Resistant psoriasis: Lifelong therapies increase risks for cutaneous malignancies

January 1, 2009

Psoriasis patients treated for many years with PUVA therapy may be more susceptible to develop cutaneous carcinomas, such as basal cell carcinoma, especially when combined with short regimens of cyclosporine A. Physicians who must turn to this combination regimen in therapy-resistant psoriasis patients should be aware of the possible increased risk for the development of skin cancers in these patients.

Key Points

Though photochemotherapy with PUVA (psoralen + ultraviolet A) has proven its therapeutic value in many dermatoses, including psoriasis, this cornerstone therapy that is widely used in psoriatics may be instrumental in the eventual development of cutaneous carcinomas, such as basal cell carcinomas (BCCs), a recent case study shows.

Case study

No complete remission of the disease was achieved, despite continuous immunosuppressive treatments that included systemic acitretin, cyclosporine A, methotrexate, UVB and PUVA therapy, as well as topical treatments such as anthralin.

The patient responded best to PUVA therapy and, therefore, received more than 150 exposures to UVA. However, exacerbations of the psoriasis with erythroderma frequently occurred, leading Dr. Narbutt to sometimes combine the PUVA therapy with cyclosporine A.

Soon thereafter, the patient developed several nodular cutaneous lesions on the trunk that were diagnosed clinically as nodular BCCs, confirmed with histology, and subsequently treated with cryotherapy. A few months later, another BCC lesion arose (histologically confirmed) on the lateral trunk, which had a rapid growth up to 5 cm x 5 cm within a few months, and was then surgically removed.

"Treating therapy-resistant psoriasis patients can be very challenging. PUVA therapy may be very effective for treating psoriasis; however, multiple treatment sessions can, unfortunately, cause the development of basal cell carcinomas, as witnessed in this patient," Dr. Narbutt tells Dermatology Times.

A 'fine line'

According to Dr. Narbutt, dermatologists sometimes need to walk a very fine line when treating therapy-resistant psoriasis patients.

Years of constant psoriasis therapy, and sometimes combination therapies, are needed to control the disease, and aggressive combination therapies are sometimes warranted, especially in cases of exacerbated disease.

The downside is that the immune system can become so compromised that basal cell carcinomas can develop.

Dr. Narbutt suspects that the BCCs developed as a result of the combination therapy with PUVA and cyclosporine A. However, the combination of cyclosporine A and PUVA therapy can prove to be disastrous for the patient in terms of the increased risk of cutaneous malignancies. This may be especially true if the two regimens are given in close succession.

"Ideally, there should be at least a three-month interval between these two therapies in any patient, but in the case of a therapy-resistant psoriasis patient who develops erythrodermic psoriasis, there are not many choices on the table. We managed to improve and control the exacerbation, but the patient developed skin cancers. Therefore, these particular patients must be closely followed," Dr. Narbutt says.

Biologics

The advent of the biologics has given hope for psoriasis patients, as the current clinical results are promising, but, according to Dr. Narbutt, long-term safety studies are still lacking, and the true safety of the biologics will only be seen years later.

Acitretin is also used to treat psoriasis and does not increase the patient's risk of developing cutaneous malignancies; however, the drug is not always effective in treating psoriasis.

Individualized treatment

Elderly patients are more susceptible to developing skin cancers, such as BCCs, whether due to years of sun exposure resulting in sundamaged skin or due to the immuno-suppression commonly seen in this patient population.

According to Dr. Narbutt, the repeated PUVA therapy combined with the cyclosporine was most likely responsible for the patient's development of BCCs.

"I believe that the treatment for psoriasis should be individualized. Young psoriasis patients should be started on PUVA treatment because it simply is the least aggressive therapy available today, especially when compared to immunosuppressive drug therapies like cyclosporine and methotrexate," Dr. Narbutt says.

Disclosure: Dr. Narbutt reports no relevant financial disclosures.

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