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The usefulness of reflectance spectrophotometric measurements during psoralens and ultraviolet A therapy for psoriasis
The usefulness of reflectance spectrophotometric measurements during psoralens and ultraviolet A therapy for psoriasis K. S. Ryatt, M . R . C . P . , J. W. Feather, B.A., J. B. Dawson, Ph.D., F.Inst.P., and J. A. Cotterill, M . D . , F.R.C.P.
Leeds, England Reflectance spectrophotometry was used to obtain indices of the hemoglobin and melanin content of psoriatic lesions and adjacent clinically normal skin in thirteen patients undergoing photochemotherapy. The pretreatment lesional hemoglobin index was 2.8 times greater than that of adjacent uninvolved skin. With therapy, this index decreased rapidly initially, and during the second or third week approached that of the uninvolved skin. The ratio of lesional and uninvolved skin hemoglobin indices decreased to approximately 1.3, and continuation of PUVA treatment failed to reduce it further. Termination of treatment at this stage, which occurs before clinical resolution, resulted in subsequent clearance of psoriasis. The decrease in the lesional hemoglobin index and the clearance time appeared to be dose-dependent, and, indeed, a more aggressive regimen resulted in approximately 50% reduction in both the number of treatments and the cumulative dose required to achieve a stable hemoglobin index ratio and subsequent clinical clearance. (J AM ACAD DERMATOL 9:558-562, 1983.)
Photochemotherapy with psoralens and ultraviolet A (PUVA) is an effective method of treatment for refractory psoriasis. However, since phototoxic erythema is the main limiting factor in treatment, not only the dose of UVA but also treatment frequency are likely to be important for optimum results. Treatment progress is usually monitored visually and the dose of UVA, though measured instrumentally, is decided upon subjectively with the use of guidelines based on the min-
From the Departments of Dermatology and Medical Physics, Leeds General Infirmary, Supported by the Yorkshire Regional Health Authority. Accepted for publication Jan. 28, 1983. Reprint requests to: Dr. J. A, Cotterill, Department of Dermatology, The General Infirmary at Leeds, Great George St,, Leeds LS1 3EX, Yorkshire.
558
imal phototoxicity dose (MPD) and the photosensitivity pigmentation index (PPI). 1 The purpose of this study was to investigate the clinical usefulness of reflectance spcctrophotometry for measuring changes in skin hemoglobin and melanin content during PUVA therapy, as it is known that neither the early development of melanin pigmentation nor the persisting erythema during later PUVA therapy can be detected accurately by the human eye. 2 Three different treatment schedules were studied to try and define optimum therapeutic conditions. METHOD
Thirteen patients with long histories of recalcitrant psoriasis refractory to dithranol (anthralin) treatment were investigated. Dithranol had been discontinued at least 2 weeks prior to PUVA. The dose of 8-methoxy-
Volume 9 Number 4 October, 1983
Reflectance spectrophotometric measurements during PUVA therapy
MEAN ERYTHEMA INDICES AND ERYTHEMA PSORIATIC LESION AND NORMAL SKIN
RATIOS
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Fig. 1. Mean erythema index responses to PUVA therapy. psoralen (8-MOP), 0.6 mg/kg, and patient skin typing were as recommended by Wolff et al. ~ In the initial study, four patients (three male and one female, mean age, 44 years, one each of skin types 2 and 4 and two each of skin type 3) were treated. The initial UVA exposures were 1.5 joules/cm 2 irrespective of skin type, and subsequent increments 0.5 to 1.0 joules/cm 2 on alternate treatment days were in accordance with the increase in the erythema and pigmentation of the subjects. Therapy was given three times a week until 90% clearance of lesions was achieved. This was followed by twice-weekly treatments to produce complete clinical clearance. Treatment was reduced to once weekly for a fortnight and then to once fortnightly for a month and then discontinued. The duration of treatment ranged from 7 to 15 weeks. In the second study the response of two different regimes (a very short treatment program and a more aggressive treatment regime) was investigated. In the first regime, four patients, two male and two female, mean age, 38 years, two of skin type 2 and two of skin type 3, were treated with 2.25, 2.75, and 3.75 joules/ cm2 on average on alternate days in 1 week only. The responses were monitored before each treatment and then weekly over the ensuing 4 weeks. In the second regime, five patients, three male and two female, mean age, 38 years, one each of skin types 2 and 4 and three of skin type 3, were treated more aggressively, with an average starting dose of 3.5 joules/cm z, followed by subsequent increments in
