Commentaries
Conflicts of interest None declared. New York University Langone Center for Musculoskeletal Care, 333 East 38th Street – 4th Floor, New York, NY 10016, U.S.A. E-mail: [email protected]
G. SOLOMON
References 1 Naldi L, Conti A, Cazzaniga S et al. Diet and physical exercise in psoriasis: a randomized trial. Br J Dermatol 2014; 170:634–42. 2 Kumar S, Han J, Li T, Qureshi AA. Obesity, waist circumference, weight change and the risk of psoriasis in US women. J Eur Acad Dermatol Venereol 2013; 10:1293–8. 3 Hamminga EA, van derLely AJ, Neumann HA, Thio HB. Chronic inflammation in psoriasis and obesity, implications for therapy. Med Hypotheses 2006; 67:768–73. 4 Mehta NN, Yu Y, Saboury B et al. Systemic and vascular inflammation in patients with moderate to severe psoriasis as measured by 18F-fluorodeoxyglucose positron emission tomography–computed tomography (FDG-PET-CT): a pilot study. Arch Dermatol 2011; 147:1031–9. 5 Gisondi P, Del Giglio M, Di Francesco V et al. Weight loss improves the response of obese patients with moderate-to-severe chronic plaque psoriasis to low-dose cyclosporine therapy: a randomized, controlled investigator-blinded clinical trial. Am J Clin Nutr 2008; 88:1242–7. 6 Roongpisuthipong W, Pongpudpunth M, Roongpisuthipong C, Rajatanavin N. The effect of weight loss in obese patients with chronic stable plaque-type psoriasis. Dermatol Res Practice 2013; 2013:795932. 7 Di Minno MN, Peluso R, Iervolino S et al. Weight loss and achievement of minimal disease activity in patients with psoriatic arthritis starting treatment with tumor necrosis factor a blockers. Ann Rheum Dis 2013; (in press). 8 Faurschou A, Zachariae C, Skov L et al. Gastric bypass surgery: improving psoriasis through a GLP-1 dependent mechanism? Med Hypotheses 2011; 77:1098–101. 9 Glossman H, Reider N. A marriage of two ‘Methusalem’ drugs for the treatment of psoriasis? Arguments for a pilot trial with metformin as add-on for methotrexate. Dermatoendocrinol 2013; 5:252–63.
Chemotherapy, oestrogens and hair loss DOI: 10.1111/bjd.12891 ORIGINAL ARTICLE, p 643 Chemotherapy alopecia is a common and distressing complication of cytotoxic chemotherapy. There is extensive coverage of the topic in the oncological literature, but dermatologists are not often involved in its management, and chemotherapy alopecia has attracted less attention from the hair research com© 2014 British Association of Dermatologists
493
munity than other hair-loss disorders. In this edition of BJD Kanti et al.1 report the results of a study in which they used an automated phototrichogram method to measure the changes in hair growth in two groups of patients receiving drug treatments for cancer. In the first group of patients, who received cytotoxic chemotherapy, they demonstrate the time course and hair cycle changes that occur during chemotherapy alopecia. Although the results are not altogether surprising, they provide a much greater degree of precision than has previously been the case in this field. As expected, cytotoxic therapy caused a rapid and profound reduction in anagen hairs, which recovered to pretreatment levels by 28 weeks. However, a novel finding was a transient increase in telogen hairs, suggesting that some hair follicles respond to the cytotoxic insult by telogen conversion rather than abrupt termination of anagen. The authors speculate that the nature of the individual follicular response may be determined by the pretreatment anagen stage – follicles in late anagen may more readily convert to telogen than those in early or midanagen, a concept that has also been proposed to explain the changes that occur in the early stages of alopecia areata.2 In their second patient group the authors studied the hair growth response to treatment with the oestrogen-response modifier tamoxifen. In other mammals oestrogens have an inhibitory effect on hair growth but, although the beta (but not alpha) form of the oestrogen receptor is expressed in human hair follicles,3 it is not clear whether oestrogens have any role in human hair biology. The Summary of Product Characteristics documents for the antioestrogen drugs currently licensed in the U.K. (tamoxifen, letrozole, anastrozole) all list alopecia as an adverse effect, i.e. the opposite of that expected from animal studies. The few published case reports to back up this advice are of dubious validity, but in a recent meta-analysis of 19 clinical trials of various hormonal therapies in patients with cancer the authors concluded that an average of 64% of patients taking tamoxifen