prescribed as an anti-inflammatory treatment for lupus; however, they can increase one's risk for heart disease, high cholesterol, and atherosclerosis.


Lungs

SLE can cause pleuritic pain as well as inflammation of the
pleurae The pulmonary pleurae (''sing.'' pleura) are the two opposing layers of serous membrane overlying the lungs and the inside of the surrounding chest walls. The inner pleura, called the visceral pleura, covers the surface of each lung and dips bet ...
known as
pleurisy Pleurisy, also known as pleuritis, is inflammation of the membranes that surround the lungs and line the chest cavity (pleurae). This can result in a sharp chest pain while breathing. Occasionally the pain may be a constant dull ache. Other sy ...
, which can rarely give rise to shrinking lung syndrome involving a reduced lung volume. Other associated lung conditions include
pneumonitis Pneumonitis describes general inflammation of lung tissue. Possible causative agents include radiation therapy of the chest, exposure to medications used during chemo-therapy, the inhalation of debris (e.g., animal dander), aspiration, herbicides ...
, chronic diffuse
interstitial lung disease Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD), is a group of respiratory diseases affecting the interstitium (the tissue and space around the alveoli (air sacs)) of the lungs. It concerns alveolar epithelium, pulmo ...
, pulmonary hypertension,
pulmonary emboli Pulmonary embolism (PE) is a blockage of an artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include shortness of breath, chest pain particularly upon breathing ...
, and
pulmonary hemorrhage Pulmonary hemorrhage (or pulmonary haemorrhage) is an acute bleeding from the lung, from the upper respiratory tract and the trachea, and the pulmonary alveoli. When evident clinically, the condition is usually massive.blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
or protein in the urine may often be the only presenting sign of kidney involvement. Acute or chronic renal impairment may develop with
lupus nephritis Lupus nephritis is an inflammation of the kidneys caused by systemic lupus erythematosus (SLE), an autoimmune disease. It is a type of glomerulonephritis in which the glomeruli become inflamed. Since it is a result of SLE, this type of glomerulon ...
, leading to acute or end-stage
kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
. Because of early recognition and management of SLE with immunosuppressive drugs or corticosteroids, end-stage renal failure occurs in less than 5% of cases; except in the black population, where the risk is many times higher. The histological hallmark of SLE is membranous
glomerulonephritis Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys). Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the ...
with "wire loop" abnormalities. This finding is due to immune complex deposition along the
glomerular basement membrane The glomerular basement membrane of the kidney is the basal lamina layer of the glomerulus. The glomerular endothelial cells, the glomerular basement membrane, and the filtration slits between the podocytes perform the filtration function of the ...
, leading to a typical granular appearance in
immunofluorescence Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on microbiological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specif ...
testing.


Neuropsychiatric

Neuropsychiatric Neuropsychiatry or Organic Psychiatry is a branch of medicine that deals with psychiatry as it relates to neurology, in an effort to understand and attribute behavior to the interaction of neurobiology and social psychology factors. Within neurop ...
syndromes can result when SLE affects the
central Central is an adjective usually referring to being in the center of some place or (mathematical) object. Central may also refer to: Directions and generalised locations * Central Africa, a region in the centre of Africa continent, also known as ...
or
peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...
. The
American College of Rheumatology The American College of Rheumatology (ACR; until 1985 called American Rheumatism Association) is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy ...
defines 19 neuropsychiatric syndromes in systemic lupus erythematosus. The diagnosis of neuropsychiatric syndromes concurrent with SLE (now termed as NPSLE), is one of the most difficult challenges in medicine, because it can involve so many different patterns of symptoms, some of which may be mistaken for signs of infectious disease or stroke. A common
neurological disorder A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weakn ...
people with SLE have is
headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...
, although the existence of a specific
lupus headache Lupus headache is a proposed, specific headache disorder in patients with systemic lupus erythematosus (SLE). Research shows that headache is a symptom commonly described by SLE patients —57% in one meta-analysis, ranging in different studies fr ...
and the optimal approach to headache in SLE cases remains controversial. Other common neuropsychiatric manifestations of SLE include
cognitive dysfunction Cognitive disorders (CDs), also known as neurocognitive disorders (NCDs), are a category of mental health disorders that primarily affect cognitive abilities including learning, memory, perception, and problem solving. Neurocognitive disorders in ...
,
mood disorder A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the person's mood is the main underlying feature. The classification is in the ''Diagnostic and Stat ...
,
cerebrovascular disease Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders. The ...
,
seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
,
polyneuropathy Polyneuropathy ( poly- + neuro- + -pathy) is damage or disease affecting peripheral nerves (peripheral neuropathy) in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. It usually begins in the hand ...
,
anxiety disorder Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physi ...
,
psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...
, depression, and in some extreme cases, personality disorders.
Steroid psychosis Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS), are steroidal androgens that include natural androgens like testosterone as well as synthetic androgens that are structurally related and have similar effects t ...
can also occur as a result of treating the disease. It can rarely present with
intracranial hypertension syndrome Intracranial hypertension syndrome is characterized by an elevated intracranial pressure, papilledema, and headache with occasional abducens nerve paresis, absence of a space-occupying lesion or ventricular enlargement, and normal cerebrospinal fl ...
, characterized by an elevated
intracranial pressure Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 Millimeter of mercury, mmHg ...
,
papilledema Papilledema or papilloedema is optic disc swelling that is caused by increased intracranial pressure due to any cause. The swelling is usually bilateral and can occur over a period of hours to weeks. Unilateral presentation is extremely rare. In ...
, and
headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...
with occasional
abducens nerve The abducens nerve or abducent nerve, also known as the sixth cranial nerve, cranial nerve VI, or simply CN VI, is a cranial nerve in humans and various other animals that controls the movement of the lateral rectus muscle, one of the extraocula ...
paresis In medicine, paresis () is a condition typified by a weakness of voluntary movement, or by partial loss of voluntary movement or by impaired movement. When used without qualifiers, it usually refers to the limbs, but it can also be used to desc ...
, absence of a space-occupying lesion or ventricular enlargement, and normal
cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
chemical A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., wi ...
and
hematological Hematology ( always spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to blood. It involves treating diseases that affect the produc ...
constituents. More rare manifestations are
acute confusional state Delirium (also known as acute confusional state) is an organically caused decline from a previous baseline of mental function that develops over a short period of time, typically hours to days. Delirium is a syndrome encompassing disturbances in ...
,
Guillain–Barré syndrome Guillain–Barré syndrome (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. Typically, both sides of the body are involved, and the initial symptoms are changes in sensation or pain often ...
,
aseptic meningitis Aseptic meningitis is the inflammation of the meninges, a membrane covering the brain and spinal cord, in patients whose cerebral spinal fluid test result is negative with routine bacterial cultures. Aseptic meningitis is caused by viruses, myco ...
, autonomic disorder, demyelinating syndrome,
mononeuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or o ...
(which might manifest as
mononeuritis multiplex Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
),
movement disorder Movement disorder refers to any clinical syndrome with either an excess of movement or a paucity of voluntary and involuntary movements, unrelated to weakness or spasticity. Movement disorders are synonymous with basal ganglia or extrapyramidal d ...
(more specifically,
chorea Chorea (or choreia, occasionally) is an abnormal involuntary movement disorder, one of a group of neurological disorders called dyskinesias. The term ''chorea'' is derived from the grc, χορεία ("dance"; see choreia), as the quick movement ...
),
myasthenia gravis Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, dro ...
,
myelopathy Myelopathy describes any neurologic deficit related to the spinal cord. The most common form of myelopathy in humans, '' cervical spondylotic myelopathy (CSM)'', also called ''degenerative cervical myelopathy'', results from narrowing of the spina ...
,
cranial Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position pro ...
neuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or o ...
and
plexopathy Plexopathy is a disorder of the wikt:network, network of nerves in the brachial plexus, brachial or lumbosacral plexus. Symptoms include pain, muscle weakness, and sensory deficits (numbness). Types There are two main types of plexopathy, based on ...
. Neurological disorders contribute to a significant percentage of morbidity and mortality in people with lupus. As a result, the neural side of lupus is being studied in hopes of reducing morbidity and mortality rates. One aspect of this disease is severe damage to the epithelial cells of the
blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
. In certain regions, depression affects up to 60% of women with SLE.