doses varying from 1 to 2 joules/cm 2 in accordance with the subjective increases of erythema and pigmentation of the subjects. Four patients were treated until clinical clearance of psoriasis; the fifth was treated only until the ratio of the erythema index of the lesion (El) and that of the adjacent unaffected skin (Eu) had become constant. The erythema and melanin indices of a psoriatic lesion and adjacent normal skin were determined just before each PUVA treatment with the use of reflectance spectrophotometry. Details of the instrumentation and methodology of the reflectance spectrophotometric technic for skin color measurement have been given in an earlier paper. 2 RESULTS AND DISCUSSION
Initial study A single measurement o f both e r y t h e m a and melanin indices was m a d e at each site, and the data in Figs. 1 and 2 present the a v e r a g e of the three readings taken during each w e e k ' s treatment. Erythema index ratios (E1/Eu) w e r e used as these partially corrected the s p o n t a n e o u s and environmentally induced changes in the cutaneous h e m o g l o b i n content o f the psoriatic lesions and the adjacent unaffected skin. Irregularities in the curves after the first 7 weeks arise f r o m the occasional failure of patients to attend for treatment, resulting in the m e a n values being calculated f r o m
560
Journal of the American Academy of Dermatology
Ryatt e/a]
M E A N MELANIN INDICES OF PSORIATIC LESIONS AND NORMAL SKIN
A--~, NORMAL
SKIN
O--O LESIOIV$
x _z Z
z<
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9
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.
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10 11 12 13 14 115 116 ;7 ,~
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Fig. 2. Mean melanin index responses to PUVA therapy.
Table I. Initial study (comparison of the average number of days [joules/cm 2] and treatments between stable EI/Eu stage and at clearance"
No. ofjoules/em ~ J Treatment steps
EI/Eu stability Clearance
No.
of days 28 62
Range
38.5-52 109-193
I
Mean
No. of' treatments
44.6
12
138
22
the results of the various combinations of the four patients. The mean initial erythema index of uninvolved skin (Eu = 33) increased rapidly to a maximum and then gradually decreased as melanin pigmentatio n increased. The peak (Eu = 54.0) occurred in all but one patient within 4 weeks of start of treatment, when a mean cumulative dose of 44.6 joules/cm'-' had been given (Table I). Initially the high mean erythema index of the lesion (El = 108.0) decreased rapidly. This rapid phase was followed by a slow decrease, and after 4 weeks the response was similar to that of uninvolved skin. This is shown more clearly when the EI/Eu is plotted against time (Fig. 1).
Fig. 2 shows the average melanin indices of psoriatic lesions and adjacent uninvolved skin. There was an unexpected decrease in two of four lesional and in one of four uninvolved skin melanin indices at their second or third measurement after commencement of therapy. The average uninvolved skin and lesional melanin index (Mu = 3.0, MI = 1.5) increased rapidly and linearly for the first 6 weeks (average cumulative dose of 80 j0ules/cm2), followed by a more gradual increase and then a decrease which did not occur for at least 5 weeks after cessation of therapy. The disparity in the melanin indices of the lesion and the uninvolved skin could be due to the high epidermal cell turnover in the psoriatic lesion, diluting the normal amount of melanin present, or to the abnormal cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP) ratio seen in psoriasis, :~'4 and to the fact that cAMP and cGMP have been shown to be second messengers for melanocyte-stimulating hormone (MSH) and melatonin, respectively. '~ The erythema and melanin response patterns in general were similar, but individual responses depended upon the dose rate of UVA, the melanotic potential of the site, and the skin type of the subject.
