Systemic lupus erythematosus
Encyclopedia
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease (or autoimmune
connective tissue disease
) that can affect any part of the body. As occurs in other autoimmune diseases, the immune system
attacks the body's cells and tissue, resulting in inflammation
and tissue damage. It is a Type III hypersensitivity reaction
caused by antibody-immune complex formation.
SLE most often harms the heart
, joint
s, skin
, lung
s, blood vessel
s, liver
, kidney
s, and nervous system. The course of the disease is unpredictable, with periods of illness (called flares) alternating with remissions. The disease occurs nine times more often in women than in men, especially in women in child-bearing years ages 15 to 35, and is also more common in those of non-European descent.
SLE is treatable using immunosuppression, mainly with cyclophosphamide
, corticosteroid
s and other immunosuppressants
; there is currently no cure. SLE can be fatal, although with recent medical advances, fatalities are becoming increasingly rare. Survival for people with SLE in the United States, Canada, and Europe has risen to approximately 95% at five years
, 90% at 10 years, and 78% at 20 years, and now approaches that of matched controls without lupus.
Childhood systemic lupus erythematosus generally presents between the ages of 3 and 15, with girls outnumbering boys 4:1, and typical skin manifestations being butterfly eruption on the face and photosensitivity.
s" because it often mimics or is mistaken for other illnesses. SLE is a classical item in differential diagnosis
, because SLE symptoms vary widely and come and go unpredictably. Diagnosis can thus be elusive, with some people suffering unexplained symptoms of untreated SLE for years.
Common initial and chronic complaints include fever
, malaise
, joint pains
, myalgia
s, fatigue, and temporary loss of cognitive abilities. Because they are so often seen 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 (see below), however, they are considered suggestive.
Dermatological manifestations:
As many as 30% of sufferers have some dermatological symptoms (and 65% suffer such symptoms at some point), with 30% to 50% suffering from the classic malar rash
(or butterfly rash
) associated with the disease. Some may exhibit thick, red scaly patches on the skin (referred to as discoid lupus). Alopecia
; mouth
, nasal, urinary tract and vaginal
ulcers, and lesions on the skin are also possible manifestations. Tiny tears in delicate tissue around the eyes can occur after even minimal rubbing.
Musculoskeletal:
The most commonly sought medical attention is for joint pain, with the small joints of the hand and wrist usually affected, although all joints are at risk. The Lupus Foundation of America
estimates more than 90 percent of those affected will experience joint and/or muscle pain at some time during the course of their illness. Unlike rheumatoid arthritis
, lupus arthritis is less disabling and usually does not cause severe destruction of the joints. Fewer than ten percent of people with lupus arthritis will develop deformities of the hands and feet. SLE patients are at particular risk of developing osteoarticular tuberculosis
.
A possible association between rheumatoid arthritis
and SLE has been suggested, and SLE may be associated with an increased risk of bone fracture
s in relatively young women.
Hematological:
Anemia
may develop in up to 50% of cases. Low platelet
and white blood cell
counts may be due to the disease or a side effect of pharmacological treatment. People with SLE may have an association with antiphospholipid antibody syndrome
(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
(which usually occurs in hemorrhagic disorders) and a positive test for antiphospholipid antibodies; the combination of such findings have earned the term "lupus anticoagulant
-positive". Another autoantibody finding in SLE is the anticardiolipin antibody, which can cause a false positive test for syphilis
.
Cardiac:
A person with SLE may have inflammation of various parts of the heart
, such as pericarditis
, myocarditis
, and endocarditis
. The endocarditis of SLE is characteristically noninfective (Libman-Sacks endocarditis
), and involves either the mitral valve
or the tricuspid valve
. Atherosclerosis
also tends to occur more often and advances more rapidly than in the general population.
Pulmonary:
Lung and pleura inflammation can cause pleuritis
, pleural effusion
, lupus pneumonitis, chronic diffuse interstitial lung disease, pulmonary hypertension
, pulmonary emboli
, pulmonary hemorrhage
, and shrinking lung syndrome.
Renal:
Painless hematuria
or proteinuria
may often be the only presenting renal symptom. Acute or chronic renal impairment may develop with lupus nephritis
, leading to acute or end-stage renal failure
. Because of early recognition and management of SLE, end-stage renal failure occurs in less than 5% of cases.
A histological hallmark of SLE is membranous glomerulonephritis
with "wire loop" abnormalities. This finding is due to immune complex deposition along the glomerular basement membrane
, leading to a typical granular appearance in immunofluorescence
testing.
Neuropsychiatric:
Neuropsychiatric
syndromes can result when SLE affects the central
or peripheral nervous system
s. The American College of Rheumatology
defines 19 neuropsychiatric syndromes in systemic lupus erythematosus. The diagnosis of neuropsychiatric syndromes concurrent with SLE 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.
The most common neuropsychiatric disorder people with SLE have is headache
, although the existence of a specific lupus headache
and the optimal approach to headache in SLE cases remains controversial.
Other common neuropsychiatric manifestation of SLE include cognitive dysfunction
, mood disorder
, cerebrovascular disease
, seizures, polyneuropathy
, anxiety disorder
, and psychosis
. It can rarely present with intracranial hypertension syndrome
, 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 fluid
chemical and hematological constituents.
More rare manifestations are acute confusional state
, Guillain-Barré syndrome
, aseptic meningitis
, autonomic disorder, demyelinating syndrome
, mononeuropathy (which might manifest as mononeuritis multiplex), movement disorder
(more specifically, chorea), myasthenia gravis
, myelopathy
, cranial
neuropathy and plexopathy
.
Neurological
Neural symptoms contribute to a significant percentage of morbidity and mortality in patients with lupus. As a result, the neural side of lupus is being studied in hopes of reducing morbidity and mortality rates. The neural manifestation of lupus is known as neuropsychiatric systematic lupus erythematosus (NPSLE). One aspect of this disease is severe damage to the epithelial cells of the blood-brain barrier
.
Lupus has a wide range of symptoms which span the body. The neurological symptoms include headaches, depression
, seizures, cognitive dysfunction
, mood disorder
, cerebrovascular disease
, polyneuropathy
, anxiety disorder
, psychosis
, and in some extreme cases, personality disorders. In certain regions, depression reportedly affects up to 60% of women suffering from SLE.
Reproductive
SLE causes an increased rate of fetal death in utero and spontaneous abortion (miscarriage). The overall live-birth rate in SLE patient has been estimated to be 72%. Pregnancy outcome appears to be worse in SLE patients whose disease flares up during pregnancy.
Neonatal lupus is the occurrence of SLE symptoms in an infant
born from a mother with SLE, most commonly presenting with a rash resembling discoid lupus erythematosus
, and sometimes with systemic abnormalities such as heart block
or hepatosplenomegaly
. Neonatal lupus is usually benign and self-limited.
Systemic:
Fatigue in SLE is probably multifactorial and has been related to not only disease activity or complications such as anemia
or hypothyroidism
, but also to pain
, depression
, poor sleep
quality, poor physical fitness
and perceived lack of social support
.
link. SLE does run in families, but no single causal gene has been identified. Instead, multiple genes appear to influence a person's chance of developing lupus when triggered by environmental factors. The most important genes are located in the HLA
region on chromosome 6
, where mutations may occur randomly (de novo) or may be inherited. HLA class I, class II, and class III are associated with SLE, but only classes I and II contribute independently to increased risk
of SLE. Other genes which contain risk variants for SLE are IRF5
, PTPN22
, STAT4
, CDKN1A, ITGAM, BLK
, TNFSF4 and BANK1
. Some of the susceptibility genes may be population specific.
Researchers have sought to find a connection between certain infectious agents (virus
es and bacteria
), but no pathogen can be consistently linked to the disease. Some researchers have found that women with silicone
gel-filled breast implants have produced antibodies to their own collagen
, but it is not known how often these antibodies occur in the general population, and there are no data that show these antibodies cause connective tissue disease
s such as SLE. There is also a small but growing body of evidence linking SLE to lipstick usage.
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
, hydralazine
, quinidine
, and phenytoin
.
, a type of programmed cell death in which aging or damaged cells are neatly disposed of as a part of normal growth or functioning.
"All the key components of the immune system are involved in the underlying mechanisms [of SLE]" according to Rahman, and SLE is the prototypical autoimmune disease. In order to preserve homeostasis, the immune system must balance between being sensitive enough to protect against infection, and becoming sensitized to attack the body's own proteins (autoimmunity). During an immune reaction to a foreign stimulus, such as bacteria, virus, or allergen, immune cells that would normally be deactivated due to their affinity for self tissues can be abnormally activated by signaling sequences of antigen-presenting cells. Thus triggers may include viruses, bacteria, allergens (both IgE
and hypersensitivity
), and can be aggravated by environmental stimulants such as ultraviolet light and certain drug reactions. These stimuli begin a reaction that leads to destruction
of other cells in the body and exposure of their DNA, histones, and other proteins, particularly parts of the cell nucleus. The body's sensitized B-lymphocyte cells will now produce antibodies against these nuclear-related proteins. These antibodies clump into antibody-protein complexes which stick to surfaces and damage blood vessels in critical areas of the body, such as the glomeruli of the kidney; these antibody attacks are the cause of SLE. Researchers are now identifying the individual genes, the proteins they produce, and their role in the immune system. Each protein is a link on the autoimmune chain, and researchers are trying to find drugs to break each of those links.
SLE is a chronic inflammatory
disease believed to be a type III hypersensitivity response with potential type II involvement. Reticulate and stellate acral pigmentation should be considered a possible manifestation of SLE and high titers of anticardiolipin antibodies, or a consequence of therapy.
Tingible body macrophage
s (TBMs) – large phagocytic cells in the germinal center
s of secondary lymph node
s – express CD68 protein. These cells normally engulf B cells that have undergone apoptosis after somatic hypermutation
. 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
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 cells and make this material available for activating other B cells that may have randomly acquired self-specificity through somatic hypermutation
.
The exact mechanisms for the development of SLE are still unclear, since the pathogenesis is a multifactorial event. Beside discussed causations, impaired clearance of dying cells is a potential pathway for the development of this systemic autoimmune disease
. This includes deficient phagocytic activity and scant serum components in addition to increased apoptosis
.
Monocytes isolated from whole blood
of SLE sufferers show reduced expression of CD44 surface molecules involved in the uptake of apoptotic cells. Most of the monocytes and tingible body macrophages (TBMs), which are found in the germinal centres of lymph nodes, even show a definitely different morphology; they are smaller or scarce and die earlier. Serum components like complement
factors, CRP
, and some glycoproteins are, furthermore, decisively important for an efficiently operating phagocytosis. With SLE, these components are often missing, diminished, or inefficient.
