Journal of the American Academy of Dermatology
Smith et al.
31.
32. 33. 34. 35.
membrane antigens of nonlymphoid accessory cells in oral hairy leukoplakia. Hum Pathol 1990;21:897-904. Greenspaa D, Greenspan JS, Conant M, et al. Oral "hairy" leukoplakia in male homosexuals: evidence of association with both papillomavirusand a herpes-group virus. Lancet 1984;2:831-4. Alessi E, Berti E, Cusini M, et al. Oral hairy leukoplakia. J AM A c ~ DERMATOL1990;22:79-86. Greenspan D, Greenspan JS, de Souza Y, et al. Oral hairy leukoplakia in an HIV negative renal transplant recipient. J Oral Pathol Med 1989;1:32-4. Itin P, Ruff T, Rudlinger R, et al. Oral hairy leukoplakia in a HIV-negative renal transplant patient: A marker for immunosuppression? Dermatologica t988;177:126-8. Purtilo DT, Osato T, eds. Lymphotrophic viruses, immune deficiencyand human cancers. AIDS Res 1986;2(suppl):l196.
I
|11
36. Stingl G, Tschachler E, Groh V, et al. The immune functions of epidermal cells. In: Norris DA ed. Immune mechanisms in cutaneous disease. New York: Marcel Dekker, 1989:3-72. 37. Charley MR, Deng J-S. Murine models of graft-versushost disease with features of scleroderma. In: Norris DA, ed. Immune mechanisms in cutaneous disease. New York: Marcel Dek.ker, 1989:625-40. 38. Gendelman HE, Orenstein JM, Baca LM, et al. The macrophage in the persistence and pathogenesis of HIV infection. AIDS 1989;3:474-95. 39. Me[lea W, Kleinschmidt A, Schmidt J, et al. Infection of human fibroblasts and osteoblast-like cells with HIV-1. AIDS 1990;4:527-35. 40. Mahoney SE, Duvic M, NickoloffBJ, et al. HIV transcripts in HIV-associated Kaposi's sarcoma and psoriasis [Abstract]. J Invest Dermatol 1990;94:550.
II
III
I
Quantification of skin color in patients undergoing maintenance hemodialysis F. Deleixhe-Mauhin, MD, a J. M. Krezinski, MD, b G. Rorive, MD, PhD, b and G. E. Pi6rard, MD, PhD a Libge, Belgium
Background: In patients undergoing long.term hemodialysis,a peculiar hyperpigmentation develops, the intensity of which may or may not be related to the duration of treatment and use of erythropoietin. Objective: Our purpose was to conduct a comparative cross-sectional study of white patients with distinct diseases that modify their skin color. Methods: A reflected-light eolorimeter was used to compare the color of the forehead and forearms of 61 white patients receiving hemodialysis with that of matched controls and of patients with anemia or icterus. Results: Significant differences were found in both reflectance and chromaticity between these groups of patients. Duration of hemodialysis and use of erythropoietin did not significantly influence the colorimetric measurements. Conclusion: The use of a color-reflectance meter allows precise evaluation of subtle changes in skin color and may be used to monitor several diseases. (J AM ACAD DERMATOL I992;27:950-3.)
In patients with chronic renal failure who are undergoing maintenance hemodialysis cutaneous hyperpigmentation develops, caused by changes in the amount of chromogens such as melanin, hemoglobin, lipochromes, and carotenoids. 1"3 The visual evaluation of skin color is highly subjective and influenced by the type and intensity of
ambient light. However, the color of skin may be accurately measured by ahand-held color-reflectance meter. 411 The aim of this study is to evaluate skin color in patients undergoing hemodialysis with a quantitative noninvasive instrument and to compare it with skin color in other clinical conditions.
From the Departmentsof Dermatopathology"and Nephrology,b Universityof Li6ge. Acceptedfor publicationJune 8, 1992. Reprint requests: G. E. Pi6rard, Department of Dermatopathology, CHU du Sart Tilman,4000 Li6ge,Belgium.
M A T E R I A L AND M E T H O D S
16/1/40024 950
Subjects Sixty-one white patients on dialysis were included. Their ages ranged from 21 to 77 years, and they had been undergoing hemodialysis for 1 month to 18 years. Thir-
Volume 27 Number 6, Part 1 December 1992
Skin color and hemodialysis 951
Table I. Reproducibility of measurements Coef~cient of variation(%) Material
No.