Eyes

Eye involvement is seen in up to one-third of people. The most common diseases are
dry eye syndrome Dry eye syndrome (DES), also known as keratoconjunctivitis sicca (KCS), is the condition of having dry eyes. Other associated symptoms include irritation, redness, discharge, and easily fatigued eyes. Blurred vision may also occur. Symptoms range ...
and secondary Sjögren's syndrome, but
episcleritis Episcleritis is a benign, self-limiting inflammatory disease affecting part of the eye called the episclera. The episclera is a thin layer of tissue that lies between the conjunctiva and the connective tissue layer that forms the white of the ey ...
,
scleritis Scleritis is a serious inflammatory disease that affects the white outer coating of the eye, known as the sclera. The disease is often contracted through association with other diseases of the body, such as granulomatosis with polyangiitis or ...
,
retinopathy Retinopathy is any damage to the retina of the eyes, which may cause vision impairment. Retinopathy often refers to retinal vascular disease, or damage to the retina caused by abnormal blood flow. Age-related macular degeneration is technically inc ...
(more often affecting both eyes than one),
ischemic optic neuropathy Ischemic optic neuropathy (ION) is the loss of structure and function of a portion of the optic nerve due to obstruction of blood flow to the nerve (i.e. ischemia). Ischemic forms of optic neuropathy are typically classified as either anterior is ...
,
retinal detachment Retinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blin ...
, and secondary angle-closure glaucoma may occur. In addition, the medications used to treat SLE can cause eye disease: long-term
glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
use can cause
cataract A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...
s and secondary open-angle glaucoma, and long-term
hydroxychloroquine Hydroxychloroquine, sold under the brand name Plaquenil among others, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine. Other uses include treatment of rheumatoid arthritis, lupus, an ...
treatment can cause vortex keratopathy and
maculopathy A maculopathy is any pathological condition of the macula, an area at the centre of the retina that is associated with highly sensitive, accurate vision. Forms of maculopathies * Age-Related Macular Degeneration is a degenerative maculopathy ass ...
.


Reproductive

While most pregnancies have positive outcomes, there is a greater risk of adverse events occurring during pregnancy. SLE causes an increased rate of fetal death ''in utero'' and
spontaneous abortion Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...
(miscarriage). The overall live-birth rate in people with SLE has been estimated to be 72%. Pregnancy outcome appears to be worse in people with SLE whose disease flares up during pregnancy.
Neonatal lupus Neonatal lupus erythematosus is an autoimmune disease in an infant born to a mother with anti-Ro/SSA and with or without anti-La/SSB antibodies. The disease most commonly presents with a rash resembling subacute cutaneous lupus erythematosus and c ...
is the occurrence of SLE symptoms in an
infant An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...
born from a mother with SLE, most commonly presenting with a rash resembling
discoid lupus erythematosus Discoid lupus erythematosus is the most common type of chronic cutaneous lupus (CCLE), an autoimmune skin condition on the lupus erythematosus spectrum of illnesses. It presents with red, painful, inflamed and coin-shaped patches of skin with a sc ...
, and sometimes with systemic abnormalities such as
heart block Heart block (HB) is a disorder in the heart's rhythm due to a fault in the natural pacemaker. This is caused by an obstruction – a block – in the electrical conduction system of the heart. Sometimes a disorder can be inherited. Despite the se ...
or enlargement of the liver and spleen.thefreedictionary.com > neonatal lupus
Citing: Dorland's Medical Dictionary for Health Consumers. Copyright 2007
Neonatal lupus is usually benign and self-limited. Medications for treatment of SLE can carry severe risks for female and male reproduction.
Cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
(also known as Cytoxan), can lead to infertility by causing
premature ovarian insufficiency Primary ovarian insufficiency (POI) (also called premature ovarian insufficiency, premature menopause, and premature ovarian failure) is the partial or total loss of reproductive and hormonal function of the ovaries before age 40 because of fol ...
(POI), the loss of normal function of one's ovaries prior to age forty.
Methotrexate Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...
can cause termination or deformity in fetuses and is a common
abortifacient An abortifacient ("that which will cause a miscarriage" from Latin: ''abortus'' "miscarriage" and '' faciens'' "making") is a substance that induces abortion. This is a nonspecific term which may refer to any number of substances or medications, ...
, and for men taking a high dose and planning to father, a discontinuation period of 6 months is recommended before insemination.


Systemic

Fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
in SLE is probably multifactorial and has been related to not only disease activity or complications such as
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
or
hypothyroidism Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...
, but also to
pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
, depression, poor
sleep Sleep is a sedentary state of mind and body. It is characterized by altered consciousness, relatively inhibited sensory activity, reduced muscle activity and reduced interactions with surroundings. It is distinguished from wakefulness by a de ...
quality, poor
physical fitness Physical fitness is a state of health and well-being and, more specifically, the ability to perform aspects of Outline of sports, sports, occupations and daily activities. Physical fitness is generally achieved through proper nutrition, moderate ...
and lack of
social support Social support is the perception and actuality that one is cared for, has assistance available from other people, and most popularly, that one is part of a supportive social network. These supportive resources can be emotional (e.g., nurturance), ...
.


Causes

SLE is presumably caused by a genetic susceptibility coupled with an environmental trigger which results in defects in the immune system. One of the factors associated with SLE is
vitamin D deficiency Vitamin D deficiency or hypovitaminosis D is a vitamin D level that is below normal. It most commonly occurs in people when they have inadequate exposure to sunlight, particularly sunlight with adequate ultraviolet B rays (UVB). Vitamin D defic ...
.


