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Hyperkeratotic Skin Adverse Events Induced by Anticancer Treatments: A Comprehensive Review

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Abstract

Hyperkeratotic skin adverse events are a group of toxic effects, characterized by the disruption of epidermal homeostasis and interaction with keratinocyte proliferation/differentiation or keratinocyte survival, and frequently reported with systemic anticancer treatments. These types of reactions include hand–foot skin reaction or palmoplantar keratoderma, induced psoriasis, keratosis pilaris-like or pityriasis rubra pilaris-like rashes, Grover’s disease, and contact hyperkeratosis. Cutaneous squamoproliferative lesions are also described because of the presence of abnormal keratinocyte proliferation. They are usually observed with tyrosine kinase inhibitors but have also been described in association with cytotoxic chemotherapeutic agents. Their pathogenesis is related mainly to the disruption of epidermal homeostasis and interaction with keratinocyte proliferation/differentiation or keratinocyte survival caused by anticancer treatment. Early recognition and adequate management are critical to prevent exacerbation of the lesions, to limit treatment interruption, and to minimize impairment of quality of life. This review summarizes the current knowledge concerning the presentation, pathogenesis, and management of secondary hyperkeratotic reactions to anticancer therapies. It also includes hyperkeratotic reactions that have been more recently described with newly approved targeted therapies or immune checkpoint inhibitors, such as keratosis pilaris-like exanthema with second-generation BCR-ABL inhibitors, lamellar ichthyosis-like lesions with ponatinib, pityriasis rubra pilaris with the newly approved selective phosphoinositide 3 kinase inhibitor idelalisib, or psoriasis with anti-programmed death-1 and programmed death ligand-1.

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References

  1. Sibaud V. Dermatologic reactions to immune checkpoint inhibitors: skin toxicities and immunotherapy. Am J Clin Dermatol. 2018;19(3):345–61.

    PubMed  Google Scholar 

  2. Boussemart L, Routier E, Mateus C, Opletalova K, Sebille G, Kamsu-Kom N, et al. Prospective study of cutaneous side-effects associated with the BRAF inhibitor vemurafenib: a study of 42 patients. Ann Oncol. 2013;24:1691–7.

    CAS  PubMed  Google Scholar 

  3. Carlos G, Anforth R, Clements A, Menzies AM, Carlino MS, Chou S, et al. Cutaneous Toxic Effects of BRAF Inhibitors Alone and in Combination With MEK Inhibitors for Metastatic Melanoma. JAMA Dermatol. 2015;151:1103–9.

    PubMed  Google Scholar 

  4. Alloo A, Sheu J, Butrynski JE, DeAngelo DJ, George S, Murphy GF, et al. Ponatinib-induced pityriasiform, folliculocentric and ichthyosiform cutaneous toxicities. Br J Dermatol. 2015;173:574–7.

    CAS  PubMed  Google Scholar 

  5. Ding F, Liu B, Wang Y. Risk of hand-foot skin reaction associated with VEGFR-TKIs: a meta-analysis of 57 randomized controlled trials involving 24956 patients. J Am Acad Dermatol. 2019;S0190–9622(19):30607-3.

    Google Scholar 

  6. Robert C, Mateus C, Spatz A, Wechsler J, Escudier B. Dermatologic symptoms associated with the multikinase inhibitor sorafenib. J Am Acad Dermatol. 2009;60:299–305.

    PubMed  Google Scholar 

  7. Drucker AM, Wu S, Busam KJ, Berman E, Amitay-Laish I, Lacouture ME. Rash with the multitargeted kinase inhibitors nilotinib and dasatinib: meta-analysis and clinical characterization. Eur J Haematol. 2013;90:142–50.

    CAS  PubMed  Google Scholar 

  8. Delgado L, Giraudier S, Ortonne N, Zehou O, Cordonnier C, Hulin A, et al. Adverse cutaneous reactions to the new second-generation tyrosine kinase inhibitors (dasatinib, nilotinib) in chronic myeloid leukemia. J Am Acad Dermatol. 2013;69:839–40.