Paper Forearm Forehead
1 8 8
0.01 0.68-0.97 0.77-1.22
0.23 1.34-2,96 1.68-7,84
0.36 2.41-4.02 1.94-3,85
Reproducibilityof seriesof 15 successivecolorimetricevaluationsperformedon a sheetof paperand in eightvolunteers.Data are expressedby the range of the coefficientsof variation(%) determinedfor luminance(L*) and chromaticity(a* and b*) for eachsubject.
Table II. Colorimetric characteristics of the skin
Hemodialysis Normal Ictera Anemia
Forearm Forehead Forearm Forehead Forearm Forehead Forearm Forehead
64.8 60.5 69.9 66.3 67.2 65.9 71.2 69.6
_ 2.6 _ 2.5 __+3.1 _ 2.8 + 1.8 _+ 2.9 _+ 2.6 _+ 2.4
7.4 12 7.9 11.2 6.2 6.8 5.8 6.1
___ 1.5 _ 2.4 _ 3.1 +_ 0.9 _+ 2.4 + 2.6 + 1.9 + 2.8
16.1 16.2 11.6 12.3 32.8 33.5 11.6 11.5
+ 2.1 __. 2,1 _,+ 1.9 + 1.8 + 3.4 _+ 2.7 + 2.6 _+ 2.1
Evaluation of luminance(L*) and chromaticity(a* and b*) in the four groupsof subjects.
ty-nine with a hematocrit value less than 30% were being treated with erythropoietfll. Fifty-six age-matched healthy white volunteers were the normal controls. Fifteen patients with severe icterus and eight patients with severe anemia were also studied.
Colorimeter A reflected-light colorirneter (Minolta Chromameter model CR-200, Osaka, Japan) was used to measure skin color in the L* a* b* system as recommended by the Commission Internationale de l'Eclairage, lz The color is defined by its reflectance (L*) and chromaticity (a* and b*). The L* value gives the level of brightness ranging from black (L* = 0) to white (L* = 100). The a* value represents the balance between red (positive values up to +100) and green (negative values up to -100). The b* value represents the balance between yellow (positive values up to + 100) and blue (negative values up to - 100). Differences between reflectance L* or chromaticity a* and b* are represented by AL*, Aa*, and Ab*, respectively. Any difference in the overall evaluation of color is expressed according to the formula: AE*ab = [(AL*) 2 + (Aa*)2 + (Ab*)2] '~
sites were measured, the forehead and the anterior aspect of the forearm. The probe of the apparatus was placed with minimal pressure on the skin. Reproducibility of the colorimetric measurements was assessed by 15 successive evaluations at the same site, on the forearm and forehead in eight volunteers. The same experiment was also performed on a pink sheet of paper.
Statistical analysis Reproducibility of measurements made at the same site was evaluated by the coefficient of variation V = SD X M -x. Statistical analysis of series of measurements was performed by the Student-Newman-Keuls test, RESULTS
Reproducibility of colorimetric evaluations Results are presented in Table I. The Chromarneter provided highly reproducible color evaluations of inert material because the coefficients of variation were less than 0.4%. Evaluations of the skin color revealed larger intraindividual variations, mostly for the chromaticities a* and b*. Nonetheless, the coefficients of variation remained less than 8%.
Experimental design
Colorimetric characteristics of the skin
Measurements of skin color were performed during winter to minimize the influence of solar irradiation. Two
Colorimetric characteristics of the skin are presented in Table II and Fig, I.
Journal of the American Academy of Dermatology
952 D e l e i x h e - M a u h i n et al.
FOREARM Colorimetrio difference 20 15 10 5 0 -5 -10 -15 -20 Ictera
Normal
A
[]
~L*
[]
~a*
[]
Anemia
Ab*
[]
~E*ab
FOREHEAD Colorimetric difference 20 15 10 5 0 -5 -10 -15 -20 Normal B
[]
~L*
Ictera []
~a"
[]
Anemia Ab*
[]
z~E~ ab
Fig. 1. A and B. Differences in luminance (AL*), chromaticity (~xa* and Ab*) and overall color (zkE*ab) between skin of patients receiving hemodialysis and the other groups of subjects.
The skin color of patients receiving hemodialysis was different from that of normal controls, on both the forearms and forehead. These patients had a darker skin (lower L*, 2xL*; p < 0.01) with a pronounced yellow hue (higher b*, ~b*; p < 0.01). No difference was evident in the redness of the skin (Aa* not significant), Furthermore, no difference was found in the chromaticity a* between patients receMng erythropoietin and the other hemodialyzed patients.
