Given the growing body of evidence that cutaneous lupus erythematosus (LE) has systemic implications, “I’m beginning more and more patients earlier on antimalarials,” Dr. Jeffrey P. Callen said at a symposium sponsored by the American College of Rheumatology.
He cited findings from an Oklahoma Medical Research Foundation study in which investigators identified 130 U.S. military personnel who met ACR criteria for systemic LE (SLE). Twenty-six of them were previously treated with hydroxychloroquine (Plaquenil) when their disease was limited to the skin. The median time from their first skin lesions to diagnosis of SLE was 1.08 years, compared with 0.29 years in patients who did not receive hydroxychloroquine for their limited skin involvement.
The hydroxychloroquine-treated cohort also had a lower rate of autoantibody accumulation and fewer autoantibody specificities at the time they were diagnosed with SLE and thereafter. All of this is consistent with the notion that hydroxychloroquine therapy delays SLE onset, according to Dr. Callen, professor of medicine and chief of the division of dermatology at the University of Louisville (Ky).
In contrast, treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) had no impact on the length of time between onset of cutaneous LE and development of SLE (Lupus 2007;16:401-9).
Independent evidence that cutaneous LE not uncommonly progresses to SLE comes from a recent retrospective population-based Mayo Clinic study involving the entire population of Olmsted County, Minn. The investigators found that the collective incidence of all subtypes of cutaneous LE, exclusive of drug-induced LE, was 4.3 cases per 100,000 population during 1965-2005. That’s comparable with published figures for the incidence of SLE. The age- and gender-adjusted prevalence of cutaneous LE in early 2006 was 73.2 cases per 100,000 in this predominantly white population.
Cutaneous LE progressed to SLE in 12% of individuals, with a mean 8.2 years between the two diagnoses (Arch. Dermatol. 2009;145:249-53).
Dr. Callen noted that a prospective, blinded clinical trial would be needed to establish definitively that antimalarial therapy delays or prevents SLE. Even in the absence of such compelling evidence, he said he is a big believer in the early use of antimalarial agents in cutaneous LE for another reason: topical corticosteroids, widely advocated as first-line therapy, are not all that effective.
“They work well in clinical trials. They don’t work in clinical practice,” the dermatologist said.
The reason? They’re so messy and inconvenient that many patients simply do not use them as directed.
Intralesional corticosteroid injections are effective, but the benefits are temporary and many patients would rather take an oral medication than come in to the office for repeated injections, he continued.
His first-line systemic therapy is oral hydroxychloroquine at a maximum dose of 6.5 mg/kg of ideal body weight. At that dose, he has not encountered problems with ocular toxicity. Nonetheless, he tries to lower the dose once a patient’s disease is well controlled. Chloroquine seems to be slightly more effective than hydroxychloroquine but also more oculotoxic, according to Dr. Callen.
Smokers with cutaneous LE respond less robustly to antimalarials. If they can be persuaded to quit they will see further clinical improvement, although it often takes close to a year to become evident.
Sun-protective clothing and a broad-spectrum sunscreen are essential parts of the treatment of cutaneous LE. Dr. Callen recommends Neutrogena UltraSheer, which has desirable characteristics and is easy to find, to his patients with lupus or dermatomyositis.
A careful drug history is a must in patients with subacute cutaneous LE because the skin disease may be drug induced in upwards of one-fifth of cases. The most common offenders are hydrochlorothiazide and terbinafine. Others include ACE inhibitors, calcium channel blockers, bupropion, phenothiazines, anti–tumor necrosis factor agents, and statins. If a patient has been on a drug for more than 6 months prior to onset of cutaneous LE, the lesions are probably not drug induced. Clinical improvement or resolution of drug-induced subacute cutaneous LE typically occurs within a few weeks to 6 months after stopping the offending drug.
“If we in dermatology and you in rheumatology don’t get a careful drug history from the patients and alter the drugs they’re on, we’ll miss the opportunity to cure this disease,” he stressed.
In cutaneous LE patients who do not respond to or cannot tolerate antimalarials, there are good alternative systemic options.
“Thalidomide is a teratogen, but if you pick the right patients it works really well. Almost all patients with cutaneous lupus will respond to thalidomide, more than half with a complete response and the rest partially,” Dr. Callen said.