    PubMed  Google Scholar 

  9. Patel AB, Solomon AR, Mauro MJ, Ehst BD. Unique cutaneous reaction to second- and third-generation tyrosine kinase inhibitors for chronic myeloid leukemia. Dermatology. 2016;232:122–5.

    CAS  PubMed  Google Scholar 

  10. Hansen T, Little AJ, Miller JJ, Ioffreda MD. A case of inflammatory nonscarring alopecia associated with the tyrosine kinase inhibitor nilotinib. JAMA Dermatol. 2013;149:330–2.

    PubMed  Google Scholar 

  11. Cortes JE, Kim DW, Pinilla-Ibarz J, Le Coutre PD, Paquette R, Chuah C, et al. Ponatinib efficacy and safety in Philadelphia chromosome–positive leukemia: final 5-year results of the phase 2 PACE trial. Blood. 2018;132:393–404.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Lipton JH, Chuah C, Guerci-Bresler A, Rosti G, Simpson D, Assouline S, et al. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17(5):612–21.

    CAS  PubMed  Google Scholar 

  13. Jack A, Mauro MJ, Ehst BD. Pityriasis rubra pilaris-like eruption associated with the multikinase inhibitor ponatinib. J Am Acad Dermatol. 2013;69(5):e249–50.

    PubMed  Google Scholar 

  14. Eber AE, Rosen A, Oberlin KE, Giubellino A, Romanelli P. Ichthyosiform pityriasis rubra pilaris-like eruption secondary to ponatinib therapy: case report and literature review. Drug Saf Case Rep. 2017;4:19.

    PubMed  PubMed Central  Google Scholar 

  15. Örenay ÖM, Tamer F, Sarıfakıoğlu E, Yıldırım U. Lamellar ichthyosis-like eruption associated with ponatinib. Acta Dermatovenerol Alp Pannonica Adriat. 2016;25(3):59–60.

    PubMed  Google Scholar 

  16. Derlino F, Barruscotti S, Zappasodi P, Brazzelli V, Vassallo C. Ponatinib-induced widespread ichthyosiform eruption. J Eur Acad Dermatol Venereol. 2017;31(12):e519–21.

    CAS  PubMed  Google Scholar 

  17. Lacouture ME, Duvic M, Hauschild A, Prieto VG, Robert C, Schadendorf D, et al. Analysis of dermatologic events in vemurafenib-treated patients with melanoma. Oncologist. 2013;18:314–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Sanlorenzo M, Choudhry A, Vujic I, Posch C, Chong K, Johnston K, et al. Comparative profile of cutaneous adverse events: bRAF/MEK inhibitor combination therapy versus BRAF monotherapy in melanoma. J Am Acad Dermatol. 2014;71:1102–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Dummer R, Ascierto PA, Gogas HJ, Arance A, Mandala M, Liszkay G, et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2018;19(5):603–15.

    CAS  PubMed  Google Scholar 

  20. Graf NP, Koelblinger P, Galliker N, Conrad S, Barysch M, Mangana J, et al. The spectrum of cutaneous adverse events during encorafenib and binimetinib treatment in B-rapidly accelerated fibrosarcoma-mutated advanced melanoma. J Eur Acad Dermatol Venereol. 2019;33(4):686–92.

    CAS  PubMed  Google Scholar 

  21. Kong HH, Turner ML. Array of cutaneous adverse effects associated with sorafenib. J Am Acad Dermatol. 2009;61:360–1.

    PubMed  PubMed Central  Google Scholar 

  22. Dewan AK, Sowerby L, Jadeja S, Lian C, Wen P, Brown JR, Fisher DC, LeBoeuf NR. Pityriasis rubra pilaris-like erythroderma secondary to phosphoinositide 3-kinase inhibition. Clin Exp Dermatol. 2018;43(8):890–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Anforth R, Fernandez-Peñas P, Long GV. Cutaneous toxicities of RAF inhibitors. Lancet Oncol. 2013;14(1):e11–8.

    CAS  PubMed  Google Scholar 

  24. Gantz M, Butler D, Goldberg M, Ryu J, McCalmont T, Shinkai K. Atypical features and systemic associations in extensive cases of Grover disease: a systematic review. J Am Acad Dermatol. 2017;77:952–7.