Volume 9 Number 4 October, 1983
Reflectance spectrophotometric measurements during PUVA therapy
561
MEAN ERYTHEMA INDEX RATIOS
DURATION OF THERAPY A = 1 WEEK B ~ 1 MONTH
o re"
< FuJ
-AB
i
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4/7
1
2
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Fig. 3. Comparison of short and longer term therapy. Table II. Second study (comparison of the average number of days [joules/cm '2] and treatments for different skin types) No. of days Skin type
Cumulative dose
Treatment steps
2
3
4
Mean (days)
E1/Eu stability Clearance Average total treatment
11.0 25.0 28.0
14.0 24.3 24.7
9.0 32.0 32.0
12.4 26.0 26.8
2
Skin type . [3 [
16.5 37.5 49.5
37.5 79.7 90.3
Second study Fig. 3, curve A shows the results of the shortterm study. There was an initial rapid decrease in the mean E1/Eu ratio of the four subjects during the first week, which continued, though at a slower rate, in the next week. Beyond the third week the trend was that of regression toward the original values. This clearly showed that 1 week's treatment was insufficient to maintain the initial rapid fall in the erythema index ratio to achieve the stable E1/Eu ratio of approximately 1.3. Fig. 3, curve B shows the average E1/Eu values during the more aggressive regime. For individual patients, this ratio decreased rapidly initially and
No. of treatments (n) Skin type
4
Mean (joules/cm 'z)
2
26.0 173 173
31.0 89.9 96.7
5.0 9.0 11.0
[
3
5.3 9.0 10.3
]
Mean 4
(n)
4,0 15.0 15.0
5.0 10.2 11.4
then stabilized at around 1.3 after 12.4 days on average. This rapid initial decrease (Figs. 1 and 3, curve B) became more marked in the second week and was noted especially in subjects with high initial lesional erythema values. Individual E1/Eu responses showed that the initial responses were dose-dependent up to the slowly changing part of the response curve, suggesting that a higher dose rate might result in a more rapid remission of psoriasis. This could lead to a reduction in the total cumulative dose, as higher doses are needed toward the latter part of the treatment program when an increased amount of protective pigmentation is present.
562
Journal of the American Academyof Dermatology
Ryatt et al
Table II shows the average number of days, joules/cm 2, and treatments given in total to reach the E1/Eu nadir and clinical clearance for skin types 2, 3, and 4, with the aggressive regime. Therapy was continued a little beyond when clearance had occurred in three patients as a precautionary measure, since they had missed one or two treatments in the last or the penultimate week of the treatment program. This is responsible for the slightly greater total duration, cumulative dose of UVA, and number o f treatments given than that actually required for clinical clearance. The average time to E1/Eu stabilization and clinical clearance of psoriasis was shorter than that in our pilot study, but the ratio of the time to reach E1/Eu nadir to the time to clearance was similar. The shortening of the time to clearance is probably due to the greater dose rate of UVA in the second study, which is associated with a more rapid fall in the E1/Eu ratios. The marked alteration in response of the lesion after 4 weeks and 12.4 days (initial and second study, respectively) may indicate a return toward normal of the psoriatic abnormality of the vascular bed, and cessation of treatment at that time may bring an earlier return of the erythema index of the lesion to near normal values. Erythema and scaling were still present clinically, but this might be expected as a reversion to normal epidermal cell tnrnover may not become evident until some weeks later. Moreover, the continuation of PUVA therapy, as is the usual practice, increases the erythema index of the lesion to a higher value than that of the surrounding skin, perhaps because the site is relatively unprotected by melanin and thus may create the impression that an active lesion is still present. The final erythema index of lesions 1 month after the last maintenance dose of UVA was greater than that of the normal sites and confirms that the abnormal vascular pattern seen in psoriasis rarely disappears completely, even after apparent remission. 6 During the follow-up period of 12 weeks, the E1/Eu ratio of three patients remained close to the value noted at cessation o f therapy. Two, however, developed the occasional guttate lesions on the body while the site previously scanned was still clear. One showed a rapid rise in the EI/Eu ratio 1 month after the last treatment and, indeed, relapsed 4 weeks later. Early recognition of a re-
