Lupus is defined in Taber's Cyclopedic Medical Dictionary as 'originally any chronic, progressive, usually ulcerating, skin disease. In current usage when the word is used alone, it has no precise meaning' (Taber, 1273). This definition tends to underscore the enigma that is lupus, especially considering the simple definition provides eight different forms of lupus following it.
When the term 'lupus' is used on House, it is almost always referring to systemic lupus erythematosus, or SLE. This disease has acute episodes that is characterized as a chronic autoimmune disease that involves multiple organ systems.
Systemic lupus erythematosus, often abbreviated as SLE or lupus, is a systemic autoimmune disease (or autoimmune connective tissue disease) in which the body’s immune system mistakenly attacks healthy tissue. There are many kinds of lupus. The most common type is systemic lupus erythematosus (SLE), which affects many internal organs in the body. SLE most often harms the heart, joints, skin,lungs, blood vessels, liver, kidneys, and nervous system. The course of the disease is unpredictable, with periods of illness (called flare-ups) alternating with remissions.
The cause is believed to be an environmental trigger, which results in a misdirected immune response in people who are genetically susceptible. A normal immune system makes proteins called antibodies that protect against pathogens such as viruses and bacteria. Lupus is characterized by the presence of antibodies against a person's own proteins; these are most commonly anti-nuclear antibodies, which are found in nearly all cases. These antibodies lead to inflammation.
There is no cure for SLE. It is mainly treated with immunosuppressants such as cyclophosphamide and steroids, the goal of which is to keep symptoms under control. SLE can be fatal. The leading cause of death is from cardiovascular disease due to accelerated atherosclerosis. Life expectancy has improved over the decades. The 10-year survival rate is 92–95% and is close to that of people without lupus. This is due in part to better treatments, but also to identification of milder cases.
Global rates of disease varies from 20 to 70 per 100,000. The disease occurs nine times more often in women than in men, especially in women of child-bearing years (ages 15 to 35). It is also more common in those of African-American or Caribbean descent. Rates of disease in the developing world are unclear. Childhood systemic lupus erythematosus generally presents between the ages of 3 and 15, with girls outnumbering boys 4:1, and typical skin manifestations being a butterfly-shaped rash on the face, and photosensitivity. Lupus is Latin for wolf. In the 18th century, when lupus was just starting to be recognized as a disease, it was thought that it was caused by a wolf's bite. This may have been because of the distinctive malar rash characteristic of lupus. (Once full-blown, the round, disk-shaped rashes heal from the inside out, leaving a bite-like imprint.)
- 1 Signs and symptoms
- 2 Causes
- 3 Pathophysiology
- 4 Diagnosis
- 5 Treatment
- 6 Prognosis
- 7 Epidemiology
- 8 History
- 9 Research
- 10 Notable cases
- 11 On the Series
Signs and symptoms
SLE is one of several diseases known as "the great imitators" 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 having unexplained symptoms of untreated SLE for years. Common initial and chronic complaints include fever, malaise, joint pains, muscle pains, and fatigue. Because these symptoms are so often seen in association with other diseases, these signs and symptoms are not part of the diagnostic criteria for SLE. When occurring in conjunction with other signs and symptoms (see below), however, they are considered suggestive.
As many as 70% of people with lupus have some dermatological symptoms. The three main categories of lesions are chronic cutaneous (discoid) lupus, subacute cutaneous lupus, and acute cutaneous lupus. People with discoid lupus may exhibit thick, red scaly patches on the skin. Similarly, subacute cutaneous lupus manifests as red, scaly patches of skin but with distinct edges. Acute cutaneous lupus manifests as a rash. Some have the classic malar rash (or butterfly rash) associated with the disease. This rash occurs in 30 to 60% of cases.
Hair loss, mouth, nasal, urinary tract, and vaginal ulcers, and lesions on the skin are other possible manifestations. Tiny tears in the delicate tissue around the eyes can occur after even minimal rubbing.
Muscles and bones
The most common reason lupus patients seek 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.
People with SLE 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 fractures in relatively young women.
Anemia is common in children with SLE and develops in about 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 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.
A person with SLE may have inflammation of various parts of the heart, such as inflammation of the pericardium, heart muscle, and inner lining of the heart. The endocarditis of SLE is chracteristically 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.
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.
Painless passage of blood or protein in the urine may often be the only presenting sign of kidney involvement. Acute or chronic renal impairment may develop with lupus nephritis, leading to acute or end-stage kidney 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 syndromes can result when SLE affects the central or peripheral nervous systems. 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 delirium, Guillain-Barré syndrome, aseptic meningitis, autonomic neuropathy, demyelinating syndrome, mononeuropathy (which might manifest as mononeuritis multiplex), movement disorder (more specifically, chorea), myasthenia gravis, myelopathy, cranial neuropathy and plexopathy.