    PubMed  Google Scholar 

  25. Villalon G, Martin JM, Monteagudo C, Alonso V, Ramon D, Jorda E. Clinicopathological spectrum of chemotherapy induced Grover’s disease. J Eur Acad Dermatol Venereol. 2007;21(8):1145–7.

    CAS  PubMed  Google Scholar 

  26. Anforth RM, Blumetti TC, Kefford RF, Sharma R, Scolyer RA, Kossard S, et al. Cutaneous manifestations of dabrafenib (GSK2118436): a selective inhibitor of mutant BRAF in patients with metastatic melanoma. Br J Dermatol. 2012;167:1153–60.

    CAS  PubMed  Google Scholar 

  27. Anforth R, Carlos G, Clements A, Kefford R, Fernandez-Peñas P. Cutaneous adverse events in patients treated with BRAF inhibitor-based therapies for metastatic melanoma for longer than 52 weeks. Br J Dermatol. 2015;172:239–43.

    CAS  PubMed  Google Scholar 

  28. Chen WS, Tetzlaff MT, Diwan H, Jahan-Tigh R, Diab A, Nelson K, et al. Suprabasal acantholytic dermatologic toxicities associated checkpoint inhibitor therapy: a spectrum of immune reactions from paraneoplastic pemphigus-like to Grover-like lesions. J Cutan Pathol. 2018;45(10):764–73.

    PubMed  Google Scholar 

  29. Sibaud V, Lebœuf NR, Roche H, Belum VR, Gladieff L, Deslandres M, et al. Dermatological adverse events with taxane chemotherapy. Eur J Dermatol. 2016;26:427–43.

    PubMed  PubMed Central  Google Scholar 

  30. Cagiano R, Bera I, Vermesan D, Flace P, Sabatini R, Bottalico L, et al. Psoriasis disappearance after the first phase of an oncologic treatment: a serendipity case report. Clin Ter. 2008;159:421–5.

    CAS  PubMed  Google Scholar 

  31. Landi D, Santini D, Vincenzi B, La Cesa A, Dianzani C, Tonini G. Dramatic improvement of psoriasis with gemcitabine monotherapy. Br J Dermatol. 2003;149:1306–7.

    CAS  PubMed  Google Scholar 

  32. Akman A, Yilmaz E, Mutlu H, Ozdogan M. Complete remission of psoriasis following bevacizumab therapy for colon cancer. Clin Exp Dermatol. 2009;34:e202–4.

    CAS  PubMed  Google Scholar 

  33. Narayanan S, Callis-Duffin K, Batten J, Agarwal N. Improvement of psoriasis during sunitinib therapy for renal cell carcinoma. Am J Med Sci. 2010;339:580–1.

    PubMed  Google Scholar 

  34. Fournier C, Tisman G. Sorafenib-associated remission of psoriasis in hypernephroma: case report. Dermatol Online J. 2010;16:17.

    PubMed  Google Scholar 

  35. Crawshaw AA, Griffiths CE, Young HS. Investigational VEGF antagonists for psoriasis. Expert Opin Investig Drugs. 2012;21(1):33–43.

    CAS  PubMed  Google Scholar 

  36. Kuang YH, Lu Y, Liu YK, Liao LQ, Zhou XC, Qin QS, et al. Topical Sunitinib ointment alleviates Psoriasis-like inflammation by inhibiting the proliferation and apoptosis of keratinocytes. Eur J Pharmacol. 2018;824:57–63.

    CAS  PubMed  Google Scholar 

  37. Yiu ZZ, Ali FR, Griffiths CE. Paradoxical exacerbation of chronic plaque psoriasis by sorafenib. Clin Exp Dermatol. 2016;41:407–9.

    CAS  PubMed  Google Scholar 

  38. Du-Thanh A, Girard C, Pageaux GP, Guillot B, Dereure O. Sorafenib-induced annular pustular psoriasis (Milian-Katchoura type). Eur J Dermatol. 2013;23:900–1.