lapse may thus be possible, and, if followed by a short course of aggressive therapy, may sustain remissions for much longer periods, with a resultant reduction in the cumulative dose of UVA. Five of eight patients with recalcitrant psoriasis, in an ongoing study in which therapy was similar to that of the aggressive regime but terminated when the E1/Eu had stabilized at approximately 1.3, showed clinical clearance during follow-up in the ensuing 4 weeks. Treatment was discontinued in two patients because of default in one and intolerable pruritus in the other. One patient with severe psoriasis was put on cytotoxic therapy as his psoriasis failed to respond to PUVA treatment. Although the numbers are small, these observations suggest that the disease activity may well be mirrored by that in the vascular compartment of the psoriatic skin. The recent evidence claiming primary events to be epidermal and vascular proliferation to be secondary seems to support this. 7 The marked change in the erythema response pattern of the lesion, not apparent to the naked eye, can thus be recognized and used as a basis for terminating PUVA therapy despite presence of some psoriasis clinically. Also, a more aggressive treatment regime with greater initial and subsequent increments of dose of UVA could result in much earlier remission, with a consequent reduction in the cumulative dose, thereby lessening the risk of nonmelanotic skin cancer and saving both nursing and patient time. REFERENCES
1. WolffK, Gschnait F, Honigsmann H, et al: Phototesting and dosimetry for photochemotherapy. Br J Dermat01 96:1-18, 1977. 2. DawsonJB, Barker DJ, Ellis DJ, et al: A theoretical and experimental study of light absorption and scatteringby in-vivo skin. Phys Med Biol 25:695-709, 1980. 3. MarcelloCL, Duell EA, Stawiski MA, et al: CyclicAMP levels in psoriatic and normal keratomed epidermis. J Invest Dermatol 72:20-24, 1979. 4. Geerdink JPM, Bergers M, Van Erp PEJ, et al: Cyclic AMP is decreased in mononuclear leukocytes from psoriatic patients. Br J Dermatol 103:107-108, 1980. 5. Weatherhead B, Logan A: Interaction of o~-melanocytestimulating hormone, melatonin, cyclic AMP and cyclic GMP in the control of rnelanogenesis in hair follicle melanocytes in vitro. J Endocrinol 90:89-96, 1981. 6. LawlerJC, VineyardWK: The effect of treatmenton the vascular compartment of the psoriatic lesion. Arch Dermatol 82: 190-193, 1960. 7. Braverman IM, Sibley J: Role of the microcirculationin the treatment and pathogenesis of psoriasis. J Invest Dermatol 78:I2-17, 1982.
Leeds, England Reflectance spectrophotometry was used to obtain indices of the hemoglobin and melanin content of psoriatic lesions and adjacent clinically normal skin in thirteen patients undergoing photochemotherapy. The pretreatment lesional hemoglobin index was 2.8 times greater than that of adjacent uninvolved skin. With therapy, this index decreased rapidly initially, and during the second or third week approached that of the uninvolved skin. The ratio of lesional and uninvolved skin hemoglobin indices decreased to approximately 1.3, and continuation of PUVA treatment failed to reduce it further. Termination of treatment at this stage, which occurs before clinical resolution, resulted in subsequent clearance of psoriasis. The decrease in the lesional hemoglobin index and the clearance time appeared to be dose-dependent, and, indeed, a more aggressive regimen resulted in approximately 50% reduction in both the number of treatments and the cumulative dose required to achieve a stable hemoglobin index ratio and subsequent clinical clearance. (J AM ACAD DERMATOL 9:558-562, 1983.)
Photochemotherapy with psoralens and ultraviolet A (PUVA) is an effective method of treatment for refractory psoriasis. However, since phototoxic erythema is the main limiting factor in treatment, not only the dose of UVA but also treatment frequency are likely to be important for optimum results. Treatment progress is usually monitored visually and the dose of UVA, though measured instrumentally, is decided upon subjectively with the use of guidelines based on the min-
From the Departments of Dermatology and Medical Physics, Leeds General Infirmary, Supported by the Yorkshire Regional Health Authority. Accepted for publication Jan. 28, 1983. Reprint requests to: Dr. J. A, Cotterill, Department of Dermatology, The General Infirmary at Leeds, Great George St,, Leeds LS1 3EX, Yorkshire.
558
imal phototoxicity dose (MPD) and the photosensitivity pigmentation index (PPI). 1 The purpose of this study was to investigate the clinical usefulness of reflectance spcctrophotometry for measuring changes in skin hemoglobin and melanin content during PUVA therapy, as it is known that neither the early development of melanin pigmentation nor the persisting erythema during later PUVA therapy can be detected accurately by the human eye. 2 Three different treatment schedules were studied to try and define optimum therapeutic conditions. METHOD
Thirteen patients with long histories of recalcitrant psoriasis refractory to dithranol (anthralin) treatment were investigated. Dithranol had been discontinued at least 2 weeks prior to PUVA. The dose of 8-methoxy-
Volume 9 Number 4 October, 1983
Reflectance spectrophotometric measurements during PUVA therapy
MEAN ERYTHEMA INDICES AND ERYTHEMA PSORIATIC LESION AND NORMAL SKIN
RATIOS
OF
e--®
Q\,
I=~m •~ i T T II1---.---=1 l J.