Neural symptoms contribute to a significant percentage of morbidity and mortality in people with lupus. As a result, the neural side of lupus is being studied in hopes of reducing morbidity and mortality rates. The neural manifestation of lupus is known as neuropsychiatric systemic 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, clinical depression, seizures, cognitive dysfunction, mood disorder, cerebrovascular disease, polyneuropathy, anxiety disorder, psychosis, and in some extreme cases,personality disorders.
SLE causes an increased rate of fetal death in utero and miscarriage. The overall live-birth rate in people with SLE has been estimated to be 72%. Pregnancy outcome appears to be worse in people with SLE whose disease flares up during pregnancy.
Neonatal lupus 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 enlargement of the liver and spleen. Neonatal lupus is usually benign and self-limited.
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 lack of social support.
SLE is presumably caused by an unknown environmental trigger, acting on persons with genetic susceptibility and defects in the immune system.
SLE is associated with defects in apoptotic clearance, and the pathogenic effect of apoptotic debris. Early apoptotic cells express “eat-me” signals, of cell-surface proteins such as phosphatidylserine, that prompt immune cells to engulf them. Apoptotic cells also express “find-me” signals, to attract macrophages and dendritic cells. When apoptotic material is not removed correctly by phagocytes, they are captured instead by antigen-presenting cells, which leads to development of antinuclear antibodies.
People with SLE have intense polyclonal B-cell activation, with a population shift towards immature B cells. Memory B cells with increased CD27+/IgD- are less susceptible to immunosuppression. CD27-/IgD- memory B cells are associated with increased disease activity and renal lupus. T cells, which regulate B-cell responses and infiltrate target tissues, have defects in signaling, adhesion, co-stimulation, gene transcription, and alternative splicing. The cytokines B-lymphocyte stimulator (BLys), interleukin 6, interleukin 17. interleukin 18, type I interferons, and tumor necrosis factor α (TNFα) are involved in the inflammatory process and are potential therapeutic targets.
The first mechanism may arise genetically. Research indicates SLE may have a genetic 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. HLA class I, class II, and class III genes 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.
Drug-induced lupus erythematosus is a (generally) reversible condition that usually occurs in people being treated for a long-term illness.
Drug-induced lupus mimics SLE. However, symptoms of drug-induced lupus generally disappear once the medication that triggered the episode is stopped. More than 38 medications can cause this condition, the most common of which are procainamide, isoniazid, hydralazine, quinidine, and phenytoin.
Non-systemic forms of lupus
Discoid (cutaneous) lupus is limited to skin symptoms and is diagnosed by biopsy of rash on the face, neck, scalp or arms. Approximately 5% of people with DLE progress to SLE.
One manifestation of SLE is abnormalities in apoptosis, a type of programmed cell death in which aging or damaged cells are neatly disposed of as a part of normal growth or functioning. 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.
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, (IgE and other hypersensitivity), and can be aggravated by environmental stimulants such as ultraviolet light and certain drug reactions. These stimuli begin a reaction that leads to destruction of other cells in the body and exposure of their DNA, histones, and other proteins, particularly parts of the cell nucleus. The body's sensitized B-lymphocyte cells will now produce antibodies against these nuclear-related proteins. These antibodies clump into antibody-protein complexes which stick to surfaces and damage blood vessels in critical areas of the body, such as the glomeruli of the kidney; these antibody attacks are the cause of SLE.
Researchers are now identifying the individual genes, the proteins they produce, and their role in the immune system. Each protein is a link on the autoimmune chain, and researchers are trying to find drugs to break each of those links.
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 anti-cardiolipin antibodies, or a consequence of therapy.
Abnormalities in cell death signaling
- Apoptosis is increased in monocytes and keratinocytes
- Expression of FAS ligand by B cells and T cells is increased
- There are correlations between the apoptotic rates of lymphocytes and disease activity.
- Necrosis is increased in T lymphocytes.
Tingible body macrophages (TBMs) – large phagocytic cells in the germinal centers of secondary lymph nodes– 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 cells 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. Necrosis, a pro-inflammatory form of cell death, is increased in T lymphocytes, due to mitochondrial dysfunction, oxidative stress, and depletion of ATP.
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 people with SLE 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, C-reactive protein, 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 people with lupus (especially those with lupus nephritis) and an impairment in degrading neutrophil extracellular traps (NETs). These were due to Deoxyribonuclease I inhibiting factors (DNAse1), or NET protecting factors in people's serum, rather than abnormalities in the DNAse1 itself. DNAse1 mutations in lupus have so far only been found in some Japanese cohorts.
The clearance of early apoptotic cells is an important function in multicellular organisms. It leads to a progression of the apoptosis process and finally to secondary necrosis 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 cell 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).