developed hair loss.4 In contrast to these results, Kanti et al., using a much more sensitive method than was likely used in any of the aforementioned trials, found no evidence of an effect of tamoxifen on hair growth apart from a transient reduction in frontal hair density. Endocrine therapies are generally used in an older age group in which declining hair density is common in the population at large. Reports of hair loss in the absence of detailed and blinded longitudinal measurements in patient and control groups should therefore be viewed with some scepticism. On the other hand, the Kanti study is quite small and probably underpowered to detect a 64% effect, and the duration of observation was also rather short. A further complicating factor is the dimorphic pharmacological effect of tamoxifen on the oestrogen receptor. In breast tissue tamoxifen acts as an oestrogen receptor antagonist, but in some other tissues, such as endometrium, tamoxifen is an oestrogen receptor agonist. These uncertainties could be overcome by performing a more prolonged study in a larger group of patients taking an aromatase inhibitor. What is the relevance of this study? Firstly, it adds something new to our understanding of the human follicular response to British Journal of Dermatology (2014) 170, pp490–495
494 Commentaries
cytotoxic chemotherapy. Secondly, it demonstrates that the skills of hair biologists and clinicians in measuring hair growth, which have become de riguer in assessing treatments for other hair-loss disorders, have a place in the development of treatments aimed at the prevention of chemotherapy alopecia. In the search for more effective treatments we need precise measurements – subjective assessments of hair status are not sufficient. Thirdly, and perhaps more importantly from a biological standpoint, this study questions the role of oestrogens in regulating human hair growth. The results are not conclusive but they nevertheless cast doubt on the common assumption that oestrogens have a stimulatory effect on scalp hair growth. This has relevance, for example, to our understanding of the age-related decline in hair density in women, which is often ascribed to postmenopausal oestrogen deficiency. Devising studies that provide a more definitive answer should not be too difficult. Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JF, U.K. E-mail: [email protected]
A.G. MESSENGER
References 1 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; 170:643–650. 2 Eckert J, Church RE, Ebling FJ. The pathogenesis of alopecia areata. Br J Dermatol 1968; 80:203–10. 3 Thornton MJ, Taylor AH, Mulligan K et al. Oestrogen receptor beta is the predominant oestrogen receptor in human scalp skin. Exp Dermatol 2003; 12:181–90. 4 Saggar V, Wu S, Dickler MN, Lacouture ME. Alopecia with endocrine therapies in patients with cancer. Oncologist 2013; 18:1126–34.
Do we need a patient satisfaction score? DOI: 10.1111/bjd.12867 ORIGINAL ARTICLE, p 672 At lectures on psoriasis you can see eyes glaze over; BlackBerry addicts turn on their cell phones, and workaholics open their laptops when a speaker mentions quality of life or patient satisfaction. Quality-of-life and patient satisfaction surveys are met with groans by investigators for whom this just means more work. But the impact of patient satisfaction on patients’ current and future quality of life is critical, and the impact on their family, friends, coworkers, employers and customers is tangible. Moreover, satisfaction with therapy affects adherence to that therapy, and poor adherence is known to be an enormous problem in dermatology. In a study performed at an outpatient clinic, one-third of prescriptions were never even filled.1 In another small study, 95% of patients were found to British Journal of Dermatology (2014) 170, pp490–495
underdose topical therapies,2 and adherence to a 5-day treatment course of a topical steroid among patients with atopic dermatitis was only 40%.3 As shown in the study by Callis Duffin et al.,4 in this issue of BJD, it is not surprising that patient satisfaction is lower for topical therapies than for all other therapies. Nor is it surprising that these scores are also lower for narrowband ultraviolet (UV)B, which requires office visits up to three times per week, and for infliximab, which requires in-office infusions at least every 8 weeks. More than ever before, patient-reported outcomes are being used by the government and by insurers to justify treatments. And in an era when adherence is coming under closer