\ \
\ T
X
e_
LESION ERYTHEMA RATIO NORMAL SKIN SEM
\
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7o ,-r I--
559
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8o
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1
2
3
4
5
6
7
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-
.2 0
OF THERAPY
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11 12 13
14 15 16
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21 22
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WEEKS
Fig. 1. Mean erythema index responses to PUVA therapy. psoralen (8-MOP), 0.6 mg/kg, and patient skin typing were as recommended by Wolff et al. ~ In the initial study, four patients (three male and one female, mean age, 44 years, one each of skin types 2 and 4 and two each of skin type 3) were treated. The initial UVA exposures were 1.5 joules/cm 2 irrespective of skin type, and subsequent increments 0.5 to 1.0 joules/cm 2 on alternate treatment days were in accordance with the increase in the erythema and pigmentation of the subjects. Therapy was given three times a week until 90% clearance of lesions was achieved. This was followed by twice-weekly treatments to produce complete clinical clearance. Treatment was reduced to once weekly for a fortnight and then to once fortnightly for a month and then discontinued. The duration of treatment ranged from 7 to 15 weeks. In the second study the response of two different regimes (a very short treatment program and a more aggressive treatment regime) was investigated. In the first regime, four patients, two male and two female, mean age, 38 years, two of skin type 2 and two of skin type 3, were treated with 2.25, 2.75, and 3.75 joules/ cm2 on average on alternate days in 1 week only. The responses were monitored before each treatment and then weekly over the ensuing 4 weeks. In the second regime, five patients, three male and two female, mean age, 38 years, one each of skin types 2 and 4 and three of skin type 3, were treated more aggressively, with an average starting dose of 3.5 joules/cm z, followed by subsequent increments in
doses varying from 1 to 2 joules/cm 2 in accordance with the subjective increases of erythema and pigmentation of the subjects. Four patients were treated until clinical clearance of psoriasis; the fifth was treated only until the ratio of the erythema index of the lesion (El) and that of the adjacent unaffected skin (Eu) had become constant. The erythema and melanin indices of a psoriatic lesion and adjacent normal skin were determined just before each PUVA treatment with the use of reflectance spectrophotometry. Details of the instrumentation and methodology of the reflectance spectrophotometric technic for skin color measurement have been given in an earlier paper. 2 RESULTS AND DISCUSSION
Initial study A single measurement o f both e r y t h e m a and melanin indices was m a d e at each site, and the data in Figs. 1 and 2 present the a v e r a g e of the three readings taken during each w e e k ' s treatment. Erythema index ratios (E1/Eu) w e r e used as these partially corrected the s p o n t a n e o u s and environmentally induced changes in the cutaneous h e m o g l o b i n content o f the psoriatic lesions and the adjacent unaffected skin. Irregularities in the curves after the first 7 weeks arise f r o m the occasional failure of patients to attend for treatment, resulting in the m e a n values being calculated f r o m
560
Journal of the American Academy of Dermatology
Ryatt e/a]
M E A N MELANIN INDICES OF PSORIATIC LESIONS AND NORMAL SKIN
A--~, NORMAL
SKIN
O--O LESIOIV$
x _z Z
z<
/
t ,.~.A.,
./
,\,?/°7
\\ ~:
e~ql
¶
0
i 1
,
2
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3
,
4
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5
.
6
.
7
.
.
8
.
9
.
.
'
I
10 11 12 13 14 115 116 ;7 ,~
119 210 11
WEEKS
Fig. 2. Mean melanin index responses to PUVA therapy.
