Nail Reactions to Anticancer Therapies

  • Marisa Kardos Garshick
  • Patricia L. Myskowski


Anticancer therapies, including cytotoxic chemotherapies and targeted biologic therapies are well known to cause adverse reactions in the skin. The effect of anticancer treatments on the nails has only recently been appreciated. Although the nail changes are often asymptomatic, they can be associated with pain or functional impairment. Many of the cytotoxic chemotherapies result in changes to the nail bed or nail plate, while the newer targeted therapies tend to affect the periungual region. This chapter highlights how to recognize and manage the nail changes seen with cytotoxic chemotherapies as well as targeted therapies.


Chemotherapy Targeted therapy Epidermal growth factor receptor inhibitors Taxanes Oncology Cutaneous side effects Adverse effects Nails Nail toxicity Melanonychia Pyogenic granuloma Paronychia Onycholysis Beau’s lines Frozen gloves 

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  1. 1.
    Hackbarth M, Haas N, Fotopoulou C, Lichtenegger W, Sehouli J. Chemotherapy-induced dermatological toxicity: frequencies and impact on quality of life in women’s cancers. Results of a prospective study. Support Care Cancer. 2008;16:267–73.PubMedGoogle Scholar
  2. 2.
    Lacouture ME, Maitland M, Segaert S, Setser A, Baran R, Fox LP, et al. A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group. Support Care Cancer. 2010;18(4):509–22.PubMedGoogle Scholar
  3. 3.
    Charles C, Sultan S, Bungener C, Mateus C, Lanoy E, Dauchy S, et al. Impact of cutaneous toxicities associated with targeted therapies on quality of life. Results of a longitudinal exploratory study. Bull Cancer. 2013;100:213–22.PubMedGoogle Scholar
  4. 4.
    Susser WS, Whitaker-Worth DL, Grant-Kels JM. Mucocutaneous reactions to chemotherapy. J Am Acad Dermatol. 1999;40:367–98.PubMedGoogle Scholar
  5. 5.
    Gilbar P, Hain A, Peereboom VM. Nail toxicity induced by cancer chemotherapy. J Oncol Pharm Pract. 2009;15:143–55.PubMedGoogle Scholar
  6. 6.
    Robert C, Sibaud V, Mateus C, Verschoore M, Charles C, Lanoy E, et al. Nail toxicities induced by systemic anticancer treatments. Lancet Oncol. 2015;16:e181–9.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Shah PC, Rao KR, Patel AR. Cyclophosphamide induced nail pigmentation. Br J Dermatol. 1978;98:675–80.PubMedGoogle Scholar
  8. 8.
    Borecky DJ, Stephenson J, Keeling JH, Vukelja SJ. Idarubicin-induced pigmentary changes of the nails. Cutis. 1997;59:203–4.PubMedGoogle Scholar
  9. 9.
    Piraccini BM, Tosti A. Drug-induced nail disorders: incidence, management and prognosis. Drug Saf. 1999;21:215–21.Google Scholar
  10. 10.
    Bird BR, Elfiki T, Tucker O, O'Reilly S. Unilateral nail changes secondary to adriamycin: the protective effect of brachial plexopathy. Ann Oncol. 2006;17:527.PubMedGoogle Scholar
  11. 11.
    Hinds G, Thomas V. Malignancy and cancer treatment-related hair and nail changes. Dermatol Clin. 2008;26:59–68.PubMedGoogle Scholar
  12. 12.
    Shelly W, Humphrey GB. Transverse leukonychia (Mee’s lines) due to daunorubicin chemotherapy. Pediatr Dermatol. 1997;14:144–5.Google Scholar
  13. 13.
    Ceyhan AM, Yildirim M, Bircan HA, Karayigit DZ. Transverse leukonychia (Mees’ lines) associated with docetaxel. J Dermatol. 2010;37(2):188–9.PubMedGoogle Scholar
  14. 14.
    Lehoczky O, Pulay T. Transverse leukonychia secondary to paclitaxel-carboplatin chemotherapy in a patient with ovarian cancer. J Obstet Gynaecol. 2002;22:694.PubMedGoogle Scholar
  15. 15.
    Chen GY, Chen HY, Hsu MM, Tsao CJ, Chen WC. Onychomadesis and onycholysis associated with capecitabine. Br J Dermatol. 2001;145:521–2.PubMedGoogle Scholar
  16. 16.
    Piraccini BM, Iorizzo M. Drug reactions affecting the nail unit: diagnosis and management. Dermatol Clin. 2007;25:215–21.PubMedGoogle Scholar
  17. 17.
