British Journal of Dermatology 2002; 146: 983–991.
Therapeutics Topical corticosteroid therapy for acute radiation dermatitis: a prospective, randomized, double-blind study M.SCHMUTH, M.A.WIMMER,* S.HOFER, A.SZTANKAY,* G.WEINLICH, D.M.LINDER, P.M.ELIAS,† P.O.FRITSCH AND E.FRITSCH* Departments of Dermatology and *Radiotherapy and Radiation Oncology, University of Innsbruck, Austria †Department of Dermatology, University of California, San Francisco, CA, U.S.A. Accepted for publication 7 January 2002
Summary
Background Radiation dermatitis is a common side-effect of radiation therapy, but there is no current consensus about its appropriate therapy. Objectives To compare treatment with topical 0Æ1% methylprednisolone vs. 0Æ5% dexpanthenol in a cohort of patients undergoing fractionated radiation therapy for breast cancer. Methods In a randomized, double-blind design, treatment was initiated at the beginning of radiation therapy and continued for 2 weeks after termination of radiation. Outcomes were compared by three different measures: clinical (symptom score), functional (transepidermal water loss, TEWL) and subjective (quality of life, QOL). Results In a preliminary cohort of untreated patients undergoing radiation therapy, clinical signs and TEWL levels increased progressively during radiation therapy, reaching highest values at 5 and 4 weeks, respectively. Although neither topical treatment reduced the incidence of radiation dermatitis, both delayed the emergence of greatest clinical and TEWL scores until approximately 6 and 5 weeks, respectively. With topical corticosteroids, clinical symptoms and TEWL were less pronounced than with dexpanthenol. Whereas general QOL improved after completion of radiation therapy, skin-related QOL declined. However, the skin-related QOL decline could be at least in part reversed by use of topical corticosteroid vs. dexpanthenol-containing emollient. Conclusions We provide evidence that prophylactic and ongoing use of topical therapy with either topical corticosteroid or a dexpanthenol-containing emollient ameliorates, but does not prevent radiation dermatitis. Our data suggest, but do not prove, a benefit of a topical corticosteroid vs. a dexpanthenol-containing emollient. Further controlled studies with larger cohorts will be needed to determine optimal forms of topical therapy for radiation dermatitis. Key words: corticosteroids, inflammation, lipids, permeability barrier function, skin disease, topical therapy
In addition to surgery, chemotherapy and hormone therapy, the current management of breast cancer, one of the most prevalent malignant tumours in women,1 includes radiation therapy. A common side-effect of fractionated radiation therapy for breast cancer is radiation dermatitis.2–4 Therapeutic strategies to ameliorate the symptoms of radiation dermatitis comprise Correspondence: Matthias Schmuth, Department of Dermatology, Anichstr. 35, A-6020, Innsbruck, Austria. E-mail:
[email protected] 2002 British Association of Dermatologists
empirical topical regimens including powders,5–7 dexpanthenol-containing emollients8,9 and topical corticosteroids.10–14 Although various additional topical regimens have been reported to be either effective15–28 or ineffective,29–32 limited information is available from controlled trials.9,12–14,22,27,29–32 Accordingly, to date there is no general agreement about how to treat or prevent radiation dermatitis.5,7,24,33 However, patients frequently demand topical therapy when the first symptoms of radiation damage to the skin occur, and physicians continue to treat, most commonly with 983
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powders or emollients, on an empirical basis. In the present study we compare the efficacy of early topical therapy with a topical dexpanthenol formulation vs. a topical corticosteroid, administered to patients undergoing radiation therapy for breast cancer in a prospective, randomized, double-blind study.