Accumulation in germinal centers
In healthy conditions, apoptotic lymphocytes are removed in germinal centres (GC) by specialized phagocytes, the tingible body macrophages (TBM), which is why no free apoptotic and potential autoantigenic material can be seen. In some people with SLE, accumulation of apoptotic debris can be observed in GC because of an ineffective clearance of apoptotic cells. In close proximity to TBM, follicular dendritic cells (FDC) are localised in GC, which attach antigen material to their surface and, in contrast to bone marrow-derived DC, neither take it up nor present it via major histocompatibility complex molecules.
Autoreactive B cells can accidentally emerge during somatic hypermutation and migrate into the germinal center light zone. Autoreactive B cells, maturated coincidentally, normally do not receive survival signals by antigen planted on follicular dendritic cells, and perish by apoptosis. In the case of clearance deficiency, apoptotic nuclear debris accumulates in the light zone of GC and gets attached to FDC. This serves as a germinal centre survival signal for autoreactive B-cells. After migration into the mantle zone, autoreactive B cells require further survival signals from autoreactive helper T cells, which promote the maturation of autoantibody-producing plasma cells and B memory cells. In the presence of autoreactive T cells, a chronic autoimmune disease may be the consequence.
Autoantibodies to nRNP A and nRNP C initially targeted restricted, proline-rich sequence motifs. Antibody binding subsequently spread to other epitopes. The similarity and cross-reactivity between the initial targets of nRNP and Sm protein autoantibodies identifies a likely commonality in cause and a focal point for intermolecular epitope spreading.
Elevated expression of HMGB1 was found in the sera of people 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.
Antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic testing for SLE.
Several techniques are used to detect ANAs. Clinically the most widely used method is indirect immunofluorescence (IF). The pattern of fluorescence suggests the type of antibody present in the people's serum. Direct immunofluorescence can detect deposits of immunoglobulins and complement proteins in the people's skin. When skin not exposed to the sun is tested, a positive direct IF (the so-called lupus band test) is an evidence of systemic lupus erythematosus.
ANA screening yields positive results in many connective tissue disorders and other autoimmune diseases, and may occur in normal individuals.
Subtypes of antinuclear antibodies include LSm (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 titers also tend to reflect disease activity, although not in all cases. Other ANA that may occur in people with SLE are anti-U1 RNP (which also appears in systemic sclerosis and mixed connective tissue disease), 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), electrolytes and kidney 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 cells 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.
Some physicians make a diagnosis on the basis of the American College of Rheumatology (ACR) classification criteria. The criteria, however, were established mainly for use in scientific research including use in randomized controlled trials which require higher confidence levels, so many people with SLE may not pass the full criteria.
The American College of Rheumatology (ACR) established eleven criteria in 1982, which were revised in 1997 as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individuals and do not do well in that capacity. For the purpose of identifying people for clinical studies, a person has SLE if any 4 out of 11 symptoms are present simultaneously or serially on two separate occasions. Useful mnemonic for remembering the diagnostic findings or symptoms of SLE is SOAP BRAIN MD (S=serositis, O=oral ulcers, A=arthritis, P=photosensitivity, pulmonary fibrosis, B=blood cells, R=renal, Raynauds, A=ANA, I=immunologic (anti-Sm, anti-dsDNA), N=neuropsych, M=malar rash, D=discoid rash), however, not in order of diagnostic importance.
- Malar rash (rash on cheeks); sensitivity = 57%; specificity = 96%.
- Discoid rash (red, scaly patches on skin that cause scarring); sensitivity = 18%; specificity = 99%.
- Serositis: Pleurisy (inflammation of the membrane around the lungs) or pericarditis (inflammation of the membrane around the heart); sensitivity = 56%; specificity = 86% (pleural is more sensitive; cardiac is more specific).
- Oral ulcers (includes oral or nasopharyngeal ulcers); sensitivity = 27%; specificity = 96%.
- Arthritis: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion; sensitivity = 86%; specificity = 37%.
- Photosensitivity (exposure to ultraviolet light causes rash, or other symptoms of SLE flareups); sensitivity = 43%; specificity = 96%.
- Blood—hematologic disorder—hemolytic anemia (low red blood cell count), leukopenia (white blood cell count<4000/µl) lymphocytopenia (<1500/µl), or low platelet count (<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 proteinuria or cellular urinary casts 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 antibody, and/or false positive serological test for 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: Seizures or psychosis; sensitivity = 20%; specificity = 98%.
Other than the ACR criteria, people with lupus may also have:
- fever (over 100 °F/ 37.7 °C)
- extreme fatigue
- hair loss
- fingers turning white and/or blue when cold (Raynaud's phenomenon)
Criteria for individual diagnosis
Some people, especially those with antiphospholipid syndrome, 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:
- Simplest classification tree: SLE is diagnosed if a person has an immunologic disorder (anti-DNA antibody, anti-Smith antibody, false positive syphilis test, or LE cells) or malar rash. 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.
The treatment of SLE involves preventing flares and reducing their severity and duration when they occur.
Treatment can include corticosteroids and anti-malarial drugs. Certain types of lupus nephritis such as diffuse proliferative glomerulonephritis require bouts of cytotoxic drugs. These drugs include cyclophosphamide and mycophenolic acid.