    Wasner G, Hilpert F, Baron R, Pfisterer J. Clinical picture: nail changes secondary to docetaxel. Lancet. 2001;357:910.PubMedGoogle Scholar
  18. 18.
    Nakamura S, Kajita S, Takagi A, Hashimoto Y, Ishida-Yamamoto A, Takahashi H, et al. Improvement in docetaxel-induced nail changes associated with cyclooxygenase-2 inhibitor treatment. Clin Exp Dermatol. 2009;34:e320–1.PubMedGoogle Scholar
  19. 19.
    Alimonti A, Nardoni C, Papaldo P, Ferretti G, Caleno MP, Carlini P, et al. Nail disorders in a woman treated with ixabepilone for metastatic breast cancer. Anticancer Res. 2005;25(5):3531–2.PubMedGoogle Scholar
  20. 20.
    Hussain S, Anderson DN, Salvatti ME, Adamson B, McManus M, Braverman AS. Onycholysis as a complication of systemic chemotherapy: report of five-cases associated with prolonged weekly paclitaxel therapy and review of the literature. Cancer. 2000;88:2367–71.PubMedGoogle Scholar
  21. 21.
    Lau CP, Hui P, Chan TC. Docetaxel-induced nail toxicity: a case of severe onycholysis and topic review. Chin Med J. 2011;124:2559–60.PubMedGoogle Scholar
  22. 22.
    Childress J, Lokich J. Cutaneous hand and foot toxicity associated with cancer chemotherapy. Am J Clin Oncol. 2003;26:435–6.PubMedGoogle Scholar
  23. 23.
    Scotte F, Tourani JM, Banu E, Peyromaure M, Levy E, Marsan S, et al. Multicenter study of a frozen glove to prevent docetaxel-induced onycholysis and cutaneous toxicity of the hand. J Clin Oncol. 2005;23(19):4424–9.PubMedGoogle Scholar
  24. 24.
    Scotte F, Banu E, Medioni J, Levy E, Ebenezer C, Marsan S, et al. Matched case-control phase 2 study to evaluate the use of a frozen sock to prevent docetaxel-induced onycholysis and cutaneous toxicity of the foot. Cancer. 2008;112(7):1625–31.PubMedGoogle Scholar
  25. 25.
    Chen GY, Chen W, Huang WT. Single transverse apparent leukonychia caused by 5-fluorouracil plus leucovorin. Dermatology. 2003;207(1):86–7.PubMedGoogle Scholar
  26. 26.
    Bianchi L, Iraci S, Tomassoli M, Carrozzo AM, Nini G. Coexistence of apparent transverse leukonychia (Muehrcke’s lines type) and longitudinal melanonychia after 5-fluorouracil/adriamycin/cyclophosphamide chemotherapy. Dermatology. 1992;185(3):216–7.PubMedGoogle Scholar
  27. 27.
    Uyttendaele H, Geyer A, Scher RK. Drugs and nails. J Eur Acad Dermatol Venereol. 2004;18:124–5.PubMedGoogle Scholar
  28. 28.
    McGrath SE, Webb A, Walker-Bone K. Bleomycin-induced Raynaud’s phenomenon after single-dose exposure: risk factors and treatment with intravenous iloprost infusion. J Clin Oncol. 2013;31:e51–2.PubMedGoogle Scholar
  29. 29.
    Reiser M, Bruns C, Hartmann P, Salzberger B, Diehl V, Fatkenheuer G. Raynaud’s phenomenon and acral necrosis after chemotherapy for AIDS-related Kaposi’s sarcoma. Eur J Clin Microbiol Infect Dis. 1998;17:58–60.PubMedGoogle Scholar
  30. 30.
    Piraccini BM, Iorizzo M, Tosti A. Drug-induced nail abnormalities. Am J Clin Dermatol. 2003;4:31–7.PubMedGoogle Scholar
  31. 31.
    Paul LJ, Cohen PR. Paclitaxel-associated subungual pyogenic granuloma: report in a patient with breast cancer receiving paclitaxel and review of drug-induced pyogenic granulomas adjacent to and beneath the nail. J Drugs Dermatol. 2012;11(2):262–8.PubMedGoogle Scholar
  32. 32.
    Piguet V, Borradori L. Pyogenic granuloma-like lesions during capecitabine therapy. Br J Dermatol. 2002;147:1270–2.PubMedGoogle Scholar
  33. 33.