    PubMed  Google Scholar 

  39. Graceffa D, Maiani E, Pace A, Solivetti FM, Elia F, De Mutiis C, Bonifati C. Psoriatic Arthritis during Treatment with Bevacizumab for Anaplastic Oligodendroglioma. Case Rep Rheumatol. 2012;2012:208606.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Overbeck TR, Griesinger F. Two cases of psoriasis responding to erlotinib: time to revisiting inhibition of epidermal growth factor receptor in psoriasis therapy. Dermatology. 2012;225:179–82.

    PubMed  Google Scholar 

  41. Oyama N, Kaneko F, Togashi A, Yamamoto T. A case of rapid improvement of severe psoriasis during molecular-targeted therapy using an epidermal growth factor receptor tyrosine kinase inhibitor for metastatic lung adenocarcinoma. J Am Acad Dermatol. 2012;66:e251–3.

    PubMed  Google Scholar 

  42. Goepel L, Jacobi A, Augustin M, Radtke MA. Rapid improvement of psoriasis in a patient with lung cancer after treatment with erlotinib. J Eur Acad Dermatol Venereol. 2018;32(8):e311–3.

    CAS  PubMed  Google Scholar 

  43. Mas-Vidal A, Coto-Segura P, Galache-Osuna C, Santos-Juanes J. Psoriasis induced by cetuximab: a paradoxical adverse effect. Australas J Dermatol. 2011;52:56–8.

    PubMed  Google Scholar 

  44. Guidelli GM, Fioravanti A, Rubegni P, Feci L. Induced psoriasis after rituximab therapy for rheumatoid arthritis: a case report and review of the literature. Rheumatol Int. 2013;33:2927–30.

    CAS  PubMed  Google Scholar 

  45. Mielke F, Schneider-Obermeyer J, Dorner T. Onset of psoriasis with psoriatic arthropathy during rituximab treatment of non-Hodgkin lymphoma. Ann Rheum Dis. 2008;67:1056–7.

    CAS  PubMed  Google Scholar 

  46. Thomas L, Canoui-Poitrine F, Gottenberg JE, Economu-Dubosc A, Medkour F, Chevalier X, et al. Incidence of new-onset and flare of preexisting psoriasis during rituximab therapy for rheumatoid arthritis: data from the French AIR registry. J Rheumatol. 2012;39:893–8.

    CAS  PubMed  Google Scholar 

  47. Nagai T, Karakawa M, Komine M, Muroi K, Ohtsuki M, Ozawa K. Development of psoriasis in a patient with chronic myelogenous leukaemia during nilotinib treatment. Eur J Haematol. 2013;91:270–2.

    PubMed  Google Scholar 

  48. Shim JH, Oh SH, Jun JY, Kim JH, Park HY, Park JH, et al. Exacerbation of Psoriasis after Imatinib Mesylate Treatment. Ann Dermatol. 2016;28:409–11.

    PubMed  PubMed Central  Google Scholar 

  49. Afshar M, Martinez AD, Gallo RL, Hata TR. Induction and exacerbation of psoriasis with Interferon-alpha therapy for hepatitis C: a review and analysis of 36 cases. J Eur Acad Dermatol Venereol. 2013;27:771–8.

    CAS  PubMed  Google Scholar 

  50. Voudouri D, Nikolaou V, Laschos K, Charpidou A, Soupos N, Triantafyllopoulou I, et al. Anti-PD1/PDL1 induced psoriasis. Curr Probl Cancer. 2017;41:407–12.

    PubMed  Google Scholar 

  51. Bonigen J, Raynaud-Donzel C, Hureaux J, Kramkimel N, Blom A, Jeudy G, et al. Anti-PD1-induced psoriasis: a study of 21 patients. J Eur Acad Dermatol Venereol. 2017;31:e254–7.

    CAS  PubMed  Google Scholar 

  52. Danlos FX, Voisin AL, Dyevre V, Michot JM, Routier E, Taillade L, et al. Safety and efficacy of anti-programmed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease. Eur J Cancer. 2018;91:21–9.