Hydroxychloroquine (HCQ) was 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 belimumab (Benlysta) as a treatment for the pain and flare-ups common in lupus. The drug was approved by the FDA in March 2011.
Due to the variety of symptoms and organ system involvement with SLE, its severity in an individual must be assessed in order to successfully treat SLE. Mild or remittent disease may, sometimes, be safely left untreated. If required, nonsteroidal anti-inflammatory drugs and antimalarials may be used. Medications such as prednisone, mycophenolic acid and tacrolimus have been used in the past.
Disease-modifying antirheumatic drugs
Disease-modifying antirheumatic drugs (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 hydroxychloroquine 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.
In more severe cases, medications that modulate the immune system (primarily corticosteroids and immunosuppressants) are used to control the disease and prevent recurrence of symptoms (known as flares). Depending on the dosage, people who require steroids may develop Cushing's syndrome, symptoms of which may include obesity, puffy round face, diabetes mellitus, increased appetite, difficulty sleeping and osteoporosis. These may subside if and when the large initial dosage is reduced, but long-term use of even low doses can cause elevated blood pressure and cataracts.
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.
Since a large percentage of people with SLE have varying amounts of chronic pain, stronger prescription painkillers may be used if over-the-counter drugs (mainly NSAIDs) do not provide effective relief. Potent NSAIDs such as indomethacin and diclofenac are relatively contraindicated for people with SLE because they increase the risk of kidney failure and heart failure.
Pain is typically treated with opioids, varying in potency based on the severity of symptoms. When opioids are used for prolonged periods, drug tolerance, chemical dependency, and addiction may occur. Opiate addiction is not typically a concern, since the condition is not likely to ever completely disappear. Thus, lifelong treatment with opioids is fairly common for chronic pain symptoms, accompanied by periodic titration that is typical of any long-term opioid regimen.
Intravenous Immunoglobulins (IVIGs)
Intravenous immunoglobulins 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 complexes from the body, even though their mechanism of action is not well-understood.
Avoiding sunlight is the primary change to the lifestyle of people with SLE, as sunlight is known to exacerbate the disease, as is the debilitating effect of intense fatigue. These two problems can lead to people becoming housebound for long periods of time. Drugs unrelated to SLE should be prescribed only when known not to exacerbate the disease. Occupational exposure to silica, pesticides, and mercury can also worsen the disease.
Kidney transplants are the treatment of choice for end-stage kidney disease, which is one of the complications of lupus nephritis, but the recurrence of the full disease is common in up to 30% of people.
Antiphospholipid syndrome is also related to the onset of neural lupus symptoms in the brain. In this form of the disease the cause is very different from lupus: thromboses (blood clots or "sticky blood") form in blood vessels, which prove to be fatal if they move within the 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 people, brain scans are usually required for early detection. These scans can show localized areas of the brain where blood supply has not been adequate. The treatment plan for these people requires anticoagulation. Often, low-dose aspirin is prescribed for this purpose, although for cases involving thrombosis anticoagulants such as warfarin 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 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.
No cure is available for SLE but there are many treatments for the disease.
In the 1950s, most people diagnosed with SLE lived fewer than five years. Today, over 90% now survive for more than ten years, and many live relatively asymptomatically. 80-90% can expect to live a normal lifespan.
Prognosis is typically worse for men and children than for women; however, if symptoms are present after age 60, the disease tends to run a more benign course. Early mortality, within 5 years, is due to organ failure or overwhelming infections, both of which can be altered by early diagnosis and treatment. The mortality risk is fivefold when compared to the normal population in the late stages, which can be attributed to cardiovascular disease from accelerated atherosclerosis, the leading cause of death for people with SLE.
To reduce 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.
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.
The rate of SLE varies considerably between countries, ethnicity, sex, and changes over time. In the United States, one estimate of the rate of SLE is 53 per 100,000; other estimates range from 322,000 to over 1 million. 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.
While the onset and persistence of SLE can show disparities between genders, socioeconomic status also plays a major role. Women with SLE and of lower socioeconomic status have been shown to have higher depression scores, higher body mass index, and more restricted access to medical care than women of higher socioeconomic statuses with the illness. People with SLE had more self-reported anxiety and depression scores if they were from a lower socioeconomic status.
The global prevalence of SLE is approximately 20-70/100,000 people. The age distribution of SLE ranges from ages 2–80+. In females, rate is highest between 45-64 year of age. The lowest overall rate exist in Iceland and Japan. The highest rates exist in US and France. However, there is no sufficient evidence to conclude that SLE is less common in some countries compared to others, since there is significant environmental variability in these countries. For example, different countries receive different levels of sunlight, and exposure to UV rays affects dermatological symptoms of SLE. Certain studies hypothesize that a genetic connection exists between race and lupus which affects disease prevalence. If this is true, the racial composition of countries affects disease, and will cause the incidence in a country to change as the racial makeup changes. In order to understand if this is true, countries with largely homogenous and racially stable populations should be studied to better understand incidence.
