Systemic therapy: Doctors eye fresh approaches to cutaneous lupus

Philadelphia - Many different approaches are used to treat the clinical symptoms of cutaneous lupus erythematosus (CLE), both topically and systemically. However, when topical regimens prove insufficient to control a flare in refractory cases, clinicians must additionally implement systemic therapy.Topical therapies, such as calcineurin inhibitors, corticosteroids and stronger sunscreens, can be effective in the treatment of CLE.

Depending on how extensive the lesions are, intralesional corticosteroids can be used, especially on the scalp. In more difficult cases, however, systemic agents are added to the therapeutic regimen. Antimalarials, such as hydroxychloroquine, chloroquine and quinacrine, remain the gold standard treatment.

"Topical steroids may be effective, and calcineurin inhibitors, such as pimecrolimus and tacrolimus, can be helpful adjunctive therapy, particularly in lesions occurring on the face," says Victoria P. Werth, M.D., chief of dermatology at Philadelphia Veternas Hospital, Philadelphia, and professor of dermatology,University of Pennsylvania.

Antimalarials

Dr. Werth commonly uses antimalarials, and often combines them to more effectively treat CLE especially in refractive cases. She says that hydroxychloroquine and chloroquine cannot be used together because of additive eye toxicity, but the combination of quinacrine with either hydroxychloroquine or chloroquine can prove to be effective for patients who don’t respond to hydroxychloroquine alone.

According to Dr. Werth, patients with significant disease often warrant the combination treatment of topicals such as corticosteroids and calcineurin inhibitors with antimalarials. Immunosuppressant drugs, such as azathioprine, methotrexate, mycophenolate mofetil and thalidomide, should be reserved for those patients who have been unable to tolerate or who have failed to respond to more conservative therapies.

"For those patients who do not tolerate antimalarial therapy or have rather severe disease, we may also think about the use of thalidomide as a therapy that can work quickly. Thalidomide has a 75 percent efficacy in those cases which are refractory to antimalarials.

"The use of thalidomide is often limited because of the high incidence of developing peripheral neuropathy, which in some cases is irreversible. Thalidomide can achieve remarkable results in clearing cutaneous lesions in certain cases," Dr. Werth tells Dermatology Times.

Adjunct therapies

In very resistant and severe cases, Dr. Werth sometimes starts the patient on antimalarials, and while waiting for their therapeutic effect to begin - which can take up to two to three months - she also gives the patient thalidomide to bridge over the therapeutic gap. When the antimalarials start to work, thalidomide can then be removed from the regimen.

Dapsone is not very useful as a solitary agent in those patients who have other forms of CLE, but according to Dr. Werth, it can sometimes be helpful in bullous lupus, a rare subset of the disease. The drug can be used as an adjunct along with the antimalarials.

Intravenously administered immunoglobulins are effective in a similar disease, dermatomyositis, and there are anecdotal reports of effectiveness in CLE.

Off-label

There has been some data showing that efalizumab could be beneficial for some patients with resistant cutaneous lupus, and though not the rule, rebounds have occurred with this therapy.Efalizumab can be considered for off-label use in severe refractory patients, but there is a need for randomized controlled trials before routinely recommending this approach.

Similarly, there have not been organized studies of the use of TNF-alpha blockers in cutaneous lupus, and because of some concerns relating to the potential for exacerbating autoimmune disease, these drugs are primarily used for patients where overlapping arthritis is the primary therapeutic problem.

Photoprotection

Thorough photoprotection is crucial in the therapy of patients with CLE. The use of proper clothing that protects patients from UV exposure, as well as the use of improved sunscreens available on the market, are cornerstones of photoprotection.

According to Dr. Werth, it is helpful to educate patients about which products are best to use, and in particular those that block both UVB and UVA effectively. Also, it can sometimes be helpful for patients to have filters on their windows to block the longer wavelengths of light and to cover fluorescent light bulbs they may have at home or in the work place. DT

Disclosures: Dr. Werth consults for Celgene and has consulted for Genentech.