UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Chemotherapy-induced alopecia

Authors
Aimee S Payne, MD, PhD
Hope S Rugo, MD
Section Editors
Reed E Drews, MD
Maria Hordinsky, MD
Deputy Editor
Diane MF Savarese, MD

INTRODUCTION

Hair loss is a transient and usually (although not always) reversible consequence of cancer chemotherapy that can be psychologically devastating [1]. For some patients, the emotional trauma may be so severe as to lead to refusing or delaying treatment that might otherwise be beneficial [2-8]. Recovery generally requires a period of several months to a year, amplifying the psychological impact of the disease and its treatment.

A general overview of the anatomy and physiology of hair growth, the effects of chemotherapy on the hair follicle, and possible means for preventing or minimizing chemotherapy-induced alopecia are discussed here.

ANATOMY AND PHYSIOLOGY

The hair shaft is a layered structure that consists of three major components. The medulla, the innermost layer, is surrounded by the cortex and cuticle. The hair fiber is the product of the hair follicle, which is composed of three main parts when viewed in longitudinal section (figure 1) [9]:

The lower portion, which extends from the base of the hair follicle to the insertion of the arrector pili muscle. This lower portion, in turn, is comprised of several major components:

The hair bulb, which contains the dermal papilla and hair matrix. The dermal papilla controls the number of matrix cells, which determines hair fiber size [10]. Melanocytes, which are responsible for hair color, are present among the matrix cells of the hair bulb.

                     