Genetics

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. HLA class I, class II, and class III genes are associated with SLE, but only classes I and II contribute independently to increased
risk In simple terms, risk is the possibility of something bad happening. Risk involves uncertainty about the effects/implications of an activity with respect to something that humans value (such as health, well-being, wealth, property or the environme ...
of SLE. Other genes which contain risk variants for SLE are ''
IRF5 Interferon regulatory factor 5 is a protein that in humans is encoded by the ''IRF5'' gene. The IRF family is a group of transcription factors that are involved in signaling for virus responses in mammals along with regulation of certain cellular ...
'', ''
PTPN22 Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a cytoplasmatic protein encoded by gene ''PTPN22'' and a member of PEST Protein family, family of protein tyrosine phosphatases. This protein is also called "PEST-domain Enriched Phospha ...
'', ''
STAT4 Signal transducer and activator of transcription 4 (STAT4) is a transcription factor belonging to the STAT protein family, composed of STAT1, STAT2, STAT3, STAT5A, STAT5B, STAT6. STAT proteins are key activators of gene transcription which bind ...
'', ''
CDKN1A p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily associated ...
'', ''
ITGAM Integrin alpha M (ITGAM) is one protein subunit that forms heterodimeric integrin alpha-M beta-2 (αMβ2) molecule, also known as ''macrophage-1 antigen'' (Mac-1) or ''complement receptor 3'' (CR3). ITGAM is also known as CR3A, and cluster of dif ...
'', '' BLK'', ''
TNFSF4 OX40L is the ligand for OX40 (also known as CD134 or TNFRSF4) and is stably expressed on many antigen-presenting cells such as DC2s (a subtype of dendritic cells), macrophages, and activated B lymphocytes. The OX40 molecule, conversely, is pre ...
'' and ''
BANK1 Bank1 (B-cell scaffold protein with ankyrin repeats 1) is a protein-encoding human gene located on chromosome 4 (4q24. Signal transducing adaptor protein, Adaptor protein that binds the proteins of the family SCR with Calcium channels in the LB. . ...
''. Some of the susceptibility genes may be population specific. Genetic studies of the rates of disease in families supports the genetic basis of this disease with a
heritability Heritability is a statistic used in the fields of breeding and genetics that estimates the degree of ''variation'' in a phenotypic trait in a population that is due to genetic variation between individuals in that population. The concept of h ...
of >66%. Identical (
monozygotic Twins are two offspring produced by the same pregnancy.MedicineNet > Definition of TwinLast Editorial Review: 19 June 2000 Twins can be either ''monozygotic'' ('identical'), meaning that they develop from one zygote, which splits and forms two em ...
) twins were found to share susceptibility to the disease at >35% rate compared to fraternal (
dizygotic Twins are two offspring produced by the same pregnancy.MedicineNet > Definition of TwinLast Editorial Review: 19 June 2000 Twins can be either ''monozygotic'' ('identical'), meaning that they develop from one zygote, which splits and forms two em ...
) twins and other full siblings who only showed a 2–5%
concordance Concordance may refer to: * Agreement (linguistics), a form of cross-reference between different parts of a sentence or phrase * Bible concordance, an alphabetical listing of terms in the Bible * Concordant coastline, in geology, where beds, or la ...
in shared inheritance. Since SLE is associated with many genetic regions, it is likely an
oligogenic Oligogenic inheritance (Greek ὀλίγος – ''ὀligos'' = few, a little) describes a trait that is influenced by a few genes. Oligogenic inheritance represents an intermediate between monogenic inheritance in which a trait is determined by a ...
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 reactions

Drug-induced lupus erythematosus Drug-induced lupus erythematosus is an autoimmune disorder caused by chronic use of certain drugs. These drugs cause an autoimmune response (the body attacks its own cells) producing symptoms similar to those of systemic 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 Procainamide (PCA) is a medication of the antiarrhythmic class used for the treatment of cardiac arrhythmias. It is classified by the Vaughan Williams classification system as class Ia; thus it is a sodium channel blocker of cardiomyocytes. In add ...
,
isoniazid Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. For l ...
,
hydralazine Hydralazine, sold under the brand name Apresoline among others, is a medication used to treat high blood pressure and heart failure. This includes high blood pressure in pregnancy and very high blood pressure resulting in symptoms. It has bee ...
,
quinidine Quinidine is a class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is the enantiomer of antimalarial agent quinine, originally derived from the bark of the cinchona tree. The drug causes increased action potential duratio ...
, and
phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...
.


Non-systemic forms of lupus

Discoid (cutaneous) lupus is limited to skin symptoms and is diagnosed by biopsy of rash on the face, neck, scalp or arms. Approximately 5% of people with DLE progress to SLE.


Pathophysiology

SLE is triggered by environmental factors that are unknown. In SLE, the body's immune system produces antibodies against
self-protein Self-protein refers to all proteins endogenously produced by DNA-level transcription and translation within an organism of interest. This does not include proteins synthesized due to viral infection, but may include those synthesized by commensal b ...
, particularly against proteins in the cell nucleus. These antibody attacks are the immediate cause of SLE. SLE is a chronic inflammatory disease believed to be a
type III hypersensitivity Type III hypersensitivity, in the Gell and Coombs classification of allergic reactions, occurs when there is accumulation of immune complexes (antigen-antibody complexes) that have not been adequately cleared by innate immune cells, giving rise ...
response with potential type II involvement. Reticulate and stellate acral pigmentation should be considered a possible manifestation of SLE and high
titer Titer (American English) or titre (British English) is a way of expressing concentration. Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positiv ...
s of
anti-cardiolipin antibodies Anti-cardiolipin antibodies (ACA) are antibodies often directed against cardiolipin and found in several diseases, including syphilis, antiphospholipid syndrome, livedoid vasculitis, vertebrobasilar insufficiency, Behçet's syndrome, idiopathic s ...
, or a consequence of therapy. People with SLE have intense polyclonal B-cell activation, with a population shift towards immature B cells. Memory B cells with increased
CD27 CD27 is a member of the tumor necrosis factor receptor superfamily. It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule, and is the target of an anti-cancer drug in clinical trials. Expression During mous ...
+/
IgD Immunoglobulin D (IgD) is an antibody isotype that makes up about 1% of proteins in the plasma membranes of immature B-lymphocytes where it is usually co-expressed with another cell surface antibody called IgM. IgD is also produced in a secreted f ...
—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), also known as
B-cell activating factor B-cell activating factor (BAFF) also known as tumor necrosis factor ligand superfamily member 13B and CD257 among other names, is a protein that in humans is encoded by the ''TNFSF13B'' gene. BAFF is also known as B Lymphocyte Stimulator (BLyS) an ...
(BAFF), interleukin 6, interleukin 17, interleukin 18, type I interferons, and
tumor necrosis factor α Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...
(TNFα) are involved in the inflammatory process and are potential therapeutic targets. SLE is associated with low C3 levels in the
complement system The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and at ...
.


Cell death signaling

*Apoptosis is increased in
monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...
s and
keratinocyte Keratinocytes are the primary type of Cell (biology), cell found in the epidermis (skin), epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the stratum basale, basal layer (''str ...
s *
Expression Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, o ...
of Fas by
B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
s and
T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
s is increased *There are correlations between the apoptotic rates of lymphocytes and disease activity. *Necrosis is increased in T lymphocytes.
Tingible body macrophage A tingible body macrophage (TBMs) is a type of macrophage predominantly found in germinal centers, containing many phagocytized, apoptotic cells in various states of degradation, referred to as tingible bodies (tingible meaning stainable). Tingi ...
s (TBMs) – large
phagocytic cells Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek ', "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek '' ...
in the
germinal center Germinal centers or germinal centres (GCs) are transiently formed structures within B cell zone (follicles) in secondary lymphoid organs – lymph nodes, ileal Peyer's patches, and the spleen – where mature B cells are activated, prolifera ...
s of secondary
lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s – express
CD68 CD68 ( Cluster of Differentiation 68) is a protein highly expressed by cells in the monocyte lineage (e.g., monocytic phagocytes, osteoclasts), by circulating macrophages, and by tissue macrophages (e.g., Kupffer cells, microglia). Structure a ...
protein. These cells normally engulf B cells that have undergone apoptosis after
somatic hypermutation Somatic hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes), as seen during class switching. A major component of the process of affinity maturation, SHM dive ...
. In some people with SLE, significantly fewer TBMs can be found, and these cells rarely contain material from apoptotic B cells. 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 cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...
s 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 cell Follicular dendritic cells (FDC) are cells of the immune system found in primary and secondary lymph follicles (lymph nodes) of the B cell areas of the lymphoid tissue. Unlike dendritic cells (DC), FDCs are not derived from the bone-marrow hema ...
s and make this material available for activating other B cells that may have randomly acquired
self-protein Self-protein refers to all proteins endogenously produced by DNA-level transcription and translation within an organism of interest. This does not include proteins synthesized due to viral infection, but may include those synthesized by commensal b ...
specificity through
somatic hypermutation Somatic hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes), as seen during class switching. A major component of the process of affinity maturation, SHM dive ...
. Necrosis, a pro-inflammatory form of cell death, is increased in T lymphocytes, due to mitochondrial dysfunction, oxidative stress, and depletion of ATP.