Patients and methods Patient selection and randomization These studies were performed in accordance with the principles of the Declaration of Helsinki. Approval was secured from the Ethics Committee of the University of Innsbruck, and written informed consent was obtained from all patients prior to enrolment. After obtaining baseline data on an initial control cohort of untreated patients (n ¼ 15),34 a subsequent cohort of patients was recruited and randomized to one of two therapeutic schemes in a double-blind fashion (Table 1). Patients were allocated to each study arm using a computerized randomization scheme within blocks of four that were not disclosed to the observers. The study population was selected from consecutive patients attending the Department of Radiation Therapy, Innsbruck. Eligible patients were women aged 18–80 years, receiving radiation therapy for breast cancer. Routine staging procedures were completed prior to enrolment. As with the control cohort, exclusion criteria included: (i) Karnofsky index < 70 (as a measure of the patient’s overall neurological condition to exclude bias due to general health deterioration); (ii) prior history of radiation dermatitis; and (iii) history of prior radiation therapy to the same area. In addition, patients with skin conditions that are known to be associated with a barrier defect, including atopic dermatitis, psoriasis and ichthyosis, or those
receiving systemic corticosteroids during the 2-week period prior to or during radiation therapy were also excluded. Irradiation Following breast-conserving surgery, patients received 56 Gy of tangential field irradiation to the breast and chest wall by external beam, using photons (8 MV). Two patients received an additional boost (4 Gy) to the tumour bed using electrons (14 MeV). The radiation energy was generated by a linear accelerator (Philips SL 20, Philips Electronics U.K. Limited, Crawley, U.K.). Doses were applied in single fractions of 2 Gy, five times a week. Topical agents and treatment schedule Patients were allocated to one of the following two topical treatment regimens: (i) 0Æ5% dexpanthenol cream (Bepanthen, Hoffmann LaRoche, Berne, Switzerland; n ¼ 11), or (ii) 0Æ1% methylprednisolone aceponate cream (Advantan, Schering, Vienna, Austria; n ¼ 10). The vehicle formulations of the two study preparations are listed in Table 2. The creams, which were of comparable consistency, were placed in identical-appearing 500-g jars, labelled with a code for each patient. The contents were randomized to each jar by a pharmacist who was not involved in the study. The treatment allocation code for each patient was kept in a sealed envelope until termination of the study. Patients were instructed to apply the assigned cream to the irradiated field twice daily from the initiation of radiation therapy, and to continue twice-daily topical treatment for a 2-week period after completion of radiation therapy. The total treatment period was
Table 1. Patient characteristics 0Æ5% dexpanthenol n Median age, years (range) Tumour stage EBRT total dose (Gy) 4-Gy electron boost to tumour bed (n) Chemotherapy Tamoxifen (n)
0Æ1% methylprednisolone
Untreated control34
11 44 (35–74) pT1a-2N0)1M0 56–60 1
10 62 (39–75) pT1a-2N0)1M0 56–60 1
15 55 (29–75) pT1)3N0)2M0)1 50–60 4
CMF, 4; FAC, 1; EC, 1 4
CMF, 2 5
CMF, 5; FAC, 1, CEF, 1 3
EBRT, external beam radiation therapy; CMF, cyclophosphamide, methotrexate, 5-fluorouracil; FAC, 5-fluorouracil, adriamycin, cyclophosphamide; EC, epirubicin, cyclophosphamide; CEF, cyclophosphamide, epirubicin, 5-fluorouracil. 2002 British Association of Dermatologists, British Journal of Dermatology, 146, 983–991
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Table 2. Vehicle formulations 0Æ5% dexpanthenol 0Æ1% methylprednisolone
Phenoxyethanol, amphisol K, cetyl alcohol, isopropylmyristate, DL-pantolactone, propylene glycol, stearyl alcohol, lanolin, purified water Benzyl alcohol, decyloleate, glycerylmonostearate, cetylstearyl alcohol, adeps solidus, glycerol trifatty acid ester, macrogolstearate 2000, glycerol, sodium ethylenediamine tetraacetic acid, butylhydroxytoluol, purified water
typically 8 weeks. Patients were instructed not to use any other topical medications, emollients or powders during the study period. Two patients developed localized erosions within the irradiated field, which required routine wound care (gauze dressings).35 This did not obviate use of the study medication in adjacent, non-erosive areas. Objectives In a cohort of patients undergoing radiation therapy, we previously showed that both symptom scores and transepidermal water loss (TEWL) levels increase significantly during irradiation, reaching highest values 5 and 4 weeks after initiation of radiation therapy.34 In the present study, we tested whether early topical therapy would ameliorate radiation dermatitis. The formulations we chose to compare are routinely used in our departments: dexpanthenol formulations are commonly used to provide skin hydration in mild cases, and topical corticosteroids to suppress more severe inflammatory reactions. The primary outcome measure was the clinical course. Secondary outcome measures were adverse effects, epidermal barrier function and quality of life (QOL). Clinical assessment Patients were assessed immediately prior to the initiation of radiation therapy, and weekly thereafter, for the objective clinical signs of erythema, desquamation, erosion, induration and hyperpigmentation, on the scale: 0, none; 1, mild; 2, moderate; 3, severe. The total clinical score was the sum of the individual ratings, resulting in a theoretical maximum score at each assessment time point of 15. Epidermal permeability barrier function To assess the impact of radiation therapy on epidermal barrier function, we measured TEWL. Epidermal barrier function provides an independent and objective parameter of disease severity in a variety of dermatoses,36–38 including radiation dermatitis.34 TEWL was