The differences in skin color between patients receiving hemodialysis and other patients with icterus or anemia are quantified in Table II and Fig. 1. Significant differences (.p < 0.01 ) were found between these groups for each colorimetric factor except for Aa* on the forearms of hemodialyzed and icteric patients (Fig. 1). No significant influence of the duration of hemodialysis was found in the bE* ab compared with normal controls (Fig. 2).
Volume 27 Number 6, Part 1 December 1992
Skin color and hemodialysis
AE'ab
953
use of erythropoietin. However, there is a bias in these findings because treatment modalities have changed during the past decade. Longitudinal studies will be necessary to define the influence of hemodialysis on the uremic hue.
20
~O o
9
9
O
oZ
9
fo
2'o Y
Fig. 2. Relation between duration of hemodialysis (Y, years) and the AE*ab with normal controls. DISCUSSION Skin color is influenced by ethnic, environmental,
and metabolic factors. 9, t3 This study confirms the high reproducibility of the evaluations of skin color with a Chromameter CR-200.1~ It is evident that the skin color of patients receivhag hemodialysis is abnormal. However, it is difficult by visual scoring alone to evaluate the color changes occurring over time in a given patient. Colorimetry in the L* a* b* system is well adapted to quantify subtle differences in the hue, value, and chroma of colors. In general, in all our patients, the exposed skin of the forehead had a lower reflectance (L*) than the skin of the forearms. The two test sites, however, appeared equally suitable to rate the disease-related changes in color. We found significant differences in colorimetric measurements of the skin between patients receiving hemodialysis, others with anemia or icterus, and normal persons. We failed to disclose any evident change in skin color related to the duration of hemodialysis and the
REFERENCES 1. Gupta AK, Gupta MA, Cardella C J, et al. Cutaneous associations of chronic renal failure and dialysis. Int J Dermatol 1986;25:498-504. 2. Gilkes JJH, Eady RAJ, Rees LH, et al. Plasma immunoreactive melanotrophic hormones in patients on maintenance haemodialysis. Br Med J 1975;1:656-8. 3. Smith AG, Schuster S, Thody A J, et al. Role of the kidney in regulating plasma immunoreactive beta-melanocytestimulating hormone. Br Med J 1976;1:874-6. 4. BabulakSW, Rhein LD, Scala DD, et al. Quantification of erythema in a soap chamber test using the Minolta Chroma (Reflectance) Meter: comparison of instrumental results withvisualassessments. JSoc Cosmet Chem 1986;37:475-9. 5. Westerhof W, Van Hassett BAAM, Kammeijer A. Quantification of UV-induced ery-thema with a portable computer controlled ehromameter. Photoderm 1986;3:310-4. 6. Porges SB, Kaidbey KH, Grove GL. Quantification of light-induced melanogenesis in human skin. Photodermatology 1988;5:197-200. 7. Seitz JC, Whitmore CG. Measurement of erythema and tanning responses in human skin using a tri-stimulus colorimeter. Dermatologica 1988;177:70-5. 8. Wilhelm KP, Surber C, Maibaeh HI. Quantification of sodium iauryl sulfate irritant dermatitis in man: comparison of four techniques: skin colour reflectance, transepidermal water loss, laser Doppler flow measurement and visual scores. Arch Dermatol Res 1989;281:293-5. 9. Andreassi L, Casini L, Simorti S, et al, Measurement of cutaneous eolour and assessment of skin type. Photodermatol Photoimmunol Photomed 1990;7:20-4. 10. Serup J, Agner T. Colorimetric quantification of erythema: a comparison of two colorimeters (Lange Micro Color and Minolta Chroma Meter CR-200) with a clinical scoring scheme and laser-doppler flowmetry. Clin Exp Dermatol 1990;15:267-72. 11. Queille-Roussel C, Parcel M, Schaefer H. Quantification of skin-colour changes induced by topical corticosteroid perparations using the Minolta Chroma Meter. Br J Dermatol 1991;124:264-70. 12. Robertson AR. The CIE 1976 color difference formulas. Cot Res Appl 1977;2:7-11. 13. Pirrard GE, Pirrard-Franchimont C, Laso DosaI F, et al. Pigmentary changes in skin senescence. J Appl Cosmetol 1991;9:57-63.