Clearance deficiency

Impaired clearance of dying cells is a potential pathway for the development of this systemic
autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
. This includes deficient phagocytic activity, impaired lysosomal degradation, and scant serum components in addition to increased
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
. SLE is associated with defects in
apoptotic Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes includ ...
clearance, and the damaging effects caused by apoptotic debris. Early apoptotic cells express “eat-me” signals, of cell-surface proteins such as phosphatidylserine, that prompt immune cells to engulf them. Apoptotic cells also express
find-me signals Find-me signals Cells destined for apoptosis release molecules referred to as find me signals. These signal molecules are used to attract phagocytes which engulf and eliminate damaged cells. Find-me signals are typically released by the apoptotic c ...
to attract macrophages and dendritic cells. When apoptotic material is not removed correctly by phagocytes, they are captured instead by antigen-presenting cells, which leads to the development of antinuclear antibodies.
Monocytes Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also infl ...
isolated from
whole blood Whole blood (WB) is human blood from a standard blood donation. It is used in the treatment of massive bleeding, in exchange transfusion, and when people donate blood to themselves. One unit of whole blood (~517 mls) brings up hemoglobin lev ...
of people with SLE show reduced expression of
CD44 The CD44 antigen is a cell-surface glycoprotein involved in cell–cell interactions, cell adhesion and migration. In humans, the CD44 antigen is encoded by the ''CD44'' gene on chromosome 11. CD44 has been referred to as HCAM (homing cell adhesi ...
surface molecules involved in the uptake of apoptotic cells. Most of the monocytes and tingible body macrophages (TBMs), which are found in the
germinal centre Germinal centers or germinal centres (GCs) are transiently formed structures within B cell zone (follicles) in secondary lymphoid organs – lymph nodes, ileal Peyer's patches, and the spleen – where mature B cells are activated, prolifera ...
s of
lymph nodes A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
, even show a definitely different morphology; they are smaller or scarce and die earlier. Serum components like
complement A complement is something that completes something else. Complement may refer specifically to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-class ...
factors, CRP, and some
glycoproteins Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
are, furthermore, decisively important for an efficiently operating phagocytosis. With SLE, these components are often missing, diminished, or inefficient. Macrophages during SLE fail to mature their
lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prot ...
s and as a result have impaired degradation of internalized apoptotic debris, which results in chronic activation of
Toll-like receptor Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are Bitopic protein, single-pass membrane-spanning Receptor (biochemistry), receptors usually expressed on sentinel cells such as macrophage ...
s and permeabilization of the phagolysosomal membrane, allowing activation of cytosolic sensors. In addition, intact apoptotic debris recycles back to the cell membrane and accumulate on the surface of the cell. Recent research has found an association between certain people with lupus (especially those with
lupus nephritis Lupus nephritis is an inflammation of the kidneys caused by systemic lupus erythematosus (SLE), an autoimmune disease. It is a type of glomerulonephritis in which the glomeruli become inflamed. Since it is a result of SLE, this type of glomerulon ...
) and an impairment in degrading
neutrophil extracellular traps Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind pathogens. Neutrophils are the immune system's first line of defense against infection and have conventionally bee ...
(NETs). These were due to DNAse1 inhibiting factors, or NET protecting factors in people's serum, rather than abnormalities in the DNAse1 itself. DNAse1 mutations in lupus have so far only been found in some Japanese cohorts. 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 Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
of the cells if this ability is disturbed. Necrotic cells release nuclear fragments as potential
autoantigens In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...
, as well as internal danger signals, inducing maturation of
dendritic cells Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. The ...
(DCs) since they have lost their membranes' integrity. Increased appearance of apoptotic cells also stimulates inefficient clearance. That leads to the maturation of DCs and also to the presentation of intracellular antigens of late apoptotic or secondary necrotic cells, via MHC molecules.
Autoimmunity In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...
possibly results from the extended exposure to nuclear and intracellular autoantigens derived from late apoptotic and secondary necrotic cells. B and
T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
tolerance for apoptotic cells is abrogated, and the
lymphocytes A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adap ...
get activated by these autoantigens;
inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
and the production of autoantibodies by
plasma cells Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B lymphocytes and secrete large quantities of proteins called antibodies in response to being presented specific substan ...
is initiated. A clearance deficiency in the skin for apoptotic cells has also been observed in people with cutaneous lupus erythematosus (CLE).


Germinal centers

In healthy conditions, apoptotic lymphocytes are removed in
germinal center Germinal centers or germinal centres (GCs) are transiently formed structures within B cell zone (follicles) in secondary lymphoid organs – lymph nodes, ileal Peyer's patches, and the spleen – where mature B cells are activated, prolifera ...
s (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, a buildup of apoptotic
debris Debris (, ) is rubble, wreckage, ruins, litter and discarded garbage/refuse/trash, scattered remains of something destroyed, or, as in geology, large rock fragments left by a melting glacier, etc. Depending on context, ''debris'' can refer to ...
can be observed in GC because of an ineffective clearance of apoptotic cells. Close to TBM,
follicular dendritic cells Follicular dendritic cells (FDC) are cells of the immune system found in primary and secondary lymph follicles (lymph nodes) of the B cell areas of the lymphoid tissue. Unlike dendritic cells (DC), FDCs are not derived from the bone-marrow hema ...
(FDC) are localised in GC, which attach antigen material to their surface and, in contrast to
bone marrow Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...
-derived DC, neither take it up nor present it via MHC molecules. Autoreactive
B cells B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
can accidentally emerge during
somatic hypermutation Somatic hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes), as seen during class switching. A major component of the process of affinity maturation, SHM dive ...
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 An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
may be the consequence.


Anti-nRNP autoimmunity

Anti-nRNP Anti-nRNP is a type of antibody. They are autoantibodies against some ribonucleoproteins. Anti-nRNP antibodies can be elevated in mixed connective tissue disease Mixed connective tissue disease, commonly abbreviated as MCTD, is an autoimmune dis ...
autoantibodies An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. Pr ...
to nRNP A and nRNP C initially targeted restricted,
proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...
-rich motifs. Antibody binding subsequently spread to other
epitopes An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds. The p ...
. The similarity and
cross-reactivity Cross-reactivity, in a general sense, is the reactivity of an observed agent which initiates reactions outside the main reaction expected. This has implications for any kind of test or assay, including diagnostic tests in medicine, and can be a ...
between the initial targets of nRNP and Sm autoantibodies identifies a likely commonality in cause and a focal point for intermolecular epitope spreading.


Others

Elevated expression of
HMGB1 High mobility group box 1 protein, also known as high-mobility group protein 1 (HMG-1) and amphoterin, is a protein that in humans is encoded by the ''HMGB1'' gene. HMG-1 belongs to the high mobility group and contains a HMG-box domain. Functio ...
was found in the sera of people and mice with systemic lupus erythematosus, high mobility group box 1 (
HMGB1 High mobility group box 1 protein, also known as high-mobility group protein 1 (HMG-1) and amphoterin, is a protein that in humans is encoded by the ''HMGB1'' gene. HMG-1 belongs to the high mobility group and contains a HMG-box domain. Functio ...
) is a
nuclear Nuclear may refer to: Physics Relating to the nucleus of the atom: * Nuclear engineering *Nuclear physics *Nuclear power *Nuclear reactor *Nuclear weapon *Nuclear medicine *Radiation therapy *Nuclear warfare Mathematics *Nuclear space *Nuclear ...
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
participating in
chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
architecture Architecture is the art and technique of designing and building, as distinguished from the skills associated with construction. It is both the process and the product of sketching, conceiving, planning, designing, and constructing building ...
and
transcriptional regulation In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from alt ...
. Recently, there is increasing evidence HMGB1 contributes to the pathogenesis of chronic inflammatory and
autoimmune diseases An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
due to its inflammatory and immune stimulating properties.