    CAS  PubMed  Google Scholar 

  53. Lidar M, Giat E, Garelick D, Horowitz Y, Amital H, Steinberg-Silman Y, et al. Rheumatic manifestations among cancer patients treated with immune checkpoint inhibitors. Autoimmun Rev. 2018;17(3):284–9.

    CAS  Google Scholar 

  54. Fattore D, Annunziata MC, Panariello L, Marasca C, Fabbrocini G. Successful treatment of psoriasis induced by immune checkpoint inhibitors with apremilast. Eur J Cancer. 2019;110:107–9.

    CAS  PubMed  Google Scholar 

  55. Sibaud V, Dalenc F, Chevreau C, Roché H, Delord JP, Mourey L, et al. HFS-14, a specific quality of life scale developed for patients suffering from hand-foot syndrome. Oncologist. 2011;16:1469–78.

    PubMed  PubMed Central  Google Scholar 

  56. Lacouture ME, Wu S, Robert C, Atkins MB, Kong HH, Guitart J, et al. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist. 2008;13:1001–11.

    CAS  PubMed  Google Scholar 

  57. Belum VR, Wu S, Lacouture ME. Risk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: a meta-analysis. Invest New Drugs. 2013;31:1078–86.

    CAS  PubMed  Google Scholar 

  58. Belum VR, Serna-Tamayo C, Wu S, Lacouture ME. Incidence and risk of hand-foot skin reaction with cabozantinib, a novel multikinase inhibitor: a meta-analysis. Clin Exp Dermatol. 2016;41:8–15.

    CAS  PubMed  Google Scholar 

  59. Chu D, Lacouture ME, Weiner E, Wu S. Risk of hand-foot skin reaction with the multitargeted kinase inhibitor sunitinib in patients with renal cell and non-renal cell carcinoma: a meta-analysis. Clin Genitourin Cancer. 2009;7:11–9.

    PubMed  Google Scholar 

  60. Chu D, Lacouture ME, Fillos T, Wu S. Risk of hand-foot skin reaction with sorafenib: a systematic review and meta-analysis. Acta Oncol. 2008;47:176–86.

    CAS  PubMed  Google Scholar 

  61. Balagula Y, Wu S, Su X, Feldman DR, Lacouture ME. The risk of hand foot skin reaction to pazopanib, a novel multikinase inhibitor: a systematic review of literature and meta-analysis. Invest New Drugs. 2012;30:1773–81.

    CAS  PubMed  Google Scholar 

  62. Fischer A, Wu S, Ho AL, Lacouture ME. The risk of hand-foot skin reaction to axitinib, a novel VEGF inhibitor: a systematic review of literature and meta-analysis. Invest New Drugs. 2013;31:787–97.

    CAS  PubMed  Google Scholar 

  63. Chanprapaph K, Rutnin S, Vachiramon V. Multikinase Inhibitor-Induced Hand-Foot Skin Reaction: a Review of Clinical Presentation, Pathogenesis, and Management. Am J Clin Dermatol. 2016;17:387–402.

    PubMed  Google Scholar 

  64. Wang P, Tan G, Zhu M, Li W, Zhai B, Sun X. Hand-foot skin reaction is a beneficial indicator of sorafenib therapy for patients with hepatocellular carcinoma: a systemic review and meta-analysis. Expert Rev Gastroenterol Hepatol. 2018;12:1–8.

    PubMed  Google Scholar 

  65. Zuo RC, Apolo AB, DiGiovanna JJ, Parnes HL, Keen CM, Nanda S, et al. Cutaneous adverse effects associated with the tyrosine-kinase inhibitor cabozantinib. JAMA Dermatol. 2015;151:170–7.

    PubMed  PubMed Central  Google Scholar 

  66. Lee WJ, Lee JL, Chang SE, Lee MW, Kang YK, Choi JH, et al. Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib. Br J Dermatol. 2009;161:1045–51.

    CAS  PubMed  Google Scholar 

  67. Yang CH, Lin WC, Chuang CK, Chang YC, Pang ST, Lin YC, et al. Hand-foot skin reaction in patients treated with sorafenib: a clinicopathological study of cutaneous manifestations due to multitargeted kinase inhibitor therapy. Br J Dermatol. 2008;158:592–6.