Recent research has found an association between certain lupus patients (especially those with lupus nephritis
) and an impairment in degrading neutrophil extracellular traps
(NETs). These were due to DNAse1
inhibiting factors, or NET protecting factors in patient 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
of the cells if this ability is disturbed. Necrotic cells release nuclear fragments as potential autoantigens, as well as internal danger signals, inducing maturation of dendritic cells (DCs), since they have lost their membranes' integrity. Increased appearance of apoptotic cells also simulates inefficient clearance. That leads to maturation of DCs and also to the presentation of intracellular antigens of late apoptotic or secondary necrotic cells, via MHC molecules.
Autoimmunity
possibly results by the extended exposure to nuclear and intracellular autoantigens derived from late apoptotic and secondary necrotic cells. B and T cell
tolerance for apoptotic cells is abrogated, and the lymphocytes get activated by these autoantigens; inflammation
and the production of autoantibodies by plasma cells is initiated. A clearance deficiency in the skin for apoptotic cells has also been observed in people with cutaneous lupus erythematosus (CLE).
of apoptotic debris
can be observed in GC because of an ineffective clearance of apoptotic cells. In close proximity to TBM, follicular dendritic cells
(FDC) are localised in GC, which attach antigen material to their surface and, in contrast to bone marrow
-derived DC, neither take it up nor present it via MHC
molecules.
Autoreactive B cells can accidentally emerge during somatic hypermutation
and migrate into the GC light zone. Autoreactive B cells, maturated coincidentally, normally do not receive survival signals by antigen planted on follicular dendritic cells, and perish by apoptosis. In the case of clearance deficiency, apoptotic nuclear debris accumulates in the light zone of GC and gets attached to FDC. This serves as a germinal centre survival signal for autoreactive B-cells. After migration into the mantle zone, autoreactive B cells require further survival signals from autoreactive helper T cells, which promote the maturation of autoantibody-producing plasma cells and B memory cells. In the presence of autoreactive T cells, a chronic autoimmune disease
may be the consequence.
-rich motifs
. Antibody binding subsequently spread to other epitopes. The similarity and cross-reactivity
between the initial targets of nRNP and Sm autoantibodies identifies a likely commonality in cause and a focal point for intermolecular epitope spreading.
was found in the sera of patients and mice with systemic lupus erythematosus, high mobility group box 1 (HMGB1
) is a nuclear
protein
participating in chromatin
architecture
and transcriptional regulation
. Recently, there is increasing evidence HMGB1 contributes to the pathogenesis of chronic
inflammatory
and autoimmune diseases due to its proinflammatory and immunostimulatory properties.
testing for SLE. Several techniques are used to detect ANAs. Clinically the most widely used method is indirect immunofluorescence
. The pattern of fluorescence suggests the type of antibody present in the patient's serum.
ANA screening yields positive results in many connective tissue disorders and other autoimmune diseases, and may occur in normal individuals. Subtypes of antinuclear antibodies include anti-Smith
and anti-double stranded DNA
(dsDNA) antibodies (which are linked to SLE) and anti-histone antibodies
(which are linked to drug-induced lupus). 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. The anti-dsDNA antibody titer
s also tend to reflect disease activity, although not in all cases. Other ANA that may occur in SLE sufferers are anti-U1 RNP
(which also appears in systemic sclerosis), SS-A (or anti-Ro) and SS-B (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
levels (low levels suggest consumption by the immune system), electrolyte
s and renal function
(disturbed if the kidney is involved), liver enzymes, and complete blood count
.
The lupus erythematosus (LE) cell test was commonly used for diagnosis, but it is no longer used because the LE cell
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.
(ACR) classification criteria. The criteria, however, were established mainly for use in scientific research including use in randomized controlled trial
s which require higher confidence levels, so some people with SLE may not pass the full criteria.
, may have SLE without four of the above criteria, and also SLE may present with features other than those listed in the criteria.
Recursive partitioning
has been used to identify more parsimonious criteria. This analysis presented two diagnostic classification trees:
Other alternative criteria have been suggested, e.g. the St. Thomas' Hospital "alternative" criteria in 1998.
As longevity of people with SLE increases, the likelihood of complication
s also increases in four areas: cardiovascular disease
, infection
s, osteoporosis
, and cancer
. Standard preventive measures, screening for related diseases may be necessary to deal with the increased risks due to the side effects of medications. Extra vigilance is considered warranted in particular for cancers affecting the immune system.
Treatment can include corticosteroid
s and anti-malarial drugs. Certain types of lupus nephritis such as diffuse proliferative glomerulonephritis require bouts of cytotoxic drugs. These drugs include cyclophosphamide
and mycophenolate.
Hydroxychloroquine
(HCQ) was the last medication approved by the FDA 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 Benlysta (belimumab) as a treatment for the pain and flare-ups common in lupus. The drug was approved by the FDA in March 2011.
may be used. Medications such as Prednisone, Cellcept and Prograf have been used in the past. A number of potential treatments are in clinical trials.
s (DMARDs) are used preventively to reduce the incidence of flares, the process of the disease, and lower the need for steroid use; when flares occur, they are treated with corticosteroids. DMARDs commonly in use are antimalarials such as plaquenil and immunosuppressants (e.g. methotrexate
and azathioprine
). 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
is used for severe glomerulonephritis
or other organ-damaging complications. Mycophenolic acid
is also used for treatment of lupus nephritis, but it is not FDA-approved for this indication, and FDA is investigating reports that it may be associated with birth defects when used by pregnant women.
) are used to control the disease and prevent recurrence of symptoms (known as flares). Depending on the dosage, people who require steroids may develop Cushing's syndrome
, symptoms of which may include obesity
, puffy round face, diabetes mellitus
, increased appetite, difficulty sleeping and osteoporosis
. These may subside if and when the large initial dosage is reduced, but long-term use of even low doses can cause elevated blood pressure
and cataracts.
Numerous new immunosuppressive drugs are being actively tested for SLE. Rather than suppressing the immune system nonspecifically, as corticosteroids do, they target the responses of individual [types of] immune cells. Some of these drugs are already FDA-approved for treatment of rheumatoid arthritis
. See also Belimumab
and Atacicept
. Lupuzor has given encouraging results in a phase IIb trial
, stronger prescription analgesics (pain killers) may be used if over-the-counter drugs (mainly nonsteroidal anti-inflammatory drugs) do not provide effective relief. Potent NSAIDs such as indomethacin and diclofenac are relatively contraindicated for patients with SLE because they increase the risk of kidney failure and heart failure.
Moderate pain is typically treated with mild prescription opiates such as dextropropoxyphene
and co-codamol
. Moderate to severe chronic pain is treated with stronger opioids, such as hydrocodone
or longer-acting continuous-release opioids, such as oxycodone
, MS Contin
, or methadone
. The fentanyl duragesic transdermal patch is also a widely-used treatment option for the chronic pain caused by complications because of its long-acting timed release and ease of use. 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.
s may be used to control SLE with organ involvement, or vasculitis
. It is believed that they reduce antibody
production or promote the clearance of immune complex
es from the body, even though their mechanism of action
is not well-understood. Unlike immunosuppressives and corticosteroids, IVIGs do not suppress the immune system
, so there is less risk of serious infection
s with these drugs.
s and mercury
can also make the disease worsen.
, but the recurrence of the full disease is common in up to 30% of patients.
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 blood stream. If the thromboses migrate to the brain, they can potentially cause a stroke
by blocking the blood supply to the brain.
If this disorder is suspected in patients, 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 patients requires anticoagulation. Often, low-dose aspirin
is prescribed for this purpose, although for cases involving thrombosis anticoagulants such as warfarin
are used.
Contraception
and other reliable forms of pregnancy prevention is routinely advised for women with SLE, since getting pregnant during active disease was found to be harmful. Lupus nephritis
was the most common manifestation.
In the 1950s, most people diagnosed with SLE lived fewer than five years. Advances in diagnosis and treatment have improved survival to the point where over 90% now survive for more than ten years, and many can live relatively asymptomatically. (It is important to note that "ten years" in this statistic does not indicate an average survival rate, but is merely the length of the referenced study. According to the Lupus Foundation of America, "the majority of people with lupus today can expect to live a normal lifespan.")
Prognosis is normally 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 modified 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 diseases acquired from corticosteroid therapy, the leading cause of death for people with SLE.
To reduce 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. High serum creatinine, hypertension, nephrotic syndrome
, anemia and hypoalbuminemia are poor prognostic factors.
The ANA is the most sensitive screening test for evaluation, whereas anti-Sm (anti-Smith) is the most specific. The dsDNA (double-stranded DNA
) antibody is also fairly specific and often fluctuates with disease activity; as such, the dsDNA titre is sometimes useful to monitor disease flares or response to treatment.
of SLE is estimated to be about 53 per 100,000, translating to about 159,000 out of 300 million people in the US being affected. 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.
SLE, like many autoimmune diseases, affects females more frequently than males, at a rate of almost 9 to 1.
The incidence
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 to increasing frequency of the disease is unknown.
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.
and saw the description of the dermatological manifestation of the disorder. The term lupus is attributed to 12th-century physician
Rogerius
, who used it to describe the classic malar rash. The neoclassical period was heralded by Móric Kaposi
's recognition in 1872 of the systemic manifestations of the disease. The modern period began in 1948 with the discovery of the LE cell (the lupus erythematosus cell—a misnomer, as it occurs with other diseases as well) and is characterised by advances in our knowledge of the pathophysiology and clinical-laboratory features of the disease, as well as advances in treatment.
Medical historians have theorized that people with porphyria
(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
was first reported as an effective therapy. Four years later, the use of salicylate
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
s in the treatment of SLE.
Several papers discuss the importance of the presence of antibodies in the brain that are only produced in patients with lupus. One such paper highlights the inhibition of astrocyte proliferation in brain tissue from lupus patient serum. Astrocytes are glial cells in the brain that participate in the support of cells that form the blood brain barrier. They are extremely useful in that they provide a nutritional balance between ions in the brain, keeping it at a normal level. In this study, researchers used immunofluorescence to track the antibodies near the corpus callosum
to determine whether anticardiolipin antibodies have an inhibitory effect on brain cells and whether they elicit thrombus formation in brain vessels, which plays a part in neuropsychiatric lupus.
However, the majority of the recent papers focus on the effect of lupus on blood-brain barrier integrity. It was found that 20–70% of lupus patients with neurological symptoms have some form of a central nervous system involvement. This can be determined using various imaging methods as well as lumbar puncture (spinal tap) to assess cerebrospinal fluid.
In a study conducted in London, researchers measured the albumin content in the brain using imaging and spinal fluid. The images were used to illustrate blood brain barrier damage while the spinal tap was used to measure the protein content in the brain. Albumin is a protein that can be carried into the brain through the blood brain barrier by other transport proteins. If the ratio of albumin outside the barrier to inside the barrier is high, this means that either the barrier is damaged, or the transport proteins are not functioning well. This blood brain barrier damage can impact lupus patients by increasing their discomfort and increasing the intensity of the disease.
A study called BLISS-76 tested the drug, Belimumab (HGS1006, LymphoStat-B ), a fully human monoclonal anti-BLyS antibody. BLyS stimulates and extends the life of B lymphocytes, which produce antibodies against foreign and self cells. The drug, branded Benlysta, was approved by the FDA in March 2011. Notwithstanding the approval, the FDA emphasized that the drug will not work in all cases, and that more research and advanced therapies are called for.
At Stanford School of Medicine Institute for Immunity Transplantation and Infection, trials are underway for use of DHEA as a therapeutic agent for the treatment of mild to moderate SLE.
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
connective tissue disease
Connective tissue disease
A connective tissue disease is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs...
) that can affect any part of the body. As occurs in other autoimmune diseases, the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
attacks the body's cells and tissue, resulting in inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and tissue damage. It is a Type III hypersensitivity reaction
Type III hypersensitivity
Type III hypersensitivity occurs when antigens and antibodies are present in roughly equal amounts, causing extensive cross-linking.-Presentation:...
caused by antibody-immune complex formation.
SLE most often harms the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
, joint
Joint
A joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.-Classification:...
s, skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
, lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s, blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s, and nervous system. The course of the disease is unpredictable, with periods of illness (called flares) alternating with remissions. The disease occurs nine times more often in women than in men, especially in women in child-bearing years ages 15 to 35, and is also more common in those of non-European descent.
SLE is treatable using immunosuppression, mainly with cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s and other immunosuppressants
Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
; there is currently no cure. SLE can be fatal, although with recent medical advances, fatalities are becoming increasingly rare. Survival for people with SLE in the United States, Canada, and Europe has risen to approximately 95% at five years
Five-year survival rate
The five-year survival rate is a term used in medicine for estimating the prognosis of a particular disease.Analysis performed against the Surveillance, Epidemiology, and End Results database facilitates calculation of Five-year survival rates....
, 90% at 10 years, and 78% at 20 years, and now approaches that of matched controls without lupus.
Childhood systemic lupus erythematosus generally presents between the ages of 3 and 15, with girls outnumbering boys 4:1, and typical skin manifestations being butterfly eruption on the face and photosensitivity.
Signs and symptoms
SLE is one of several diseases known as "the great imitatorThe great imitator
The Great Imitator is a phrase used for medical conditions that feature nonspecific symptoms and may be confused with a number of other diseases. Most great imitators are systemic in nature...
s" because it often mimics or is mistaken for other illnesses. SLE is a classical item in differential diagnosis
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...
, because SLE symptoms vary widely and come and go unpredictably. Diagnosis can thus be elusive, with some people suffering unexplained symptoms of untreated SLE for years.
Common initial and chronic complaints include fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, malaise
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
, joint pains
Arthralgia
Arthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
, myalgia
Myalgia
Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
s, fatigue, and temporary loss of cognitive abilities. Because they are so often seen 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 (see below), however, they are considered suggestive.
Dermatological manifestations:
As many as 30% of sufferers have some dermatological symptoms (and 65% suffer such symptoms at some point), with 30% to 50% suffering from the classic malar rash
Malar rash
In medicine, malar rash , also called butterfly rash, is a medical sign consisting of a characteristic form of facial rash. It is often seen in Lupus erythematosus but is not pathognomonic - it is also seen in other diseases such as Pellagra, dermatomyositis and Bloom Syndrome.The malar rash of...
(or butterfly rash
Malar rash
In medicine, malar rash , also called butterfly rash, is a medical sign consisting of a characteristic form of facial rash. It is often seen in Lupus erythematosus but is not pathognomonic - it is also seen in other diseases such as Pellagra, dermatomyositis and Bloom Syndrome.The malar rash of...
) associated with the disease. Some may exhibit thick, red scaly patches on the skin (referred to as discoid lupus). Alopecia
Alopecia
Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...
; mouth
Mouth ulcer
A mouth or oral ulcer is an open sore in the mouth, or rarely a break in the mucous membrane or the epithelium on the lips or surrounding the mouth. The types of mouth ulcers are diverse, with a multitude of associated causes including: physical abrasion, acidic fruit, infection, other medical...
, nasal, urinary tract and vaginal
Genital ulcer
A Genital ulcer is an ulcer located on the genital area, usually caused by a sexually transmitted disease such as genital herpes, syphilis, chancroid, or thrush. Some other signs of having genital ulcers include enlarged lymph nodes in the groin area, or vesicular lesions, which are small, elevated...
ulcers, and lesions on the skin are also possible manifestations. Tiny tears in delicate tissue around the eyes can occur after even minimal rubbing.
Musculoskeletal:
The most commonly sought medical attention is for joint pain, with the small joints of the hand and wrist usually affected, although all joints are at risk. The Lupus Foundation of America
Lupus Foundation of America
The Lupus Foundation of America is the largest national non-profit voluntary health organization dedicated to finding the causes of and cure for lupus and providing support, services and hope to all people affected by lupus....
estimates more than 90 percent of those affected will experience joint and/or muscle pain at some time during the course of their illness. Unlike rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
, 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. SLE patients are at particular risk of developing osteoarticular tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
.
A possible association between rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
and SLE has been suggested, and SLE may be associated with an increased risk of bone fracture
Bone fracture
A bone fracture is a medical condition in which there is a break in the continuity of the bone...
s in relatively young women.
Hematological:
Anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
may develop in up to 50% of cases. Low platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
and white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
counts 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
Antiphospholipid syndrome or antiphospholipid antibody syndrome , often also Hughes syndrome, is an autoimmune, hypercoagulable state caused by antibodies against cell-membrane phospholipids that provokes blood clots in both arteries and veins as well as pregnancy-related complications such as...
(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
Partial thromboplastin time
The partial thromboplastin time or activated partial thromboplastin time is a performance indicator measuring the efficacy of both the "intrinsic" and the common coagulation pathways...
(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
Lupus anticoagulant is an immunoglobulin that binds to phospholipids and proteins associated with the cell membrane. It is important to note that this disease name is actually a misnomer...
-positive". Another autoantibody finding in SLE is the anticardiolipin antibody, which can cause a false positive test for syphilis
Syphilis
Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...
.
Cardiac:
A person with SLE may have inflammation of various parts of the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
, such as pericarditis
Pericarditis
Pericarditis is an inflammation of the pericardium . A characteristic chest pain is often present.The causes of pericarditis are varied, including viral infections of the pericardium, idiopathic causes, uremic pericarditis, bacterial infections of the precardium Pericarditis is an inflammation of...
, myocarditis
Myocarditis
Myocarditis is inflammation of heart muscle . It resembles a heart attack but coronary arteries are not blocked.Myocarditis is most often due to infection by common viruses, such as parvovirus B19, less commonly non-viral pathogens such as Borrelia burgdorferi or Trypanosoma cruzi, or as a...
, and endocarditis
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 even on intracardiac devices...
. The endocarditis of SLE is characteristically noninfective (Libman-Sacks endocarditis
Libman-Sacks endocarditis
Libman-Sacks endocarditis is a form of nonbacterial endocarditis that is seen in systemic lupus erythematosus. It is one of the most common cardiac manifestations of lupus ....
), and involves either the mitral valve
Mitral valve
The mitral valve is a dual-flap valve in the heart that lies between the left atrium and the left ventricle...
or the tricuspid valve
Tricuspid valve
The tricuspid valve, or right atrioventricular valve, is on the right dorsal side of the mammalian heart, between the right atrium and the right ventricle. The normal tricuspid valve usually has three leaflets and three papillary muscles. They are connected to the papillary muscles by the chordae...
. Atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
also tends to occur more often and advances more rapidly than in the general population.
Pulmonary:
Lung and pleura inflammation can cause pleuritis
Pleurisy
Pleurisy is an inflammation of the pleura, the lining of the pleural cavity surrounding the lungs. Among other things, infections are the most common cause of pleurisy....
, pleural effusion
Pleural effusion
Pleural effusion is excess fluid that accumulates between the two pleural layers, the fluid-filled space that surrounds the lungs. Excessive amounts of such fluid can impair breathing by limiting the expansion of the lungs during ventilation.-Pathophysiology:...
, lupus pneumonitis, chronic diffuse interstitial lung disease, pulmonary hypertension
Pulmonary hypertension
In medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...
, pulmonary emboli
Pulmonary embolism
Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
, pulmonary hemorrhage
Pulmonary hemorrhage
Pulmonary hemorrhage is an acute bleeding from the lung, especially in the upper respiratory tract and the endotracheal tube. When evident clinically, the condition is usually massive, associated with bleeding in other sites as well as more than one third of the lungs...
, and shrinking lung syndrome.
Renal:
Painless hematuria
Hematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
or proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
may often be the only presenting renal symptom. Acute or chronic renal impairment may develop with lupus nephritis
Lupus nephritis
Lupus nephritis is an inflammation of the kidney caused by systemic lupus erythematosus , a disease of the immune system. Apart from the kidneys, SLE can also damage the skin, joints, nervous system and virtually any organ or system in the body....
, leading to acute or end-stage renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
. Because of early recognition and management of SLE, end-stage renal failure occurs in less than 5% of cases.
A histological hallmark of SLE is membranous glomerulonephritis
Glomerulonephritis
Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys...
with "wire loop" abnormalities. This finding is due to immune complex deposition along the glomerular basement membrane
Glomerular basement membrane
The glomerular basement membrane is the basal laminal portion of the glomerulus. The Glomerular capillary endothelial cells, the GBM and the filtration slits between the podocytes perform the filtration function of the glomerulus, separating the blood in the capillaries from the filtrate that...
, leading to a typical granular appearance in immunofluorescence
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
testing.
Neuropsychiatric:
Neuropsychiatric
Neuropsychiatry
Neuropsychiatry is the branch of medicine dealing with mental disorders attributable to diseases of the nervous system. It preceded the current disciplines of psychiatry and neurology, in as much as psychiatrists and neurologists had a common training....
syndromes can result when SLE affects the central
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
or peripheral nervous system
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
s. The American College of Rheumatology
American College of Rheumatology
The American College of Rheumatology is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with arthritis and rheumatic and...
defines 19 neuropsychiatric syndromes in systemic lupus erythematosus. The diagnosis of neuropsychiatric syndromes concurrent with SLE 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.
