Strategic treatment targets immune system function

Chicago - New skin treatments are becoming increasingly specialized to treat the immune system in specific ways, Neal Bhatia, M.D., tells Dermatology Times.

Dermatologists should think of the mechanisms of the immune system and the mechanisms of available drugs and match them based on the immunologic profile of disease states, says Dr. Bhatia, a Milwaukee-based dermatologist and assistant clinical professor at the University of Wisconsin, Madison, Wis.

"You would consider whether a disease has a cellular profile, versus an antibody profile, or if it is an autoimmune-based disease or an infectious type. Then, you would think about which drugs would affect white blood cells versus neutrophils, versus an overall immunosurveillance, and fit the mechanism of the disease state so that you could modify the whole disease process and not just what is in front of you."

If one thinks of the T-helper cell, which Dr. Bhatia calls the "quarterback of the immune system," there are several drugs that affect interleukin (IL)-2, which is the main cytokine that the T-helper cell uses to create its effect.

"That is versus the Langerhans' cells, which is what we use to process antigen. When the Langerhans' are not working, then we have lost our ability to fight off tumors," Dr. Bhatia says.

For example, steroids, which are nonspecific, affect the Langerhans' and T-helper cells equally. However, drugs such as pimecrolimus or tacrolimus ointment 0.1 percent have a targeted affect only on the T-helper cells, he says.

"You know that because if you assay the amount of IL-1, it is not affected but the amount of IL-2 is," he adds.

This theory refutes claims that pimecrolimus could cause cancer in children, according to Dr. Bhatia, because the Langerhans' cells are not affected by the drug - so tumor surveillance should be intact.

Dermatologists treat psoriasis using biologic drugs but would not use imiquimod 5 percent cream because imiquimod enhances cellular immunity and psoriasis is already a disease of overactive cellular immunity.

"We would actually be creating a problem with Aldara (imiquimod) because it would recruit the same cytokines that are already at high levels. Whereas, Enbrel (Immunex) blocks the receptor for tumor necrosis factor (TNF) or drugs like efalizumab block the activity of the lymphocytes," he says.

Eczema, or atopic dermatitis, on the other hand, is a disease of antibody immunity or mast cells, which involves a different cytokine profile.

Atopic dermatitis is considered a disease of Th2 immunity. Imiquimod shifts the profile to more cellular immunity or Th1 immunity. Researchers doing trials on molluscum contagiosum, found that participants' eczema got better after imiquimod treatment, he says.

"Some say we should be using steroids and Elidel (Novartis) or Protopic (Fujisawa) because they make the inflammation go down," Dr. Bhatia says. "But you can also make the case that imiquimod, which makes the immune profile switch from an antibody profile to a cellular profile, might also impact the process causing atopic dermatitis. Researchers are using similar compounds to modify the disease process in asthma and not just addressing the flare-ups using imiquimod."

According to Dr. Bhatia, dermatologists can use the drugs at the same time in molluscum patients, even though they have opposite effects on the immune system because the Elidel is not impairing the effect of Aldara (3M Pharmaceuticals) on the individual lesions. There is not a subclinical process as there is with actinic keratoses and photo damage.

Other developments

Scientists are working on a topical dapsone formulation for acne targeted at neutrophils that cause the pustular component in acne, Dr. Bhatia says. The treatment is aimed not just at treating the open pores or comedones, but rather working on a different cell line to reduce inflammation, he says.

To treat warts, dermatologists used to use Candida antigens and squaric acid to stimulate immune responses against the infected keratinocytes; now, they use imiquimod to make the immune system work harder against the virus that is causing the wart.

Dermatologists typically use steroids to treat alopecia areata. So why would they want to use something like Aldara?