Rates of disease are the developing work is unclear.
There are assertions that race affects the rate of SLE. However, a 2010 review of studies which correlate race and SLE identified several sources of systematic and methodological error, indicating that the connection between race and SLE may be spurious. For example, studies show that social support is a modulating factor which buffers against SLE-related damage and maintains physiological functionality. Studies have not been conducted to determine whether people of different racial backgrounds receive differing levels of social support. If there is a difference, this could act as a confounding variable in studies correlating race and SLE. Another caveat to note when examining studies about SLE is that symptoms are often self-reported. This process introduces additional sources of methodological error. Studies have shown that self-reported data is affected by more than just the patients experience with the disease- social support, level of helplessness, and abnormal illness-related behaviors also factor into a self-assessment. Additionally, other factors like the degree of social support which a person receives, socioeconomic status, health insurance, and access to care can contribute to an individual’s disease progression. It is important to note that racial differences in lupus progression have not been found in studies that control for the socioeconomic status of participants. Studies that control for the SES of its participants have found that non-white people have more abrupt disease onset compared to white people, and that their disease progresses more quickly. Non-white patients often report more hematological, serosal, neurological, and renal symptoms. However, the severity of symptoms and mortality are both similar in white and non-white patients. Studies that report different rates of disease progression in late stage SLE are most likely reflecting differences in socioeconomic status and the corresponding access to care. The people who receive medical care often have accrued less disease-related damage, and are less likely to be below the poverty line.
SLE, like many autoimmune diseases, affects females more frequently than males, at a rate of almost 9 to 1. The X chromosome carries immunological related genes, which can mutate and contribute to the onset of SLE. The Y chromosome has no identified mutations associated with autoimmune disease.
Hormonal mechanisms could explain the increased incidence of SLE in females. The onset of SLE could be attributed to the elevated hydroxylation of estrogen and the abnormally decreased levels of androgens in females. In addition, differences in GnRH signalling have also shown to contribute to the onset of SLE. While females are more likely to relapse than males, the intensity of these relapses is the same for both sexes.
In addition to hormonal mechanisms, specific genetic influences found on the X chromosome may also contribute to the development of SLE. Studies indicate that the X chromosome can determine the levels of sex hormones. A study has shown an association between Klinefelter syndrome and SLE. XXY males with SLE have an abnormal X-Y translocation resulting the in the partial triplication of the PAR1 gene region.
Changing rate of disease
The rate of SLE in the United States increased from 1.0 in 1955 to 7.6 in 1974. Whether the increase is due to better diagnosis or to increasing frequency of the disease is unknown.
The history of SLE can be divided into three periods: classical, neoclassical, and modern. In each period, research and documentation advanced the understanding and diagnosis of SLE, leading to its classification as an autoimmune disease in 1851, and to the various diagnostic options and treatments now available to people with SLE. The advances made by medical science in the diagnosis and treatment of SLE has dramatically improved the life expectancy of a person diagnosed with SLE.
There are several explanations ventured for the term lupus erythematosus. Lupus is Latin for "wolf", and "erythro" is derived from "ερυθρός", Greek for "red." All explanations originate with the reddish, butterfly-shaped malar rash that the disease classically exhibit across the nose and cheeks.
- In various accounts, some doctors thought the rash resembled the pattern of fur on a wolf's face. More likely is that it is derived from the similarity in distribution to lupus vulgaris or chronic facial tuberculosis where the lesions are ragged and punched out and are said to resemble the bite of a wolf
- 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."
The classical period began when the disease was first recognized in the Middle Ages. The term lupus is attributed to 12th-century Italian physician Rogerius, who used it to describe ulcerating sores on the legs of people. No formal treatment for the disease existed and the resources available to physicians to help people was limited.
The neoclassical period began in 1851 when the skin disease now known as discoid lupus erythematosus was documented by French physician, Pierre Cazenave. Cazenave termed the illness lupus and added the word erythematosus to distinguish this disease from other illnesses that affected the skin except they were infectious. Cazenave observed the disease in several people and made very detailed notes to assist others in its diagnosis. He was one of the first to document that lupus affected adults from adolescence into the early thirties and that the facial rash is its most distinguishing feature.
Research and documentation of the disease continued in the neoclassical period with the work of Ferdinand von Hebra and his son-in-law, Moritz Kaposi. They documented the physical effects of lupus as well as some insights into the possibility that the disease caused internal trauma. von Hebra observed that lupus symptoms could last many years and that the disease could go "dormant" after years of aggressive activity and then re-appear with symptoms following the same general pattern. These observations led Hebra to term lupus a chronic disease in 1872.