The most common neuropsychiatric disorder people with SLE have is headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, although the existence of a specific lupus headache
Lupus headache
Lupus headache is a proposed, specific headache disorder in patients suffering from systemic lupus erythematosus .Research shows that headache is a symptom commonly described by SLE patients —57% in one meta-analysis, ranging in different studies from 33% to 78%; of which migraine 31.7% and...
and the optimal approach to headache in SLE cases remains controversial.
Other common neuropsychiatric manifestation of SLE include cognitive dysfunction
Cognitive dysfunction
Cognitive dysfunction is defined as unusually poor mental function, associated with confusion, forgetfulness and difficulty concentrating...
, mood disorder
Mood disorder
Mood disorder is the term designating a group of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders classification system where a disturbance in the person's mood is hypothesized to be the main underlying feature...
, cerebrovascular disease
Cerebrovascular disease
Cerebrovascular disease is a group of brain dysfunctions related to disease of the blood vessels supplying the brain. Hypertension is the most important cause; it damages the blood vessel lining, endothelium, exposing the underlying collagen where platelets aggregate to initiate a repairing process...
, seizures, polyneuropathy
Polyneuropathy
Polyneuropathy is a neurological disorder that occurs when many peripheral nerves throughout the body malfunction simultaneously. It may be acute and appear without warning, or chronic and develop gradually over a longer period of time. Many polyneuropathies have both motor and sensory...
, anxiety disorder
Anxiety disorder
Anxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Conditions now considered anxiety disorders only came under the aegis of psychiatry at the end of the 19th century. Gelder, Mayou & Geddes explains that anxiety disorders are...
, and psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
. It can rarely present with intracranial hypertension syndrome
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 fluid chemical and hematological constituents....
, characterized by an elevated intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
, papilledema
Papilledema
Papilledema is optic disc swelling that is caused by increased intracranial pressure. The swelling is usually bilateral and can occur over a period of hours to weeks. Unilateral presentation is extremely rare....
, and headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
with occasional abducens nerve
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...
paresis
Paresis
Paresis is a condition typified by partial loss of voluntary movement or by impaired movement. When used without qualifiers, it usually refers to the limbs, but it also can be used to describe the muscles of the eyes , the stomach , and also the vocal cords...
, absence of a space-occupying lesion or ventricular enlargement, and normal cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
chemical and hematological constituents.
More rare manifestations are acute confusional state
Delirium
Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...
, Guillain-Barré syndrome
Guillain-Barré syndrome
Guillain–Barré syndrome , sometimes called Landry's paralysis, is an acute inflammatory demyelinating polyneuropathy , a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom...
, aseptic meningitis
Aseptic meningitis
Aseptic meningitis, or sterile meningitis, is a condition in which the layers lining the brain, meninges, become inflamed and a pyogenic bacterial source is not to blame. Meningitis is diagnosed on a history of characteristic symptoms and certain examination findings...
, autonomic disorder, demyelinating syndrome
Demyelinating disease
A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged. This impairs the conduction of signals in the affected nerves, causing impairment in sensation, movement, cognition, or other functions depending on which nerves are involved.The term...
, mononeuropathy (which might manifest as mononeuritis multiplex), movement disorder
Movement disorder
Movement disorders include:* Akathisia * Akinesia * Associated Movements * Athetosis...
(more specifically, chorea), myasthenia gravis
Myasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
, myelopathy
Myelopathy
Myelopathy refers to pathology of the spinal cord. When due to trauma, it is known as spinal cord injury. When inflammatory, it is known as myelitis. Disease that is vascular in nature is known as vascular myelopathy....
, cranial
Cranial nerves
Cranial nerves are nerves that emerge directly from the brain, in contrast to spinal nerves, which emerge from segments of the spinal cord. In humans, there are traditionally twelve pairs of cranial nerves...
neuropathy and plexopathy
Plexopathy
Plexopathy is a disorder affecting a network of nerves, blood vessels, or lymph vessels. The region of nerves it affects are at the brachial or lumbosacral plexus. Symptoms include pain, loss of motor control, and sensory deficits....
.
Neurological
Neural symptoms contribute to a significant percentage of morbidity and mortality in patients with lupus. As a result, the neural side of lupus is being studied in hopes of reducing morbidity and mortality rates. The neural manifestation of lupus is known as neuropsychiatric systematic lupus erythematosus (NPSLE). One aspect of this disease is severe damage to the epithelial cells of the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
.
Lupus has a wide range of symptoms which span the body. The neurological symptoms include headaches, depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
, seizures, cognitive dysfunction
Cognitive dysfunction
Cognitive dysfunction is defined as unusually poor mental function, associated with confusion, forgetfulness and difficulty concentrating...
, mood disorder
Mood disorder
Mood disorder is the term designating a group of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders classification system where a disturbance in the person's mood is hypothesized to be the main underlying feature...
, cerebrovascular disease
Cerebrovascular disease
Cerebrovascular disease is a group of brain dysfunctions related to disease of the blood vessels supplying the brain. Hypertension is the most important cause; it damages the blood vessel lining, endothelium, exposing the underlying collagen where platelets aggregate to initiate a repairing process...
, polyneuropathy
Polyneuropathy
Polyneuropathy is a neurological disorder that occurs when many peripheral nerves throughout the body malfunction simultaneously. It may be acute and appear without warning, or chronic and develop gradually over a longer period of time. Many polyneuropathies have both motor and sensory...
, anxiety disorder
Anxiety disorder
Anxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Conditions now considered anxiety disorders only came under the aegis of psychiatry at the end of the 19th century. Gelder, Mayou & Geddes explains that anxiety disorders are...
, psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
, and in some extreme cases, personality disorders. In certain regions, depression reportedly affects up to 60% of women suffering from SLE.
Reproductive
SLE causes an increased rate of fetal death in utero and spontaneous abortion (miscarriage). The overall live-birth rate in SLE patient has been estimated to be 72%. Pregnancy outcome appears to be worse in SLE patients whose disease flares up during pregnancy.
Neonatal lupus is the occurrence of SLE symptoms in an infant
Infant
A newborn or baby is the very young offspring of a human or other mammal. A newborn is an infant who is within hours, days, or up to a few weeks from birth. In medical contexts, newborn or neonate refers to an infant in the first 28 days after birth...
born from a mother with SLE, most commonly presenting with a rash resembling discoid lupus erythematosus
Discoid lupus erythematosus
Discoid lupus erythematosus 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 does not progress to systemic lupus erythematosus in dogs. SLE can also have skin symptoms, but it appears that the two are...
, and sometimes with systemic abnormalities such as heart block
Heart block
A heart block can be a blockage at any level of the electrical conduction system of the heart .* Blocks that occur within the sinoatrial node are described as SA nodal blocks....
or hepatosplenomegaly
Hepatosplenomegaly
Hepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis or infectious mononucleosis, or it can be the sign of a serious and life threatening lysosomal storage disease...
. Neonatal lupus is usually benign and self-limited.
Systemic:
Fatigue in SLE is probably multifactorial and has been related to not only disease activity or complications such as anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
or hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
, but also to pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
, depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, poor sleep
Sleep
Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...
quality, poor physical fitness
Physical fitness
Physical fitness comprises two related concepts: general fitness , and specific fitness...
and perceived lack of social support
Social support
Social support can be defined and measured in many ways. It can loosely be defined as feeling that one is cared for by and has assistance available from other people and that one is part of a supportive social network...
.
Causes
There is no one specific cause of SLE. There are, however, a number of environmental triggers and a number of genetic susceptibilities.Genetics
The first mechanism may arise genetically. Research indicates SLE may have a geneticGenetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
link. SLE does run in families, but no single causal gene has been identified. Instead, multiple genes appear to influence a person's chance of developing lupus when triggered by environmental factors. The most important genes are located in the HLA
Human leukocyte antigen
The human leukocyte antigen system is the name of the major histocompatibility complex in humans. The super locus contains a large number of genes related to immune system function in humans. This group of genes resides on chromosome 6, and encodes cell-surface antigen-presenting proteins and...
region on chromosome 6
Chromosome 6 (human)
Chromosome 6 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 6 spans more than 170 million base pairs and represents between 5.5 and 6% of the total DNA in cells...
, where mutations may occur randomly (de novo) or may be inherited. HLA class I, class II, and class III are associated with SLE, but only classes I and II contribute independently to increased risk
Risk
Risk is the potential that a chosen action or activity will lead to a loss . The notion implies that a choice having an influence on the outcome exists . Potential losses themselves may also be called "risks"...
of SLE. Other genes which contain risk variants for SLE are IRF5
IRF5
Interferon regulatory factor 5 is a protein that in humans is encoded by the IRF5 gene.- Function :IRF5 is a member of the interferon regulatory factor family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth,...
, PTPN22
PTPN22
Protein tyrosine phosphatase, non-receptor type 22 , also known as PTPN22, is a protein that in humans is encoded by the PTPN22 gene. Alternative splicing of this gene results in two transcript variants encoding distinct isoforms...
, STAT4
STAT4
STAT4 is a human gene. The protein encoded by this gene is a member of the STAT protein family of transcription factors....
, CDKN1A, ITGAM, BLK
BLK (gene)
Tyrosine-protein kinase BLK also known as B lymphocyte kinase is an enzyme that in humans is encoded by the BLK gene.-Interactions:The tyrosine-protein kinase BLK has been shown to interact with UBE3A.-Further reading:...
, TNFSF4 and BANK1
Bank1
BANK1 is a gene that encodes a B-cell-specific scaffold protein and tyrosine kinase substrate that promotes tyrosine phosphorylation of inositol 1,4,5-trisphosphate receptors.-Genomics:...
. Some of the susceptibility genes may be population specific.
Environmental triggers
The second mechanism may be due to environmental factors. These factors may not only exacerbate existing SLE conditions, but also trigger the initial onset.Researchers have sought to find a connection between certain infectious agents (virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es and bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
), but no pathogen can be consistently linked to the disease. Some researchers have found that women with silicone
Silicone
Silicones are inert, synthetic compounds with a variety of forms and uses. Typically heat-resistant and rubber-like, they are used in sealants, adhesives, lubricants, medical applications , cookware, and insulation....
gel-filled breast implants have produced antibodies to their own collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
, but it is not known how often these antibodies occur in the general population, and there are no data that show these antibodies cause connective tissue disease
Connective tissue disease
A connective tissue disease is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs...
s such as SLE. There is also a small but growing body of evidence linking SLE to lipstick usage.
