Systemic lupus erythematosus (SLE) is the prototypic autoimmune disease with diverse clinical manifestations, affecting virtually all organ systems. A wide variety of medications are used for treatment, depending on organ involvement and severity. This article summarizes the adverse effects associated with different drugs currently used to treat SLE.
A wide variety of medications are used to treat systemic lupus erythematosus, depending on organ involvement and severity.
Some of these drugs, especially immunosuppressive and cytotoxic agents, often lead to significant toxicity.
Physicians must familiarize themselves with the adverse effects of each of these drugs and discuss them with patients to facilitate educated decision making.
Several antimalarial medications have been used to treat SLE for more than 100 years. Hydroxychloroquine (Plaquenil) is currently the most commonly used, although chloroquine (Aralen) and quinacrine (Atabrine, Mepacrine) also remain in use. Several recent studies have highlighted the many benefits of antimalarials in patients with SLE, including
An improvement in lipid profiles
Reduction of SLE activity
Prevention of thrombotic events
Although antimalarials are generally well tolerated and possess good safety profiles, they are associated with adverse events (AEs), although these are infrequent and generally mild. The most common AEs are gastrointestinal and cutaneous, whereas the most serious AE, although rare, is retinopathy. In one study comparing the toxicities associated with hydroxychloroquine and chloroquine, 28% of patients receiving chloroquine experienced AEs compared with 15% of those receiving hydroxychloroquine ( P <.00001).
The risk of retinopathy ( Fig. 1 ) from hydroxychloroquine is low, especially compared with chloroquine. In a study performed in Thailand, 37 of 139 patients (27%) receiving chloroquine experienced retinopathy. In contrast, in a large series of 1207 patients taking hydroxychloroquine for rheumatic diseases, only 1 case of definite retinal toxicity was identified. In a more recent study, definite or probable retinal toxicity occurred in 0.65% of 3995 patients taking hydroxychloroquine. Although the toxicity rate remained low with longer durations, an increase in toxicity was seen after approximately 6 years of use, or with a cumulative dose of 800 g. For this reason, the American Academy of Ophthalmology recommends that all patients starting on hydroxychloroquine or chloroquine have a baseline examination within the first year of starting the drug. Annual screening should then be performed after 5 years of use in all patients, and from initiation of therapy for patients with maculopathy or unusual risk factors. Recommended screening procedures include careful ocular examination, automated visual field testing, and, when available, testing with one or more objective tests of anatomic or functional damage.
Cutaneous side effects are common in patients taking antimalarials. Cutaneous pigmentary changes have been found in up to 25% of patients taking these medications for more than 3 months. Any of the antimalarials may produce localized blue-black pigmentation, which predominantly affects the pretibial areas, face, gums, hard palate, and subungual regions, although it has most commonly been seen with chloroquine ( Figs. 2 and 3 ). This effect was seen in 25 of 300 patients receiving antimalarials for collagen diseases. Early lesions resembled ecchymoses, but with continued therapy, the areas coalesced and became darker. The duration of therapy varied from 4 to 70 months, and the pigmentation decreased several months after cessation of therapy. African Americans seemed to have a lower incidence of pigmentary changes.