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Mar 2017. | This topic last updated: Mar 20, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. Choi EK, Kim IR, Chang O, et al. Impact of chemotherapy-induced alopecia distress on body image, psychosocial well-being, and depression in breast cancer patients. Psychooncology 2014; 23:1103.
  2. Dorr VJ. A practitioner's guide to cancer-related alopecia. Semin Oncol 1998; 25:562.
  3. Hussein AM. Chemotherapy-induced alopecia: new developments. South Med J 1993; 86:489.
  4. McGarvey EL, Baum LD, Pinkerton RC, Rogers LM. Psychological sequelae and alopecia among women with cancer. Cancer Pract 2001; 9:283.
  5. Mulders M, Vingerhoets A, Breed W. The impact of cancer and chemotherapy: perceptual similarities and differences between cancer patients, nurses and physicians. Eur J Oncol Nurs 2008; 12:97.
  6. Lemieux J, Maunsell E, Provencher L. Chemotherapy-induced alopecia and effects on quality of life among women with breast cancer: a literature review. Psychooncology 2008; 17:317.
  7. Hesketh PJ, Batchelor D, Golant M, et al. Chemotherapy-induced alopecia: psychosocial impact and therapeutic approaches. Support Care Cancer 2004; 12:543.
  8. van den Hurk CJ, Mols F, Vingerhoets AJ, Breed WP. Impact of alopecia and scalp cooling on the well-being of breast cancer patients. Psychooncology 2010; 19:701.
  9. Elder D, Elenitsas R, Johnson BL, Murphy GF. Lever's Histopathology of the Skin, 9th ed, Lippincott Williams & Wilkins, Philadelphia 2004. p.1229.
  10. Paus R, Cotsarelis G. The biology of hair follicles. N Engl J Med 1999; 341:491.
  11. Liu Y, Lyle S, Yang Z, Cotsarelis G. Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge. J Invest Dermatol 2003; 121:963.
  12. Cotsarelis G, Millar SE. Towards a molecular understanding of hair loss and its treatment. Trends Mol Med 2001; 7:293.
  13. Sato N, Leopold PL, Crystal RG. Effect of adenovirus-mediated expression of Sonic hedgehog gene on hair regrowth in mice with chemotherapy-induced alopecia. J Natl Cancer Inst 2001; 93:1858.
  14. Paus R, Haslam IS, Sharov AA, Botchkarev VA. Pathobiology of chemotherapy-induced hair loss. Lancet Oncol 2013; 14:e50.
  15. Chon SY, Champion RW, Geddes ER, Rashid RM. Chemotherapy-induced alopecia. J Am Acad Dermatol 2012; 67:e37.
  16. Yun SJ, Kim SJ. Hair loss pattern due to chemotherapy-induced anagen effluvium: a cross-sectional observation. Dermatology 2007; 215:36.
  17. Kanti V, Nuwayhid R, Lindner J, et al. Analysis of quantitative changes in hair growth during treatment with chemotherapy or tamoxifen in patients with breast cancer: a cohort study. Br J Dermatol 2014; 170:643.
  18. Dean JC, Salmon SE, Griffith KS. Prevention of doxorubicin-induced hair loss with scalp hypothermia. N Engl J Med 1979; 301:1427.
  19. van den Hurk CJ, Peerbooms M, van de Poll-Franse LV, et al. Scalp cooling for hair preservation and associated characteristics in 1411 chemotherapy patients - results of the Dutch Scalp Cooling Registry. Acta Oncol 2012; 51:497.
  20. Fehr MK, Welter J, Sell W, et al. Sensor-controlled scalp cooling to prevent chemotherapy-induced alopecia in female cancer patients. Curr Oncol 2016; 23:e576.
  21. Wu CY, Chen GS, Lan CC. Erosive pustular dermatosis of the scalp after gefitinib and radiotherapy for brain metastases secondary to lung cancer. Clin Exp Dermatol 2008; 33:106.
  22. Donovan JC, Ghazarian DM, Shaw JC. Scarring alopecia associated with use of the epidermal growth factor receptor inhibitor gefitinib. Arch Dermatol 2008; 144:1524.
  23. Murillas R, Larcher F, Conti CJ, et al. Expression of a dominant negative mutant of epidermal growth factor receptor in the epidermis of transgenic mice elicits striking alterations in hair follicle development and skin structure. EMBO J 1995; 14:5216.
  24. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007; 356:125.
  25. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359:378.
  26. Ratain MJ, Eisen T, Stadler WM, et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2006; 24:2505.
  27. Autier J, Escudier B, Wechsler J, et al. Prospective study of the cutaneous adverse effects of sorafenib, a novel multikinase inhibitor. Arch Dermatol 2008; 144:886.
  28. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 2011; 378:1931.
