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Author: Robert A. Kalish, M.D.

1. Systemic Lupus Erythematosus

SLE is the prototypic autoimmune disease belonging to a family of diseases often referred to as "connective tissue diseases" a term deriving from the observation that the connective tissues of multiple organs were abnormal in these diseases in the absence of obvious infection or neoplasm. This family also includes scleroderma, Sjogren's syndrome, dermatomyositis and polymyositis among others. SLE is characterized by a loss of tolerance to self that leads to an autoimmune response that results in damage to multiple tissues. Its hallmark is the production of antibodies against self or “autoantibodies”. The mechanism of immune system dysregulation that allows for the development of SLE remains unknown. The clinical manifestations of SLE can affect nearly every organ system and vary tremendously from individual to individual. For example, one patient with SLE may have disease characterized by occasional flares of rash and arthritis and require only infrequent visits to the rheumatologist while the next patient may have severe glomerulonephritis, hemolytic anemia and life-threatening vasculitis requiring intensive treatment and multiple hospitalizations.

1.1. Learning objectives

  1. To understand the theories regarding the pathogenesis of the autoimmune state that is seen in SLE and the mechanism of tissue damage in this disease.
  2. To become familiar with the use of antinuclear antibodies and other autoantibodies in the diagnosis and evaluation of patients with SLE.
  3. To identify the clinical criteria for the diagnosis of SLE and the various manifestations of the disease.
  4. To learn the histopathology and the commonly used classification systems for lupus nephritis.
  5. To appreciate the various treatment strategies for SLE.

2. Epidemiology

2.1. Prevalence

Population studies have shown an incidence ranging from 2 to 50 cases/100,000 with clear variation according to ethnic group (In contrast rheumatoid arthritis affects 1% of the population across diverse ethnic lines). SLE is more prevalent in and probably more severe in African-Americans and many Asian populations. Sex - In young adults the female:male ratio is as high as 10:1 but this ratio is lower in children and "older-onset" SLE.

2.2. Socioeconomic

The clinical status is worse in those with less education.

3. Pathogenesis

Several factors are important:

3.1. Genetic factors

Several pieces of evidence support an important role for genetics in the pathogenesis of SLE:

  1. There is an increased frequency of SLE and asymptomatic immunologic abnormalities in close relatives of SLE patients.
  2. There is a 30-50% concordance but not 100% concordance of disease in monozygotic twins.
  3. Ethnic differences in disease susceptibility support a genetic influence.
  4. Certain histocompatibility antigens (HLA) are weakly associated with lupus (eg: HLA- DR2, DR3)

3.2. Environmental factors

Drug induced lupus:
Certain drugs can induce lupus-like syndromes that resolve once the drug is discontinued. eg: procainamide, hydralazine, isoniazid, chlorpromazine, minocycline
Diet:
Nutritional factors may modify disease but this has not been adequately studied. Alfalfa sprouts cause SLE-like disease in monkeys!
Infectious:
Viral and other infectious etiologies have been closely looked for but not yet documented as the consistent cause or trigger of SLE.