Diagnosis


Laboratory tests

Antinuclear antibody Antinuclear antibodies (ANAs, also known as antinuclear factor or ANF) are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human prote ...
(ANA) testing and anti-extractable nuclear antigen (
anti-ENA Extractable nuclear antigens (ENAs) are over 100 different soluble cytoplasmic and nuclear antigens. They are known as "extractable" because they can be removed from cell nuclei using saline and represent six main proteins: Ro, La, Sm, RNP, Scl-70, ...
) form the mainstay of
serologic Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mi ...
testing for SLE. If ANA is negative the disease can be ruled out. Several techniques are used to detect ANAs. The most widely used is indirect
immunofluorescence Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on microbiological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specif ...
(IF). The pattern of fluorescence suggests the type of antibody present in the people's serum.
Direct immunofluorescence A direct fluorescent antibody (DFA or dFA), also known as "direct immunofluorescence", is an antibody that has been tagged in a direct fluorescent antibody test. Its name derives from the fact that it directly tests the presence of an antigen with ...
can detect deposits of immunoglobulins and complement proteins in people's skin. When skin not exposed to the sun is tested, a positive direct IF (the so-called
lupus band test Lupus band test is done upon skin biopsy, with direct immunofluorescence staining, in which, if positive, IgG and complement depositions are found at the dermoepidermal junction.Marks, James G; Miller, Jeffery (2006). ''Lookingbill and Marks' Pr ...
) is 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 Anti-histone antibodies are autoantibodies that are a subset of the anti-nuclear antibody family, which specifically target histone protein subunits or histone complexes. They were first reported by Henry Kunkel, H.R. Holman, and H.R.G. Dreicher i ...
(which are linked to drug-induced lupus). Anti-dsDNA antibodies are highly specific for SLE; they are present in 70% of cases, whereas they appear in only 0.5% of people without SLE. Laboratory tests can also help distinguish between closely related connective tissue diseases. A multianalyte panel (MAP) of autoantibodies, including ANA,
anti-dsDNA Anti-double stranded DNA (Anti-dsDNA) antibodies are a group of anti-nuclear antibodies (ANA) the target antigen of which is double stranded DNA. Blood tests such as enzyme-linked immunosorbent assay (ELISA) and immunofluorescence are routinely p ...
, and anti-Smith in combination with the measurement of
cell-bound complement activation products Cell-Bound Complement Activation Products (CB-CAPs) or complement split products, refers to complement activation fragments, C4d, that are bound covalently to somatic cells, as a result of activation of the classical complement pathway. They appea ...
(CB-CAPs) with an integrated algorithm has demonstrated 80% diagnostic sensitivity and 86% specificity in differentiating diagnosed SLE from other autoimmune connective tissue diseases. The MAP approach has been further studied in over 40,000 patients tested with either the MAP or traditional ANA testing strategy (tANA), demonstrating patients who test MAP positive are at up to 6-fold increased odds of receiving a new SLE diagnosis and up to 3-fold increased odds of starting a new SLE medication regimen as compared to patients testing positive with the tANA approach. The anti-dsDNA antibody
titer Titer (American English) or titre (British English) is a way of expressing concentration. Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positiv ...
s also tend to reflect disease activity, although not in all cases. Other ANA that may occur in people with SLE are anti-U1 RNP (which also appears in
systemic sclerosis Systemic scleroderma, or systemic sclerosis, is an autoimmune rheumatic disease characterised by excessive production and accumulation of collagen, called fibrosis, in the skin and internal organs and by injuries to small arteries. There are two m ...
and
mixed connective tissue disease Mixed connective tissue disease, commonly abbreviated as MCTD, is an autoimmune disease characterized by the presence of elevated blood levels of a specific autoantibody, now called anti-U1 ribonucleoprotein (RNP) together with a mix of symptoms of ...
),
SS-A Anti-SSA autoantibodies (anti–Sjögren's-syndrome-related antigen A autoantibodies, also called anti-Ro, or similar names including anti-SSA/Ro, anti-Ro/SSA, anti–SS-A/Ro, and anti-Ro/SS-A) are a type of anti-nuclear autoantibodies that are a ...
(or
anti-Ro Anti-SSA autoantibodies (anti–Sjögren's-syndrome-related antigen A autoantibodies, also called anti-Ro, or similar names including anti-SSA/Ro, anti-Ro/SSA, anti–SS-A/Ro, and anti-Ro/SS-A) are a type of anti-nuclear autoantibodies that are a ...
) and
SS-B Antinuclear antibodies (ANAs, also known as antinuclear factor or ANF) are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human prote ...
(or anti-La; both of which are more common in Sjögren's syndrome). SS-A and SS-B confer a specific risk for heart conduction block in neonatal lupus. Other tests routinely performed in suspected SLE are
complement system The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and at ...
levels (low levels suggest consumption by the immune system),
electrolyte An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon dis ...
s and
kidney function Assessment of kidney function occurs in different ways, using the presence of symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging. Functions of a healthy kidney include maintaining a person's fluid ...
(disturbed if the kidney is involved),
liver enzyme Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...
s, and
complete blood count A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cell ...
. The
lupus erythematosus Lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blo ...
(LE) cell test was commonly used for diagnosis, but it is no longer used because the
LE cell A lupus erythematosus cell (LE cell), also known as Hargraves cell, is a neutrophil or macrophage that has phagocytized (engulfed) the denatured nuclear material of another cell. The denatured material is an absorbed hematoxylin body (also called ...
s are only found in 50–75% of SLE cases and they are also found in some people with rheumatoid arthritis, scleroderma, and drug sensitivities. Because of this, the LE cell test is now performed only rarely and is mostly of historical significance.


Diagnostic criteria

Some physicians make a diagnosis based on the
American College of Rheumatology The American College of Rheumatology (ACR; until 1985 called American Rheumatism Association) is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy ...
(ACR) classification criteria. However, these criteria were primarily established for use in scientific research, including selection for
randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical te ...
s, which require higher confidence levels. As a result, many people with SLE may not meet the full ACR criteria.


Criteria

The American College of Rheumatology (ACR) established eleven criteria in 1982, which were revised in 1997 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. #
Malar rash A malar rash (from Latin ‘jaw, cheek-bone’), also called butterfly rash, is a medical sign consisting of a characteristic form of facial rash. It is often seen in lupus erythematosus. More rarely, it is also seen in other diseases, such as pel ...
(rash on cheeks); sensitivity = 57%; specificity = 96%. # Discoid rash (red, scaly patches on skin that cause scarring); sensitivity = 18%; specificity = 99%. # Serositis:
Pleurisy Pleurisy, also known as pleuritis, is inflammation of the membranes that surround the lungs and line the chest cavity (pleurae). This can result in a sharp chest pain while breathing. Occasionally the pain may be a constant dull ache. Other sy ...
(inflammation of the membrane around the lungs) or
pericarditis Pericarditis is inflammation of the pericardium, the fibrous sac surrounding the heart. Symptoms typically include sudden onset of sharp chest pain, which may also be felt in the shoulders, neck, or back. The pain is typically less severe when sit ...
(inflammation of the membrane around the heart); sensitivity = 56%; specificity = 86% (pleural is more sensitive; cardiac is more specific). # Oral ulcers (includes oral or nasopharyngeal ulcers); sensitivity = 27%; specificity = 96%. #
Arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...
: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion; sensitivity = 86%; specificity = 37%. #
Photosensitivity Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicity. ...
(exposure to ultraviolet light causes rash, or other symptoms of SLE flareups); sensitivity = 43%; specificity = 96%. # Blood—hematologic disorder—
hemolytic anemia Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...
(low
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
count),
leukopenia Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of inf ...
(white blood cell count<4000/µl),
lymphopenia Lymphocytopenia is the condition of having an abnormally low level of lymphocytes in the blood. Lymphocytes are a white blood cell with important functions in the immune system. It is also called lymphopenia. The opposite is lymphocytosis, which re ...
(<1500/µl), or
low platelet count Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients and ...
(<100000/µl) in the absence of offending drug; sensitivity = 59%; specificity = 89%. Hypocomplementemia is also seen, due to either consumption of C3 and C4 by immune complex-induced inflammation or to congenitally complement deficiency, which may predispose to SLE. # Renal disorder: More than 0.5 g per day protein in urine or cellular casts seen in urine under a microscope; sensitivity = 51%; specificity = 94%. #
Antinuclear antibody Antinuclear antibodies (ANAs, also known as antinuclear factor or ANF) are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human prote ...
test positive; sensitivity = 99%; specificity = 49%. # Immunologic disorder: Positive anti-Smith, anti-ds DNA,
antiphospholipid antibody Antiphospholipid syndrome, or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy-re ...
, or false positive
serological Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mi ...
test for
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...
; sensitivity = 85%; specificity = 93%. Presence of anti-ss DNA in 70% of cases (though also positive with rheumatic disease and healthy persons). # Neurologic disorder:
Seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...
s or
psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...
; sensitivity = 20%; specificity = 98%. Other than the ACR criteria, people with lupus may also have: * Fever (over 100 °F/ 37.7 °C) * Extreme fatigue * Hair loss * Fingers turning white or blue when cold (
Raynaud's phenomenon Raynaud syndrome, also known as Raynaud's phenomenon, eponymously named after the physician Auguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862, is a medical condition in which the spasm of small arteries cau ...
)