  29. Zhang L, Zhou Q, Ma L, et al. Meta-analysis of dermatological toxicities associated with sorafenib. Clin Exp Dermatol 2011; 36:344.
  30. Chang AL, Solomon JA, Hainsworth JD, et al. Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor, vismodegib. J Am Acad Dermatol 2014; 70:60.
  31. Finn RS, Martin M, Rugo HS, et al. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med 2016; 375:1925.
  32. Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. N Engl J Med 2016; 375:1738.
  33. Piraccini BM, Patrizi A, Fanti PA, et al. RASopathic alopecia: hair changes associated with vemurafenib therapy. J Am Acad Dermatol 2015; 72:738.
  34. Saggar V, Wu S, Dickler MN, Lacouture ME. Alopecia with endocrine therapies in patients with cancer. Oncologist 2013; 18:1126.
  35. Gallicchio L, Calhoun C, Helzlsouer KJ. Aromatase inhibitor therapy and hair loss among breast cancer survivors. Breast Cancer Res Treat 2013; 142:435.
  36. Machado M, Moreb JS, Khan SA. Six cases of permanent alopecia after various conditioning regimens commonly used in hematopoietic stem cell transplantation. Bone Marrow Transplant 2007; 40:979.
  37. Palamaras I, Misciali C, Vincenzi C, et al. Permanent chemotherapy-induced alopecia: a review. J Am Acad Dermatol 2011; 64:604.
  38. Ljungman P, Hassan M, Békássy AN, et al. Busulfan concentration in relation to permanent alopecia in recipients of bone marrow transplants. Bone Marrow Transplant 1995; 15:869.
  39. Vowels M, Chan LL, Giri N, et al. Factors affecting hair regrowth after bone marrow transplantation. Bone Marrow Transplant 1993; 12:347.
  40. Choi M, Kim MS, Park SY, et al. Clinical characteristics of chemotherapy-induced alopecia in childhood. J Am Acad Dermatol 2014; 70:499.
  41. Tallon B, Blanchard E, Goldberg LJ. Permanent chemotherapy-induced alopecia: case report and review of the literature. J Am Acad Dermatol 2010; 63:333.
  42. Kluger N, Jacot W, Frouin E, et al. Permanent scalp alopecia related to breast cancer chemotherapy by sequential fluorouracil/epirubicin/cyclophosphamide (FEC) and docetaxel: a prospective study of 20 patients. Ann Oncol 2012; 23:2879.
  43. de Jonge ME, Mathôt RA, Dalesio O, et al. Relationship between irreversible alopecia and exposure to cyclophosphamide, thiotepa and carboplatin (CTC) in high-dose chemotherapy. Bone Marrow Transplant 2002; 30:593.
  44. Toda N, Fujimoto N, Kato T, et al. Erosive pustular dermatosis of the scalp-like eruption due to gefitinib: case report and review of the literature of alopecia associated with EGFR inhibitors. Dermatology 2012; 225:18.
  45. Costa DB, Kobayashi S, Schumer ST. Erlotinib-associated alopecia in a lung cancer patient. J Thorac Oncol 2007; 2:1136.
  46. Hepper DM, Wu P, Anadkat MJ. Scarring alopecia associated with the epidermal growth factor receptor inhibitor erlotinib. J Am Acad Dermatol 2011; 64:996.
  47. Komen MM, Smorenburg CH, van den Hurk CJ, Nortier JW. Factors influencing the effectiveness of scalp cooling in the prevention of chemotherapy-induced alopecia. Oncologist 2013; 18:885.
  48. van den Hurk CJ, Breed WP, Nortier JW. Short post-infusion scalp cooling time in the prevention of docetaxel-induced alopecia. Support Care Cancer 2012; 20:3255.
  49. Komen MM, Breed WP, Smorenburg CH, et al. Results of 20- versus 45-min post-infusion scalp cooling time in the prevention of docetaxel-induced alopecia. Support Care Cancer 2016; 24:2735.
  50. Vendelbo Johansen L. Scalp hypothermia in the prevention of chemotherapy-induced alopecia. Acta Radiol Oncol 1985; 24:113.
  51. Tollenaar RA, Liefers GJ, Repelaer van Driel OJ, van de Velde CJ. Scalp cooling has no place in the prevention of alopecia in adjuvant chemotherapy for breast cancer. Eur J Cancer 1994; 30A:1448.
  52. Symonds RP, McCormick CV, Maxted KJ. Adriamycin alopecia prevented by cold air scalp cooling. Am J Clin Oncol 1986; 9:454.
  53. Gregory RP, Cooke T, Middleton J, et al. Prevention of doxorubicin-induced alopedia by scalp hypothermia: relation to degree of cooling. Br Med J (Clin Res Ed) 1982; 284:1674.
  54. Hillen HF, Breed WP, Botman CJ. Scalp cooling by cold air for the prevention of chemotherapy-induced alopecia. Neth J Med 1990; 37:231.
  55. Shin H, Jo SJ, Kim DH, et al. Efficacy of interventions for prevention of chemotherapy-induced alopecia: a systematic review and meta-analysis. Int J Cancer 2015; 136:E442.
  56. Parker R. The effectiveness of scalp hypothermia in preventing cyclophosphamide-induced alopecia. Oncol Nurs Forum 1987; 14:49.
  57. Knobf M, Kalm D, Mealia M. Clinical observations of scalp cooling in patients receiving multidrug chemotherapy. Oncol Nurs Forum 1989; 16(suppl):200.
  58. Middleton J, Franks D, Buchanan RB, et al. Failure of scalp hypothermia to prevent hair loss when cyclophosphamide is added to doxorubicin and vincristine. Cancer Treat Rep 1985; 69:373.
  59. Wheelock JB, Myers MB, Krebs HB, Goplerud DR. Ineffectiveness of scalp hypothermia in the prevention of alopecia in patients treated with doxorubicin and cisplatin combinations. Cancer Treat Rep 1984; 68:1387.
  60. Cline BW. Prevention of chemotherapy-induced alopecia: a review of the literature. Cancer Nurs 1984; 7:221.
  61. Breed W, van den Hurk C, Peerbooms M. Presentation, impact and prevention of chemotherapy-induced hair loss: scalp cooling potentials and limitations. Expert Rev Dermatol 2011; 6:109.
  62. Satterwhite B, Zimm S. The use of scalp hypothermia in the prevention of doxorubicin-induced hair loss. Cancer 1984; 54:34.
  63. Macduff C, Mackenzie T, Hutcheon A, et al. The effectiveness of scalp cooling in preventing alopecia for patients receiving epirubicin and docetaxel. Eur J Cancer Care (Engl) 2003; 12:154.
  64. Giaccone G, Di Giulio F, Morandini MP, Calciati A. Scalp hypothermia in the prevention of doxorubicin-induced hair loss. Cancer Nurs 1988; 11:170.
  65. Katsimbri P, Bamias A, Pavlidis N. Prevention of chemotherapy-induced alopecia using an effective scalp cooling system. Eur J Cancer 2000; 36:766.
  66. Friedrichs K, Carstensen MH. Successful reduction of alopecia induced by anthracycline and taxane containing adjuvant chemotherapy in breast cancer - clinical evaluation of sensor-controlled scalp cooling. Springerplus 2014; 3:500.
  67. Cigler T, Isseroff D, Fiederlein B, et al. Efficacy of Scalp Cooling in Preventing Chemotherapy-Induced Alopecia in Breast Cancer Patients Receiving Adjuvant Docetaxel and Cyclophosphamide Chemotherapy. Clin Breast Cancer 2015; 15:332.
  68. Rugo HS, Klein, P, Melin SA, et al. Clinical performance of the DigniCap system, a scalp hypothermia system, in preventing chemotherapy-induced alopecia (abstract). J Clin Oncol 33, 2015 (suppl; abst 9518). Abstract available online at http://meetinglibrary.asco.org/content/149240-156 (Accessed on October 05, 2015).
  69. Rugo HS, Klein P, Melin SA, et al. Association Between Use of a Scalp Cooling Device and Alopecia After Chemotherapy for Breast Cancer. JAMA 2017; 317:606.
  70. Nangia J, Wang T, Osborne C, et al. Effect of a Scalp Cooling Device on Alopecia in Women Undergoing Chemotherapy for Breast Cancer: The SCALP Randomized Clinical Trial. JAMA 2017; 317:596.
  71. Lemenager M, Lecomte S, Bonneterre ME, et al. Effectiveness of cold cap in the prevention of docetaxel-induced alopecia. Eur J Cancer 1997; 33:297.
  72. Grevelman EG, Breed WP. Prevention of chemotherapy-induced hair loss by scalp cooling. Ann Oncol 2005; 16:352.
  73. Massey CS. A multicentre study to determine the efficacy and patient acceptability of the Paxman Scalp Cooler to prevent hair loss in patients receiving chemotherapy. Eur J Oncol Nurs 2004; 8:121.
  74. Belum VR, de Barros Silva G, Laloni MT, et al. Cold thermal injury from cold caps used for the prevention of chemotherapy-induced alopecia. Breast Cancer Res Treat 2016; 157:395.
  75. Breed WP. Response to "Hair 'regrowth' during chemotherapy after scalp cooling technique". Int J Dermatol 2016; 55:e465.
  76. Hershman DL. Scalp Cooling to Prevent Chemotherapy-Induced Alopecia: The Time Has Come. JAMA 2017; 317:587.
  77. West HJ. Do the Data on Scalp Cooling for Patients With Breast Cancer Warrant Broad Adoption? JAMA Oncol 2017.
  78. Witman G, Cadman E, Chen M. Misuse of scalp hypothermia. Cancer Treat Rep 1981; 65:507.
  79. van den Hurk CJ, van de Poll-Franse LV, Breed WP, et al. Scalp cooling to prevent alopecia after chemotherapy can be considered safe in patients with breast cancer. Breast 2013; 22:1001.
  80. Lemieux J, Amireault C, Provencher L, Maunsell E. Incidence of scalp metastases in breast cancer: a retrospective cohort study in women who were offered scalp cooling. Breast Cancer Res Treat 2009; 118:547.