measured weekly over four different areas within the irradiated field (one test site per quadrant), and over one control area on the volar forearm using an Evaporimeter (Servomed, Stockholm, Sweden), under comparable environmental conditions.34,39 The highest of four measurements at each time point was used for subsequent analyses. Recordings were not taken over skin that showed extensive erosions. To calculate deviations of measurements from pretreatment baseline values, the following formula was employed: {(TEWL irradiation area at indicated time ⁄ TEWL control area at indicated time) ⁄ (TEWL irradiation area before irradiation ⁄ TEWL control area before irradiation) ) 1} · 100%. TEWL measurements were obtained before radiation therapy, weekly during therapy and at 2 weeks postirradiation. Quality of life assessment Questionnaire-based scoring was used to evaluate both skin-specific (Skindex40) and general outcome measures (SF-3641). The specific content of each inventory is described in Appendix 1. Both the conceptualization of QOL, and the rationale for choosing these scales, were based on prior studies that demonstrated their utility for the study of skin disease.40,42–46 QOL assessments were performed at the beginning of radiation therapy and after completion of the follow-up period (approximately 8 weeks later). Of the 21 patients who completed the study, one patient was deemed mentally incapable of completing the questionnaires accurately. Of the remaining 20 patients, four (Skindex) and three (SF-36) were excluded from QOL analysis because they completed fewer than 50% of the instruments or left an entire page blank. Thus, usable questionnaires were completed by 16 and 17 patients for the Skindex and SF-36 questionnaires, respectively, yielding final response rates of 76% and 81%, respectively. Statistical analyses Statistical analyses were performed with GraphPad Instat and Prism software (GraphPad Software Inc., San Diego, CA, U.S.A.). Outcome measures were clinical
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score, TEWL readings and QOL scores. The unpaired t-test was used to calculate differences in clinical and QOL scores between the treatment arms. Greatest TEWL values and post-treatment QOL scores were compared with the pretreatment baseline by the paired t-test. TEWL readings in both treatment arms were compared with readings from the untreated patient cohort using analysis of variance. All statistical procedures were two-sided. Data are expressed as mean ± SEM.
Results Untreated control group A preliminary cohort of patients who did not receive topical therapy during radiation therapy (n ¼ 15) served as a control group for both treatment groups (Table 1). We have reported previously that these patients developed most severe clinical symptoms at 5 weeks, and also that TEWL levels peaked in these patients about 1 week prior to the appearance of clinical signs of radiation dermatitis (mean highest values approximately twofold over controls; Table 3).34
comparable with that in the untreated control group.34 In three patients, symptoms were transient and mild. In the remaining 16 patients, the severity score increased to peak levels of ‡ 2, including eight in whom levels were ‡ 4 (not shown). There were fewer patients with scores ‡ 4 in the methylprednisolone than in the dexpanthenol group (P < 0Æ05, data not shown). The greatest values typically occurred about 6 weeks after initiation of therapy and were significantly increased over pretreatment readings (both study arms: P < 0Æ005, Fig. 2). Clinical scores were not available from the historical, untreated control group, but the mean time to most severe symptoms was shorter (approximately 5 weeks) than in patients who received topical therapy (indicated in Fig. 2 by an arrow). Comparison of mean severity scores between the treatment groups suggested a less severe clinical course in patients who received methylprednisolone (n ¼ 10) than in those who received the dexpanthenol formulation (n ¼ 11), but the differences did not reach statistical significance (Fig. 2; P ¼ 0Æ1 at the 6- and
Treatment groups Patients were recruited between April and November 1999. They were followed for 8 weeks, including approximately 6 weeks of fractionated radiation therapy and a 2-week follow-up period after its completion. The participant flow for each group is shown in Figure 1 and the characteristics of the final patient cohorts are summarized in Table 1. Changes in clinical severity Despite the use of topical therapy from the beginning of radiation therapy, 19 of 21 patients treated developed clinical signs of radiation dermatitis, an incidence Table 3. Transepidermal water loss (TEWL) measurements 0Æ5% 0Æ1% Untreated dexpanthenol methylprednisolone control (n ¼ 11) (n ¼ 10) (n ¼ 15)34 Greatest TEWL levels (mean percentage of pretreatment readings) Time to greatest TEWL (mean number of days)
136
125
199
35
33
27
Figure 1. Participant flow diagram. The numbers of participants randomly assigned, receiving intended treatment, analysed for the primary outcome, and completing the study protocol are shown. *In two cases radiation therapy had to be prolonged for < 3 days because of holidays or technical problems with the accelerator. In one case radiation therapy had to be prolonged because of holidays or technical problems with the accelerator.