Smith et al.
31.
32. 33. 34. 35.
membrane antigens of nonlymphoid accessory cells in oral hairy leukoplakia. Hum Pathol 1990;21:897-904. Greenspaa D, Greenspan JS, Conant M, et al. Oral "hairy" leukoplakia in male homosexuals: evidence of association with both papillomavirusand a herpes-group virus. Lancet 1984;2:831-4. Alessi E, Berti E, Cusini M, et al. Oral hairy leukoplakia. J AM A c ~ DERMATOL1990;22:79-86. Greenspan D, Greenspan JS, de Souza Y, et al. Oral hairy leukoplakia in an HIV negative renal transplant recipient. J Oral Pathol Med 1989;1:32-4. Itin P, Ruff T, Rudlinger R, et al. Oral hairy leukoplakia in a HIV-negative renal transplant patient: A marker for immunosuppression? Dermatologica t988;177:126-8. Purtilo DT, Osato T, eds. Lymphotrophic viruses, immune deficiencyand human cancers. AIDS Res 1986;2(suppl):l196.
I
|11
36. Stingl G, Tschachler E, Groh V, et al. The immune functions of epidermal cells. In: Norris DA ed. Immune mechanisms in cutaneous disease. New York: Marcel Dekker, 1989:3-72. 37. Charley MR, Deng J-S. Murine models of graft-versushost disease with features of scleroderma. In: Norris DA, ed. Immune mechanisms in cutaneous disease. New York: Marcel Dek.ker, 1989:625-40. 38. Gendelman HE, Orenstein JM, Baca LM, et al. The macrophage in the persistence and pathogenesis of HIV infection. AIDS 1989;3:474-95. 39. Me[lea W, Kleinschmidt A, Schmidt J, et al. Infection of human fibroblasts and osteoblast-like cells with HIV-1. AIDS 1990;4:527-35. 40. Mahoney SE, Duvic M, NickoloffBJ, et al. HIV transcripts in HIV-associated Kaposi's sarcoma and psoriasis [Abstract]. J Invest Dermatol 1990;94:550.
II
III
I
Quantification of skin color in patients undergoing maintenance hemodialysis F. Deleixhe-Mauhin, MD, a J. M. Krezinski, MD, b G. Rorive, MD, PhD, b and G. E. Pi6rard, MD, PhD a Libge, Belgium
Background: In patients undergoing long.term hemodialysis,a peculiar hyperpigmentation develops, the intensity of which may or may not be related to the duration of treatment and use of erythropoietin. Objective: Our purpose was to conduct a comparative cross-sectional study of white patients with distinct diseases that modify their skin color. Methods: A reflected-light eolorimeter was used to compare the color of the forehead and forearms of 61 white patients receiving hemodialysis with that of matched controls and of patients with anemia or icterus. Results: Significant differences were found in both reflectance and chromaticity between these groups of patients. Duration of hemodialysis and use of erythropoietin did not significantly influence the colorimetric measurements. Conclusion: The use of a color-reflectance meter allows precise evaluation of subtle changes in skin color and may be used to monitor several diseases. (J AM ACAD DERMATOL I992;27:950-3.)
In patients with chronic renal failure who are undergoing maintenance hemodialysis cutaneous hyperpigmentation develops, caused by changes in the amount of chromogens such as melanin, hemoglobin, lipochromes, and carotenoids. 1"3 The visual evaluation of skin color is highly subjective and influenced by the type and intensity of
ambient light. However, the color of skin may be accurately measured by ahand-held color-reflectance meter. 411 The aim of this study is to evaluate skin color in patients undergoing hemodialysis with a quantitative noninvasive instrument and to compare it with skin color in other clinical conditions.
From the Departmentsof Dermatopathology"and Nephrology,b Universityof Li6ge. Acceptedfor publicationJune 8, 1992. Reprint requests: G. E. Pi6rard, Department of Dermatopathology, CHU du Sart Tilman,4000 Li6ge,Belgium.
M A T E R I A L AND M E T H O D S
16/1/40024 950
Subjects Sixty-one white patients on dialysis were included. Their ages ranged from 21 to 77 years, and they had been undergoing hemodialysis for 1 month to 18 years. Thir-
Volume 27 Number 6, Part 1 December 1992
Skin color and hemodialysis 951
Table I. Reproducibility of measurements Coef~cient of variation(%) Material
No.