scrutiny, treatments associated with greater patient satisfaction are likely to lead to greater adherence. Clinical scores such as the Psoriasis Activity and Severity Index are helpful, even if imperfect. Those scores generally correlate well with quality-of-life scores and patient satisfaction scores. However, looking only at clinical scores, it is easy for physicians to overlook the side-effects of treatments that work – but these emerge much more clearly in patient satisfaction scores. Methotrexate, for example, requires more laboratory monitoring and is often associated with nausea, oral ulcers and a sense of malaise, not to mention the symptoms associated with megaloblastic anaemia. Yet, all of us have heard the methotrexate enthusiast who says: ‘I’ve never had a patient with side-effects from methotrexate and it works for everyone.’ It’s amazing how many of our colleagues don’t realize their patients are doing well only because they’ve gone to other dermatologists who prescribed more satisfying treatments. By now, we all should realize that the justifiable enthusiasm for methotrexate should be related to its price, as it has been shown to be less effective and have more side-effects than at least one of our biological therapies for which a headto-head comparison has been performed.5 The challenge is to come up with an easy quality-of-life or patient satisfaction measure that takes little time on the part of investigators and clinicians. The Treatment Satisfaction Questionnaire for Medication version II (TSQM) consists of 11 items concerning key points: effectiveness, adverse effects, convenience of therapies and satisfaction with those therapies.6 Using that simple questionnaire, Callis Duffin et al. have shown that patients receiving methotrexate monotherapy had significantly lower patient-reported effectiveness scores than those receiving subcutaneously administered biologics (adalimumab, etanercept, ustekinumab), narrowband UVB phototherapy or adalimumab with methotrexate. Conversely, methotrexate monotherapy was significantly more convenient than topical therapies, infliximab or narrowband UVB phototherapy. Because we are all under pressure by insurers to see more patients in less time, and because clinical evaluations of psoriasis correlate with patient satisfaction and quality of life, it is unlikely that surveys like the TSQM will be performed in clinical practice. But in a study setting, the TSQM provides valuable information that can be used to influence regulatory agencies and insurers. © 2014 British Association of Dermatologists
Conflicts of interest None declared. New York University Langone Center for Musculoskeletal Care, 333 East 38th Street – 4th Floor, New York, NY 10016, U.S.A. E-mail: [email protected]
G. SOLOMON
References 1 Naldi L, Conti A, Cazzaniga S et al. Diet and physical exercise in psoriasis: a randomized trial. Br J Dermatol 2014; 170:634–42. 2 Kumar S, Han J, Li T, Qureshi AA. Obesity, waist circumference, weight change and the risk of psoriasis in US women. J Eur Acad Dermatol Venereol 2013; 10:1293–8. 3 Hamminga EA, van derLely AJ, Neumann HA, Thio HB. Chronic inflammation in psoriasis and obesity, implications for therapy. Med Hypotheses 2006; 67:768–73. 4 Mehta NN, Yu Y, Saboury B et al. Systemic and vascular inflammation in patients with moderate to severe psoriasis as measured by 18F-fluorodeoxyglucose positron emission tomography–computed tomography (FDG-PET-CT): a pilot study. Arch Dermatol 2011; 147:1031–9. 5 Gisondi P, Del Giglio M, Di Francesco V et al. Weight loss improves the response of obese patients with moderate-to-severe chronic plaque psoriasis to low-dose cyclosporine therapy: a randomized, controlled investigator-blinded clinical trial. Am J Clin Nutr 2008; 88:1242–7. 6 Roongpisuthipong W, Pongpudpunth M, Roongpisuthipong C, Rajatanavin N. The effect of weight loss in obese patients with chronic stable plaque-type psoriasis. Dermatol Res Practice 2013; 2013:795932. 7 Di Minno MN, Peluso R, Iervolino S et al. Weight loss and achievement of minimal disease activity in patients with psoriatic arthritis starting treatment with tumor necrosis factor a blockers. Ann Rheum Dis 2013; (in press). 8 Faurschou A, Zachariae C, Skov L et al. Gastric bypass surgery: improving psoriasis through a GLP-1 dependent mechanism? Med Hypotheses 2011; 77:1098–101. 9 Glossman H, Reider N. A marriage of two ‘Methusalem’ drugs for the treatment of psoriasis? Arguments for a pilot trial with metformin as add-on for methotrexate. Dermatoendocrinol 2013; 5:252–63.