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136%), but this difference did not reach statistical significance (Table 3). A comparison of the treatment groups with the historical untreated control group suggested that either of the two topical regimens was superior to no treatment, with respect to TEWL measurements, but differences were not statistically significant (Table 3; P > 0Æ05: methylprednisolone 125%, dexpanthenol 136% vs. untreated 199% TEWL increase over pretreatment readings). TEWL levels did not differ between patients who received adjuvant chemotherapy and those who did not. Quality of life assessment Figure 2. Clinical signs of radiation dermatitis occurred in both treatment groups during radiation therapy, with highest scores at 6 weeks. The clinical scores are shown as the sum of the individual clinical ratings (mean ± SEM). The increase in clinical score vs. pretreatment baseline is significant at 6 weeks (P < 0Æ005). The difference between topical corticosteroid vs. dexpanthenol treatment did not reach clinical significance (P ¼ 0Æ1 at 6 and 8 weeks). The arrow indicates the occurrence of most severe symptoms in untreated patients.
8-week time points). In the dexpanthenol group, the six patients who received adjuvant chemotherapy either before or after radiation therapy exhibited higher scores than patients who did not receive additional chemotherapy. In the methylprednisolone group no such difference was detected (not shown). Adverse effects Potential adverse effects of the study medications consisted of itching in three patients (dexpanthenol n ¼ 1, methylprednisolone n ¼ 2), and burning in one patient (dexpanthenol n ¼ 1). One patient exhibited a papular skin eruption in addition to itching by week 8 (dexpanthenol n ¼ 1; an allergic contact dermatitis to the study medication was excluded by patch testing in this case). Permeability barrier function TEWL values increased significantly in both treatment groups (Table 3; P < 0Æ05 vs. pretreatment), but to a lesser extent than in the untreated control group.34 Greatest levels were reached after approximately 5 weeks, i.e. about 1 week later than in the untreated control group (Table 3). TEWL increases appeared slightly less pronounced with topical methylprednisolone than with dexpanthenol treatment (125% vs.
General health outcome (SF-36). Clinical judgement and bioengineering techniques alone cannot reflect the potential impact of a skin condition on patients’ lives. Therefore, we compared clinical and functional parameters with questionnaire-based QOL assessments of each patient’s own experience of their disease and response to therapy. Our data show that QOL dimensions, reflecting general health, improved after the termination of radiation therapy, as indicated by increased SF-36 scores in post-treatment vs. pretreatment (baseline) scores (Fig. 3A, not significant). However, as no QOL data were available from the untreated individuals, it was not possible to distinguish to what extent the improvement in SF-36 scores at the termination of the study reflected an impact of topical therapy alone or in addition to the prospect of conclusion of the cancer treatment. Skin-related health outcome (Skindex). Responses to the SF-36 questionnaire, which is designed as a general health assessment, may be dominated by the underlying disease and its therapy;44 therefore, we also employed another questionnaire, the Skindex inventory, which specifically assesses skin-related mental health issues. Overall, the Skindex scores largely deteriorated from pretreatment (baseline) to post-treatment, reflecting the appearance of radiation dermatitis in virtually all subjects (Fig. 3B). In the dexpanthenol group, this deterioration reached statistical significance for the dimensions of depression, embarrassment, discomfort and limitations (P < 0Æ05 not shown). While all dimensions worsened in the dexpanthenoltreated group, only four of seven dimensions worsened in the corticosteroid group (Fig. 3B), indicating that topical corticosteroids may in part reverse the negative impact of radiation dermatitis on QOL. The difference between the two treatment groups was significant for the dimension of embarrassment (Fig. 3B, P < 0Æ05)
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Figure 3. Topical corticosteroids reverse the negative impact of radiation therapy on skin-related quality of life (QOL). Data represent the patient responses to QOL questionnaires at the beginning of radiation therapy vs. after completion of radiation therapy (approximately 8 weeks later). Data are expressed as the mean ± SEM difference between post-treatment and pretreatment total scores. An increased score in the SF-36 (A) indicates improvement, while an increased score in the Skindex (B) means worsening. The difference between topical corticosteroid vs. dexpanthenol treatment was significant for the dimension of embarrassment (P < 0Æ05).
and approached significance for the dimensions of fear (P ¼ 0Æ06) and physical discomfort (P ¼ 0Æ057).