Drug reactions
Drug-induced lupus erythematosusDrug-induced lupus erythematosus
Drug-induced lupus erythematosus is an autoimmune disorder caused by chronic use of certain drugs. These drugs cause an autoimmune response producing symptoms similar to those of SLE...
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
Procainamide INN is a pharmaceutical antiarrhythmic agent used for the medical treatment of cardiac arrhythmias, classified by the Vaughan Williams classification system as class Ia.-History:...
, hydralazine
Hydralazine
Hydralazine is a direct-acting smooth muscle relaxant used to treat hypertension by acting as a vasodilator primarily in arteries and arterioles...
, quinidine
Quinidine
Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree.-Mechanism:...
, and phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
.
Non-SLE 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.Pathophysiology
One manifestation of SLE is abnormalities in apoptosisApoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, a type of programmed cell death in which aging or damaged cells are neatly disposed of as a part of normal growth or functioning.
Transmission
In SLE, the body's immune system produces antibodies against itself, particularly against proteins in the cell nucleus. SLE is triggered by environmental factors that are unknown."All the key components of the immune system are involved in the underlying mechanisms [of SLE]" according to Rahman, and SLE is the prototypical autoimmune disease. In order to preserve homeostasis, the immune system must balance between being sensitive enough to protect against infection, and becoming sensitized to attack the body's own proteins (autoimmunity). During an immune reaction to a foreign stimulus, such as bacteria, virus, or allergen, immune cells that would normally be deactivated due to their affinity for self tissues can be abnormally activated by signaling sequences of antigen-presenting cells. Thus triggers may include viruses, bacteria, allergens (both IgE
IGE
IGE was one of the largest services company buying and selling virtual currencies and accounts for MMORPG. During its peak time, it had offices in Los Angeles, China , and headquarters & customer service centre in Hong Kong. IGE was one of the main monopoly in virtual economy services, also known...
and hypersensitivity
Hypersensitivity
Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification...
), and can be aggravated by environmental stimulants such as ultraviolet light and certain drug reactions. These stimuli begin a reaction that leads to destruction
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
of other cells in the body and exposure of their DNA, histones, and other proteins, particularly parts of the cell nucleus. The body's sensitized B-lymphocyte cells will now produce antibodies against these nuclear-related proteins. These antibodies clump into antibody-protein complexes which stick to surfaces and damage blood vessels in critical areas of the body, such as the glomeruli of the kidney; these antibody attacks are the cause of SLE. Researchers are now identifying the individual genes, the proteins they produce, and their role in the immune system. Each protein is a link on the autoimmune chain, and researchers are trying to find drugs to break each of those links.
SLE is a chronic inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
disease believed to be a type III hypersensitivity response with potential type II involvement. Reticulate and stellate acral pigmentation should be considered a possible manifestation of SLE and high titers of anticardiolipin antibodies, or a consequence of therapy.
Abnormalities in apoptosis
- Apoptosis is increased in monocyteMonocyteMonocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
s and keratinocyteKeratinocyteKeratinocytes are the predominant cell type in the epidermis, the outermost layer of the human skin, constituting 95% of the cells found there. Those keratinocytes found in the basal layer of the skin are sometimes referred to as "basal cells" or "basal keratinocytes"...
s - ExpressionGene expressionGene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
of FasFAS ligandFas ligand is a type-II transmembrane protein that belongs to the tumor necrosis factor family. Its binding with its receptor induces apoptosis. Fas ligand/receptor interactions play an important role in the regulation of the immune system and the progression of cancer.- Structure :Fas ligand or...
by B cellB cellB cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
s and T cellT cellT cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s is increased - There are correlations between the apoptotic rates of lymphocytes and disease activity.
Tingible body macrophage
Tingible body macrophage
A Tingible body macrophage 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...
s (TBMs) – large phagocytic cells in the germinal center
Germinal center
Germinal centers are sites within lymph nodes where mature B lymphocytes rapidly proliferate, differentiate, mutate their antibodies , and class switch their antibodies during a normal immune response to an infection...
s of secondary lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
s – express CD68 protein. These cells normally engulf B cells that have undergone apoptosis after somatic hypermutation
Somatic hypermutation
Somatic hypermutation is a mechanism inside cells that is part of the way the immune system adapts to the new foreign elements that confront it . SHM diversifies the receptors used by the immune system to recognize foreign elements and allows the immune system to adapt its response to new threats...
. 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 cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
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 cells and make this material available for activating other B cells that may have randomly acquired self-specificity through somatic hypermutation
Somatic hypermutation
Somatic hypermutation is a mechanism inside cells that is part of the way the immune system adapts to the new foreign elements that confront it . SHM diversifies the receptors used by the immune system to recognize foreign elements and allows the immune system to adapt its response to new threats...
.
Clearance deficiency
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
. This includes deficient phagocytic activity and scant serum components in addition to increased apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
.
Monocytes isolated from whole blood
Whole blood
Whole blood is a term used in transfusion medicine for human blood from a standard blood donation. The blood is typically combined with an anticoagulant during the collection process, but is generally otherwise unprocessed...
of SLE sufferers show reduced expression of CD44 surface molecules involved in the uptake of apoptotic cells. Most of the monocytes and tingible body macrophages (TBMs), which are found in the germinal centres of lymph nodes, even show a definitely different morphology; they are smaller or scarce and die earlier. Serum components like complement
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
factors, CRP
C-reactive protein
C-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...
, and some glycoproteins are, furthermore, decisively important for an efficiently operating phagocytosis. With SLE, these components are often missing, diminished, or inefficient.
Recent research has found an association between certain lupus patients (especially those with lupus nephritis
Lupus nephritis
Lupus nephritis is an inflammation of the kidney caused by systemic lupus erythematosus , a disease of the immune system. Apart from the kidneys, SLE can also damage the skin, joints, nervous system and virtually any organ or system in the body....
) and an impairment in degrading neutrophil extracellular traps
Neutrophil extracellular traps
Neutrophil extracellular traps are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind pathogens....
(NETs). These were due to DNAse1
Deoxyribonuclease I
Deoxyribonuclease I , is an endonuclease coded by the human gene DNASE1.DNase I is a nuclease that cleaves DNA preferentially at phosphodiester linkages adjacent to a pyrimidine nucleotide, yielding 5'-phosphate-terminated polynucleotides with a free hydroxyl group on position 3', on average...
inhibiting factors, or NET protecting factors in patient 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
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
of the cells if this ability is disturbed. Necrotic cells release nuclear fragments as potential autoantigens, as well as internal danger signals, inducing maturation of dendritic cells (DCs), since they have lost their membranes' integrity. Increased appearance of apoptotic cells also simulates inefficient clearance. That leads to maturation of DCs and also to the presentation of intracellular antigens of late apoptotic or secondary necrotic cells, via MHC molecules.
Autoimmunity
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
possibly results by the extended exposure to nuclear and intracellular autoantigens derived from late apoptotic and secondary necrotic cells. B and T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
tolerance for apoptotic cells is abrogated, and the lymphocytes get activated by these autoantigens; inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and the production of autoantibodies by plasma cells is initiated. A clearance deficiency in the skin for apoptotic cells has also been observed in people with cutaneous lupus erythematosus (CLE).
Accumulation in germinal centers
In healthy conditions, apoptotic lymphocytes are removed in germinal centres 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, accumulationAccumulation
Accumulation may refer to:* Accumulation: None, a 2002 lo-fi album* Capital accumulation, the gathering of objects of value* Glacier ice accumulation, an element in the glacier mass balance formula...
of apoptotic debris
Debris
Debris is rubble, wreckage, ruins, litter and discarded garbage/refuse/trash, scattered remains of something destroyed, or, in geology, large rock fragments left by a melting glacier etc. The singular form of debris is debris...
can be observed in GC because of an ineffective clearance of apoptotic cells. In close proximity to TBM, follicular dendritic cells
Follicular dendritic cells
Follicular dendritic cells are cells of the immune system found in lymph follicles of secondary lymphoid organs and tertiary lymphoid organs. They are probably not of hematopoietic origin, though they look similar to true dendritic cells due to their filiform dendritic processes, but are of...
(FDC) are localised in GC, which attach antigen material to their surface and, in contrast to bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
-derived DC, neither take it up nor present it via MHC
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
molecules.
Autoreactive B cells can accidentally emerge during somatic hypermutation
Somatic hypermutation
Somatic hypermutation is a mechanism inside cells that is part of the way the immune system adapts to the new foreign elements that confront it . SHM diversifies the receptors used by the immune system to recognize foreign elements and allows the immune system to adapt its response to new threats...
and migrate into the GC 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
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
may be the consequence.
Anti-nRNP autoimmunity
Autoantibodies to nRNP A and nRNP C initially targeted restricted, prolineProline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
-rich motifs
Sequence motif
In genetics, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and has, or is conjectured to have, a biological significance...
. Antibody binding subsequently spread to other epitopes. The similarity and cross-reactivity
Cross-reactivity
Cross-reactivity is the reaction between an antibody and an antigen that differs from the immunogen. It is sometimes also referred to as crossimmunity or cross-protective immunity...
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 HMGB1HMGB1
High-mobility group protein B1, also known as high-mobility group protein 1 and amphoterin, is a protein that in humans is encoded by the HMGB1 gene.HMG-1 belongs to high mobility group.-Role in Inflammation:...
was found in the sera of patients and mice with systemic lupus erythematosus, high mobility group box 1 (HMGB1
HMGB1
High-mobility group protein B1, also known as high-mobility group protein 1 and amphoterin, is a protein that in humans is encoded by the HMGB1 gene.HMG-1 belongs to high mobility group.-Role in Inflammation:...
) is a nuclear
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
participating in chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
architecture
Architecture
Architecture is both the process and product of planning, designing and construction. Architectural works, in the material form of buildings, are often perceived as cultural and political symbols and as works of art...
and transcriptional regulation
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
. Recently, there is increasing evidence HMGB1 contributes to the pathogenesis of chronic
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and autoimmune diseases due to its proinflammatory and immunostimulatory properties.
Diagnosis
Laboratory tests
Antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologicSerology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...
testing for SLE. Several techniques are used to detect ANAs. Clinically the most widely used method is indirect immunofluorescence
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
. The pattern of fluorescence suggests the type of antibody present in the patient's serum.
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
LSm
In biology, LSm proteins are a family of RNA-binding proteins found in virtually every cellular organism. LSm is a contraction of 'like Sm', because the first identified members of the LSm protein family were the Sm proteins...
and anti-double stranded DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
(dsDNA) antibodies (which are linked to SLE) and anti-histone antibodies
Anti-histone antibodies
Anti-histone antibodies are autoantibodies that are found in 50%-70% of patients with systemic lupus erythematosus and in more than 95% of patients with drug-induced lupus erythematosus...