Kaposi observed that lupus assumed two forms: the skin lesions (now known as discoid lupus) and a more aggravated form that affected not only the skin but also caused fever, arthritis, and other systemic disorders in people. The latter also presented a rash confined to the face, appearing on the cheeks and across the bridge of the nose; he called this the "butterfly rash". Kaposi also observed those patients who developed the "butterfly rash" (or malar rash) often were afflicted with another disease such as tuberculosis or anemia which often caused death. Kaposi was one of the first persons to recognize what is now termed systemic lupus erythematosus in his documentation of the remitting and relapsing nature of the disease and the relationship of skin and systemic manifestations during disease activity.
The 19th century's research into lupus continued with the work of Sir William Osler who, in 1895, published the first of his three papers about the internal complications of erythema exudativum multiforme. Not all the patient cases in his paper had SLE but Osler's work expanded the knowledge of systemic diseases and documented extensive and critical visceral complications for several diseases including lupus. Noting that many people with lupus had a disease that not only affected the skin but many other organs in the body as well, Osler added the word "systemic" to the term lupus erythematosus to distinguish this type of disease from discoid lupus erythematosus. Osler's second paper noted that reoccurrence is a special feature of the disease and that attacks can be sustained for months or even years. Further study of the disease led to a third paper, published in 1903, documenting afflictions such as arthritis, pneumonia, the inability to form coherent ideas, delirium, and central nervous system damage as all affecting patients diagnosed with SLE.
The modern period, beginning in 1920, saw major developments in research into the cause and treatment of discoid and systemic lupus. Research conducted in the 1920s and 1930s led to the first detailed pathologic descriptions of lupus and demonstrated how the disease affected the kidney, heart, and lung tissue. A major breakthrough was made in 1948 with the discovery of the LE cell (the lupus erythematosus cell—a misnomer, as it occurs with other diseases as well). Discovered by a team of researchers at the Mayo Clinic, they discovered that the white blood cells contained the nucleus of another cell that was pushing against the white's cell proper nucleus. Noting that the invading nucleus was coated with anti-body that allowed it to be ingested by a phagocytic or scavenger cell, they named the antibody that causes one cell to ingest another the LE factor and the two-nuclei cell result the LE cell. The LE cell, it was determined, was a part of an anti-nuclear antibody (ANA) reaction; the body produces antibodies against its own tissue. This discovery led to one of the first definitive tests for lupus since LE cells are found in approximately 60% of all people diagnosed with lupus. The LE cell test is rarely performed as a definitive lupus test today as LE cells do not always occur in people with SLE and can occur in individuals with other autoimmune diseases. Their presence can be helpful in establishing a diagnosis but no longer indicates a definitive SLE diagnosis.
The discovery of the LE cell led to further research and this resulted in more definitive tests for lupus. Building on the knowledge that those with SLE had auto-antibodies that would attach themselves to the nuclei of normal cells, causing the immune system to send white blood cells to fight off these "invaders", a test was developed to look for the anti-nuclear antibody (ANA) rather than the LE cell specifically. This ANA test was easier to perform and led not only to a definitive diagnosis for lupus but also many other related diseases. This discovery led to the development of what are now known as autoimmune diseases.
To ensure that the person has lupus and not another autoimmune disease, the American College of Rheumatology (ACR) established a list of clinical and immunologic criteria that, in any combination, point to SLE. The criteria include symptoms that the person can identify (e.g. pain) and things that a physician can detect in a physical examination and through laboratory test results. The list was originally compiled in 1971, initially revised in 1982, and further revised and improved in 2009.
Medical historians have theorized that people with porphyria (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 salicylates (e.g. aspirin) 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 corticosteroids in the treatment of SLE.
Research is geared towards finding a possible cause, a cure, and more effective treatments for people with lupus.
A study called BLISS-76 tested the drug, belimumab, a fully human monoclonal anti-BAFF (or anti-BLyS) antibody.
- Charles Kuralt, former anchor of CBS Sunday Morning, died of SLE complications in 1997.
- Donald Byrne, American chess player who died from SLE complications in 1976.
- Ferdinand Marcos, former Philippine president, died of SLE complications in 1989.
- Flannery O'Connor, American fiction writer who died of SLE complications in 1964.
- Hugh Gaitskell, British politician who died of SLE complications in 1963 aged 56.
- Inday Ba (also known as N'Deaye Ba), a Swedish-born actress who died from SLE complications at age 32.
- J Dilla (also known as Jay Dee), a hip-hop producer and beat maker who died of SLE complications in 2006.
- Lauren Shuler Donner, American movie producer.
- Lucy Vodden, inspiration for the Beatles song Lucy In The Sky With Diamonds. Meeting Vodden later in life and realizing her illness, Julian Lennon campaigned to raise awareness of lupus and following Vodden's death in 2009 has been an active member of the Lupus Foundation of America.
- Mercedes Scelba-Shorte, America's Next Top Model Season Two runner-up and model.
- Michael Jackson had both SLE and vitiligo. Diagnosed in 1986, and confirmed by his dermatologist, Arnold Klein, who presented legal documents during court depositions.