Table I. Initial study (comparison of the average number of days [joules/cm 2] and treatments between stable EI/Eu stage and at clearance"
No. ofjoules/em ~ J Treatment steps
EI/Eu stability Clearance
No.
of days 28 62
Range
38.5-52 109-193
I
Mean
No. of' treatments
44.6
12
138
22
the results of the various combinations of the four patients. The mean initial erythema index of uninvolved skin (Eu = 33) increased rapidly to a maximum and then gradually decreased as melanin pigmentatio n increased. The peak (Eu = 54.0) occurred in all but one patient within 4 weeks of start of treatment, when a mean cumulative dose of 44.6 joules/cm'-' had been given (Table I). Initially the high mean erythema index of the lesion (El = 108.0) decreased rapidly. This rapid phase was followed by a slow decrease, and after 4 weeks the response was similar to that of uninvolved skin. This is shown more clearly when the EI/Eu is plotted against time (Fig. 1).
Fig. 2 shows the average melanin indices of psoriatic lesions and adjacent uninvolved skin. There was an unexpected decrease in two of four lesional and in one of four uninvolved skin melanin indices at their second or third measurement after commencement of therapy. The average uninvolved skin and lesional melanin index (Mu = 3.0, MI = 1.5) increased rapidly and linearly for the first 6 weeks (average cumulative dose of 80 j0ules/cm2), followed by a more gradual increase and then a decrease which did not occur for at least 5 weeks after cessation of therapy. The disparity in the melanin indices of the lesion and the uninvolved skin could be due to the high epidermal cell turnover in the psoriatic lesion, diluting the normal amount of melanin present, or to the abnormal cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP) ratio seen in psoriasis, :~'4 and to the fact that cAMP and cGMP have been shown to be second messengers for melanocyte-stimulating hormone (MSH) and melatonin, respectively. '~ The erythema and melanin response patterns in general were similar, but individual responses depended upon the dose rate of UVA, the melanotic potential of the site, and the skin type of the subject.
Volume 9 Number 4 October, 1983
Reflectance spectrophotometric measurements during PUVA therapy
561
MEAN ERYTHEMA INDEX RATIOS
DURATION OF THERAPY A = 1 WEEK B ~ 1 MONTH
o re"
< FuJ
-AB
i
i
i
i
i
I
0
2/7
4/7
1
2
3
.,
I
I
i
i
4
5
6
7
WEEKS
Fig. 3. Comparison of short and longer term therapy. Table II. Second study (comparison of the average number of days [joules/cm '2] and treatments for different skin types) No. of days Skin type
Cumulative dose
Treatment steps
2
3
4
Mean (days)
E1/Eu stability Clearance Average total treatment
11.0 25.0 28.0
14.0 24.3 24.7
9.0 32.0 32.0
12.4 26.0 26.8
2
Skin type . [3 [
16.5 37.5 49.5
37.5 79.7 90.3
Second study Fig. 3, curve A shows the results of the shortterm study. There was an initial rapid decrease in the mean E1/Eu ratio of the four subjects during the first week, which continued, though at a slower rate, in the next week. Beyond the third week the trend was that of regression toward the original values. This clearly showed that 1 week's treatment was insufficient to maintain the initial rapid fall in the erythema index ratio to achieve the stable E1/Eu ratio of approximately 1.3. Fig. 3, curve B shows the average E1/Eu values during the more aggressive regime. For individual patients, this ratio decreased rapidly initially and
No. of treatments (n) Skin type
4
Mean (joules/cm 'z)
2
26.0 173 173
31.0 89.9 96.7
5.0 9.0 11.0
[
3
5.3 9.0 10.3
]
Mean 4
(n)
4,0 15.0 15.0
5.0 10.2 11.4
then stabilized at around 1.3 after 12.4 days on average. This rapid initial decrease (Figs. 1 and 3, curve B) became more marked in the second week and was noted especially in subjects with high initial lesional erythema values. Individual E1/Eu responses showed that the initial responses were dose-dependent up to the slowly changing part of the response curve, suggesting that a higher dose rate might result in a more rapid remission of psoriasis. This could lead to a reduction in the total cumulative dose, as higher doses are needed toward the latter part of the treatment program when an increased amount of protective pigmentation is present.
