Clinical and Experimental Dermatology
Permanent chemotherapy-induced nonscarring alopecia and premature ovarian failure C. Champagne,1 M. Taylor2 and P. Farrant3 1 Department of Dermatology, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, UK; and Departments of 2Cellular Pathology; and 3Dermatology, Brighton and Sussex University Hospitals, Brighton, UK
doi:10.1111/ced.12596 doi: 10.1111/ced.12596
A 22-year-old woman presented with diffuse hair loss. Five years earlier she had been diagnosed with acute myeloid leukaemia and had received myeloablative umbilical cord transplant. The conditioning treatment included busulfan, fludarabine, thiotepa and antithymocyte globulin. Following the stem cell transplant, the patient had lost the majority of her scalp hair, and the alopecia continued despite some initial regrowth. She had not had a menstrual period since treatment began. On physical examination, the patient was found to have extensive hair loss, which was clinically nonscarred (Fig. 1a,b). There was marked miniaturization (Fig. 1c) without evidence of perifollicular inflammation or scale, and the hair pull test was negative. There was preservation of the eyebrows, eyelashes and body hair. Blood tests revealed normal levels of testosterone and sex hormone-binding globulin but raised levels of lutinising hormone (LH) (102.5 IU/L; normal range 2.4–13.0 IU/L) and follicle stimulating hormone (FSH) (190 IU/L; 3.5– 13.0 IU/L), confirming premature ovarian failure. Paired scalp biopsies were taken for horizontal and vertical sectioning. These revealed a reduced number of hair follicles, with only eight terminal anagen hairs. There were numerous fibrous tracts, presence of miniaturized hairs, and preservation of sebaceous glands and arrector pili muscles (Fig. 2). There was no significant perifollicular or periadnexal inflammation. These findings were consistent with a nonscarring but permanent alopecia. The patient now requires treatment with hormone replacement therapy (HRT), and she uses a scalp prosthesis. Postchemotherapy alopecia is usually reversible, but there are increasing numbers of reports of permanent chemotherapy-induced alopecia (PCIA).1 This has been
(a)
(b)
(c)
Correspondence: Dr Caroline Champagne, Dermatology Department, Churchill Hospital, Oxford University Hospitals NHS Trust, Old Rd, Oxford, Oxfordshire, OX3 7LE, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 10 September 2014
ª 2015 British Association of Dermatologists
Figure 1 (a,b) Diffuse alopecia mainly affecting androgen-depen-
dent sites; (c) marked miniaturization of hairs.
Clinical and Experimental Dermatology (2015) 40, pp589–590
589
D CP
CED
CPD • A memorable patient
D
CP
A memorable patient
A few reports have reviewed the endocrine status of patients with PCIA.1,3,4 In a study of 20 female patients with PCIA, 14 were premenopausal, and all displayed biological menopause with raised FSH and LH levels, low oestradiol levels, and no androgen excess.1 A separate case series found that all the young female patients with PCIA became menopausal.4 Although it has been suggested that PCIA may result from toxic damage to follicle stem cells in the hair bulge or from disruption of signalling to the secondary hair germ, endocrine dysfunction has also been considered, as this condition often resembles androgenetic alopecia.1 Even though androgens may be important in female pattern hair loss, biochemical evidence of hyperandrogenism is often not present, suggesting that androgen-independent mechanisms may also play a role.5 In our patient, as in those reported by Kluger et al.,1 there was no evidence of androgen excess, but loss of ovarian oestrogen may have been a factor in her alopecia. However, evidence in the literature that oestrogens affect human hair growth is conflicting.6 Clinicians should be aware of this rare complication of chemotherapy, and patients should be counselled appropriately. It is also important to enquire about the regularity of the menstrual cycle, as abnormalities may indicate premature ovarian failure requiring HRT, as in our patient. Both the potential role of diminished oestrogens and chemotherapeutic effects on hair follicle stem cells in PCIA require further research.