Criteria for individual diagnosis

Some people, especially those with
antiphospholipid syndrome Antiphospholipid syndrome, or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy- ...
, 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 Recursive partitioning is a statistical method for multivariable analysis. Recursive partitioning creates a decision tree that strives to correctly classify members of the population by splitting it into sub-populations based on several dichotomous ...
has been used to identify more parsimonious criteria. This analysis presented two diagnostic classification trees: # Simplest classification tree: SLE is diagnosed if a person has an immunologic disorder (anti-DNA antibody, anti-Smith antibody, false positive syphilis test, or LE cells) or
malar rash A malar rash (from Latin ‘jaw, cheek-bone’), also called butterfly rash, is a medical sign consisting of a characteristic form of facial rash. It is often seen in lupus erythematosus. More rarely, it is also seen in other diseases, such as pel ...
. It has sensitivity = 92% and specificity = 92%. # Full classification tree: Uses 6 criteria. It has sensitivity = 97% and specificity = 95%. Other alternative criteria have been suggested, e.g. the St. Thomas' Hospital "alternative" criteria in 1998.


Treatment

The treatment of SLE involves preventing flares and reducing their severity and duration when they occur. Treatment can include
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
s and anti-malarial drugs. Certain types of lupus nephritis such as diffuse proliferative glomerulonephritis require intermittent cytotoxic drugs. These drugs include
cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
and
mycophenolate Mycophenolic acid (MPA) is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and live ...
. Cyclophosphamide increases the risk of developing infections, pancreas problems, high blood sugar, and high blood pressure.
Hydroxychloroquine Hydroxychloroquine, sold under the brand name Plaquenil among others, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine. Other uses include treatment of rheumatoid arthritis, lupus, an ...
was approved by the
FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...
for lupus in 1955. Some drugs approved for other diseases are used for SLE 'off-label'. In November 2010, an FDA advisory panel recommended approving
belimumab Belimumab, sold under the brand name Benlysta, is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), also known as B-lymphocyte stimulator (BLyS). It is approved in the United States, Canada, and the European Union to treat ...
(Benlysta) as a treatment for the pain and flare-ups common in lupus. The drug was approved by the FDA in March 2011. In terms of healthcare utilization and costs, one study found that "patients from the US with SLE, especially individuals with moderate or severe disease, utilize significant healthcare resources and incur high medical costs."


Medications

Due to the variety of symptoms and organ system involvement with SLE, its severity in an individual must be assessed to successfully treat SLE. Mild or remittent disease may, sometimes, be safely left untreated. If required,
nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
s and
antimalarials Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young c ...
may be used. Medications such as
prednisone Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...
,
mycophenolic acid Mycophenolic acid (MPA) is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and live ...
and
tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...
have been used in the past.


Disease-modifying antirheumatic drugs

Disease-modifying antirheumatic drug Disease-modifying antirheumatic drugs (DMARDs) comprise a category of otherwise unrelated disease-modifying drugs defined by their use in rheumatoid arthritis to slow down disease progression. The term is often used in contrast to nonsteroidal ...
s (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 Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involve ...
. DMARDs commonly in use are antimalarials such as
hydroxychloroquine Hydroxychloroquine, sold under the brand name Plaquenil among others, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine. Other uses include treatment of rheumatoid arthritis, lupus, an ...
and
immunosuppressants Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified into ...
(e.g.
methotrexate Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...
and
azathioprine Azathioprine (AZA), sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus, ...
). 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.
Cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
is used for severe
glomerulonephritis Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys). Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the ...
or other organ-damaging complications.
Mycophenolic acid Mycophenolic acid (MPA) is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and live ...
is also used for the 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.


Immunosuppressive drugs

In more severe cases, medications that modulate the immune system (primarily corticosteroids and
immunosuppressants Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified into ...
) 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 Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, ...
, symptoms of which may include
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
, puffy round face,
diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
, increased appetite, difficulty sleeping, and
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
. 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 Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...
and
cataracts A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...
. Numerous new immunosuppressive drugs are being actively tested for SLE. Rather than broadly suppressing the immune system, as corticosteroids do, they target the responses of specific types of immune cells. Some of these drugs are already FDA-approved for treatment of
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
, however due to high-toxicity, their use remains limited.


Analgesia

Since a large percentage of people with SLE have varying amounts of
chronic pain Chronic pain is classified as pain that lasts longer than three to six months. In medicine, the distinction between Acute (medicine), acute and Chronic condition, chronic pain is sometimes determined by the amount of time since onset. Two commonly ...
, stronger prescription
analgesics An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It i ...
(painkillers) may be used if over-the-counter drugs (mainly
nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
s) do not provide effective relief. Potent NSAIDs such as
indomethacin Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription drug, prescription medication to reduce fever, pain, joint stiffness, stiffness, and swelling (medical), swelling from infl ...
and
diclofenac Diclofenac, sold under the brand name Voltaren, among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout. It is taken by mouth or rectally in a suppository, used by injection, or ...
are relatively contraindicated for people with SLE because they increase the risk of kidney failure and heart failure. Pain is typically treated with
opioids Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...
, 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 (IVIGs)

Intravenous immunoglobulin Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin or NHIG) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory dem ...
s may be used to control SLE with organ involvement, or
vasculitis Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily caused b ...
. It is believed that they reduce
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
production or promote the clearance of
immune complex An immune complex, sometimes called an antigen-antibody complex or antigen-bound antibody, is a molecule formed from the binding of multiple antigens to antibodies. The bound antigen and antibody act as a unitary object, effectively an antigen of ...
es from the body, even though their
mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targe ...
is not well understood. Unlike
immunosuppressive Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reacti ...
s and
corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involve ...
,
IVIG Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin or NHIG) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory dem ...
s do not suppress the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
, so there is less risk of serious
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
s with these drugs.


Lifestyle changes

Avoiding sunlight in SLE is critical since sunlight is known to exacerbate skin manifestations of the disease. Avoiding activities that induce fatigue is also important since those with SLE fatigue easily and it can be 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 Silicon dioxide, also known as silica, is an oxide of silicon with the chemical formula , most commonly found in nature as quartz and in various living organisms. In many parts of the world, silica is the major constituent of sand. Silica is one ...
,
pesticide Pesticides are substances that are meant to control pests. This includes herbicide, insecticide, nematicide, molluscicide, piscicide, avicide, rodenticide, bactericide, insect repellent, animal repellent, microbicide, fungicide, and lampri ...
s, and
mercury Mercury commonly refers to: * Mercury (planet), the nearest planet to the Sun * Mercury (element), a metallic chemical element with the symbol Hg * Mercury (mythology), a Roman god Mercury or The Mercury may also refer to: Companies * Merc ...
can also worsen the disease.