(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. The anti-dsDNA antibody titer
Titer
A titer 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 positive or negative. The titer corresponds to the highest dilution factor that still yields a positive...
s also tend to reflect disease activity, although not in all cases. Other ANA that may occur in SLE sufferers are anti-U1 RNP
U1 spliceosomal RNA
U1 spliceosomal RNA is the small nuclear RNA component of U1 snRNP , an RNA-protein complex that combines with other snRNPs, unmodified pre-mRNA, and various other proteins to assemble a spliceosome, a large RNA-protein molecular complex upon which splicing of pre-mRNA occurs...
(which also appears in systemic sclerosis), SS-A (or anti-Ro) and SS-B (or anti-La; both of which are more common in Sjögren's syndrome
Sjögren's syndrome
Sjögren's syndrome , also known as "Mikulicz disease" and "Sicca syndrome", is a systemic autoimmune disease in which immune cells attack and destroy the exocrine glands that produce tears and saliva....
). 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
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
levels (low levels suggest consumption by the immune system), electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
s and renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
(disturbed if the kidney is involved), liver enzymes, and complete blood count
Complete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
.
The lupus erythematosus (LE) cell test was commonly used for diagnosis, but it is no longer used because the LE cell
LE cell
An LE cell is a neutrophil or macrophage that has phagocytized the denatured nuclear material of another cell. The denatured material is seen as an LE body....
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 on the basis of the American College of RheumatologyAmerican College of Rheumatology
The American College of Rheumatology is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with arthritis and rheumatic and...
(ACR) classification criteria. The criteria, however, were established mainly for use in scientific research including use in randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
s which require higher confidence levels, so some people with SLE may not pass the full criteria.
Criteria
The American College of Rheumatology 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 patients for clinical studies, a person has SLE if any 4 out of 11 symptoms are present simultaneously or serially on two separate occasions.- Malar rashMalar rashIn medicine, malar rash , also called butterfly rash, is a medical sign consisting of a characteristic form of facial rash. It is often seen in Lupus erythematosus but is not pathognomonic - it is also seen in other diseases such as Pellagra, dermatomyositis and Bloom Syndrome.The malar rash of...
(rash on cheeks); sensitivitySensitivity and specificitySensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
= 57%; specificitySensitivity and specificitySensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
= 96%. - Discoid rash (red, scaly patches on skin that cause scarring); sensitivity = 18%; specificity = 99%.
- Serositis: PleurisyPleurisyPleurisy is an inflammation of the pleura, the lining of the pleural cavity surrounding the lungs. Among other things, infections are the most common cause of pleurisy....
(inflammation of the membrane around the lungs) or pericarditisPericarditisPericarditis is an inflammation of the pericardium . A characteristic chest pain is often present.The causes of pericarditis are varied, including viral infections of the pericardium, idiopathic causes, uremic pericarditis, bacterial infections of the precardium Pericarditis is an inflammation of...
(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%.
- ArthritisArthritisArthritis is a form of joint disorder that involves inflammation of one or more joints....
: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion; sensitivity = 86%; specificity = 37%. - PhotosensitivityPhotodermatitisPhotodermatitis, sometimes referred to as "sun poisoning" or photoallergy is a form of allergic contact dermatitis in which the allergen must be activated by light to sensitize the allergic response, and to cause a rash or other systemic effects on subsequent exposure...
(exposure to ultraviolet light causes rash, or other symptoms of SLE flareups); sensitivity = 43%; specificity = 96%. - Blood—hematologic disorder—hemolytic anemiaHemolytic anemiaHemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
(low red blood cellRed blood cellRed blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
count) or leukopeniaLeukopeniaLeukopenia is a decrease in the number of white blood cells found in the blood, which places individuals at increased risk of infection....
(white blood cell count<4000/µl), lymphopenia (<1500/µl) or thrombocytopeniaThrombocytopeniaThrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
(<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 urineProteinuriaProteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
or cellular castsUrinary castsUrinary casts are cylindrical structures produced by the kidney and present in the urine in certain disease states. They form in the distal convoluted tubule and collecting ducts of nephrons, then dislodge and pass into the urine, where they can be detected by microscopy.They form via precipitation...
seen in urine under a microscope; sensitivity = 51%; specificity = 94%. - Antinuclear antibody test positive; sensitivity = 99%; specificity = 49%.
- Immunologic disorder: Positive anti-Smith, anti-ds DNA, antiphospholipid antibodyAntiphospholipid syndromeAntiphospholipid syndrome or antiphospholipid antibody syndrome , often also Hughes syndrome, is an autoimmune, hypercoagulable state caused by antibodies against cell-membrane phospholipids that provokes blood clots in both arteries and veins as well as pregnancy-related complications such as...
, and/or false positive serologicalSerologySerology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...
test for syphilisSyphilisSyphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...
; sensitivity = 85%; specificity = 93%. Presence of anti-ss DNA in 70% of cases (though also positive with rheumatic disease and healthy persons). - Neurologic disorder: SeizureSeizureAn epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s or psychosisPsychosisPsychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
; sensitivity = 20%; specificity = 98%.
Criteria for individual diagnosis
Some people, especially those with antiphospholipid syndromeAntiphospholipid syndrome
Antiphospholipid syndrome or antiphospholipid antibody syndrome , often also Hughes syndrome, is an autoimmune, hypercoagulable state caused by antibodies against cell-membrane phospholipids that provokes blood clots in both arteries and veins as well as pregnancy-related complications such as...
, 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
Recursive partitioning is a statistical method for multivariable analysis. Recursive partitioning creates a decision tree that strives to correctly classify members of the population based on several dichotomous dependent variables....
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 rashMalar rashIn medicine, malar rash , also called butterfly rash, is a medical sign consisting of a characteristic form of facial rash. It is often seen in Lupus erythematosus but is not pathognomonic - it is also seen in other diseases such as Pellagra, dermatomyositis and Bloom Syndrome.The malar rash of...
. 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.
Prevention
SLE is not understood well enough to be prevented, but, when the disease develops, quality of life can be improved through flare prevention. The warning signs of an impending flare include increased fatigue, pain, rash, fever, abdominal discomfort, headache, and dizziness. Early recognition of warning signs and good communication with a doctor can help individuals remain active, experience less pain, and reduce medical visits.As longevity of people with SLE increases, the likelihood of complication
Complication (medicine)
Complication, in medicine, is an unfavorable evolution of a disease, a health condition or a medical treatment. The disease can become worse in its severity or show a higher number of signs, symptoms or new pathological changes, become widespread throughout the body or affect other organ systems. A...
s also increases in four areas: cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
, infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s, osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
, and cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. Standard preventive measures, screening for related diseases may be necessary to deal with the increased risks due to the side effects of medications. Extra vigilance is considered warranted in particular for cancers affecting the immune system.
Treatment
The treatment of SLE involves preventing flares and reducing their severity and duration when they occur.Treatment can include corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s and anti-malarial drugs. Certain types of lupus nephritis such as diffuse proliferative glomerulonephritis require bouts of cytotoxic drugs. These drugs include cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
and mycophenolate.
Hydroxychloroquine
Hydroxychloroquine
Hydroxychloroquine is an antimalarial drug, sold under the trade names Plaquenil,Axemal, Dolquine, and Quensyl, also used to reduce inflammation in the treatment of rheumatoid arthritis and lupus...
(HCQ) was the last medication approved by the FDA 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 Benlysta (belimumab) as a treatment for the pain and flare-ups common in lupus. The drug was approved by the FDA in March 2011.
Medications
Due to the variety of symptoms and organ system involvement with SLE, its severity in an individual must be assessed in order to successfully treat SLE. Mild or remittent disease may, sometimes, be safely left untreated. If required, nonsteroidal anti-inflammatory drugs and antimalarialsMalaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
may be used. Medications such as Prednisone, Cellcept and Prograf have been used in the past. A number of potential treatments are in clinical trials.
Disease-modifying antirheumatic drugs
Disease-modifying antirheumatic drugDisease-modifying antirheumatic drug
Disease-modifying antirheumatic drugs is a category of otherwise unrelated drugs defined by their use in rheumatoid arthritis to slow down disease progression...
s (DMARDs) are used preventively to reduce the incidence of flares, the process of the disease, and lower the need for steroid use; when flares occur, they are treated with corticosteroids. DMARDs commonly in use are antimalarials such as plaquenil and immunosuppressants (e.g. methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
and azathioprine
Azathioprine
Azathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
). Hydroxychloroquine
Hydroxychloroquine
Hydroxychloroquine is an antimalarial drug, sold under the trade names Plaquenil,Axemal, Dolquine, and Quensyl, also used to reduce inflammation in the treatment of rheumatoid arthritis and lupus...
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
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
is used for severe glomerulonephritis
Glomerulonephritis
Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys...
or other organ-damaging complications. Mycophenolic acid
Mycophenolic acid
Mycophenolic acid INN or mycophenolate is an immunosuppressant drug used to prevent rejection in organ transplantation. It inhibits an enzyme needed for the growth of T cells and B cells. It was initially marketed as the prodrug mycophenolate mofetil to improve oral bioavailability. More...
is also used for treatment of lupus nephritis, but it is not FDA-approved for this indication, and FDA is investigating reports that it may be associated with birth defects when used by pregnant women.
Immunosuppressive drugs
In more severe cases, medications that modulate the immune system (primarily corticosteroids and immunosuppressantsImmunosuppressive drug
Immunosuppressive drugs or immunosuppressive agents are drugs that inhibit or prevent activity of the immune system. They are used in immunosuppressive therapy to:...
) 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
Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...
, symptoms of which may include obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
, puffy round face, diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
, increased appetite, difficulty sleeping and osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
. 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
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
and cataracts.
Numerous new immunosuppressive drugs are being actively tested for SLE. Rather than suppressing the immune system nonspecifically, as corticosteroids do, they target the responses of individual [types of] immune cells. Some of these drugs are already FDA-approved for treatment of rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
. See also Belimumab
Belimumab
Belimumab is a fully human monoclonal antibody that inhibits B-lymphocyte stimulator , also known as B cell activation factor of the TNF family...
and Atacicept
Atacicept
Atacicept is a recombinant fusion protein designed to inhibit B cells, thereby suppressing autoimmune disease. The designer protein combines the binding site for two cytokines that regulate maturation, function, and survival of B cells, B-lymphocyte stimulator and a proliferation-inducing ligand ,...