    Wantzin GL, Thomsen K. Acute paronychia after high-dose methotrexate therapy. Arch Dermatol. 1983;119:623–4.PubMedGoogle Scholar
  34. 34.
    Manalo FB, Marks A, Davis HL Jr. Doxorubicin toxicity. Onycholysis, plantar callus formation, and epidermolysis. J Am Med Assoc. 1975;233:56–7.Google Scholar
  35. 35.
    Freiman A, Bouganim N, O’Brien EA. Case reports: mitoxantrone – induced onycholysis associated with subungual abscess, paronychia, and pyogenic granuloma. J Drugs Dermatol. 2005;4(4):490–2.PubMedGoogle Scholar
  36. 36.
    Nicolopoulos J, Howard A. Docetaxel-induced nail dystrophy. Australas J Dermatol. 2002;43(4):293–6.PubMedGoogle Scholar
  37. 37.
    Tiseo M, Leprovite M, Ardizzoni A. Epidermal growth factor receptor inhibitors: a new prospective in the treatment of lung cancer. Curr Med Chem Anticancer Agents. 2004;4:139–48.PubMedGoogle Scholar
  38. 38.
    Fox LP. Nail toxicity associated with epidermal growth factor receptor inhibitor therapy. J Am Acad Dermatol. 2007;56:460–5.PubMedGoogle Scholar
  39. 39.
    Peuvrel L, Querex G, Brocard A, Saint-Jean M, Dreno B. Onychopathy induced by temsirolimus, a mammalian target of rapamycin inhibitor. Dermatology. 2012;224:204–8.PubMedGoogle Scholar
  40. 40.
    Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer. 2006;6:803–12.PubMedGoogle Scholar
  41. 41.
    Garden BC, Wu S, Lacouture ME. The risk of nail changes with epidermal growth factor receptor inhibitors: a systematic review of the literature and meta-analysis. J Am Acad Dermatol. 2012;67:400–8.PubMedGoogle Scholar
  42. 42.
    Sibaud V, Dalenc F, Mourey L, Chevreau C. Paronychia and pyogenic granuloma induced by new anticancer mTOR inhibitors. Acta Derm Venereol. 2011;91:584–5.PubMedGoogle Scholar
  43. 43.
    Lee MW, Seo C, Kim SW, Yang HJ, Lee HW, Choi JH, et al. Cutaneous side effects in non-small cell lung cancer patients treated with Iressa (ZD1839), an inhibitor of epidermal growth factor. Acta Derm Venereol. 2004;84:23–6.PubMedGoogle Scholar
  44. 44.
    Hu JC, Sadeghi P, Pinter-Brown LC, Yashar S, Chiu MW. Cutaneous side effects of epidermal growth factor receptor inhibitors: clinical presentation, pathogenesis, and management. J Am Acad Dermatol. 2007;56:317–26.PubMedGoogle Scholar
  45. 45.
    Chang GC, Yang T, Chen KC, Yin MC, Wang RC, Lin YC. Complications of therapy in cancer patients: case 1. Paronychia and skin hyperpigmentation induced by gefitinib in advanced non-small-cell lung cancer. J Clin Oncol. 2004;22:4646–8.PubMedGoogle Scholar
  46. 46.
    Eames T, Grabein B, Kroth J, Wollenberg A. Microbiological analysis of epidermal growth factor receptor inhibitor therapy-associated paronychia. J Eur Acad Dermatol Venereol. 2010;24:958–60.PubMedGoogle Scholar
  47. 47.
    Sibaud V, Robert C. Pigmentary disorders induced by anticancer agents. Part II: targeted therapies. Ann Dermatol Venerel. 2013;140:266–73.Google Scholar
  48. 48.
    Prabhash K, Biswas G, Prasad N, Karant N, Sastry PS, Parikh PM. Imatinib-induced nail hyperpigmentation in chronic myeloid leukemia. Indian J Dermatol Venereol Leprol. 2006;72:63–4.PubMedGoogle Scholar
  49. 49.
    Scheinfeld N. Imatinib mesylate and dermatology part 2: a review of the cutaneous side effects of imatinib mesylate. J Drugs Dermatol. 2006;5:228–31.PubMedGoogle Scholar
  50. 50.
    Steele JC, Triantafyllou A, Rajlawat BP, Field EA. Oral mucosal hyperpigmentation and horizontal melanonychia caused by imatinib. Clin Exp Dermatol. 2012;37(4):432–3.PubMedGoogle Scholar
  51. 51.