- Michael Wayne, Hollywood director, and producer, part owner of Batjac Productions, son of legendary actor John Wayne, died of heart failure resulting from SLE complications in 2003.
- Pumpuang Duangjan, "Queen of Thai Country Music"
- Ray Walston, character actor who died of SLE complications in 2001 after a six-year battle with the disease.
- Selena Gomez, American actress and singer.
- Sophie Howard, British glamour model
- Teddi King, American singer, died of SLE complications in 1977.
- Tim Raines, former major league baseball player
- Toni Braxton was hospitalized in Los Angeles in December 2012 because of "minor health issues" related to Lupus.
On the Series
Lupus was quickly recognized by fans and critics alike as the most commonly suggested differential diagnosis on the series. By the House, M.D. - Season Two DVD, the series creators decided to embrace this by creating the "It could be Lupus" supercut containing all of the instances where lupus was suggested, as well as being immediately dismissed by House.
However, this served a very important rhetorical device on the series, highlighting the relationship between Gregory House and the person who always suggested lupus, Allison Cameron. It constantly showed us how House was trying to teach his fellows while reminding us how much Cameron had to learn.
Of course, Cameron always suggested lupus because she was a specialist in immunology. Lupus is a perfect example of a "medical school disease". Although it is fairly rare, medical students are universally familiar with it when they leave medical school because it is commonly misdiagnosed and shows up in many case studies. In immunology, the problem becomes even worse - immunologists routinely are trained to include lupus in a differential as, ironically, if an immunologist has a patient with a mysterious disease, lupus is the most likely candidate. It is more common than most of the other serious autoimmune conditions.
House, naturally, is trying to break Cameron from this habit. He reminded his fellows as early as The Socratic Method that in many cases when you choose your specialist, you choose your diagnosis as specialists rarely consider possibilities outside of their specialty. Moreover, although lupus is a zebra, and House often calls other doctors idiots, in fact House believes that in most cases doctors are competent to reach reasonable disgnoses. He finds it hard to believe that a physician would be incompetent enough to miss lupus as a possibility before a case came to his attention. His message to Cameron is also "do you think that all the other doctors who saw this patient first also didn't consider lupus?". Idiocy, in House's eyes, is not stretching ones imagination to consider the rare and unusual.
It's finally lupus
It was only a matter of time before a case of lupus did come to House's attention, the magician Flynn in You Don't Want to Know. However, it came in through the back door and it was the sports medicine specialist Lawrence Kutner who didn't think of it. Moreover, the presentation was atypical, without the obvious signs such as the malar rash. In addition, they only hit upon the diagnosis through a fluke of treatment.
Flynn had suffered a heart attack and bleeding from his mouth while performing a magic trick in a water filled glass booth. However, every test of this heart showed it was normal with no sign of heart disease. In retrospect, Flynn may have been suffering from a flare-up of his condition which affected his heart - a rare presentation of lupus.
The blood transfusion was unrelated to Flynn's condition - he suffered internal bleeding from an MRI mishap. However, he had an adverse reaction to the transfusion because it was the wrong type. This clued House into the cause - his blood typing test was wrong because he tested positive for antibodies he shouldn't have.
Unfortunately, very little of the medicine in this episode was correct. Medical critic Polite Dissent gave the episode's medicine a D and pointed out that just about everything about, including House's explanation of mistyping and transfusion reactions, was wrong.
Elsewhere in the differential
- Ezra Powell - possible scarring of the lungs and abnormalities in the bone marrow suggested some type of autoimmune condition. House put lupus in the differential at this point and orders IVIG.
- Jeff Forrester - the patient's fatigue pointed to systemic disease and Chase suggests lupus as one of the possibilities. House agrees and allows an ANA test.
- Anica Jovanovich - Cameron suggests lupus and a couple of other conditions to explain Anica's bruising. House goes with a test for Cushing's disease instead because lupus wouldn't explain the seizure.
- Fletcher Stone - Cameron suggests that the patient's fever is caused by an autoimmune condition and mentions lupus. However, House thinks an infection is more likely and orders antibiotics and anti-virals.
- Maggie Archer - When the patient's eyes start bleeding, Kutner suggests lupus along with two other possibilities. House decides on a bone marrow aspiration to get more information about why her platelets have dropped.
- Bob Palko - Foreman suggests lupus to explain itching and a rash. However, House also realized heavy metal poisoning explained all the symptoms and turned back to it as a possibility.
- Keith Foster - Cameron suggested lupus to explain the anemia. House allowed testing, but the ANA, lack of sensitivity to light, lack of a rash and lack of a family history ruled it out.
- Megan Bradberry - Leon the janitor suggested lupus because his grandmother suffered from it. House actually agreed and ordered an autoimmune panel.