Discussion Radiation dermatitis is a frequent side-effect of fractionated radiation therapy for breast cancer. It is
associated with characteristic clinical symptoms2–4 that became most pronounced after about 5 weeks in untreated patients, which were delayed to approximately 6 weeks in patients who received either type of topical therapy from the first day of irradiation. In addition, we observed that the increase in TEWL that occurred after 4 weeks in untreated patients34 was again delayed to 5 weeks in treated patients. Moreover, QOL assessment revealed an improvement of general health-related measures, but a worsening of skinspecific dimensions, when postirradiation questionnaires were compared with pretreatment baseline (Fig. 3). In contrast to earlier controversies in the literature about the efficacy of topical corticosteroids for radiation dermatitis,10,12–14,16,47–50 we observed a reduced clinical severity in corticosteroid-treated patients compared with patients treated with a dexpanthenol-containing emollient and with untreated patients. The application of topical corticosteroids to irradiated skin did not only lead to an amelioration of clinical signs, but also to less damage to the permeability barrier. Finally, topical corticosteroids reversed the negative impact of radiation therapy on skin-related QOL. Importantly, our study design required topical treatment of irradiated skin beginning on the first day of irradiation,10,14 as opposed to other studies.12,13 Whether rescue therapy at the time of onset of symptoms would have been equally or less effective was not assessed in our study. Because of relatively large interindividual differences, and the limited sample size in this study, the benefit of topical corticosteroid treatment vs. the dexpanthenolcontaining emollient was only statistically significant for skin-related QOL, but not for reductions either in clinical scores or in TEWL measurements, although these showed a clear trend. The experimental approach used in this study, however, should facilitate the evaluation of prophylactic and ⁄ or therapeutic strategies for radiation dermatitis in future studies enrolling larger patient series. Because of the known barrier impairment in radiation dermatitis, one approach to treatment is to prevent further damage to the barrier. Accordingly, patients are routinely advised to avoid alkaline soaps that remove lipids from the stratum corneum.51 In addition, in the mouse model, other types of manipulations have been shown to aggravate radiation dermatitis, including tape stripping, plucking of hair and ultraviolet B exposure.52,53 Conversely, therapeutic strategies that are designed to strengthen the epidermal barrier could be of benefit. Previous studies
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reported ameliorating effects of formulations with putative barrier-enhancing activity on radiation dermatitis.23,28 The effects of the dexpanthenol-containing formulation in the present study support this hypothesis, because barrier-enhancing properties have been described for dexpanthenol54 and nicotinamide.55 In the case of topical corticosteroids, however, the beneficial effects on epidermal barrier function presumably reflect a reduction in overall disease severity: while both systemic and topical corticosteroids can exert negative effects on epidermal barrier repair in adult skin,56 in the setting of radiation dermatitis, topical corticosteroids may ameliorate the inflammatory response, which in turn could result from radiationinduced barrier disruption.57 It is also possible that the barrier repair machinery in radiation dermatitis is damaged to an extent that does not allow an adequate repair response. If so, then topical, physiological lipid formulations consisting of optimized molar ratios of cholesterol, free fatty acids and sphingolipids, which are known to accelerate barrier repair,58,59 would be ineffective. In contrast, non-physiological lipids, such as petrolatum and lanolin, could be effective simply through provision of an artificial permeability barrier.60 Because lipid ratios were not determined in either of the formulations used in this study, future studies should evaluate scientifically based lipid formulations in the setting of radiation therapy. In summary, our data suggest that topical therapy within the irradiation field during and after radiation therapy is superior to no treatment, and that topical corticosteroids may be more effective than topical dexpanthenol emollients alone.