(a)
(b)
Figure 2 Punch biopsy specimens from vertex of scalp: (a) hori-
zontal section showing reduced follicular density and miniaturization (arrows); and (b) vertical section showing preservation of sebaceous glands. Haematoxylin and eosin, original magnification (a) 9 20; (b) 9 4.
described most commonly with busulfan, but has also been observed following docetaxel, paclitaxel and other cytotoxic agents.1,2 The clinical features include incomplete hair regrowth with diffuse thinning, often resembling an androgenetic pattern, although miniaturized hairs are rarely mentioned.1–3 More patchy alopecia has also been observed, and hair loss may affect nonscalp hair as well.1–3 Histologically, there is a reduction in the number of terminal hairs without fibrosis.3 Peribulbar inflammation is usually absent, and increased numbers of miniaturized hairs are often reported.1–3 Factors such as graft-versus-host disease (GVHD) have been implicated in PCIA following stem cell transplantation, but PCIA can also occur without evidence of GVHD.4 Histological follicular miniaturization has been found in cases of PCIA linked both to taxanes in breast cancer and following stem cell transplantation with agents such as busulfan.3
590
Clinical and Experimental Dermatology (2015) 40, pp589–590
References 1 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: 2879–84. 2 Palamaras I, Misciali C, Vincenzi C et al. Permanent chemotherapy-induced alopecia: a review. J Am Acad Dermatol 2011; 64: 604–6. 3 Miteva M, Misciali C, Fanti P et al. Permanent alopecia after systemic chemotherapy: a clinicopathological study of 10 cases. Am J Dermatopathol 2011; 33: 345–50. 4 Machado M, Moreb J, Khan S. Six cases of permanent alopecia after various conditioning regimens commonly used in hematopoietic stem cell transplantation. Bone Marrow Transplant 2007; 40: 979–82. 5 Birch M, Lalla S, Messenger A. Female pattern hair loss. Clin Exp Dermatol 2002; 27: 383–8. 6 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: 643–50.
ª 2015 British Association of Dermatologists
Permanent chemotherapy-induced nonscarring alopecia and premature ovarian failure C. Champagne,1 M. Taylor2 and P. Farrant3 1 Department of Dermatology, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, UK; and Departments of 2Cellular Pathology; and 3Dermatology, Brighton and Sussex University Hospitals, Brighton, UK
doi:10.1111/ced.12596 doi: 10.1111/ced.12596
A 22-year-old woman presented with diffuse hair loss. Five years earlier she had been diagnosed with acute myeloid leukaemia and had received myeloablative umbilical cord transplant. The conditioning treatment included busulfan, fludarabine, thiotepa and antithymocyte globulin. Following the stem cell transplant, the patient had lost the majority of her scalp hair, and the alopecia continued despite some initial regrowth. She had not had a menstrual period since treatment began. On physical examination, the patient was found to have extensive hair loss, which was clinically nonscarred (Fig. 1a,b). There was marked miniaturization (Fig. 1c) without evidence of perifollicular inflammation or scale, and the hair pull test was negative. There was preservation of the eyebrows, eyelashes and body hair. Blood tests revealed normal levels of testosterone and sex hormone-binding globulin but raised levels of lutinising hormone (LH) (102.5 IU/L; normal range 2.4–13.0 IU/L) and follicle stimulating hormone (FSH) (190 IU/L; 3.5– 13.0 IU/L), confirming premature ovarian failure. Paired scalp biopsies were taken for horizontal and vertical sectioning. These revealed a reduced number of hair follicles, with only eight terminal anagen hairs. There were numerous fibrous tracts, presence of miniaturized hairs, and preservation of sebaceous glands and arrector pili muscles (Fig. 2). There was no significant perifollicular or periadnexal inflammation. These findings were consistent with a nonscarring but permanent alopecia. The patient now requires treatment with hormone replacement therapy (HRT), and she uses a scalp prosthesis. Postchemotherapy alopecia is usually reversible, but there are increasing numbers of reports of permanent chemotherapy-induced alopecia (PCIA).1 This has been
(a)
(b)
(c)
Correspondence: Dr Caroline Champagne, Dermatology Department, Churchill Hospital, Oxford University Hospitals NHS Trust, Old Rd, Oxford, Oxfordshire, OX3 7LE, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 10 September 2014
ª 2015 British Association of Dermatologists
Figure 1 (a,b) Diffuse alopecia mainly affecting androgen-depen-
dent sites; (c) marked miniaturization of hairs.