- Abigail Ralphean - When it became clear the disease was systemic, Cameron suggested an autoimmune condition like lupus and recommended steroids. Cuddy agreed with Wilson that steroids were too risky and allowed an ANA test instead.
- Lucy - The patient's double vision and heart problems suggested an autoimmune condition and Cameron noted that lupus was one of the most common in six-year-olds. House thought it was a different autoimmune condition and ordered an ANA and steroids.
- Lupe - A buildup of white blood cells suggested an autoimmune condition given that Lupe had no fever. Foreman noted that no matter what autoimmune condition it was, even lupus, steroids were the appropriate treatment. House agreed.
- Matty - Cameron suggested the fibrous tissues in his muscles was most likely the result of an autoimmune condition. House ordered tests for lupus.
- Casey Alfonso - When the patient started running a fever and delerium,Taub noted that the speed of its progression suggested lupus and Amber agreed because all the brain and body symptoms pointed to an autoimmune disease. However, Foreman noted the patient wasn't suffering from kidney failure, which is usually the case when lupus progresses this quickly. He ordered interferon for multiple sclerosis but allowed the applicants to test for lupus. The ANA was a weak positive and the sed rate was also indicative of lupus, but Foreman noted that the test results pointed more conclusively to MS so he didn't allow steroids. Taub and Amber ignored Foreman and gave her steroids anyway. Although Casey's fever dropped, she developed paralysis.
- Roz - House suggests lupus to explain her heart problems and what he feels is her altered mental state. He orders a stress test, but it rules out the condition.
- Cate Milton - The patient's inflammation and kidney failure pointed to lupus. The patient refused to use her limited supply of steroids on a guess, and House refused to let her go outside to see if her condition would improve. Unable to perform an ANA, Wilson realizes that all they need to do an LE Prep is to mix her blood with something that will damage the blood cells, like a paper clip.
- Evan Greer - After the patient suffered multiple organ failures, Taub realized it was an autoimmune condition. House realized lupus was one of the possibilities, but didn't want to waste time on an ANA. However, the patient soon developed a high fever, which seemed to rule out lupus.
- Jackson Smith - Thirteen thought that the patient's testosterone supplements had set off an autoimmune reaction and suggested lupus as a possibility. House agreed and ordered steroids and progesterone.
- Jack Randall - Cameron believed the rash on the patient's chest pointed to a combination of lupus and vasculitis. However, House rejected the diagnosis because the patient didn't have a stiff neck and vasculitis could have shown up in a previous biopsy.
- James Sidas - Taub suggested lupus to explain the patient's paralysis, but the patient's ANA was normal.
- Carnell Hall - The team ran numerous tests to explain the patient's perception of electric shocks, but the normal ANA ruled out lupus.
- Adam Kelvey - House believes that Adam could be suffering from chest pain given the fact he was clutching his chest and screaming. He orders an ANA in the event it is lupus.
- Arlene Cuddy - In the secret differential, Taub suggested that the patient's recurring rashes and fever pointed to lupus. However, her attending, Dr. Kaufman, had already started her on prednisone because he had reached the same conclusion.
- Alice Tanner - Taub notes that in the patient's manuscript, the patient's literary alter ego is suffering from joint pain, fatigue, photosensitivity and depression. This points to lupus. House doesn't want to diagnose her with it because it's incurable and she will inevitably choose suicide over living with the pain. However, he agrees to an ANA. When he tells the patient about it, she becomes paralyzed, which points to another condition.
- Stevie Weathers - When the lungs became discolored when they started immunoglobulin, Dr. Simpson suggested lupus, which House immediately dismissed.
- Nick - House believed Nick's joint pain and slight fever were a sign of lupus. He later found a rash on Nick's thigh and Adams agreed to give him prednisone. However, when Nick broke his arm when he was pushed against a wall, he realized he was wrong.
- Drew Lemayne - House believes that Drew's mysterious illness might have been lupus and asks Emory if Drew ever had a rash. Emory denies it.
- Moira Parker - After Chase finds nodules on an artery, House suggests lupus, but the patient's ANA was normal.
- Will Westwood - Adams suggests lupus to explain the patient's hypercoagulability. However, House realized that Behcet's disease was more likely and they would have missed any visual symptoms because the patient was blind.
- Emily Lawson - When Emily's hands turn blue (Reynauds phenomena) Taub suggests lupus as the obvious cause. However, her mother Dr. Elizabeth Lawson felt that heavy metal poisoning was more likely even though Chase pointed out lupus fit the symptoms better.
Elsewhere in the series
- In Finding Judas, we discover that House keeps a stash of Vicodin in a lupus textbook in his office because "It's never lupus"
- In The Right Stuff, The Twins start arguing between themselves about possible diagnoses, but when they reach lupus, House cuts them off and tells them they're distracting the males in the room because all of them are thinking about having sex with them. This was part of a running gag at the beginning of Season 4 where someone always suggested lupus.
SLE at Wikipedia - This article uses text from Wikipedia used under the Creative Commons License
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