Kidney transplantation

Kidney transplants are the treatment of choice for
end-stage kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vom ...
, which is one of the complications of
lupus nephritis Lupus nephritis is an inflammation of the kidneys caused by systemic lupus erythematosus (SLE), an autoimmune disease. It is a type of glomerulonephritis in which the glomeruli become inflamed. Since it is a result of SLE, this type of glomerulon ...
, but the recurrence of the full disease is common in up to 30% of people.


Antiphospholipid syndrome

Approximately 20% of people with SLE have clinically significant levels of antiphospholipid antibodies, which are associated with
antiphospholipid syndrome Antiphospholipid syndrome, or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy- ...
. Antiphospholipid syndrome is also related to the onset of neural lupus symptoms in the brain. In this form of the disease, the cause is very different from lupus: thromboses (blood clots or "sticky blood") form in blood vessels, which prove to be fatal if they move within the bloodstream. If the thromboses migrate to the brain, they can potentially cause a
stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
by blocking the blood supply to the brain. 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 Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
is prescribed for this purpose, although for cases involving thrombosis anticoagulants such as
warfarin Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent strok ...
are used.


Management of pregnancy

While most infants born to mothers who have SLE are healthy, pregnant mothers with SLE should remain under medical care until delivery.
Neonatal lupus Neonatal lupus erythematosus is an autoimmune disease in an infant born to a mother with anti-Ro/SSA and with or without anti-La/SSB antibodies. The disease most commonly presents with a rash resembling subacute cutaneous lupus erythematosus and c ...
is rare, but identification of mothers at the 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 Anti-SSA autoantibodies (anti–Sjögren's-syndrome-related antigen A autoantibodies, also called anti-Ro, or similar names including anti-SSA/Ro, anti-Ro/SSA, anti–SS-A/Ro, and anti-Ro/SS-A) are a type of anti-nuclear autoantibodies that are a ...
(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 Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent unwanted pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth contr ...
and other reliable forms of pregnancy prevention are routinely advised for women with SLE since getting pregnant during active disease was found to be harmful.
Lupus nephritis Lupus nephritis is an inflammation of the kidneys caused by systemic lupus erythematosus (SLE), an autoimmune disease. It is a type of glomerulonephritis in which the glomeruli become inflamed. Since it is a result of SLE, this type of glomerulon ...
was the most common manifestation.


Prognosis

No cure is available for SLE but there are many treatments for the disease. In the 1950s, most people diagnosed with SLE lived fewer than five years. Today, over 90% now survive for more than ten years, and many live relatively symptom-free. 80–90% can expect to live a normal lifespan. Mortality rates are however elevated compared to people without SLE. 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. To reduce the potential for cardiovascular issues, high blood pressure and high cholesterol should be prevented or treated aggressively. 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.


Epidemiology

The global rates of SLE are approximately 20–70 per 100,000 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 not sufficient evidence to conclude why SLE is less common in some countries compared to others; it could be the 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. To understand if this is true, countries with largely homogenous and racially stable populations should be studied to better understand incidence. Rates of disease in the developing world are unclear. The rate of SLE varies between countries, ethnicity, and sex, and changes over time. In the United States, one estimate of the
rate Rate or rates may refer to: Finance * Rates (tax), a type of taxation system in the United Kingdom used to fund local government * Exchange rate, rate at which one currency will be exchanged for another Mathematics and science * Rate (mathema ...
of SLE is 53 per 100,000; another estimate places the total affected population at 322,000 to over 1 million (98 to over 305 per 100,000). In Northern Europe the rate is about 40 per 100,000 people. SLE occurs more frequently and with greater severity among those of non-European descent. That rate has been found to be as high as 159 per 100,000 among those of Afro-Caribbean descent. Childhood-onset systemic lupus erythematosus generally presents between the ages of 3 and 15 and is four times more common in girls. 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.


Ethnicity

There are assertions that race affects the rate of SLE. However, a 2010 review of studies that correlate race and SLE identified several sources of systematic and methodological error, indicating that the connection between race and SLE may be spurious. For example, studies show that social support is a modulating factor which buffers against SLE-related damage and maintains physiological functionality. Studies have not been conducted to determine whether people of different racial backgrounds receive differing levels of social support. If there is a difference, this could act as a confounding variable in studies correlating race and SLE. 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 patient's experience with the disease- social support, the level of helplessness, and abnormal illness-related behaviors also factor into a self-assessment. Additionally, other factors like the degree of social support that a person receives, socioeconomic status, health insurance, and access to care can contribute to an individual's disease progression. Racial differences in lupus progression have not been found in studies that control for the socioeconomic status ESof participants. Studies that control for the SES of its participants have found that non-white people have more abrupt disease onset compared to white people and that their disease progresses more quickly. 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. The people who receive medical care have often accrued less disease-related damage and are less likely to be below the poverty line. Additional studies have found that education, marital status, occupation, and income create a social context that affects disease progression.


Sex

SLE, like many autoimmune diseases, affects females more frequently than males, at a rate of about 9 to 1. The X chromosome carries immunological related genes, which can mutate and contribute to the onset of SLE. 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 In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group () into an organic compound. *(ii) the ''degree of hydroxylation'' refers to the number of OH groups in a ...
of
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
and the abnormally decreased levels of
androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
s in females. In addition, differences in
GnRH Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released f ...
signalling have also been shown to contribute to the onset of SLE. 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. Studies indicate that the X chromosome can determine the levels of sex hormones. A study has shown an association between
Klinefelter syndrome Klinefelter syndrome (KS), also known as 47,XXY, is an aneuploid genetic condition where a male has an additional copy of the X chromosome. The primary features are infertility and small, poorly functioning testicles. Usually, symptoms are su ...
and SLE. XXY males with SLE have an abnormal X–Y translocation resulting in the partial triplication of the PAR1 gene region.


Changing rate of disease

The rate of SLE in the United States increased from 1.0 in 1955 to 7.6 in 1974. Whether the increase is due to better diagnosis or an increased frequency of the disease is unknown.


History

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 In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...
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.


Etymology

There are several explanations ventured for the term lupus erythematosus. Lupus is
Latin Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...
for "wolf", and "erythro" is derived from , Greek for "red". All explanations originate with the reddish, butterfly-shaped malar rash that the disease classically exhibits across the nose and cheeks. The reason the term lupus was used to describe this disease comes from the mid-19th century. Many diseases that caused ulceration or necrosis were given the term "lupus" due to the wound being reminiscent of a wolf's bite. This is similar to the naming of
lupus vulgaris Lupus vulgaris (also known as tuberculosis luposa) are painful cutaneous tuberculosis skin lesions with nodular appearance, most often on the face around the nose, eyelids, lips, cheeks, ears and neck. It is the most common ''Mycobacterium tuberc ...
or chronic facial tuberculosis, where the lesions are ragged and punched out and are said to resemble the bite of a wolf.


Classical period

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. No formal treatment for the disease existed and the resources available to physicians to help people were limited.