. Lupuzor has given encouraging results in a phase IIb trial
Analgesia
Since a large percentage of people with SLE suffer from varying amounts of chronic painChronic pain
Chronic pain has several different meanings in medicine. Traditionally, the distinction between acute and chronic pain has relied upon an arbitrary interval of time from onset; the two most commonly used markers being 3 months and 6 months since the initiation of pain, though some theorists and...
, stronger prescription analgesics (pain killers) may be used if over-the-counter drugs (mainly nonsteroidal anti-inflammatory drugs) do not provide effective relief. Potent NSAIDs such as indomethacin and diclofenac are relatively contraindicated for patients with SLE because they increase the risk of kidney failure and heart failure.
Moderate pain is typically treated with mild prescription opiates such as dextropropoxyphene
Dextropropoxyphene
Dextropropoxyphene, manufactured by Eli Lilly and Company, is an analgesic in the opioid category. It is intended to treat mild pain and has, in addition, anti-tussive and local anesthetic effects. It has been taken off the market in Europe and the US due to concerns of fatal overdoses and...
and co-codamol
Co-codamol
Co-codamol is a non-proprietary name used to denote a compound analgesic, a combination of codeine phosphate and paracetamol . Co-codamol Co-codamol (BAN) is a non-proprietary name used to denote a compound analgesic, a combination of codeine phosphate and paracetamol (acetaminophen). Co-codamol...
. Moderate to severe chronic pain is treated with stronger opioids, such as hydrocodone
Hydrocodone
Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from either of two naturally occurring opiates: codeine and thebaine. It is an orally active narcotic analgesic and antitussive...
or longer-acting continuous-release opioids, such as oxycodone
Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
, MS Contin
MS Contin
MS Contin is a brand of a time-released formulation of morphine sulfate, usually taken every twelve hours for chronic pain. MS Contin is a trademark of Purdue Pharma....
, or methadone
Methadone
Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...
. The fentanyl duragesic transdermal patch is also a widely-used treatment option for the chronic pain caused by complications because of its long-acting timed release and ease of use. 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 immunoglobulinIntravenous immunoglobulin
Intravenous immunoglobulin is a blood product administered intravenously. It contains the pooled IgG extracted from the plasma of over one thousand blood donors. IVIG's effects last between 2 weeks and 3 months...
s may be used to control SLE with organ involvement, or vasculitis
Vasculitis
Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...
. It is believed that they reduce antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
production or promote the clearance of immune complex
Immune complex
An immune complex is formed from the integral binding of an antibody to a soluble antigen. The bound antigen acting as a specific epitope, bound to an antibody is referred to as a singular immune complex....
es from the body, even though their mechanism of action
Mechanism of action
In pharmacology, the term mechanism of action refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect...
is not well-understood. Unlike immunosuppressives and corticosteroids, IVIGs do not suppress the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
, so there is less risk of serious infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s with these drugs.
Lifestyle changes
Avoiding sunlight is the primary change to the lifestyle of SLE sufferers, as sunlight is known to exacerbate the disease, as is the debilitating effect of intense fatigue. These two problems can lead to patients 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, pesticidePesticide
Pesticides are substances or mixture of substances intended for preventing, destroying, repelling or mitigating any pest.A pesticide may be a chemical unicycle, biological agent , antimicrobial, disinfectant or device used against any pest...
s and mercury
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...
can also make the disease worsen.
Renal transplantation
Renal transplants are the treatment of choice for end-stage renal disease, which is one of the complications of lupus nephritisLupus nephritis
Lupus nephritis is an inflammation of the kidney caused by systemic lupus erythematosus , a disease of the immune system. Apart from the kidneys, SLE can also damage the skin, joints, nervous system and virtually any organ or system in the body....
, but the recurrence of the full disease is common in up to 30% of patients.
Antiphospholipid syndrome
Antiphospholipid syndromeAntiphospholipid syndrome
Antiphospholipid syndrome or antiphospholipid antibody syndrome , often also Hughes syndrome, is an autoimmune, hypercoagulable state caused by antibodies against cell-membrane phospholipids that provokes blood clots in both arteries and veins as well as pregnancy-related complications such as...
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 blood stream. If the thromboses migrate to the brain, they can potentially cause a stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
by blocking the blood supply to the brain.
If this disorder is suspected in patients, 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 patients requires anticoagulation. Often, low-dose aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
is prescribed for this purpose, although for cases involving thrombosis anticoagulants such as warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
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 is rare, but identification of mothers at highest risk for complications allows for prompt treatment before or after birth. In addition, SLE can flare up during pregnancy, and proper treatment can maintain the health of the mother longer. Women pregnant and known to have anti-Ro (SSA) or anti-La antibodies (SSB) often have echocardiograms during the 16th and 30th weeks of pregnancy to monitor the health of the heart and surrounding vasculature.Contraception
Contraception
Contraception is the prevention of the fusion of gametes during or after sexual activity. The term contraception is a contraction of contra, which means against, and the word conception, meaning fertilization...
and other reliable forms of pregnancy prevention is routinely advised for women with SLE, since getting pregnant during active disease was found to be harmful. Lupus nephritis
Lupus nephritis
Lupus nephritis is an inflammation of the kidney caused by systemic lupus erythematosus , a disease of the immune system. Apart from the kidneys, SLE can also damage the skin, joints, nervous system and virtually any organ or system in the body....
was the most common manifestation.
Prognosis
SLE is considered incurable, but highly treatable.In the 1950s, most people diagnosed with SLE lived fewer than five years. Advances in diagnosis and treatment have improved survival to the point where over 90% now survive for more than ten years, and many can live relatively asymptomatically. (It is important to note that "ten years" in this statistic does not indicate an average survival rate, but is merely the length of the referenced study. According to the Lupus Foundation of America, "the majority of people with lupus today can expect to live a normal lifespan.")
Prognosis is normally 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 modified 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 diseases acquired from corticosteroid therapy, the leading cause of death for people with SLE.
To reduce 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. High serum creatinine, hypertension, nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
, anemia and hypoalbuminemia are poor prognostic factors.
The ANA is the most sensitive screening test for evaluation, whereas anti-Sm (anti-Smith) is the most specific. The dsDNA (double-stranded DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
) antibody is also fairly specific and often fluctuates with disease activity; as such, the dsDNA titre is sometimes useful to monitor disease flares or response to treatment.
Epidemiology
The rate of SLE varies considerably between countries, ethnicity, gender, and changes over time. In the United States the prevalencePrevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
of SLE is estimated to be about 53 per 100,000, translating to about 159,000 out of 300 million people in the US being affected. 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.
SLE, like many autoimmune diseases, affects females more frequently than males, at a rate of almost 9 to 1.
The incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
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 to increasing frequency of the disease is unknown.
Etymology
There are several explanations ventured for the term lupus erythematosus. Lupus is LatinLatin
Latin is an Italic language originally spoken in Latium and Ancient Rome. It, along with most European languages, is a descendant of the ancient Proto-Indo-European language. Although it is considered a dead language, a number of scholars and members of the Christian clergy speak it fluently, and...
for wolf, and "erythro" is derived from , Greek for "red." All explanations originate with the reddish, butterfly-shaped malar rash
Malar rash
In medicine, malar rash , also called butterfly rash, is a medical sign consisting of a characteristic form of facial rash. It is often seen in Lupus erythematosus but is not pathognomonic - it is also seen in other diseases such as Pellagra, dermatomyositis and Bloom Syndrome.The malar rash of...
that the disease classically exhibits across the nose and cheeks.
- In various accounts, some doctors thought the rash resembled the pattern of fur on a wolf's face.
- In other accounts, doctors thought that the rash, which was often more severe in earlier centuries, created lesions that resembled wolf bites or scratches.
- Another account claims that the term "lupus" did not come from Latin directly, but from the term for a French style of mask that women reportedly wore to conceal the rash on their faces. The mask is called a "loup," French for "wolf."
History
The history of SLE can be divided into three periods: classical, neoclassical, and modern. The classical period began when the disease was first recognized in the Middle AgesMiddle Ages
The Middle Ages is a periodization of European history from the 5th century to the 15th century. The Middle Ages follows the fall of the Western Roman Empire in 476 and precedes the Early Modern Era. It is the middle period of a three-period division of Western history: Classic, Medieval and Modern...
and saw the description of the dermatological manifestation of the disorder. The term lupus is attributed to 12th-century physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
Rogerius
Rogerius (physician)
Rogerius , also called Rogerius Salernitanus, Roger Frugard, Roger Frugardi, Roggerio Frugardo, Rüdiger Frutgard and Roggerio dei Frugardi, was a Salernitan surgeon who wrote a work on medicine entitled Practica Chirurgiae around 1180...
, who used it to describe the classic malar rash. The neoclassical period was heralded by Móric Kaposi
Móric Kaposi
Moritz Kaposi was a Hungarian physician and dermatologist who discovered the skin tumor that received his name .-Early life and name:...
's recognition in 1872 of the systemic manifestations of the disease. The modern period began in 1948 with the discovery of the LE cell (the lupus erythematosus cell—a misnomer, as it occurs with other diseases as well) and is characterised by advances in our knowledge of the pathophysiology and clinical-laboratory features of the disease, as well as advances in treatment.
Medical historians have theorized that people with porphyria
Porphyria
Porphyrias are a group of inherited or acquired disorders of certain enzymes in the heme bio-synthetic pathway . They are broadly classified as acute porphyrias and cutaneous porphyrias, based on the site of the overproduction and accumulation of the porphyrins...
(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
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
was first reported as an effective therapy. Four years later, the use of salicylate
Salicylic acid
Salicylic acid is a monohydroxybenzoic acid, a type of phenolic acid and a beta hydroxy acid. This colorless crystalline organic acid is widely used in organic synthesis and functions as a plant hormone. It is derived from the metabolism of salicin...
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
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s in the treatment of SLE.
Notable cases
- Michael JacksonMichael JacksonMichael Joseph Jackson was an American recording artist, entertainer, and businessman. Referred to as the King of Pop, or by his initials MJ, Jackson is recognized as the most successful entertainer of all time by Guinness World Records...
suffered from both SLE and vitiligoVitiligoVitiligo is a condition that causes depigmentation of sections of skin. It occurs when melanocytes, the cells responsible for skin pigmentation, die or are unable to function. The cause of vitiligo is unknown, but research suggests that it may arise from autoimmune, genetic, oxidative stress,...
