Report
A COMPARATIVE CLINICAL EVALUATION OF TRIMETHYLPSORALEN, PSORALEN AND 8-METHOXYPSORALEN IN TREATING VITILIGO V. N. SEHGAL, M.D., M.A.M.S.
ABSTRACT: Trimethylpsoralen, psoralen and 8-methoxypsoralen were administered in 10 mg dosage orally to 37, 29 and 23 patients with vitiligo. Complete improvement was noted in 8.9 % and partial improvement was recorded in 59.5 %. The overall results produced by trimethylpsoralen and psoralen were superior to those of 8-methoxypsora/en . There was no significant therapeutic difference noticed in regards to age, sex, duration and type of vitiligo.
Photosensitizers continue to be supe.r ior to other medications in the management of vitiligo. Many studies have been done with various photosensitizers. I. z. 4 . 6-s. i 1.1 3, is Experimentally, attempts have been made to study the various structurally different psoralens in order to find the most potent. The evidence from these studies overwhelmingly indicates that psoralen, 8-methoxypsoralen and 4,5,8-trimethylpsoralen are the most active photosensitizers, 9 · 10 with equipotent activity. Considering these observations, it was decided to compare clinically the efficacy of these psoralens in treating patients with vitiligo. To our knowledge, no similar report is available.
From the Department of Venereology and Dermatology, Goa Medical College, Goa, India
lier.1.i. 14 The investigations of blood count urine and stool analysis, blood glucose level and liver function tests were performed on all patients periodically. Of the 89 patients, 37 were given trimethylpsoralen, 29 psoralen and 23 were given 8-methoxypsoralen. To each patient 10 mg of drug was administered orally in the morning after a cup of milk. The affected vitiliginous areas were exposed to morning sunshine after an interval of 2.5 hours. Initially the exposure time was 15 minutes; this was gradually increased to a stage of tolerance. The therapeutic response to the treatment was assessed by appearance of erythema and/ or repigmentation. A serial photographic record was kept of the lesions before, during and after the completion of the therapy.
Results Patients and Methods
There were 13 males and 24 females in the trimethylpsoralen group, while 9 males and 14 females were recorded in the 8-methoxypsoralen group. The details of clinical data are shown in each category in Table 1. The complete re-
Eighty-nine patients with vitiligo were treated from January 1971 through June 1973. The diagnosis in these cases was made on clinical examination. These cases were classified as outlined ear-
205
INTERN ATION A L JOURNA L OF DERM ATOLOG Y April 1975
206
Tabl e 1.
Vol. 14
Evaluation of Trimethylpsoralen, Psoralen and 8-Methoxypsoralen Trim ethylpso ralen
Improvement Parameters
Males Females
Sex
Total
Nil
Partial
Complete
Total
4(31%) 7(29%)
9(69%) 13(54%)
4(17 % )
13(35% ) 24(65 % )
11(30% )
22(60%)
4(11 % )
37(100%)
Age
M edian
26
Duration
Median
6 mo
3 yr
2.5 mo
Area ta Acrofacialis Vulgaris Zosteriform is Mucosae
2(12 % )
10(63 % )
4(25 % )
3(60%) 2(25 % )
2(40 %) 6( 75%)
5(14 % ) 8(27%)
1(20%) 3(100% )
4(80%)
5(14%) 3(8% )
20
23
of Disease Clinical type
Total Duration of Treatment
Median
11
22
4
3wk
11.5 wk
17 wk
pigmentation of vitiliginous areas were observed in 4 (11 % ) g iven tri methyl psoralen , 1 (4%) given psoralen and 3 (13%) given 8-methoxypsoralen . Incidentally, al I the patients in th is category happened to be females. In the partial improvement group there were 22 (60 % ) given trimethylpsoralen ; 21 (72%) were given psoralen therapy, while 10 (44 % ) reported a partial improvement with 8-methoxypsoralen . The over-all percentage improvement in both the sexes given psoralen and trimethylpsoralen is better than with those given 8-methoxypsoralen, although the over-all complete improvement is recorded as highest with 8-methoxypsoralen and trimethylpsoralen. In the rest
16(43 % )
37
of the patients there was no appreciable clinical improvement with any of the three psoralens. The median age was 221/2, 22 and 24 years in the complete improvement group, while this was recorded as 20, 15 and 13 years in the partial improvement group. The median duration of the disease was usually short in the complete and the partial improvement groups. There was no clear-cut association of improvement with clinical type of vitiligo in the different treatment regimens. However, a complete improvement was recorded in 4 patients with vitiligo areata who received trimethylpsoralen, while 2 other patients with vitiligo areata improved on 8-methoxypsoralens.
No. 3
VITILIGO THERAPY • Sehgal
207
Table 1. (continued)
Psoralen
8-Methoxypsorafen
Improvement
Improvement
Nil
Partial
Complete
Total
4(24 %) 3(25%)
13(77% ) 8(67% )
1(8% )
17(59%) 12(41%)
7(24%)
21 (72% )
1(4%)
29(100%)
21
15
2 yr
6mo
3(21%)
11(79% )
1(25%)
3(75%)
4(14%)
3(60%)
2(40%) 2(100%)
5(17 % ) 2(7%)
3(75%)
1(25%)
29
10
10
3
3.5 wk
20wk
26wk
3(75 %)
Nil
Partial
Complete
Total
5(56 % ) 5(36%)
4(44%) 6(43%)
3(21 %)
9(39 % ) 14(61 % )
10(44% )
10(44%)
3(13%)
23(100%)
22
19
13
28
4 mo
1 yr 3 mo
9.5 mo
3 yr
14(48%)
5(38%)
6(46%)
2(16%)
4(14%)
2(100%) 3(75%)
1(25%)
1(25%
7
21
1
4wk
9wk
18 wk
The median duration of treatment was 17 and 18 weeks with trimethylpsoralen and psoralen, respectively, in the complete improvement group, while it was 26 weeks in the 8-methoxypsoralen complete improvement group. A similar trend was recorded in the partial improvement group. There were 2 patients who complained of severe gastric disturbances with 8-methoxypsoralen. Another who took psoralen had agranulocytosis. On discontinuing the treatment, the patient recovered. The enhanced pigmentation of normal sun-exposed skin was a common phenomenon seen in some patients who did not protect their skin from the sunlight.