Clinical and Experimental Dermatology (2015) 40, pp589–590
589
D CP
CED
CPD • A memorable patient
D
CP
A memorable patient
A few reports have reviewed the endocrine status of patients with PCIA.1,3,4 In a study of 20 female patients with PCIA, 14 were premenopausal, and all displayed biological menopause with raised FSH and LH levels, low oestradiol levels, and no androgen excess.1 A separate case series found that all the young female patients with PCIA became menopausal.4 Although it has been suggested that PCIA may result from toxic damage to follicle stem cells in the hair bulge or from disruption of signalling to the secondary hair germ, endocrine dysfunction has also been considered, as this condition often resembles androgenetic alopecia.1 Even though androgens may be important in female pattern hair loss, biochemical evidence of hyperandrogenism is often not present, suggesting that androgen-independent mechanisms may also play a role.5 In our patient, as in those reported by Kluger et al.,1 there was no evidence of androgen excess, but loss of ovarian oestrogen may have been a factor in her alopecia. However, evidence in the literature that oestrogens affect human hair growth is conflicting.6 Clinicians should be aware of this rare complication of chemotherapy, and patients should be counselled appropriately. It is also important to enquire about the regularity of the menstrual cycle, as abnormalities may indicate premature ovarian failure requiring HRT, as in our patient. Both the potential role of diminished oestrogens and chemotherapeutic effects on hair follicle stem cells in PCIA require further research.
(a)
(b)
Figure 2 Punch biopsy specimens from vertex of scalp: (a) hori-
zontal section showing reduced follicular density and miniaturization (arrows); and (b) vertical section showing preservation of sebaceous glands. Haematoxylin and eosin, original magnification (a) 9 20; (b) 9 4.
described most commonly with busulfan, but has also been observed following docetaxel, paclitaxel and other cytotoxic agents.1,2 The clinical features include incomplete hair regrowth with diffuse thinning, often resembling an androgenetic pattern, although miniaturized hairs are rarely mentioned.1–3 More patchy alopecia has also been observed, and hair loss may affect nonscalp hair as well.1–3 Histologically, there is a reduction in the number of terminal hairs without fibrosis.3 Peribulbar inflammation is usually absent, and increased numbers of miniaturized hairs are often reported.1–3 Factors such as graft-versus-host disease (GVHD) have been implicated in PCIA following stem cell transplantation, but PCIA can also occur without evidence of GVHD.4 Histological follicular miniaturization has been found in cases of PCIA linked both to taxanes in breast cancer and following stem cell transplantation with agents such as busulfan.3
590
Clinical and Experimental Dermatology (2015) 40, pp589–590
References 1 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: 2879–84. 2 Palamaras I, Misciali C, Vincenzi C et al. Permanent chemotherapy-induced alopecia: a review. J Am Acad Dermatol 2011; 64: 604–6. 3 Miteva M, Misciali C, Fanti P et al. Permanent alopecia after systemic chemotherapy: a clinicopathological study of 10 cases. Am J Dermatopathol 2011; 33: 345–50. 4 Machado M, Moreb J, Khan S. Six cases of permanent alopecia after various conditioning regimens commonly used in hematopoietic stem cell transplantation. Bone Marrow Transplant 2007; 40: 979–82. 5 Birch M, Lalla S, Messenger A. Female pattern hair loss. Clin Exp Dermatol 2002; 27: 383–8. 6 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: 643–50.
ª 2015 British Association of Dermatologists