562
Journal of the American Academyof Dermatology
Ryatt et al
Table II shows the average number of days, joules/cm 2, and treatments given in total to reach the E1/Eu nadir and clinical clearance for skin types 2, 3, and 4, with the aggressive regime. Therapy was continued a little beyond when clearance had occurred in three patients as a precautionary measure, since they had missed one or two treatments in the last or the penultimate week of the treatment program. This is responsible for the slightly greater total duration, cumulative dose of UVA, and number o f treatments given than that actually required for clinical clearance. The average time to E1/Eu stabilization and clinical clearance of psoriasis was shorter than that in our pilot study, but the ratio of the time to reach E1/Eu nadir to the time to clearance was similar. The shortening of the time to clearance is probably due to the greater dose rate of UVA in the second study, which is associated with a more rapid fall in the E1/Eu ratios. The marked alteration in response of the lesion after 4 weeks and 12.4 days (initial and second study, respectively) may indicate a return toward normal of the psoriatic abnormality of the vascular bed, and cessation of treatment at that time may bring an earlier return of the erythema index of the lesion to near normal values. Erythema and scaling were still present clinically, but this might be expected as a reversion to normal epidermal cell tnrnover may not become evident until some weeks later. Moreover, the continuation of PUVA therapy, as is the usual practice, increases the erythema index of the lesion to a higher value than that of the surrounding skin, perhaps because the site is relatively unprotected by melanin and thus may create the impression that an active lesion is still present. The final erythema index of lesions 1 month after the last maintenance dose of UVA was greater than that of the normal sites and confirms that the abnormal vascular pattern seen in psoriasis rarely disappears completely, even after apparent remission. 6 During the follow-up period of 12 weeks, the E1/Eu ratio of three patients remained close to the value noted at cessation o f therapy. Two, however, developed the occasional guttate lesions on the body while the site previously scanned was still clear. One showed a rapid rise in the EI/Eu ratio 1 month after the last treatment and, indeed, relapsed 4 weeks later. Early recognition of a re-
lapse may thus be possible, and, if followed by a short course of aggressive therapy, may sustain remissions for much longer periods, with a resultant reduction in the cumulative dose of UVA. Five of eight patients with recalcitrant psoriasis, in an ongoing study in which therapy was similar to that of the aggressive regime but terminated when the E1/Eu had stabilized at approximately 1.3, showed clinical clearance during follow-up in the ensuing 4 weeks. Treatment was discontinued in two patients because of default in one and intolerable pruritus in the other. One patient with severe psoriasis was put on cytotoxic therapy as his psoriasis failed to respond to PUVA treatment. Although the numbers are small, these observations suggest that the disease activity may well be mirrored by that in the vascular compartment of the psoriatic skin. The recent evidence claiming primary events to be epidermal and vascular proliferation to be secondary seems to support this. 7 The marked change in the erythema response pattern of the lesion, not apparent to the naked eye, can thus be recognized and used as a basis for terminating PUVA therapy despite presence of some psoriasis clinically. Also, a more aggressive treatment regime with greater initial and subsequent increments of dose of UVA could result in much earlier remission, with a consequent reduction in the cumulative dose, thereby lessening the risk of nonmelanotic skin cancer and saving both nursing and patient time. REFERENCES
1. WolffK, Gschnait F, Honigsmann H, et al: Phototesting and dosimetry for photochemotherapy. Br J Dermat01 96:1-18, 1977. 2. DawsonJB, Barker DJ, Ellis DJ, et al: A theoretical and experimental study of light absorption and scatteringby in-vivo skin. Phys Med Biol 25:695-709, 1980. 3. MarcelloCL, Duell EA, Stawiski MA, et al: CyclicAMP levels in psoriatic and normal keratomed epidermis. J Invest Dermatol 72:20-24, 1979. 4. Geerdink JPM, Bergers M, Van Erp PEJ, et al: Cyclic AMP is decreased in mononuclear leukocytes from psoriatic patients. Br J Dermatol 103:107-108, 1980. 5. Weatherhead B, Logan A: Interaction of o~-melanocytestimulating hormone, melatonin, cyclic AMP and cyclic GMP in the control of rnelanogenesis in hair follicle melanocytes in vitro. J Endocrinol 90:89-96, 1981. 6. LawlerJC, VineyardWK: The effect of treatmenton the vascular compartment of the psoriatic lesion. Arch Dermatol 82: 190-193, 1960. 7. Braverman IM, Sibley J: Role of the microcirculationin the treatment and pathogenesis of psoriasis. J Invest Dermatol 78:I2-17, 1982.