Jashin J. Wu (ed.)Clinical Cases in PsoriasisClinical Cases in Dermatology10.1007/978-3-319-52779-6_16

16. 69-Year-Old with Psoriasis and a History of Skin Cancer

Daniel J. No¹, Mina Amin², Kavita Darji³ and Jashin J. Wu⁴

(1)

Loma Linda University School of Medicine, Loma Linda, CA, USA

(2)

University of California, Riverside School of Medicine, Riverside, CA, USA

(3)

Saint Louis University School of Medicine, St. Louis, MO, USA

(4)

Wu Medical Associates, Inc., Los Angeles, CA, USA

Jashin J. Wu

Email: jashinwu@gmail.com

Keywords

Squamous cell carcinomaBasal cell carcinomaSkin cancerMalignancySystemicAcitretinBiologic

A 69-year-old female with a long history of psoriasis presented to the clinic for follow-up after undergoing electrodesiccation and curettage of nonmetastatic squamous cell carcinoma on the left knee. Her psoriasis and psoriatic arthritis have been managed with methotrexate for the past 5 months. She has no prior history of cancer, but multiple actinic keratoses and squamous cell carcinoma have been noted in previous visits. Two previous squamous cell carcinomas were found on the left forearm and left lateral shin and treated similarly with electrodesiccation and curettage. Follow-up visits have not shown signs of recurrence. The patient denies a history of smoking, exposure to radiation, and use of other immunosuppressant medications. She does admit to excessive ultraviolet light exposure and minimal use of sunscreen. The patient has a family history of psoriasis. However, she denies a family history of cancer, including skin cancer.

On physical examination, there were erythematous scaly papules and plaques on the face and legs. Erythematous well-demarcated plaques were found on both inframammary skin folds. The total affected body surface area was approximately 10%. The left lateral knee showed a well-healed scar with no visible signs of recurrence. Multiple rough, scaly actinic keratoses were found on the face, hands, and ears.

Based on the case description, what is the best treatment recommendation for this patient?

1.

Ustekinumab
2.

Acitretin
3.

Methotrexate
4.

Adalimumab
5.

Cyclosporine

Treatment

Acitretin

Discussion

The chronic inflammatory nature of psoriasis and the frequent use of immunosuppressive medications both raise concern for malignancy. Although some systemic medications used in the treatment of psoriasis increase the risk of malignancy, studies have shown that they are not the sole cause. Pouplard et al. demonstrated that patients with a history of psoriasis had a statistically significant increased risk of developing non-melanoma skin cancer (NMSC) (Pouplard et al. 2013). Melanoma, however, does not appear to be associated with psoriasis (Chiesa Fuxench et al. 2016). Of note, many studies exhibit a trend of increased risk of malignancy with increasing psoriasis severity.

The majority of systemic medications used in the treatment of psoriasis are considered immunomodulators. Although the level of immunosuppression is relatively low, theoretically they have the potential to increase the risk of NMSC and cancer. It is widely recognized that solid organ transplant recipients receiving long-term immunosuppression are at a significantly increased risk of developing NMSC (Tessari and Girolomoni 2012). Skin cancer likely results from the downregulation of mechanisms involved in cancer immunosurveillance (Ulrich et al. 2008). Consequently, all patients using medications associated with malignancy should consider routine skin cancer surveillance and follow general measures such as photoprotection. Patients with a known history of NMSC should avoid the use of medications correlated with an increased risk of malignancy.

Unlike many systemic medications used in the treatment of psoriasis, acitretin does not suppress the immune system or increase the potential for malignancy. Acitretin is a well-documented chemopreventive agent commonly used in immunosuppressed patients such as organ transplant recipients. Numerous studies have shown acitretin to be effective in reducing the incidence of NMSC in high-risk patients (Bettoli et al. 2013). Given these facts, acitretin is a valuable form of treatment for patients with psoriasis and a personal history of NMSC.

Apremilast, a phosphodiesterase-4 inhibitor, modulates key inflammatory mediators that are vital to the pathogenesis of psoriasis. The effect of apremilast is primarily anti-inflammatory and thus far has not shown clinical signs of immunosuppression (Chimenti et al. 2015). A 52-week study evaluating the safety of apremilast reported the development of cutaneous squamous cell carcinoma (SCC) in only 2 out of 804 patients (Papp et al. 2015). Additionally, the incidence rates of malignancies in ESTEEM 1 and ESTEEM 2 trials were comparable between apremilast and placebo (Paul et al. 2015).

Biologic agents are considered immunosuppressive medications and can theoretically increase the risk of cancer. In spite of this, IL-17-targeting biologics have not been shown to increase the risk of cutaneous malignancies. The findings of a 52-week study demonstrated that the incidence of NMSC and tumors are not increased in patients using secukinumab (Blauvelt 2016). Of the participants who developed NMSC, the majority had a history of prior phototherapy.

Narrowband ultraviolet B (NB-UVB) phototherapy is generally considered to be safe, and the majority of published data suggests no associated cancer risk. A study found no significant increase in the incidence of NMSC or melanoma in 3876 patients receiving NB-UVB treatment (Hearn et al. 2008). A literature review of 11 studies with approximately 3400 patients came to a consensus that none of the published studies showed an increase in skin risk with UVB phototherapy (Lee et al. 2004). However, one study did show an increased incidence of genital SCC in men exposed to both PUVA and UVB radiation. The data on melanoma incidence is not as complete; however, the risk of melanoma does not appear to be increased in comparison to the general public. Caution should be exercised in those with a history of melanoma or multiple NMSC.

Oral psoralen and ultraviolet A light (PUVA) treatments of psoriasis increase the risk of cutaneous malignancies. A systemic literature review determined the most frequent malignancy reported with PUVA therapy is SCC (Archier et al. 2012). Additionally, their analysis revealed a significant correlation between the amount of exposure and level of risk. A higher incidence of BCC was also observed in patients who received over 100 PUVA sessions. The incidence of melanoma was doubled in patients who received at least 200 PUVA treatments. Other studies have demonstrated an additive interaction between PUVA and other systemic therapies. Patients using cyclosporine were at a higher risk of developing SCC if they were exposed to PUVA (Marcil and Stern 2001).

Cyclosporine use is associated with an increased risk of lymphoma, internal malignancy, and NMSC. The majority of findings are described in solid organ transplant recipients who require cyclosporine at high doses for long periods of time. Patients with psoriasis receive considerably lower doses for limited durations. Nonetheless, a long-term cohort study and multiple case studies have demonstrated that cyclosporine, given as a standard dose for treatment of psoriasis, increases the risk of NMSC (Lain and Markus 2004; Paul et al. 2003). For this reason, the use of cyclosporine in a patient with a history of cutaneous malignancy is discouraged.

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