  81. Rugo H, Melin A. Expert Statement on: Scalp Cooling with Adjuvant/Neoadjuvant Chemotherapy for Breast Cancer and the Risk of Scalp Metastases. St. Gallen International Breast Cancer Conference 2013; St. Gallen, Switzerland.
  82. Forsberg SA. Scalp cooling therapy and cytotoxic treatment. Lancet 2001; 357:1134.
  83. van den Hurk C, de Beer F, Dries W, et al. No prevention of radiotherapy-induced alopecia by scalp cooling. Radiother Oncol 2015; 117:193.
  84. Glaser DA, Hossain P, Perkins W, et al. Long-term safety and efficacy of bimatoprost solution 0·03% application to the eyelid margin for the treatment of idiopathic and chemotherapy-induced eyelash hypotrichosis: a randomized controlled trial. Br J Dermatol 2015; 172:1384.
  85. Rodriguez R, Machiavelli M, Leone B, et al. Minoxidil (Mx) as a prophylaxis of doxorubicin--induced alopecia. Ann Oncol 1994; 5:769.
  86. Duvic M, Lemak NA, Valero V, et al. A randomized trial of minoxidil in chemotherapy-induced alopecia. J Am Acad Dermatol 1996; 35:74.
  87. Jimenez JJ, Yunis AA. Protection from chemotherapy-induced alopecia by 1,25-dihydroxyvitamin D3. Cancer Res 1992; 52:5123.
  88. Jimenez JJ, Alvarez E, Bustamante CD, Yunis AA. Pretreatment with 1,25(OH)2D3 protects from Cytoxan-induced alopecia without protecting the leukemic cells from Cytoxan. Am J Med Sci 1995; 310:43.
  89. Hidalgo M, Rinaldi D, Medina G, et al. A phase I trial of topical topitriol (calcitriol, 1,25-dihydroxyvitamin D3) to prevent chemotherapy-induced alopecia. Anticancer Drugs 1999; 10:393.
  90. Reichel H, Koeffler HP, Norman AW. The role of the vitamin D endocrine system in health and disease. N Engl J Med 1989; 320:980.
  91. Wood LA. Possible prevention of adriamycin-induced alopecia by tocopherol. N Engl J Med 1985; 312:1060.
  92. Martin-Jimenez M, Diaz-Rubio E, Gonzalez Larriba JL, Sangro B. Failure of high-dose tocopherol to prevent alopecia induced by doxorubicin. N Engl J Med 1986; 315:894.
  93. Perez JE, Macchiavelli M, Leone BA, et al. High-dose alpha-tocopherol as a preventive of doxorubicin-induced alopecia. Cancer Treat Rep 1986; 70:1213.
  94. Davis ST, Benson BG, Bramson HN, et al. Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors. Science 2001; 291:134.
  95. Botchkarev VA, Komarova EA, Siebenhaar F, et al. p53 is essential for chemotherapy-induced hair loss. Cancer Res 2000; 60:5002.
  96. Jimenez JJ, Yunis AA. Protection from 1-beta-D-arabinofuranosylcytosine-induced alopecia by epidermal growth factor and fibroblast growth factor in the rat model. Cancer Res 1992; 52:413.
  97. Dueland S, Sauer T, Lund-Johansen F, et al. Epidermal growth factor receptor inhibition induces trichomegaly. Acta Oncol 2003; 42:345.
  98. Danilenko DM, Ring BD, Yanagihara D, et al. Keratinocyte growth factor is an important endogenous mediator of hair follicle growth, development, and differentiation. Normalization of the nu/nu follicular differentiation defect and amelioration of chemotherapy-induced alopecia. Am J Pathol 1995; 147:145.
  99. Maurer M, Handjiski B, Paus R. Hair growth modulation by topical immunophilin ligands: induction of anagen, inhibition of massive catagen development, and relative protection from chemotherapy-induced alopecia. Am J Pathol 1997; 150:1433.
  100. Shirai A, Tsunoda H, Tamaoki T, Kamiya T. Topical application of cyclosporin A induces rapid-remodeling of damaged anagen hair follicles produced in cyclophosphamide administered mice. J Dermatol Sci 2001; 27:7.
  101. Hussein AM, Stuart A, Peters WP. Protection against chemotherapy-induced alopecia by cyclosporin A in the newborn rat animal model. Dermatology 1995; 190:192.
  102. Degiannis D, Stein S, Czarnecki M, et al. Cyclosporine-induced enhancement of interleukin 1 receptor expression by PHA-stimulated lymphocytes. Transplantation 1990; 50:1074.
  103. Jimenez JJ, Wong GH, Yunis AA. Interleukin 1 protects from cytosine arabinoside-induced alopecia in the rat model. FASEB J 1991; 5:2456.
  104. Jimenez JJ, Sawaya ME, Yunis AA. Interleukin 1 protects hair follicles from cytarabine (ARA-C)-induced toxicity in vivo and in vitro. FASEB J 1992; 6:911.
  105. Hussein AM. Interleukin 1 protects against 1-beta-D-arabinofuranosylcytosine-induced alopecia in the newborn rat animal model. Cancer Res 1991; 51:3329.