SNOWMASS, COLO. - Low-dose methotrexate is highly effective for treatment of antimalarial-resistant discoid lupus or subacute cutaneous lupus erythematosus.

"If you have to pick one thing past Plaquenil [hydroxychloroquine], I’d say try methotrexate," declared Dr. Ruth Ann Vleugels at a symposium sponsored by the American College of Rheumatology. "At our institution, methotrexate is by far the next agent we choose for cutaneous lupus if the patient is able to tolerate it. We have really good luck with it, and it’s easy to prescribe," she said.

Dr. Vleugels has amassed what is believed to be the largest U.S. case series of patients treated with methotrexate for refractory cutaneous lupus erythematosus (LE). The as-yet unpublished series consists of 20 patients, most of whom received between 20 mg/week and 25 mg/week. Most were on oral methotrexate, but, if they experienced troublesome side effects, they were switched to the subcutaneous formulation.

Seventeen of the 20 patients (85%) experienced significant improvement on methotrexate. The drug was steroid sparing in 10 of 12 patients (83%). The response time was typically 8-12 weeks, according to Dr. Vleugels, a dermatologist who is director of the connective tissue disease clinic at Brigham and Women’s Hospital and codirector of the rheumatology-dermatology clinic at Children’s Hospital, both in Boston.

Although cutaneous LE is not a systemic disease, it’s essential to treat it aggressively from the get-go in order to halt the disease process and prevent irreversible scarring in discoid LE and disfiguring pigment contrast in subacute cutaneous LE, she emphasized.

The first question patients ask upon receiving the diagnosis of discoid LE is, how likely am I to develop systemic lupus erythematosus? The best available data suggest a 5%-10% risk overall, and less than that if the lesions are confined to the head and neck, she said. About one-third of discoid LE patients are antinuclear antibody–positive; this has no bearing on their risk of future systemic lupus erythematosus.

When a patient comes in with mild cutaneous LE that’s not adequately controlled with photoprotection, topical agents, and hydroxychloroquine, Dr. Vleugels may opt for combination antimalarial therapy, adding on quinacrine at 100 mg/day. Quinacrine is not immunosuppressive and has essentially no ocular toxicity. Its two downsides are that it can be obtained only at a compounding pharmacy, and it causes many patients to turn yellow. The yellow hue is more noticeable on light-skinned patients. Fortunately, the color change is completely reversible upon drug discontinuation.

If a patient’s cutaneous LE is a little more serious and it isn’t reined in using hydroxychloroquine as sole systemic therapy, Dr. Vleugels will bypass the add-on quinacrine and go straight to methotrexate because the results are so good.

Not all patients are good candidates for methotrexate, however. And some just don’t want to take an immunosuppressive medication. Under those circumstances, her second-choice option is thalidomide. It’s typically dosed at 25-100 mg once at night because it’s sedating. This is a highly effective drug with Food and Drug Administration approval for multiple myeloma and erythema nodosum leprosum, so cutaneous LE is off-label therapy.