Drug-induced systemic lupus erythematosus (SLE) is an autoimmune disease in which hypersensitivity reactions to a medication lead to formation of autoantibodies. Clinical manifestations may be similar to those seen in idiopathic lupus, but the difference is that they are related to continuous drug exposure (longer than 1 month) and cessation of symptoms occurs upon discontinuation of the drug.
Drug-induced SLE also differs in its serology, with anti-nuclear and anti-histone antibodies being the predominant type in drug-induced lupus and anti-nuclear and anti-double-stranded DNA being the major autoantibodies in idiopathic SLE.
Drugs can act in more than one way on SLE: they can trigger a flare or exacerbate pre-existing SLE, they can trigger the first onset of SLE in predisposed patients, or they may induce drug-induced lupus in patients who have no previous history of SLE and whose illness remits when the offending drug is discontinued.
In most types of drug-induced lupus, the general prodromal complaints in more than 80% of cases are arthralgias and arthritis. These are followed by constitutional symptoms of fever, fatigue, anorexia, and weight loss that gradually worsen. Additional symptoms include dry cough, shortness of breath, and occasionally effusion into serous spaces leading to pleuritis and pericardial effusion.
Drug-induced SLE can be subdivided into the classic form, which is the type seen with the majority of drugs, and the form due to anti-tumor necrosis factor (TNF)-alpha drugs.
Classic drug-induced SLE (due to drugs such as procainamide and hydralazine):
- Occurs in an older age group, with equal incidence among males and females.
- Skin findings are less common in drug-induced SLE than in idiopathic SLE. If there is cutaneous involvement, photosensitivity, purpura, and erythema nodosum predominate as opposed to the typical skin findings of idiopathic SLE such as malar rash, oral ulcers, alopecia, and discoid lesions.
- When cutaneous manifestations predominate, renal involvement and neurologic symptoms are less frequent.
- Procainamide (20% incidence) is associated with pulmonary involvement. It causes serositis and both pleural and pericardial effusions. Myalgias are also more common.
- Hydralazine (5%-8% incidence) is associated with arthritis and with a higher frequency of cutaneous involvement (but not the typical butterfly rash seen in SLE).
- Quinidine-induced lupus is also associated with a higher incidence of rash.
- Minocycline used for acne in young females has sometimes led to the onset of arthralgias, polyarthritis, fever and rash, early morning stiffness, and myalgias. Minocycline can also lead to hepatic involvement with raised liver enzymes and autoimmune hepatitis.
- D-penicillamine may lead to nephrotoxicity, which is not in line with the usual pattern of drug-induced lupus manifestations.
- Culprit drugs frequently induce asymptomatic autoantibody formation (ANA and anti-dsDNA) or rarely, a lupus-like syndrome.
- As with the classic form of drug-induced SLE, symptoms are usually less severe than those seen in idiopathic SLE. However, there is a greater degree of cutaneous, renal, and central nervous system (CNS) involvement compared with the classic form of drug-induced lupus. Antibody type also varies, with double-stranded DNA being more common in drug-induced lupus from anti-TNF-alpha and anti-histone antibodies being less common.
- Other manifestations include hematological abnormalities, photosensitivity, oral ulcers, and arthritis. Pericarditis, pleural or pericardial effusions, and polyarthritis can also be seen.
- Leukocytoclastic vasculitis may occur in concert with drug-induced lupus or as an isolated finding.
The incidence of drug-induced lupus is estimated to be at around 10% of all cases of idiopathic SLE, with 15 000 to 20 000 newly diagnosed cases every year.
Certain genetic factors predispose to the development of drug-induced lupus. Slow acetylators may develop symptoms when on medications such as procainamide and hydralazine. Other predisposing factors are the dose and duration of a given drug; usually months to years of drug exposure has occurred before the onset of symptoms. In this respect, drug-induced SLE differs markedly from other varieties of drug hypersensitivity reactions.
Elderly patients are most often affected (with both sexes equally affected), as they are more likely to be exposed to a large number of medications.
Most common drugs causing lupus: