Psoriasis Therapies and the Risk of Cutaneous Malignancy

Main Article Content

Emily E Dando
Rina A Anvekar


psoriasis, nonmelanoma skin cancer, melanoma, PUVA, ultraviolet therapy, cyclosporine, methotrexate, retinoids, biologics, TNF-alpha, IL-12/23, IL-17



Background: Systemic therapies for moderate to severe psoriasis target the dysregulated inflammatory response. However, their immunomodulatory properties may also contribute to carcinogenesis, leading to increased risk of cutaneous malignancy in patients exposed to systemic agents.

Objective: A review of the literature was performed to evaluate the risk of cutaneous malignancy associated with the following therapies for moderate to severe psoriasis: PUVA, UVB, cyclosporine, methotrexate, retinoids, TNF-a inhibitors, IL-12/23 inhibitors, and IL-17 inhibitors.

Results: Rates of NMSC, most notably SCC, increase linearly with number of PUVA exposures. UVB radiation, both narrowband and broadband, has no clear association with skin cancer. There is a well-characterized association between cyclosporine and NMSC, particularly SCCs, although it is less clear whether cyclosporine predisposes to malignant melanoma. Methotrexate appears to increase the risk of melanoma and NMSC in a dose-dependent fashion. Retinoids, on the other hand, have chemopreventative properties and may decrease risk of NMSC in patients with psoriasis. A large body of evidence supports an increased risk of NMSC, particularly SCC, in TNF-a inhibitors, but an association with melanoma is less clear. The newly-developed agents, IL-12/23 and IL-17 inhibitors, do not clearly show increased carcinogenic risk, but their long-term safety profiles are still under investigation.

Conclusions: Many systemic psoriasis therapies, including PUVA, cyclosporine, methotrexate, and TNF-a inhibitors, appear to increase the risk of cutaneous malignancy. When prescribing these agents, physicians must weigh the benefit of treatment with their carcinogenic potential. Additional post-marketing surveillance is required to better understand the long-term risks of the newer biologic agents.


1. Rachakonda, T.D., C.W. Schupp, and A.W. Armstrong, Psoriasis prevalence among adults in the United States. J Am Acad Dermatol, 2014. 70(3): p. 512-6.

2. Pouplard, C., et al., Risk of cancer in psoriasis: a systematic review and meta-analysis of epidemiological studies. J Eur Acad Dermatol Venereol, 2013. 27 Suppl 3: p. 36-46.

3. Chiesa Fuxench, Z.C., et al., The Risk of Cancer in Patients With Psoriasis: A Population-Based Cohort Study in the Health Improvement Network. JAMA Dermatol, 2016. 152(3): p. 282-90.

4. Chen, Y.J., et al., The risk of cancer in patients with psoriasis: a population-based cohort study in Taiwan. J Am Acad Dermatol, 2011. 65(1): p. 84-91.

5. Kimball, A.B., et al., Incidence rates of malignancies and hospitalized infectious events in patients with psoriasis with or without treatment and a general population in the U.S.A.: 2005-09. Br J Dermatol, 2014. 170(2): p. 366-73.

6. Stern, R.S. and P.F.-U. Study, The risk of squamous cell and basal cell cancer associated with psoralen and ultraviolet A therapy: a 30-year prospective study. J Am Acad Dermatol, 2012. 66(4): p. 553-62.

7. Marcil, I. and R.S. Stern, Squamous-cell cancer of the skin in patients given PUVA and ciclosporin: nested cohort crossover study. Lancet, 2001. 358(9287): p. 1042-5.

8. Nijsten, T.E. and R.S. Stern, Oral retinoid use reduces cutaneous squamous cell carcinoma risk in patients with psoriasis treated with psoralen-UVA: a nested cohort study. J Am Acad Dermatol, 2003. 49(4): p. 644-50.

9. Nijsten, T.E. and R.S. Stern, The increased risk of skin cancer is persistent after discontinuation of psoralen+ultraviolet A: a cohort study. J Invest Dermatol, 2003. 121(2): p. 252-8.

10. Lindelof, B., et al., PUVA and cancer risk: the Swedish follow-up study. Br J Dermatol, 1999. 141(1): p. 108-12.

11. Bruynzeel, I., et al., 'High single-dose' European PUVA regimen also causes an excess of non-melanoma skin cancer. Br J Dermatol, 1991. 124(1): p. 49-55.

12. Hannuksela-Svahn, A., et al., Psoriasis, its treatment, and cancer in a cohort of Finnish patients. J Invest Dermatol, 2000. 114(3): p. 587-90.

13. Stern, R.S., K.T. Nichols, and L.H. Vakeva, Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study. N Engl J Med, 1997. 336(15): p. 1041-5.

14. Stern, R.S. and P.F.u. Study, The risk of melanoma in association with long-term exposure to PUVA. J Am Acad Dermatol, 2001. 44(5): p. 755-61.

15. Walters, I.B., et al., Suberythemogenic narrow-band UVB is markedly more effective than conventional UVB in treatment of psoriasis vulgaris. J Am Acad Dermatol, 1999. 40(6 Pt 1): p. 893-900.

16. Lee, E., J. Koo, and T. Berger, UVB phototherapy and skin cancer risk: a review of the literature. Int J Dermatol, 2005. 44(5): p. 355-60.

17. Lim, J.L. and R.S. Stern, High levels of ultraviolet B exposure increase the risk of non-melanoma skin cancer in psoralen and ultraviolet A-treated patients. J Invest Dermatol, 2005. 124(3): p. 505-13.

18. Stern, R.S., Genital tumors among men with psoriasis exposed to psoralens and ultraviolet A radiation (PUVA) and ultraviolet B radiation. The Photochemotherapy Follow-up Study. N Engl J Med, 1990. 322(16): p. 1093-7.

19. Pittelkow, M.R., et al., Skin cancer in patients with psoriasis treated with coal tar. A 25-year follow-up study. Arch Dermatol, 1981. 117(8): p. 465-8.

20. Hearn, R.M., et al., Incidence of skin cancers in 3867 patients treated with narrow-band ultraviolet B phototherapy. Br J Dermatol, 2008. 159(4): p. 931-5.

21. Carroll, R.P., et al., Incidence and prediction of nonmelanoma skin cancer post-renal transplantation: a prospective study in Queensland, Australia. Am J Kidney Dis, 2003. 41(3): p. 676-83.

22. Lindelof, B., et al., Incidence of skin cancer in 5356 patients following organ transplantation. Br J Dermatol, 2000. 143(3): p. 513-9.

23. Hojo, M., et al., Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature, 1999. 397(6719): p. 530-4.

24. Paul, C.F., et al., Risk of malignancies in psoriasis patients treated with cyclosporine: a 5 y cohort study. J Invest Dermatol, 2003. 120(2): p. 211-6.

25. Arellano, F. and P.F. Krupp, Cutaneous malignant melanoma occurring after cyclosporin A therapy. Br J Dermatol, 1991. 124(6): p. 611.

26. Merot, Y., et al., Cutaneous malignant melanomas occurring under cyclosporin A therapy: a report of two cases. Br J Dermatol, 1990. 123(2): p. 237-9.

27. Chakravarty, E.F., K. Michaud, and F. Wolfe, Skin cancer, rheumatoid arthritis, and tumor necrosis factor inhibitors. J Rheumatol, 2005. 32(11): p. 2130-5.

28. Buchbinder, R., et al., Incidence of melanoma and other malignancies among rheumatoid arthritis patients treated with methotrexate. Arthritis Rheum, 2008. 59(6): p. 794-9.

29. Polesie, S., et al., Methotrexate treatment and risk for cutaneous malignant melanoma: a retrospective comparative registry-based cohort study. Br J Dermatol, 2016.

30. Carr, D.R., J.J. Trevino, and H.B. Donnelly, Retinoids for chemoprophylaxis of nonmelanoma skin cancer. Dermatol Surg, 2011. 37(2): p. 129-45.

31. Kraemer, K.H., et al., Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med, 1988. 318(25): p. 1633-7.

32. Bavinck, J.N., et al., Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study. J Clin Oncol, 1995. 13(8): p. 1933-8.

33. Tangrea, J.A., et al., Long-term therapy with low-dose isotretinoin for prevention of basal cell carcinoma: a multicenter clinical trial. Isotretinoin-Basal Cell Carcinoma Study Group. J Natl Cancer Inst, 1992. 84(5): p. 328-32.

34. McKenna, D.B. and G.M. Murphy, Skin cancer chemoprophylaxis in renal transplant recipients: 5 years of experience using low-dose acitretin. Br J Dermatol, 1999. 140(4): p. 656-60.

35. Weinstock, M.A., et al., Tretinoin and the prevention of keratinocyte carcinoma (Basal and squamous cell carcinoma of the skin): a veterans affairs randomized chemoprevention trial. J Invest Dermatol, 2012. 132(6): p. 1583-90.

36. Asher, A.L., et al., Murine tumor cells transduced with the gene for tumor necrosis factor-alpha. Evidence for paracrine immune effects of tumor necrosis factor against tumors. J Immunol, 1991. 146(9): p. 3227-34.

37. Askling, J., et al., Cancer risk with tumor necrosis factor alpha (TNF) inhibitors: meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data. Pharmacoepidemiol Drug Saf, 2011. 20(2): p. 119-30.

38. Mariette, X., et al., Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis. Ann Rheum Dis, 2011. 70(11): p. 1895-904.

39. Asgari, M.M., et al., Malignancy rates in a large cohort of patients with systemically treated psoriasis in a managed care population. J Am Acad Dermatol, 2017. 76(4): p. 632-638.

40. Wolfe, F. and K. Michaud, Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum, 2007. 56(9): p. 2886-95.

41. Gordon, K.B., et al., Long-term safety experience of ustekinumab in patients with moderate to severe psoriasis (Part II of II): results from analyses of infections and malignancy from pooled phase II and III clinical trials. J Am Acad Dermatol, 2012. 66(5): p. 742-51.

42. Papp, K.A., et al., Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up. Br J Dermatol, 2013. 168(4): p. 844-54.

43. Numasaki, M., et al., Interleukin-17 promotes angiogenesis and tumor growth. Blood, 2003. 101(7): p. 2620-7.

44. Benchetrit, F., et al., Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism. Blood, 2002. 99(6): p. 2114-21.

45. van de Kerkhof, P.C., et al., Secukinumab long-term safety experience: A pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol, 2016. 75(1): p. 83-98 e4.

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