Treating organ transplant recipients: Looking at topical treatment options for actinic keratosis

Key Points

Berlin - Total clearance of actinic keratosis (AK) lesions is the general aim of topical treatments such as diclofenac, imiquimod and photodynamic therapy (PDT).

This can be achieved in patients with a fully functional and strong immune system; however, in immunosuppressed individuals, such as in organ transplant recipients (OTRs), the rules change dramatically.

According to one expert, an effective long-term therapy for AKs and prevention of invasive squamous cell carcinoma (SCC) in these patients has yet to be demonstrated.

"It is important to treat AKs in OTRs because of the high rate of these precancerous lesions to progress into invasive squamous cell carcinoma, mostly as a result of the significant immunosuppression that these patients have.

"Organ transplant recipients should, therefore, be treated especially, consequently, because of the propensity for AKs to rapidly change to invasive squamous cell carcinoma," says Claas Ulrich, M.D., department of dermatology, allergy and venereology, Charite University Hospital, Berlin.

It is still unclear to what extent SCCs develop de novo and how many develop from AKs, posing a particular problem as to the "right" therapeutic approach.

Most dermatologists, however, agree that the majority of invasive SCCs occur on the basis of a previous AK lesion.

To add insult to injury, AKs often arise in the immediate vicinity of previously treated AK lesions, a phenomenon known as field cancerization.

Effective therapies

"There is evidence that topical 5-fluorouracil (5-FU) is effective in the treatment of AKs, as well as the cancerization field, which is not immediately evident to the naked eye, but a very real issue and problem," Dr. Ulrich tells Dermatology Times.

Other effective therapies for the treatment of AKs are diclofenac (Solaraze), hyaluronic acid, imiquimod (Aldara) and PDT, the latter initially viewed as a formidable therapeutic approach to the development as well as the prevention of AKs and SCCs.

Long-term efficacy

Dr. Ulrich says that long-term efficacy results of these topical therapies are lacking, and future studies should be geared to pioneer these therapeutic pathways, as an effective therapeutic regimen for these patients is direly needed.

"Clinical trials demonstrating long-term efficacy rates for PDT, diclofenac and imiquimod in OTRs in the treatment and prevention of the development of SCC, or in the controlling of the growth of AKs, are needed post-haste in order to critically and wisely be able to choose the most effective treatment approach for these patients," Dr. Ulrich says.

Combination treatment

Dr. Ulrich adds that studies have been done in which a beneficial therapeutic effect was seen in the treatment of AKs and SCCs with the combination of 5-FU and imiquimod; however, long-term studies lack here as well.

According to Dr. Ulrich, topical diclofenac, imiquimod and PDT are good alternatives to topical 5-FU, as here, the adverse-event profiles are less toxic to the patients.

No gold standard

Again, these therapies are good for the short term (months to a couple of years), but comparative studies are still needed for these medications to prove themselves as the gold standard of treatment, especially for the long-term prevention of SCCs.

"I believe it is very beneficial for such patients to combine these topical therapies with long-term sun protection. Following the application of these topical therapies, the treated areas may not be completely free of dysplasia, but much of the AK lesions were effectively treated," Dr. Ulrich says.

"In order to prevent a further progression of these precancerous lesions, patients must religiously apply strong sun screens to make sure that these sun-exposed areas are properly protected, especially in OTR patients," he adds.

mTOR inhibitors

Evolving immunosuppressive therapies that are negatively associated with skin cancers include the group of mammalian Target of Rapamycin (mTOR) inhibitors, such as Sirolimus and Everolimus, commonly administered to OTRs.

These mTOR inhibitors affect the proliferation rate and the perfusion rate of skin malignancies and, therefore, are negatively associated with skin cancers following organ transplantation, seen especially with non-melanoma skin cancer and Kaposi sarcoma.

According to Dr. Ulrich, these drugs have been on the market for some years now, but it is only recently that physicians realized that one positive side effect of the drug was to positively effect the development of AKs and SCCs.

According to Dr. Ulrich, OTRs who take mTOR inhibitors have a good chance of keeping AKs and SCCs at bay.