Acknowledgments We are indebted to the patients who shared their time and energy, and to the participating nurses and pharmacists for their assistance. This study was initiated and conducted without involvement of the pharmaceutical or cosmetic industries. Statistical advice was kindly provided by Dr H.Ulmer, Department of Biostatistics, University of Innsbruck, Austria. We are grateful to Dr G.Rumpold, Department of Medical Psychology, University of Innsbruck, Austria for help with QOL questionnaires. Permission for use of the QOL questionnaires was generously given by Dr K.Sherbourne (Santa Monica, CA, U.S.A.) and Dr M-M.Chren (San Francisco, CA, U.S.A.).
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22 Maiche AG, Isokangas OP, Gro¨hn P. Skin protection by sucralfate cream during electron beam therapy. Acta Oncol 1994; 33: 201– 3. 23 Dini D, Macchia R, Gozza A et al. Management of acute radiodermatitis. Pharmacological or nonpharmacological remedies? Cancer Nurs 1993; 16: 366–70. 24 Lavery BA. Skin care during radiotherapy: a survey of UK practice. Clin Oncol 1995; 7: 184–7. 25 Thilmann C, Adamietz IA, Mose S et al. Increase of surface dose using wound dressings during percutaneous radiotherapy with photons and electrons. Radiother Oncol 1996; 40: 181–4. 26 Keme´ny L, Trach V, Dobozy A. Effect of locally applied WEB 2086, a platelet-activating factor antagonist, on inflammatory skin conditions in mice. Arch Dermatol Res 1996; 288: 492–4. 27 Liguori V, Guillemin C, Pesce GF et al. Double blind, randomized clinical study comparing hyaluronic acid cream to placebo in patients treated with radiotherapy. Radiother Oncol 1997; 42: 155–61. 28 See A, Wright S, Denham JW. A pilot study of dermofilm in acute radiation-induced desquamative skin reactions. Clin Oncol 1998; 10: 182–5. 29 Halperin EC, Gaspar L, George S et al. A double-blind, randomized, prospective trial to evaluate topical vitamin C solution for the prevention of radiation dermatitis. CNS Cancer Consortium. Int J Radiat Oncol Biol Phys 1993; 26: 413–16. 30 Williams MS, Burk M, Loprinzi CL et al. Phase III double-blind evaluation of an aloe vera gel as a prophylactic agent for radiation-induced skin toxicity. Int J Radiat Oncol Biol Phys 1996; 36: 345–9. 31 Delaney G, Fisher R, Hook C, Barton M. Sucralfate cream in the management of moist desquamation during radiotherapy. Australas Radiol 1997; 41: 270–5. 32 Fenig E, Brenner B, Katz A et al. Topical Biafine and Lipiderm for the prevention of radiation dermatitis: a randomized prospective trial. Oncol Rep 2001; 8: 305–9. 33 Holland J. Skin care for patients receiving radiation. Oncol Nurs Forum 1995; 22: 989. 34 Schmuth M, Sztankay A, Weinlich G et al. Permeability barrier function in skin exposed to ionizing radiation. Arch Dermatol 2001; 137: 1019–23. 35 Zimmermann JS, Budach W, Do¨rr W. Individual skin care during radiation therapy. Strahlenther Onkol 1998; 174 (Suppl. 3): 74–7. 36 Grubauer G, Elias PM, Feingold KR. Transepidermal water loss: the signal for recovery of barrier structure and function. J Lipid Res 1989; 30: 323–33. 37 Watanabe M, Tagami H, Horii I et al. Functional analyses of the superficial stratum corneum in atopic xerosis. Arch Dermatol 1991; 127: 1689–92. 38 Motta S, Monti M, Sesana S et al. Abnormality of water barrier function in psoriasis. Role of ceramide fractions. Arch Dermatol 1994; 130: 452–6. 39 Pinnagoda J, Tupker RA, Smit JA et al. The intra- and interindividual variability and reliability of transepidermal water loss measurements. Contact Dermatitis 1989; 21: 255–9. 40 Chren M-M, Lasek RJ, Quinn LM et al. Skindex, a quality-of-life measure for patients with skin disease: reliability, validity, and responsiveness. J Invest Dermatol 1996; 107: 707–13. 41 Ware JEJ, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30: 473–83.
