Lupus erythematosus (also known as systemic lupus erythematosus - SLE) is an autoimmune disorder in which antibodies are created against the patient's own DNA. It classically presents with a butterfly-shaped malar rash, causing a wolf-like appearance (Lupus is Latin for wolf). Despite this very clear etymology, it has been hypothesized that lupus erythematosus may be one of the diseases that may have inspired the myth of the werewolf.

History

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 Ages and saw the description of the dermatological manifestation of the disorder. The term Lupus is attributed to the thirteenth century physician Rogerius, who used it to describe the classic malar rash. The neoclassical period was heralded by Moriz Kohn 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 (although use of these cells as diagnostic indicators has now been largely abandoned) and is characterised by advances in our knowledge of the pathopysiology and clinical-laboratory features of the disease, as well as advances in treatment.

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 in conjuction with quinine was noted to be of still greater benefit. This was the best available to patients until the middle of the twentieth century when Hench discovered the efficacy of corticosteroids in the treatment of SLE.

Signs and symptoms

Common initial and chronic complaints are fever, malaise, myalgias, fatigue and weight loss. Because they are so often seen with other diseases, these signs and symptoms are not part of the diagnostic criteria for SLE, but when occurring in conjunction with other signs and symptoms, 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), but only 30% to 50% suffer 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 and vaginal ulcers and lesions on the skin are also possible manifestations.

Musculoskeletal manifestations

Patients most often seek medical attention for joint pain, 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

Anemia and iron deficiency may develop in as many as half of patients. Low platelet and white blood cell counts 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, myocarditis and endocarditis. There may be immune complexes on the mitral valve of the heart, where bacteria can accumulate. Atherosclerosis also tends to occur more often and advance more rapidly in SLE patients than in the general population.

Renal involvement

Painless hematuria or proteinuria may often be the only presenting renal symptom. Because of early recognition and management of SLE, end stage renal failure occurs in less than 5% of patients.

Neurological manifestations

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

Diagnosis

Some physicians make a diagnosis on the basis of the ARC 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 antibody testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic testing for lupus. Antiphospholipid antibodies occur 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 system levels (low levels suggest consumption by the immune system), electrolytes and renal function (disturbed if the kidney is involved), liver enzymes and a full blood count.

Classification

The American College of Rheumatology has established eleven criteria as a classificatory instrument to operationalise the definition of SLE in clinical trials. It was not intended to be used to diagnose individual patients and does not do well in that capacity. 1982[1] (http://www.rheumatology.org/publications/classification/index.asp?aud=mem), which were revised in 1997[2] (http://www.rheumatology.org/publications/classification/SLE/1982SLEupdate.asp?aud=mem). 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.

Some patients may have SLE without four criteria and SLE is associated with manifestations other than those listed in the Criteria. A diagnostic guide to help physicians diagnose lupus has been written by Dr Graham RV Hughes entitled "Is it lupus? The St Thomas' Hospital `alternative' criteria, published in 1982[3] (http://www.lupus-support.org.uk)

1. Malar rash (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 casts seen in urine under a microscope.
7. Seizures or 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 cell count), leukopenia (low white blood cell count), lymphopenia (low lymphocyte count) or thrombocytopenia (low platelet count)
10. Anti-DNA antibody, anti-Sm antibody or false positive serological test for syphilis or antiphospholipid antibody positivity
11. Positive fluorescence antinuclear antibody test (positive ANA)

Pathophysiology

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 inflammatory disease believed to be a type III hypersensitivity response, which is characterised by the body’s production of antibodies against the nuclear components of its own cells. Some researchers have sought to find a connection between certain infectious agents (viruses and bacteria), but no pathogen can be consistently linked to the disease. Certain medications (such as some antidepressants) and environmental factors (such as exposure to sunlight) have been found to exacerbate symptoms.

Treatment

SLE is a chronic disease with no cure. There are, however, some medications, such as corticosteroids and immunosuppressants which can control the disease and prevent flares. Measures such as avoiding sunlight (to prevent problems due to photosensitivity) may also have some effect.

Epidemiology

Although SLE can occur in anyone at any age, it is most common in women of childbearing age. It affects one in 3000 people in the United States, with women suffering five to nine times more often than men. The disease appears to be more prevalent in women of African and Hispanic origin but this may be due to socioeconomic factors. People with relatives who suffer from SLE, rheumatoid arthritis or thrombotic thrombocytopenic purpura are at higher risk than the general population.

Prognosis

In the 1950s, most patients diagnosed with SLE lived less 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 infection due 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 present after age 60, the disease tends to run a more benign course.

See also

• Abzyme
• antinuclear antibody.

External links

• Alliance for Lupus Research (http://www.lupusresearch.org/)
• Lupus Foundation (http://www.lupus.org)
• Lupus Erythematosus of the skin, New Zealand Dermatological Society Incorporated (http://www.dermnetnz.org/immune/cutaneous-lupus.html)
• History of Lupus (http://www.lupus.org.nz/history.html) (NZ Lupus Trust)
• LUpus Patients Understanding & Support (LUPUS) (http://www.lupus-support.org.uk/)
• The LuPUS Message Board (http://www.lupus-forums.org.uk/)