Paper Forearm Forehead
1 8 8
0.01 0.68-0.97 0.77-1.22
0.23 1.34-2,96 1.68-7,84
0.36 2.41-4.02 1.94-3,85
Reproducibilityof seriesof 15 successivecolorimetricevaluationsperformedon a sheetof paperand in eightvolunteers.Data are expressedby the range of the coefficientsof variation(%) determinedfor luminance(L*) and chromaticity(a* and b*) for eachsubject.
Table II. Colorimetric characteristics of the skin
Hemodialysis Normal Ictera Anemia
Forearm Forehead Forearm Forehead Forearm Forehead Forearm Forehead
64.8 60.5 69.9 66.3 67.2 65.9 71.2 69.6
_ 2.6 _ 2.5 __+3.1 _ 2.8 + 1.8 _+ 2.9 _+ 2.6 _+ 2.4
7.4 12 7.9 11.2 6.2 6.8 5.8 6.1
___ 1.5 _ 2.4 _ 3.1 +_ 0.9 _+ 2.4 + 2.6 + 1.9 + 2.8
16.1 16.2 11.6 12.3 32.8 33.5 11.6 11.5
+ 2.1 __. 2,1 _,+ 1.9 + 1.8 + 3.4 _+ 2.7 + 2.6 _+ 2.1
Evaluation of luminance(L*) and chromaticity(a* and b*) in the four groupsof subjects.
ty-nine with a hematocrit value less than 30% were being treated with erythropoietfll. Fifty-six age-matched healthy white volunteers were the normal controls. Fifteen patients with severe icterus and eight patients with severe anemia were also studied.
Colorimeter A reflected-light colorirneter (Minolta Chromameter model CR-200, Osaka, Japan) was used to measure skin color in the L* a* b* system as recommended by the Commission Internationale de l'Eclairage, lz The color is defined by its reflectance (L*) and chromaticity (a* and b*). The L* value gives the level of brightness ranging from black (L* = 0) to white (L* = 100). The a* value represents the balance between red (positive values up to +100) and green (negative values up to -100). The b* value represents the balance between yellow (positive values up to + 100) and blue (negative values up to - 100). Differences between reflectance L* or chromaticity a* and b* are represented by AL*, Aa*, and Ab*, respectively. Any difference in the overall evaluation of color is expressed according to the formula: AE*ab = [(AL*) 2 + (Aa*)2 + (Ab*)2] '~
sites were measured, the forehead and the anterior aspect of the forearm. The probe of the apparatus was placed with minimal pressure on the skin. Reproducibility of the colorimetric measurements was assessed by 15 successive evaluations at the same site, on the forearm and forehead in eight volunteers. The same experiment was also performed on a pink sheet of paper.
Statistical analysis Reproducibility of measurements made at the same site was evaluated by the coefficient of variation V = SD X M -x. Statistical analysis of series of measurements was performed by the Student-Newman-Keuls test, RESULTS
Reproducibility of colorimetric evaluations Results are presented in Table I. The Chromarneter provided highly reproducible color evaluations of inert material because the coefficients of variation were less than 0.4%. Evaluations of the skin color revealed larger intraindividual variations, mostly for the chromaticities a* and b*. Nonetheless, the coefficients of variation remained less than 8%.
Experimental design
Colorimetric characteristics of the skin
Measurements of skin color were performed during winter to minimize the influence of solar irradiation. Two
Colorimetric characteristics of the skin are presented in Table II and Fig, I.
Journal of the American Academy of Dermatology
952 D e l e i x h e - M a u h i n et al.
FOREARM Colorimetrio difference 20 15 10 5 0 -5 -10 -15 -20 Ictera
Normal
A
[]
~L*
[]
~a*
[]
Anemia
Ab*
[]
~E*ab
FOREHEAD Colorimetric difference 20 15 10 5 0 -5 -10 -15 -20 Normal B
[]
~L*
Ictera []
~a"
[]
Anemia Ab*
[]
z~E~ ab
Fig. 1. A and B. Differences in luminance (AL*), chromaticity (~xa* and Ab*) and overall color (zkE*ab) between skin of patients receiving hemodialysis and the other groups of subjects.
The skin color of patients receiving hemodialysis was different from that of normal controls, on both the forearms and forehead. These patients had a darker skin (lower L*, 2xL*; p < 0.01) with a pronounced yellow hue (higher b*, ~b*; p < 0.01). No difference was evident in the redness of the skin (Aa* not significant), Furthermore, no difference was found in the chromaticity a* between patients receMng erythropoietin and the other hemodialyzed patients.
