Lupus erythematosus

 ICD9        = 710.0|

}} Lupus erythematosus (also known as systemic lupus erythematosus or SLE) is an autoimmune disorderin which antibodiesare created against the patient's own DNA. It can cause various symptoms, but the main ones relate to the skin, kidney(lupus nephritis), joints, bloodand immune system.

It is named for the Latinlupus, meaning "wolf", perhaps due to a crude similarity between the facial rash associated with the illness, and a wolf's face, although various explanations exist.

Signs and symptoms

Common initial and chronic complaints are fever, malaise, joint pains, myalgiasand fatigue. 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, however, they are considered suggestive.

Dermatological manifestations

As many as 30% of patients present with some dermatological symptoms (and 65% suffer such symptoms at some point), with 30% to 50% suffering from the classic malar(or butterfly) rash associated with the disease. Patients may present with discoid lupus (thick, red scaly patches on the skin). Alopecia, mouth, nasal, and vaginal ulcers, and lesions on the skin are also possible manifestations.

Musculoskeletal manifestations

Patients most often seek medical attention for jointpain, with small joints of the hand and wrist usually affected, although any joint is at risk. Unlike rheumatoid arthritis, SLE arthropathy is not usually destructive of bone, however, deformities caused by the disease may become irreversible in as many as 20% of patients.

Hematological manifestations

Anemiaand iron deficiency may develop in as many as half of patients. Low plateletand white blood cellcounts may be due to the disease or a side-effect of pharmacological treatment.

Cardiac manifestations

Patients may present with inflammation of various parts of the heart: pericarditis, myocarditisand endocarditis. The endocarditis of SLE is characteristically non-infective (Libman-Sacks endocarditis), and involves either the mitral valveor the tricuspid valve. Atherosclerosisalso tends to occur more often and advance more rapidly in SLE patients than in the general population. (Asanuma et al 2003, Bevra 2003, Roman et al 2003).

Renal involvement

Painless hematuriaor proteinuriamay 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 failureoccurs in less than 5% of patients.

Neurological manifestations

About 10% of patients may present with seizuresor psychosis. A third may test positive for abnormalities in the cerebrospinal fluid.

T-cell abnormalities

Abnormalities in T cellsignaling are associated with SLE, including deficiency in CD45phosphatase, increased expression of CD40 ligand. Also associated with SLE is increased expression of Fc?RI?, which replaces the TCR ? chain, which is deficient in some SLE patients. Other abnormalities include:

• increased and sustained calcium levels in T cells
• moderate increase of inositol triphosphate
• reduction in PKC phosphorylation
• reduction in Ras-MAP kinasesignalling

And deficiencies in:

• protein kinase A I activity

Diagnosis

Some physicians make a diagnosis on the basis of the ACR classification criteria (see below). The criteria, however, were established mainly for use in scientific research (i.e. inclusion in randomised controlled trials), and patients may have lupus despite never meeting the criteria.

Antinuclear antibodytesting and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic testing for lupus. Antiphospholipid antibodiesoccur more often in SLE, and can predispose for thrombosis. More specific is the anti-smith antibody. Other tests routinely performed in suspected SLE are complement systemlevels (low levels suggest consumption by the immune system), electrolytesand renal function(disturbed if the kidney is involved), liver enzymesand a full blood count.

Classification

The American College of Rheumatology has established eleven criteria in 1982[1], which were revised in 1997[2], as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individual patients and do not do well in that capacity. A patient must present with four of the eleven criteria, either simultaneously or serially, during a given period of observation, to be classified as having SLE ? for the purposes of inclusion in clinical trials.

1. Malarrash(rash on cheeks)
2. Discoid lupus (red, scaly patches on skin which cause scarring)
3. Photosensitivity(adverse reaction to sunlight)
4. Mouth ulcers
5. Arthritis
6. More than 0.5g per day protein in urine, or cellular castsseen in urine under a microscope.
7. Seizuresor psychosis
8. Pleuritis(inflammation of the membrane around the lungs) or pericarditis(inflammation of the membrane around the heart)
9. Hemolytic anemia(low red blood cellcount), leukopenia(low white blood cell count), lymphopenia(low lymphocytecount) or thrombocytopenia(low platelet count)
10. Anti-DNA antibody, anti-Sm antibody or false positive serologicaltest for syphilisor antiphospholipid antibodypositivity
11. Positive fluorescence antinuclear antibodytest (positive ANA)

Some patients may have SLE without four criteria and SLE is associated with manifestations other than those listed in the criteria. Dr Graham R.V. Hughes, an authority on lupus in the UK, has published alternative criteria to diagnose SLE[3]in 1982.

A commonly used mnemonic for these 11 criteria is SOAP BRAIN MD: Serositis (8), Oral ulcers (4), Arthritis (5), Photosensitivity (3), Blood Changes (9), Renal involvement (proteinuria or casts) (6), ANA (11), Immunological changes (10), Neurological signs (seizures, frank psychosis) (7), Malar Rash (1), Discoid Rash (2).

Etiology

The exact cause of the disease is unknown, and there is no consensus on whether it is a single condition or a group of related diseases. SLE is a chronic inflammatorydisease believed to be a type III hypersensitivity(serum sickness) response, which is characterised by the body's production of antibodies against the nuclear components of its own cells. There are three mechanisms by which lupus is thought to develop.

Genetics

The first mechanism may arise genetically. Research indicates that SLE may have a geneticlink. Several genes need to be affected for lupus to occur, and the most important genes are located on chromosome6. These genes may occur randomly or be a result of heredity. Additionally, people with SLE have an altered RUNX-1binding site, which may be either cause or contributor (or both) to the condition. Altered binding sites for RUNX-1 have also been found in people with psoriasisand rheumatoid arthritis.