Neoclassical period

The neoclassical period began in 1851 when the skin disease which is now known as
discoid lupus Discoid lupus erythematosus is the most common type of chronic cutaneous lupus (CCLE), an Autoimmune disease, autoimmune skin condition on the lupus erythematosus spectrum of illnesses. It presents with red, painful, inflamed and coin-shaped patch ...
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. Cazenave observed the disease in several people and made very detailed notes to assist others in its diagnosis. He was one of the first to document that lupus affected adults from adolescence into the early thirties and that 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 Moritz Kaposi ( hu, Kaposi Mór, ; 23 October 1837 in Kaposvár, Hungary – 6 March 1902 in Vienna, Austria-Hungary) was a Hungarian physician and dermatologist who discovered the skin tumor that received his name (Kaposi's sarcoma). Biography ...
. They documented the physical effects of lupus as well as some insights into the possibility that the disease caused internal trauma. Von Hebra observed that lupus symptoms could last many years and that the disease could go "dormant" after years of aggressive activity and then re-appear with symptoms following the same general pattern. These observations led Hebra to term lupus a chronic disease in 1872. Kaposi observed that lupus assumed two forms: the skin lesions (now known as discoid lupus) and a more aggravated form that affected not only the skin but also caused fever, arthritis, and other systemic disorders in people. The latter also presented a rash confined to the face, appearing on the cheeks and across the bridge of the nose; he called this the " butterfly rash". Kaposi also observed those patients who developed the butterfly rash were often afflicted with another disease such as tuberculosis, anemia, or chlorisis which often caused death. Kaposi was one of the first people to recognize what is now termed systemic lupus erythematosus in his documentation of the remitting and relapsing nature of the disease and the relationship of skin and systemic manifestations during disease activity. The 19th century's research into lupus continued with the work of
Sir William Osler Sir William Osler, 1st Baronet, (; July 12, 1849 – December 29, 1919) was a Canadian physician and one of the "Big Four" founding professors of Johns Hopkins Hospital. Osler created the first residency program for specialty training of phys ...
who, in 1895, published the first of his three papers about the internal complications of
erythema exudativum multiforme Erythema multiforme (EM) is a skin condition that appears with red patches evolving into target lesions, typically on both hands. It is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in the ...
. Not all the patient cases in his paper had SLE but Osler's work expanded the knowledge of systemic diseases and documented extensive and critical visceral complications for several diseases including lupus. Noting that many people with lupus had a disease that not only affected the skin but many other organs in the body as well, Osler added the word "systemic" to the term lupus erythematosus to distinguish this type of disease from discoid lupus erythematosus. Osler's second paper noted that reoccurrence is a special feature of the disease and that attacks can be sustained for months or even years. Further study of the disease led to a third paper, published in 1903, documenting afflictions such as arthritis, pneumonia, the inability to form coherent ideas, delirium, and central nervous system damage as all affecting patients diagnosed with SLE.


Modern period

The modern period, beginning in 1920, saw major developments in research into the cause and treatment of discoid and systemic lupus. Research conducted in the 1920s and 1930s led to the first detailed pathologic descriptions of lupus and demonstrated how the disease affected the kidney, heart, and lung tissue. A breakthrough was made in 1948 with the discovery of the LE cell (the lupus erythematosus cell—a misnomer, as it occurs with other diseases as well). Discovered by a team of researchers at the
Mayo Clinic The Mayo Clinic () is a nonprofit American academic medical center focused on integrated health care, education, and research. It employs over 4,500 physicians and scientists, along with another 58,400 administrative and allied health staff, ...
, they discovered that the white blood cells contained the nucleus of another cell that was pushing against the white's cell proper nucleus. Noting that the invading nucleus was coated with antibody that allowed it to be ingested by a phagocytic or scavenger cell, they named the antibody that causes one cell to ingest another the LE factor and the two nuclei cell result in the LE cell. The LE cell, it was determined, was a part of an
anti-nuclear antibody Antinuclear antibodies (ANAs, also known as antinuclear factor or ANF) are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human pro ...
(ANA) reaction; the body produces antibodies against its own tissue. This discovery led to one of the first definitive tests for lupus since LE cells are found in approximately 60% of all people diagnosed with lupus. The LE cell test is rarely performed as a definitive lupus test today as LE cells do not always occur in people with SLE and can occur in individuals with other autoimmune diseases. Their presence can help establish a diagnosis but no longer indicates a definitive SLE diagnosis. 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 is now known as autoimmune diseases. To ensure that the person has lupus and not another autoimmune disease, the American College of Rheumatology (ACR) established a list of clinical and immunologic criteria that, in any combination, point to SLE. The criteria include symptoms that the person can identify (e.g. pain) and things that a physician can detect in a physical examination and through laboratory test results. The list was originally compiled in 1971, initially revised in 1982, and further revised and improved in 2009. Medical historians have theorized that people with
porphyria Porphyria is a group of liver disorders in which substances called porphyrins build up in the body, negatively affecting the skin or nervous system. The types that affect the nervous system are also known as acute porphyria, as symptoms are ra ...
(a disease that shares many symptoms with SLE) generated folklore stories of vampires and werewolves, due to the photosensitivity, scarring, hair growth, and porphyrin brownish-red stained teeth in severe recessive forms of porphyria (or combinations of the disorder, known as dual, homozygous, or compound heterozygous porphyrias). Useful medication for the disease was first found in 1894 when
quinine Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to ''Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal leg cr ...
was first reported as an effective therapy. Four years later, the use of
salicylate Salicylic acid is an organic compound with the formula HOC6H4CO2H. A colorless, bitter-tasting solid, it is a precursor to and a metabolite of aspirin (acetylsalicylic acid). It is a plant hormone, and has been listed by the EPA Toxic Substance ...
s in conjunction with quinine was noted to be of still greater benefit. This was the best available treatment until the middle of the twentieth century when Hench discovered the efficacy of
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
s in the treatment of SLE.


Research

A study called BLISS-76 tested the drug
belimumab Belimumab, sold under the brand name Benlysta, is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), also known as B-lymphocyte stimulator (BLyS). It is approved in the United States, Canada, and the European Union to treat ...
, a fully human
monoclonal Monoclonality refers to the state of a line of cells that have been derived from a single clonal origin. Thus "monoclonal cells" can be said to form a single clone. The term ''monoclonal'' comes from the Ancient Greek ''monos'', meaning "alone" o ...
anti- BAFF (or anti-BLyS) antibody. BAFF stimulates and extends the life of
B lymphocyte B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
s, which produce antibodies against foreign and
self-protein Self-protein refers to all proteins endogenously produced by DNA-level transcription and translation within an organism of interest. This does not include proteins synthesized due to viral infection, but may include those synthesized by commensal b ...
. It was approved by the FDA in March 2011. Genetically engineered immune cells are also being studied in animal models of the disease as of 2019. In September 2022, researchers at the
University of Erlangen-Nuremberg A university () is an institution of higher (or tertiary) education and research which awards academic degrees in several academic disciplines. Universities typically offer both undergraduate and postgraduate programs. In the United States, t ...
published promising results using genetically altered immune cells to treat severely ill patients. Four women and one man received transfusions of
CAR T cells In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specific ...
modified to attack their
B cells B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
, eliminating the aberrant ones. The therapy drove the disease into remission in all five patients, who have been off lupus medication for several months after the treatment ended.


See also

*
Canine discoid lupus erythematosus Discoid lupus erythematosus (DLE) is an uncommon autoimmune disease of the basal cell layer of the skin. It occurs in humans and cats, more frequently occurring in dogs. It was first described in dogs by Griffin and colleagues in 1979. DLE is one ...
in dogs *
List of people with lupus This is a categorised, alphabetical list of notable people who have been diagnosed with lupus. Lupus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these ...


References


External links

*
Systemic Lupus Erythematosus
at the
National Institute of Arthritis and Musculoskeletal and Skin Diseases The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is one of the institutes and centers that make up the National Institutes of Health, an agency of the United States Department of Health and Human Services (HHS). ...
{{Autoimmune diseases Autoimmune diseases Cutaneous lupus erythematosus Disorders causing seizures Disorders of fascia Epstein–Barr virus–associated diseases Steroid-responsive inflammatory conditions Systemic connective tissue disorders Wikipedia medicine articles ready to translate William Osler