. Diagnosed in 1986, and confirmed by his dermatologist, Dr. Arnold Klein, who presented legal documents during court depositions. - Lady GagaLady GaGaStefani Joanne Angelina Germanotta , better known by her stage name Lady Gaga, is an American singer and songwriter. Born and raised in New York City, she primarily studied at the Convent of the Sacred Heart and briefly attended New York University's Tisch School of the Arts before withdrawing to...
has been tested borderline positive for SLE, however she claims not to be affected by the symptoms yet. The revelations caused considerable dismay amongst her fans, leading to Gaga herself addressing the matter in an interview with Larry King, saying she hopes to avoid symptoms by maintaining a healthy lifestyle. - Louisa May AlcottLouisa May AlcottLouisa May Alcott was an American novelist. She is best known for the novel Little Women and its sequels Little Men and Jo's Boys. Little Women was set in the Alcott family home, Orchard House in Concord, Massachusetts, and published in 1868...
, American author best known for her novel Little WomenLittle WomenLittle Women is a novel by American author Louisa May Alcott . The book was written and set in the Alcott family home, Orchard House, in Concord, Massachusetts. It was published in two volumes in 1868 and 1869...
, has been suggested to have had SLE. - Inday BaInday BaInday Ba , also known as N'Deaye Ba, was a Swedish-British film, stage, and television actress born in Gothenburg, Sweden....
(also known as N'Deaye Ba), a Swedish-born actress who died from SLE complications at age 32. - Donald ByrneDonald ByrneDonald Byrne was one of the USA's strongest chess players during the 1950s and 1960s.Born in New York City, he won the U.S. Open Chess Championship in 1953, was awarded the International Master title by FIDE in 1962, and played for or captained five U.S. Chess Olympiad teams between 1962 and 1972...
, American chessChessChess is a two-player board game played on a chessboard, a square-checkered board with 64 squares arranged in an eight-by-eight grid. It is one of the world's most popular games, played by millions of people worldwide at home, in clubs, online, by correspondence, and in tournaments.Each player...
player who died from SLE complications in 1976. - Caroline Dorough-Cochran, sister of Howie D.Howie DoroughHoward Dwaine "Howie D." Dorough is an American singer-songwriter, dancer, musician, entertainer, actor and member of American music group Backstreet Boys-Biography:...
of the Backstreet BoysBackstreet BoysThe Backstreet Boys are an American vocal group, formed in Orlando, Florida in 1993. The band originally consisted of A. J. McLean, Howie Dorough, Brian Littrell, Nick Carter and Kevin Richardson. They rose to fame with their debut international album, Backstreet Boys...
, died of SLE complications. He founded the Dorough Lupus Foundation in her memory. - J DillaJ DillaJames Dewitt Yancey , better known by the stage names J Dilla and Jay Dee, was an American record producer who emerged from the mid-1990s underground hip hop scene in Detroit, Michigan...
(also known as Jay Dee), a hip-hop producer and beat maker who died of SLE complications in 2006. - Lauren Shuler DonnerLauren Shuler DonnerLauren Shuler Donner is an American film producer who specializes in mainstream youth and family-oriented entertainment.-Early life and career:...
, American movie producer. - Hugh GaitskellHugh GaitskellHugh Todd Naylor Gaitskell CBE was a British Labour politician, who held Cabinet office in Clement Attlee's governments, and was the Leader of the Labour Party and Leader of the Opposition from 1955, until his death in 1963.-Early life:He was born in Kensington, London, the third and youngest...
, British politician who died of SLE complications in 1963 aged 56. - SealSeal (musician)Seal Henry Olusegun Olumide Adeola Samuel , known simply as Seal, is a British soul and R&B singer-songwriter, of Nigerian and Brazilian background. Seal has won numerous music awards throughout his career, including three Brit Awards—winning Best British Male in 1992, four Grammy Awards, and an...
, British musician (discoid lupus) - Sophie HowardSophie HowardSophie Howard is an English glamour model from Southport, England. She appears regularly on Page Three and in men's magazines, such as Maxim, Nuts and Loaded. In August 2005, Howard was voted 73rd in the FHM UK "100 Sexiest Women" poll. In the 2006 poll, she rose to 68th place.- Biography :Howard...
, British glamour model - Teddi KingTeddi KingTeddi King was an American jazz and pop vocalist. Born Theodora King in Boston, Massachusetts on September 18, 1929, she won a singing competition hosted by Dinah Shore at Boston's Tributary Theatre, later beginning work in a touring revue involved with "cheering up the military in the lull...
, American singer, died of SLE complications in 1977. - Charles KuraltCharles KuraltCharles Kuralt was an American journalist. He was most widely known for his long career with CBS, first for his "On the Road" segments on The CBS Evening News with Walter Cronkite, and later as the first anchor of CBS News Sunday Morning, a position he held for fifteen years.Kuralt's "On the Road"...
, former anchor of CBS Sunday Morning, died of SLE complications in 1997. - Ferdinand MarcosFerdinand MarcosFerdinand Emmanuel Edralin Marcos, Sr. was a Filipino leader and an authoritarian President of the Philippines from 1965 to 1986. He was a lawyer, member of the Philippine House of Representatives and a member of the Philippine Senate...
, former Philippine president, died of SLE complications in 1989. - Mary Elizabeth McDonoughMary Elizabeth McDonoughMary Elizabeth McDonough is an American actress , best known for her role as "Erin Walton" in the series The Waltons. In 1988 she married Rob Wickstrom, with whom she had a daughter Sydnee. The couple divorced in 1996. She has Lupus erythematosus, which she blames on leaking silicone breast implants...
, American actress; blames her SLE on leaky silicone breast implants. - Flannery O'ConnorFlannery O'ConnorMary Flannery O'Connor was an American novelist, short-story writer and essayist. An important voice in American literature, O'Connor wrote two novels and 32 short stories, as well as a number of reviews and commentaries...
, American fiction writer who died of SLE complications in 1964. - Elaine PaigeElaine PaigeElaine Paige OBE is an English singer and actress best known for her work in musical theatre. Raised in Barnet, North London, Paige attended the Aida Foster stage school, making her first professional appearance on stage in 1964, at the age of 16...
, British actress and singer - Tim RainesTim RainesTimothy Raines , nicknamed "Rock", is a former American professional baseball player. He played as a left fielder in Major League Baseball for six teams from 1979 to 2002 and was best known for his 13 seasons with the Montreal Expos...
, former major league baseball player - Mercedes Scelba-ShorteMercedes Scelba-ShorteMercedes Yvette Scelba-Shorte, also known as Mercedes Yvette, , is an American fashion model and actress. She was a contestant and finalist on Cycle 2 of America's Next Top Model...
, America's Next Top ModelAmerica's Next Top ModelAmerica's Next Top Model is a reality television show in which a number of women compete for the title of America's Next Top Model and a chance to start their career in the modeling industry....
Season Two runner-up and model. - Ray WalstonRay WalstonRay Walston was an American stage, television and film actor best known as the title character on the 1960s situation comedy My Favorite Martian. In addition, he is also remembered for his roles as Luther Billis in South Pacific , Mr. Applegate in Damn Yankees , J.J...
, character actor who died of SLE complications in 2001 after a six-year battle with the disease. - Michael WayneMichael WayneMichael Anthony Morrison was an American film producer and actor, and the eldest son of legendary Hollywood actor John Wayne and his first wife, Josephine Alicia Saenz.-Biography:...
, Hollywood director, and producer, part owner of Batjac ProductionsBatjac ProductionsBatjac Productions is an independent film production company founded by John Wayne in the early 1950s as a vehicle for Wayne to produce as well as star in movies. Its first release was Big Jim McLain with Warner Brothers in 1952, and its final film was also with Warner Brothers, McQ, in 1974...
, son of legendary actor John WayneJohn WayneMarion Mitchell Morrison , better known by his stage name John Wayne, was an American film actor, director and producer. He epitomized rugged masculinity and became an enduring American icon. He is famous for his distinctive calm voice, walk, and height...
, died of heart failure resulting from SLE complications in 2003. - Kéllé BryanKéllé BryanKéllé Bryan is a British singer turned actress and television personality, best known as a member of the girl group Eternal.-Biography:...
, member of 90s British pop group EternalEternal (band)Eternal were an English R&B girl group formed in 1992. The group featured two sisters Easther and Vernie Bennett, alongside Kelle Bryan and Louise Nurding...
, became ill with lupus in 1999. - Toni BraxtonToni BraxtonToni Michelle Braxton is an American R&B singer-songwriter, record producer, and actress. Braxton has won six Grammy Awards, seven American Music Awards, and five Billboard Music Awards and has sold over 60 million records worldwide...
, American R&B singer, songwriter and actress.
Research
Since lupus is considered to be currently incurable, current research is being geared towards finding a possible cause, a cure, and more effective treatment plans to extend and increase the quality of life for lupus patients.Several papers discuss the importance of the presence of antibodies in the brain that are only produced in patients with lupus. One such paper highlights the inhibition of astrocyte proliferation in brain tissue from lupus patient serum. Astrocytes are glial cells in the brain that participate in the support of cells that form the blood brain barrier. They are extremely useful in that they provide a nutritional balance between ions in the brain, keeping it at a normal level. In this study, researchers used immunofluorescence to track the antibodies near the corpus callosum
Corpus callosum
The corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication...
to determine whether anticardiolipin antibodies have an inhibitory effect on brain cells and whether they elicit thrombus formation in brain vessels, which plays a part in neuropsychiatric lupus.
However, the majority of the recent papers focus on the effect of lupus on blood-brain barrier integrity. It was found that 20–70% of lupus patients with neurological symptoms have some form of a central nervous system involvement. This can be determined using various imaging methods as well as lumbar puncture (spinal tap) to assess cerebrospinal fluid.
In a study conducted in London, researchers measured the albumin content in the brain using imaging and spinal fluid. The images were used to illustrate blood brain barrier damage while the spinal tap was used to measure the protein content in the brain. Albumin is a protein that can be carried into the brain through the blood brain barrier by other transport proteins. If the ratio of albumin outside the barrier to inside the barrier is high, this means that either the barrier is damaged, or the transport proteins are not functioning well. This blood brain barrier damage can impact lupus patients by increasing their discomfort and increasing the intensity of the disease.
A study called BLISS-76 tested the drug, Belimumab (HGS1006, LymphoStat-B ), a fully human monoclonal anti-BLyS antibody. BLyS stimulates and extends the life of B lymphocytes, which produce antibodies against foreign and self cells. The drug, branded Benlysta, was approved by the FDA in March 2011. Notwithstanding the approval, the FDA emphasized that the drug will not work in all cases, and that more research and advanced therapies are called for.
At Stanford School of Medicine Institute for Immunity Transplantation and Infection, trials are underway for use of DHEA as a therapeutic agent for the treatment of mild to moderate SLE.