Environmental causes

The second mechanism may be owing to environmental factors. These factors can not only exacerbate existing Lupus conditions, but can trigger the initial onset. They include certain medications (such as some antidepressantsand antibiotics), extreme stress, exposure to sunlight, hormones, and infections. Some researchers have sought to find a connection between certain infectious agents (virusesand bacteria), but no pathogen can be consistently linked to the disease.

Drug-induced lupus

Finally, there is drug-induced lupus. This is a reversible condition that usually occurs in patients being treated for a long-term illness. Drug-induced lupus mimics systemic lupus. Usually once a patient is taken off of the medication which triggered the episode, no signs or symptoms of lupus recur. There are about 40 medications currently in use that can cause this condition, though the most common drugs are procainamide, hydralazineand quinidine.

Pathophysiology

Abnormalities in apoptosis

• Apoptosisis increased in monocytesand keratinocytes
• Expression of Fasby B cellsand T cellsis increased
• There are correlations between the apoptotic rates of lymphocytes and disease activity

Tingible body macrophages(TBMs) are large phagocytic cells in the germinal centersof secondary lymph nodes. They express CD68 protein. These cells normally engulf B cellswhich have undergone apoptosisafter somatic hypermutation. In some patients 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 cellsand T cells.

Dendritic cellsin 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 cellsand make this material available for activating other B cellswhich may have randomly acquired self-specificity through somatic hypermutation.

Complement pathway

SLE is associated with defects in lectinsand the classical complement pathway.

Treatment

SLE is a chronic disease with no cure. There are, however, some medications, such as corticosteroidsand immunosuppressantswhich can control the disease and prevent flares. Flares are typically treated with steroids, with DMARDs(disease-modifying antirheumatic drugs) to suppress the disease process, reduce steroid needs and prevent flares. DMARDs commonly in use are the antimalarials (e.g. hydroxychloroquine) and azathioprine. Cyclophosphamideis used for severe nephritis or other organ-damaging complications.

Patients who require steroids frequently may develop obesity, diabetesand osteoporosis. Hence, steroids are avoided where possible.

Measures such as avoiding sunlight (to prevent problems due to photosensitivity) may also have some effect.

Other immunosuppressants and autologous stem cell transplantsare under investigation.

Epidemiology

Although SLE can occur in anyone at any age, it is most common in women of childbearing age. It affects 1 in 4000 people in the United States, with women suffering five to fifteen times more often than men. The disease appears to be more prevalent in women of African, Asian, Hispanic and Native American origin but this may be due to socioeconomic factors. People with relatives who suffer from SLE, rheumatoid arthritisor thrombotic thrombocytopenic purpuraare at a slightly higher risk than the general population. A person with a parent or sibling with the condition has a 10% chance of developing the condition. Only 5% of children born to a parent with lupus will develop the condition.

Prognosis

In the 1950s, most patients diagnosed with SLE lived fewer than five years. Advances in diagnosis and treatment have improved survival to the point where over 90% of patients now survive for more than ten years and many can live relatively asymptomatically. The most common cause of death is infectiondue to immunosuppression as a result of medications used to manage the disease. Prognosis is normally worse for men and children than for women and if symptoms are present after age 60, the disease tends to run a more benign course.

History

The source of the name "lupus" is unclear. All explanations originate with the characteristic butterfly-shaped malar rashthat the disease classically exhibits across the nose and cheeks. In various accounts, some doctors thought the rash resembled a wolf pattern. In other accounts doctors thought that the rash, which was often more severe in earlier centuries, created lesions that resembled wolf bites or scratches. Stranger still, is the account that the term "Lupus" didn't come from latin at all, but from the term for a French style of mask which women reportedly wore to conceal the rash on their faces.

The history of lupus erythematosus can be divided into three periods: the classical, neoclassical, and modern. The classical period began when the disease was first recognised in the Middle Agesand saw the description of the dermatological manifestation of the disorder. The term lupus is attributed to the twelfth centuryphysicianRogerius, who used it to describe the classic malar rash. The neoclassical period was heralded by Moritz Kaposi's recognition in 1872of the systemic manifestations of the disease. The modern period began in 1948with the discovery of the LE cell (although use of these cells as diagnostic indicators has now been largely abandoned) and is characterised by advances in our knowledge of the pathophysiology and clinical-laboratory features of the disease, as well as advances in treatment.

Useful medication for the disease was first found in 1894, when quininewas first reported as an effective therapy. Four years later, the use of salicylatesin conjuction with quinine was noted to be of still greater benefit. This was the best available treatment to patients until the middle of the twentieth century when Hench discovered the efficacy of corticosteroidsin the treatment of SLE.

See also

• abzyme
• antinuclear antibody

References

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External links

• Lupus Research Institute
• S.L.E. Lupus Foundation
• Lupus Erythematosus of the skin, New Zealand Dermatological Society Incorporated
• Lupus Clinical Overview
• History of Lupus(NZ Lupus Trust)
• Lupus Patients Understanding & Support (LUPUS)
• The LuPUS Message Boardde:Lupus erythematodes

fr:Lupus érythémateux disséminé it:Lupus eritematoso sistemico he:???? nl:Lupus erythematosus ja:??????????? ru:????????? ??????? ???????? sv:SLE tr:Sistemik lupus eritematozus

This article is licensed under the GNU Free Documentation License.
It uses material from the http://en.wikipedia.org/wiki/Lupus+erythematosus Wikipedia article Lupus erythematosus.