The differences in skin color between patients receiving hemodialysis and other patients with icterus or anemia are quantified in Table II and Fig. 1. Significant differences (.p < 0.01 ) were found between these groups for each colorimetric factor except for Aa* on the forearms of hemodialyzed and icteric patients (Fig. 1). No significant influence of the duration of hemodialysis was found in the bE* ab compared with normal controls (Fig. 2).
Volume 27 Number 6, Part 1 December 1992
Skin color and hemodialysis
AE'ab
953
use of erythropoietin. However, there is a bias in these findings because treatment modalities have changed during the past decade. Longitudinal studies will be necessary to define the influence of hemodialysis on the uremic hue.
20
~O o
9
9
O
oZ
9
fo
2'o Y
Fig. 2. Relation between duration of hemodialysis (Y, years) and the AE*ab with normal controls. DISCUSSION Skin color is influenced by ethnic, environmental,
and metabolic factors. 9, t3 This study confirms the high reproducibility of the evaluations of skin color with a Chromameter CR-200.1~ It is evident that the skin color of patients receivhag hemodialysis is abnormal. However, it is difficult by visual scoring alone to evaluate the color changes occurring over time in a given patient. Colorimetry in the L* a* b* system is well adapted to quantify subtle differences in the hue, value, and chroma of colors. In general, in all our patients, the exposed skin of the forehead had a lower reflectance (L*) than the skin of the forearms. The two test sites, however, appeared equally suitable to rate the disease-related changes in color. We found significant differences in colorimetric measurements of the skin between patients receiving hemodialysis, others with anemia or icterus, and normal persons. We failed to disclose any evident change in skin color related to the duration of hemodialysis and the
REFERENCES 1. Gupta AK, Gupta MA, Cardella C J, et al. Cutaneous associations of chronic renal failure and dialysis. Int J Dermatol 1986;25:498-504. 2. Gilkes JJH, Eady RAJ, Rees LH, et al. Plasma immunoreactive melanotrophic hormones in patients on maintenance haemodialysis. Br Med J 1975;1:656-8. 3. Smith AG, Schuster S, Thody A J, et al. Role of the kidney in regulating plasma immunoreactive beta-melanocytestimulating hormone. Br Med J 1976;1:874-6. 4. BabulakSW, Rhein LD, Scala DD, et al. Quantification of erythema in a soap chamber test using the Minolta Chroma (Reflectance) Meter: comparison of instrumental results withvisualassessments. JSoc Cosmet Chem 1986;37:475-9. 5. Westerhof W, Van Hassett BAAM, Kammeijer A. Quantification of UV-induced ery-thema with a portable computer controlled ehromameter. Photoderm 1986;3:310-4. 6. Porges SB, Kaidbey KH, Grove GL. Quantification of light-induced melanogenesis in human skin. Photodermatology 1988;5:197-200. 7. Seitz JC, Whitmore CG. Measurement of erythema and tanning responses in human skin using a tri-stimulus colorimeter. Dermatologica 1988;177:70-5. 8. Wilhelm KP, Surber C, Maibaeh HI. Quantification of sodium iauryl sulfate irritant dermatitis in man: comparison of four techniques: skin colour reflectance, transepidermal water loss, laser Doppler flow measurement and visual scores. Arch Dermatol Res 1989;281:293-5. 9. Andreassi L, Casini L, Simorti S, et al, Measurement of cutaneous eolour and assessment of skin type. Photodermatol Photoimmunol Photomed 1990;7:20-4. 10. Serup J, Agner T. Colorimetric quantification of erythema: a comparison of two colorimeters (Lange Micro Color and Minolta Chroma Meter CR-200) with a clinical scoring scheme and laser-doppler flowmetry. Clin Exp Dermatol 1990;15:267-72. 11. Queille-Roussel C, Parcel M, Schaefer H. Quantification of skin-colour changes induced by topical corticosteroid perparations using the Minolta Chroma Meter. Br J Dermatol 1991;124:264-70. 12. Robertson AR. The CIE 1976 color difference formulas. Cot Res Appl 1977;2:7-11. 13. Pirrard GE, Pirrard-Franchimont C, Laso DosaI F, et al. Pigmentary changes in skin senescence. J Appl Cosmetol 1991;9:57-63.