    Das A, Podder I, Kumar D, Ghosh A, Shome K. Imatinib-induced transverse melanonychia: an unusual presentation. Indian J Dermatol. 2015;60(4):412–3.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Bitar C, Farooqui MZ, Valdez J, Saba NS, Soto S, Bray A, Marti G, Wiestner A, Cowen EW. Hair and nail changes during long-term therapy with ibrutinib for chronic lymphocytic leukemia. JAMA Dermatol. 2016;152(6):698–701.PubMedGoogle Scholar
  53. 53.
    Balagula Y, Barth Huston K, Busam KJ, Lacouture ME, Chapman PB, Myskowski PL. Dermatologic side effects associated with the MEK 1/2 inhibitor selumetinib (AZD6244, ARRT-142886). Investig New Drugs. 2011;29:1114–21.Google Scholar
  54. 54.
    McLellan B, Kerr H. Cutaneous toxicities of the multikinase inhibitors sorafenib and sunitinib. Dermatol Ther. 2011;24:396–400.PubMedGoogle Scholar
  55. 55.
    Rosenbaum SE, Wu S, Newman MA, West DP, Kuzel T, Lacouture ME. Dermatological reactions to the multitargeted tyrosine kinase inhibitor sunitinib. Support Care Cancer. 2008;16:557–66.PubMedGoogle Scholar
  56. 56.
    Autier J, Escudier B, Wechsler J, Spatz A, Robert C. Prospective study of the cutaneous adverse effects of sorafenib, a novel multikinase inhibitor. Arch Dermatol. 2008;144:886–92.PubMedGoogle Scholar
  57. 57.
    Robert C, Faivre S, Raymond E, Armand J-P, Escudier B. Subungual splinter hemorrhages: a clinical window to inhibition of vascular endothelial growth factor receptors? Ann Intern Med. 2005;143:313–4.PubMedGoogle Scholar
  58. 58.
    Hong J, Park S, Choi SJ, Lee SH, Lee KC, Lee JI, et al. Nail toxicity after treatment with docetaxel: a prospective analysis in patients with advanced non-small cell lung cancer. Jpn J Clin Oncol. 2007;37:424–8.PubMedGoogle Scholar
  59. 59.
    Galimont-Collen AF, Vos L, Lavrijsen AP, Ouwekerk J, Gelderblom H. Classification and management of skin, hair, nail and mucosal side-effects of epidermal growth factor receptor (EGFR) inhibitors. Eur J Cancer. 2007;43:845–51.PubMedGoogle Scholar
  60. 60.
    Scheinfeld N, Dahdah MJ, Scher R. Vitamins and minerals: their role in nail health and disease. J Drugs Dermatol. 2007;6:782–7.Google Scholar
  61. 61.
    Lacouture ME, Anadkat M, Bensadoun RJ, Bryce J, Chan A, Epstein JB, et al. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer. 2011;19(8):1079–95.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Winther D, Saunte D, Knap M, Haahr V, Jensen AB. Nail changes due to docetaxel: a neglected side effect and nuisance for the patient. Support Care Cancer. 2007;15:1191–7.PubMedGoogle Scholar
  63. 63.
    Lacouture ME. Insights into the pathophysiology and management of dermatologic toxicities to EGFR-targeted therapies in colorectal cancer. Cancer Nurs. 2007;30(4):S17–26.PubMedGoogle Scholar
  64. 64.
    Shu KY, Kindler HL, Medenica M, Lacouture M. Doxycycline for the treatment of paronychia induced by the epidermal growth factor receptor inhibitor cetuximab. Br J Dermatol. 2006;154:191–2.PubMedGoogle Scholar
  65. 65.
    Hachisuka J, Yunotani S, Shidahara S, Moroi Y, Furue M. Effect of adapelene on cetixumab-induced painful periungual inflammation. J Am Acad Dermatol. 2011;64:e20–1.PubMedGoogle Scholar
  66. 66.
    Daniel CR, Iorizzo M, Piraccini BM, Tosti A. Grading simple chronic paronychia and onycholysis. Int J Dermatol. 2006;45(12):1447–8.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Kiyohara Y, Yamakazi N, Kishi A. Erlotinib-related skin toxicities: treatment strategies in patients with metastatic non-small cell lung cancer. J Am Acad Dermatol. 2013;69:463–72.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Marisa Kardos Garshick
    • 1
  • Patricia L. Myskowski
    • 2
  1. 1.New York Presbyterian/Weill Cornell MedicineNew YorkUSA
  2. 2.Memorial Sloan-Kettering Cancer Center, Weill Cornell MedicineNew YorkUSA

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