42 O’Neill P, Kelly P. Postal questionnaire study of disability in the community associated with psoriasis. Br Med J 1996; 313: 919– 21. 43 Finlay AY. Quality of life measurement in dermatology: a practical guide. Br J Dermatol 1997; 136: 305–14. 44 Chren M-M, Lasek RJ, Quinn LM, Covinsky KE. Convergent and discriminant validity of a generic and a disease-specific instrument to measure quality of life in patients with skin disease. J Invest Dermatol 1997; 108: 103–7. 45 Bullinger M. German translation and psychometric testing of the SF-36 Health Survey: preliminary results from the IQOLA Project. International Quality of Life Assessment. Soc Sci Med 1995; 41: 1359–66. 46 Mallon E, Newton JN, Klassen A et al. The quality of life in acne: a comparison with general medical conditions using generic questionnaires. Br J Dermatol 1999; 140: 672–6. 47 Kalz F, Scott A. Inhibition of Grenz ray erythema by one single topical hormone application. J Invest Dermatol 1956; 26: 342–4. 48 Po¨schl M. O¨rtliche Strahlenreaktion an der Haut und Cortisonbehandlung. Strahlentherapie 1957; 103: 289. 49 Hu¨ter KA, Mu¨ller HG. Strahlenreaktion der Haut bei Anwendung von Glukosteroiden. Strahlentherapie 1959; 108: 457–77. 50 Chung J, Song CW, Tamaguchi T, Tabachnick J. Effect of antiinflammatory compounds on irradiation induced radiodermatitis. Dermatologica 1972; 144: 97–107. 51 Klein G, Grubauer G, Fritsch P. The influence of daily dishwashing with synthetic detergent on human skin. Br J Dermatol 1992; 127: 131–7. 52 Hegazy MA, Fowler JF. Cell population kinetics of plucked and unplucked mouse skin. II. Irradiated skin. Cell Tissue Kinet 1973; 6: 587–602. 53 Trott KR, Shirazi A, Heasman F. Modulation of accelerated repopulation in mouse skin during daily irradiation. Radiother Oncol 1999; 50: 261–6. 54 Gehring W, Gloor M. Effect of topically applied dexpanthenol on epidermal barrier function and stratum corneum hydration. Results of a human in vivo study. Arzneimittelforschung 2000; 50: 659–63. 55 Tanno O, Ota Y, Kitamura N et al. Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier. Br J Dermatol 2000; 143: 524–31. 56 Kao J, Ahn SK, Fluhr JW et al. Basis for epidermal side-effects of topical and systemic glucocorticosteroids. J Invest Dermatol 2001; 117: 416 (Abstr.). 57 Elias PM, Feingold KR. Does the tail wag the dog? Role of the barrier in the pathogenesis of inflammatory dermatoses and therapeutic implications. Arch Dermatol 2001; 137: 1079–81. 58 Man MQ, Feingold KR, Elias PM. Exogenous lipids influence permeability barrier recovery in acetone-treated murine skin. Arch Dermatol 1993; 129: 728–38. 59 Mortz CG, Andersen KE, Halkier-Sorensen L. The efficacy of different moisturizers on barrier recovery in hairless mice evaluated by non-invasive bioengineering methods. A model to select the potentially most effective product. Contact Dermatitis 1997; 36: 297–301. 60 Halkier-Sorensen L, Menon GK, Elias PM et al. Cutaneous barrier function after cold exposure in hairless mice: a model to demonstrate how cold interferes with barrier homeostasis among workers in the fish-processing industry. Br J Dermatol 1995; 132: 391–401.
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TOPICAL STEROIDS FOR ACUTE RADIATION DERMATITIS
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Appendix 1
Skindex
Medical Outcome Study 36-Item Short Form Health Survey
The 61-item version includes two physical (discomfort, limitations) and three major psychosocial (cognitive, social, emotional) dimensions, developed to identify skin disease-specific health-related QOL.40 The emotional dimension is further divided into four subdimensions: depression, fear, embarrassment and anger. Scores are standardized to 100, higher scores indicating worse QOL. Skindex has been used to assess QOL in a variety of dermatological conditions, including acne, non-melanoma skin cancer, benign skin tumours, warts, eczema, psoriasis, rosacea, acne, nail disease, alopecia and ulcers.40,44 The instrument is designed to detect differences in individual patients as their skin disease changes.
This instrument contains 36 items measuring eight dimensions: physical functioning, role limitations due to physical problems and emotional problems, social functioning, mental health, energy and vitality, pain and general health perception, developed to identify general physical and mental components of healthrelated QOL.41 Scores are standardized to 100, higher scores indicating better QOL. The SF-36 has been used to assess QOL in dermatological patients with acne46 and psoriasis.42
2002 British Association of Dermatologists, British Journal of Dermatology, 146, 983–991