    CAS  PubMed  Google Scholar 

  68. Sibaud V, Delord JP, Chevreau C. Sorafenib-induced hand-foot skin reaction: a Koebner phenomenon? Target Oncol. 2009;4:307–10.

    CAS  PubMed  Google Scholar 

  69. McLellan B, Ciardiello F, Lacouture ME, Segaert S, Van Cutsem E. Regorafenib-associated hand-foot skin reaction: practical advice on diagnosis, prevention, and management. Ann Oncol. 2015;26(10):2017–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Anderson R, Jatoi A, Robert C, Wood LS, Keating KN, Lacouture ME. Search for evidence-based approaches for the prevention and palliation of hand-foot skin reaction (HFSR) caused by the multikinase inhibitors (MKIs). Oncologist. 2009;14:291–302.

    CAS  PubMed  Google Scholar 

  71. Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372:30–9.

    PubMed  Google Scholar 

  72. Larkin J, Ascierto PA, Dréno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371(20):1867–76.

    Google Scholar 

  73. Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371:1877–88.

    PubMed  Google Scholar 

  74. Antonioli E, Guglielmelli P, Pieri L, Finazzi M, Rumi E, Martinelli V, et al. Hydroxyurea-related toxicity in 3,411 patients with Ph’-negative MPN. Am J Hematol. 2012;87:552–4.

    PubMed  Google Scholar 

  75. Vassallo C, Passamonti F, Merante S, Ardigò M, Nolli G, Mangiacavalli S, et al. Muco-cutaneous changes during long-term therapy with hydroxyurea in chronic myeloid leukaemia. Clin Exp Dermatol. 2001;26:141–8.

    CAS  PubMed  Google Scholar 

  76. Sanchez-Palacios C, Guitart J. Hydroxyurea-associated squamous dysplasia. J Am Acad Dermatol. 2004;51:293–300.

    PubMed  Google Scholar 

  77. Chu EY, Wanat KA, Miller CJ, Amaravadi RK, Fecher LA, Brose MS, et al. Diverse cutaneous side effects associated with BRAF inhibitor therapy: a clinicopathologic study. J Am Acad Dermatol. 2012;67:1265–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Anforth R, Tembe V, Blumetti T, Fernandez-Peñas P. Mutational analysis of cutaneous squamous cell carcinomas and verrucal keratosis in patients taking BRAF inhibitors. Pigment Cell Melanoma Res. 2012;25(5):569–72.

    CAS  PubMed  Google Scholar 

  79. Belum VR, Rosen AC, Jaimes N, Dranitsaris G, Pulitzer MP, Busam KJ, et al. Clinico-morphological features of BRAF inhibition-induced proliferative skin lesions in cancer patients. Cancer. 2015;121:60–8.

    CAS  PubMed  Google Scholar 

  80. Anforth R, Menzies A, Byth K, Carlos G, Chou S, Sharma R, et al. Factors influencing the development of cutaneous squamous cell carcinoma in patients on BRAF inhibitor therapy. J Am Acad Dermatol. 2015;72:809–15.

    CAS  PubMed  Google Scholar 

  81. Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012;366:207–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Vigarios E, Lamant L, Delord JP, Fricain JC, Chevreau C, Barrés B, et al. Oral squamous cell carcinoma and hyperkeratotic lesions with BRAF inhibitors. Br J Dermatol. 2015;172:1680–2.

    CAS  PubMed  Google Scholar 

  83. Dika E, Patrizi A, Venturoli S, Fanti PA, Barbieri D, Strammiello R, et al. Human papillomavirus evaluation of vemurafenib-induced skin epithelial tumors: a case series. Br J Dermatol. 2015;172:540–2.

    CAS  PubMed  Google Scholar 

  84. Arnault JP, Wechsler J, Escudier B, Spatz A, Tomasic G, Sibaud V, et al. Keratoacanthomas and squamous cell carcinomas in patients receiving sorafenib. J Clin Oncol. 2009;27:e59–61.