Chemotherapy, oestrogens and hair loss DOI: 10.1111/bjd.12891 ORIGINAL ARTICLE, p 643 Chemotherapy alopecia is a common and distressing complication of cytotoxic chemotherapy. There is extensive coverage of the topic in the oncological literature, but dermatologists are not often involved in its management, and chemotherapy alopecia has attracted less attention from the hair research com© 2014 British Association of Dermatologists
493
munity than other hair-loss disorders. In this edition of BJD Kanti et al.1 report the results of a study in which they used an automated phototrichogram method to measure the changes in hair growth in two groups of patients receiving drug treatments for cancer. In the first group of patients, who received cytotoxic chemotherapy, they demonstrate the time course and hair cycle changes that occur during chemotherapy alopecia. Although the results are not altogether surprising, they provide a much greater degree of precision than has previously been the case in this field. As expected, cytotoxic therapy caused a rapid and profound reduction in anagen hairs, which recovered to pretreatment levels by 28 weeks. However, a novel finding was a transient increase in telogen hairs, suggesting that some hair follicles respond to the cytotoxic insult by telogen conversion rather than abrupt termination of anagen. The authors speculate that the nature of the individual follicular response may be determined by the pretreatment anagen stage – follicles in late anagen may more readily convert to telogen than those in early or midanagen, a concept that has also been proposed to explain the changes that occur in the early stages of alopecia areata.2 In their second patient group the authors studied the hair growth response to treatment with the oestrogen-response modifier tamoxifen. In other mammals oestrogens have an inhibitory effect on hair growth but, although the beta (but not alpha) form of the oestrogen receptor is expressed in human hair follicles,3 it is not clear whether oestrogens have any role in human hair biology. The Summary of Product Characteristics documents for the antioestrogen drugs currently licensed in the U.K. (tamoxifen, letrozole, anastrozole) all list alopecia as an adverse effect, i.e. the opposite of that expected from animal studies. The few published case reports to back up this advice are of dubious validity, but in a recent meta-analysis of 19 clinical trials of various hormonal therapies in patients with cancer the authors concluded that an average of 64% of patients taking tamoxifen developed hair loss.4 In contrast to these results, Kanti et al., using a much more sensitive method than was likely used in any of the aforementioned trials, found no evidence of an effect of tamoxifen on hair growth apart from a transient reduction in frontal hair density. Endocrine therapies are generally used in an older age group in which declining hair density is common in the population at large. Reports of hair loss in the absence of detailed and blinded longitudinal measurements in patient and control groups should therefore be viewed with some scepticism. On the other hand, the Kanti study is quite small and probably underpowered to detect a 64% effect, and the duration of observation was also rather short. A further complicating factor is the dimorphic pharmacological effect of tamoxifen on the oestrogen receptor. In breast tissue tamoxifen acts as an oestrogen receptor antagonist, but in some other tissues, such as endometrium, tamoxifen is an oestrogen receptor agonist. These uncertainties could be overcome by performing a more prolonged study in a larger group of patients taking an aromatase inhibitor. What is the relevance of this study? Firstly, it adds something new to our understanding of the human follicular response to British Journal of Dermatology (2014) 170, pp490–495
494 Commentaries
cytotoxic chemotherapy. Secondly, it demonstrates that the skills of hair biologists and clinicians in measuring hair growth, which have become de riguer in assessing treatments for other hair-loss disorders, have a place in the development of treatments aimed at the prevention of chemotherapy alopecia. In the search for more effective treatments we need precise measurements – subjective assessments of hair status are not sufficient. Thirdly, and perhaps more importantly from a biological standpoint, this study questions the role of oestrogens in regulating human hair growth. The results are not conclusive but they nevertheless cast doubt on the common assumption that oestrogens have a stimulatory effect on scalp hair growth. This has relevance, for example, to our understanding of the age-related decline in hair density in women, which is often ascribed to postmenopausal oestrogen deficiency. Devising studies that provide a more definitive answer should not be too difficult. Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JF, U.K. E-mail: [email protected]
A.G. MESSENGER
References 1 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; 170:643–650. 2 Eckert J, Church RE, Ebling FJ. The pathogenesis of alopecia areata. Br J Dermatol 1968; 80:203–10. 3 Thornton MJ, Taylor AH, Mulligan K et al. Oestrogen receptor beta is the predominant oestrogen receptor in human scalp skin. Exp Dermatol 2003; 12:181–90. 4 Saggar V, Wu S, Dickler MN, Lacouture ME. Alopecia with endocrine therapies in patients with cancer. Oncologist 2013; 18:1126–34.
