Who Is Most At Risk?
- There is no evidence that people with SLE are more likely to develop drug-induced lupus.
- The use of procainamide, hydralazine, isoniazid, or various anticonvulsants has not been associated with an increase in SLE disease activity or onset of flares.
- The major risk factor for developing drug-induced lupus is chronic, long-term use of a drug known to cause this problem.
- Usually DILE occurs in males over 50 years old, because they have a higher chance of developing chronic diseases that require this type of continuous medication: procainamide or quinidine is prescribed for cardiac arrhythmias, and hydralazine is prescribed for hypertension.
- The high female-to-male ratio associated with SLE is not a distinguishing feature of drug-induced lupus.
- Some evidence suggests that whites are more likely than blacks to develop DILE.
Is Heredity A Factor In DILE?
The only well-defined genetic risk factor in DILE is the slow drug acetylation phenotype. Many medications change biochemically as they pass through the liver, and people who are "fast acetylators" more efficiently metabolize procainamide and hydralazine to a form that does not induce lupus. Therefore, people who are "slow acetylators" are at higher risk for developing lupus-like disease from these two drugs. This is a characteristic of approximately 50 percent of the North American white and black populations.
Why Does Drug-Induced Lupus Occur?
Considerable controversy and disagreement exists about the processes that lead to drug-induced autoimmunity. Drug-induced lupus was first identified almost 50 years ago and has been the subject of many research studies. However, the causes of this disorder are only beginning to be understood.
- One view is that the offending drugs interfere with enzymes that would otherwise suppress certain genes. The result is a non-specific hyperimmune condition.
- Considerable circumstantial evidence suggests that it is not the drug itself but the metabolic change the drug undergoes in the body that makes it able to react with the immune system.
- One possibility is that when these drug metabolites bind to certain proteins, drug-protein complexes are produced. These then activate drug-specific lymphocytes, which damage surrounding tissue or stimulate neighboring lymphocytes.
- In one mouse study, a drug metabolite was placed in the thymus (one of the main lymphoid organs that forms T lymphocytes). The result was production of the type of autoantibodies that are seen in drug-induced lupus. These findings point to the human thymus as the place where the DILE process begins.
- It is possible that more than one process causes drug-induced lupus. Although most cases of SLE probably arise spontaneously, the similarities in the signs and symptoms between SLE and DILE suggest that similar immune problems are involved in both diseases.