    PubMed  Google Scholar 

  85. Oberholzer PA, Kee D, Dziunycz P, Sucker A, Kamsukom N, Jones R, et al. RAS mutations are associated with the development of cutaneous squamous cell tumors in patients treated with RAF inhibitors. J Clin Oncol. 2012;30:316–21.

    CAS  PubMed  Google Scholar 

  86. Frouin E, Guillot B, Larrieux M, Tempier A, Boulle N, Foulongne V, et al. Cutaneous epithelial tumors induced by vemurafenib involve the MAPK and Pi3KCA pathways but not HPV nor HPyV viral infection. PLoS One. 2014;9:e110478.

    PubMed  PubMed Central  Google Scholar 

  87. Schrama D, Groesser L, Ugurel S, Hafner C, Pastrana DV, Buck CB, et al. Presence of human polyomavirus 6 in mutation-specific BRAF inhibitor-induced epithelial proliferations. JAMA Dermatol. 2014;150:1180–6.

    PubMed  Google Scholar 

  88. Ali M, Anforth R, Senetiner F, Carlos G, Fernandez-Penas P. Mechanisms of BRAFi-induced hyperproliferative cutaneous conditions. Exp Dermatol. 2016;25:394–5.

    PubMed  Google Scholar 

  89. Anforth R, Blumetti TC, Clements A, Kefford R, Long GV, Fernandez-Peñas P. Systemic retinoids for the chemoprevention of cutaneous squamous cell carcinoma and verrucal keratosis in a cohort of patients on BRAF inhibitors. Br J Dermatol. 2013;169:1310–3.

    CAS  PubMed  Google Scholar 

  90. Aboul-Fettouh N, Nijhawan RI. Aggressive squamous cell carcinoma in a patient on the Janus kinase inhibitor ruxolitinib. JAAD Case Rep. 2018;4(5):455–7.

    PubMed  PubMed Central  Google Scholar 

  91. Fabiano A, Calzavara-Pinton P, Monari P, Moggio E, Pellacani G, Manganoni AM, Gualdi G. Eruptive squamous cell carcinomas with keratoacanthoma-like features ina patient treated with ruxolitinib. Br J Dermatol. 2015;173(4):1098–9.

    CAS  PubMed  Google Scholar 

  92. Abikhair Burgo M, Roudiani N, Chen J, et al. Ruxolitinib inhibits cyclosporine-induced proliferation of cutaneous squamous cell carcinoma. JCI Insight. 2018;3(17):e120750.

    PubMed Central  Google Scholar 

  93. Freites-Martinez A, Kwong BY, Rieger KE, Coit DG, Colevas AD, Lacouture ME. Eruptive keratoacanthomas associated with pembrolizumab therapy. JAMA Dermatol. 2017;153:694–7.

    PubMed  PubMed Central  Google Scholar 

  94. Bednarek R, Marks K, Lin G. Eruptive keratoacanthomas secondary to nivolumab immunotherapy. Int J Dermatol. 2018;57(3):e28–9.

    PubMed  Google Scholar 

  95. Peramiquel L, Dalmau J, Puig L, Roé E, Fernández-Figueras MT, Alomar A. Inflammation of actinic keratoses and acral erythrodysesthesia during capecitabine treatment. J Am Acad Dermatol. 2006;55:S119–20.

    PubMed  Google Scholar 

  96. Johnson TM, Rapini RP, Duvic M. Inflammation of actinic keratoses from systemic chemotherapy. J Am Acad Dermatol. 1987;17:192–7.

    CAS  PubMed  Google Scholar 

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Correspondence to Maria Vastarella.

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Maria Vastarella and Gabriella Fabbrocini have no conflicts of interest that are directly relevant to the content of this article. Vincent Sibaud has received fees for advisory board participation and or honoraria for presentations from BMS, Novartis, Pierre Fabre, Bayer, and Roche.

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Vastarella, M., Fabbrocini, G. & Sibaud, V. Hyperkeratotic Skin Adverse Events Induced by Anticancer Treatments: A Comprehensive Review. Drug Saf 43, 395–408 (2020). https://doi.org/10.1007/s40264-020-00907-6

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