Do we need a patient satisfaction score? DOI: 10.1111/bjd.12867 ORIGINAL ARTICLE, p 672 At lectures on psoriasis you can see eyes glaze over; BlackBerry addicts turn on their cell phones, and workaholics open their laptops when a speaker mentions quality of life or patient satisfaction. Quality-of-life and patient satisfaction surveys are met with groans by investigators for whom this just means more work. But the impact of patient satisfaction on patients’ current and future quality of life is critical, and the impact on their family, friends, coworkers, employers and customers is tangible. Moreover, satisfaction with therapy affects adherence to that therapy, and poor adherence is known to be an enormous problem in dermatology. In a study performed at an outpatient clinic, one-third of prescriptions were never even filled.1 In another small study, 95% of patients were found to British Journal of Dermatology (2014) 170, pp490–495
underdose topical therapies,2 and adherence to a 5-day treatment course of a topical steroid among patients with atopic dermatitis was only 40%.3 As shown in the study by Callis Duffin et al.,4 in this issue of BJD, it is not surprising that patient satisfaction is lower for topical therapies than for all other therapies. Nor is it surprising that these scores are also lower for narrowband ultraviolet (UV)B, which requires office visits up to three times per week, and for infliximab, which requires in-office infusions at least every 8 weeks. More than ever before, patient-reported outcomes are being used by the government and by insurers to justify treatments. And in an era when adherence is coming under closer scrutiny, treatments associated with greater patient satisfaction are likely to lead to greater adherence. Clinical scores such as the Psoriasis Activity and Severity Index are helpful, even if imperfect. Those scores generally correlate well with quality-of-life scores and patient satisfaction scores. However, looking only at clinical scores, it is easy for physicians to overlook the side-effects of treatments that work – but these emerge much more clearly in patient satisfaction scores. Methotrexate, for example, requires more laboratory monitoring and is often associated with nausea, oral ulcers and a sense of malaise, not to mention the symptoms associated with megaloblastic anaemia. Yet, all of us have heard the methotrexate enthusiast who says: ‘I’ve never had a patient with side-effects from methotrexate and it works for everyone.’ It’s amazing how many of our colleagues don’t realize their patients are doing well only because they’ve gone to other dermatologists who prescribed more satisfying treatments. By now, we all should realize that the justifiable enthusiasm for methotrexate should be related to its price, as it has been shown to be less effective and have more side-effects than at least one of our biological therapies for which a headto-head comparison has been performed.5 The challenge is to come up with an easy quality-of-life or patient satisfaction measure that takes little time on the part of investigators and clinicians. The Treatment Satisfaction Questionnaire for Medication version II (TSQM) consists of 11 items concerning key points: effectiveness, adverse effects, convenience of therapies and satisfaction with those therapies.6 Using that simple questionnaire, Callis Duffin et al. have shown that patients receiving methotrexate monotherapy had significantly lower patient-reported effectiveness scores than those receiving subcutaneously administered biologics (adalimumab, etanercept, ustekinumab), narrowband UVB phototherapy or adalimumab with methotrexate. Conversely, methotrexate monotherapy was significantly more convenient than topical therapies, infliximab or narrowband UVB phototherapy. Because we are all under pressure by insurers to see more patients in less time, and because clinical evaluations of psoriasis correlate with patient satisfaction and quality of life, it is unlikely that surveys like the TSQM will be performed in clinical practice. But in a study setting, the TSQM provides valuable information that can be used to influence regulatory agencies and insurers. © 2014 British Association of Dermatologists