13(57%) 2(9% ) 4(17%) 4(17%) 23
Discussion The over-all therapeutic and cosmetic response observed in the series under review indicates that psoralen and 4,5,8trimethylpsoralen are superior to 8-methoxypsoralen in treating vitiligo. If the recommended dosage of 20 mg of psoralen and 8-methoxypsoralen are adapted for administration in these patients, the chances of repigmentation in vitiliginous areas may increase. The usual dosage recommended for 4,5,8-trimethoxypsoralen has been 10 mg, which is lower than the other psoralen, thus insuring a margin of safety. Laboratory investigations did not show evidence of drug toxicity in any of the patients except one, who
208
INTERNATIONAL JOURNAL OF DERMATOLOGY April 1975
had agranuiocytosis. Gastric disturbances were also observed in a couple of patients taking 8-methoxypsoralen. There was no appreciable difference observed in response to treatment in either sex with the different drugs; this also was observed in the different age groups. The duration of the disease and the clinical type had no bearing on the therapeutic response in each group. The longer the duration of treatment, the better was the response of the patients in each group. The 8-methoxypsoralen group took a longer time to show comparable results than the other two groups. Acknowledgment The authors are grateful to the Dean, Goa Medical College, for permission to publi sh this report. They express their gratitude to Mac Laboratories Pvt. Limited for supplying trimethylpsoralen (Neosoralen) and 8-methoxypsoralen (Macpsoralen) and Laboratories Grimault Pvt. Limited, for supplying psoralen (Psorline) . 8-methoxypsoralen-O xsoralen Trimethylpsoralen-Trisoralen
3. El-Mofty, A. M., A preliminary clinical report on the treatment of leucoderma with Ammi majus Linn . J. Egypt Med. Assn. 31 :651 , 1942. 4. El-Mofty, A. M., Treatment of vitili go with combination of psoralens and quinolines. Br. J. Dermatol. 76:56, 1964. 5. El -Mofty, A. M ., and Nada, M. M., On the treatm ent of vitili go. Int. J. Dermatol. 10: 262, 1971. 6.
7. 8.
9.
10.
11.
12.
References 1. Bleehen, S. S., Treatment of vitiligo with oral 4,5 ',8-trimethylpsoralen (Trisoralen). Br. J. Dermatol. 86:54, 1972. 2. Dawber, R. P. R., Oral trisoralen in vitiligo. Br. J. Dermatol. 83 :386, 1970.
Vol. 14
Kelly, E. W., Jr., and Pinkers, H., Local application of 8-methoxypsoralen in vitiligo. J. Invest. Dermatol. 25:453, 1955. Kenney, J. A., Vitiligo treated by psoralens. Arch. Dermatol. 103:475, 1971. Lerner, A. B., Denton, C. R., and Fitzpatrick, T. B., Clinical and experimental studies with 8-methoxypsoralen in vitiligo. J. Invest. Dermatol. 20:299, 1953. Pathak, M. A., Fellman, J. H., and Kaufman, K. D., Effect of structural alterations on the erythemal activity of furocoumarins: psoralens. J. Invest. Dermatol. 35:165, 1960. Pathak, M . A., and Fitzpatrick, T. B., Relationship of molecular configuration to activity of furocoumarins which increase cutaneous response following long wave ultraviolet radiation. J. Invest. Dermatol. 32 :255, 1959. Sehgal, V. N., and Dube, B., Secretary StateA positive prognostic sign in vitiligo. Dermatologica 139:168, 1969. Sehgal, V. N ., Oral trimethylpsoralen in vitiligo in children. Br. J. Dermatol. 85:454, 1971.
13 . Sehgal, V. N., Evaluation of oral trimethylpsoralen in vitiligo. Cutis 11 : 682, 1973. 14. Sehgal, V. N., A clinical evaluation of 202 cases of vitiligo. Cutis, In press. 15. Sehgal, V. N., Vitil igo and methoxypsoralen. Arch. Dermatol. 103 :343, 1971.
Erratum
In th e paper by George R. Mikhail "Chemosurgery in the Treatment of Skin Cancer," which appeared in the January / February issue, reference six should ·be: Crissey, J. T. : J. Surg. On co l. 3:387, 1971 .
A COMPARATIVE CLINICAL EVALUATION OF TRIMETHYLPSORALEN, PSORALEN AND 8-METHOXYPSORALEN IN TREATING VITILIGO V. N. SEHGAL, M.D., M.A.M.S.
ABSTRACT: Trimethylpsoralen, psoralen and 8-methoxypsoralen were administered in 10 mg dosage orally to 37, 29 and 23 patients with vitiligo. Complete improvement was noted in 8.9 % and partial improvement was recorded in 59.5 %. The overall results produced by trimethylpsoralen and psoralen were superior to those of 8-methoxypsora/en . There was no significant therapeutic difference noticed in regards to age, sex, duration and type of vitiligo.
Photosensitizers continue to be supe.r ior to other medications in the management of vitiligo. Many studies have been done with various photosensitizers. I. z. 4 . 6-s. i 1.1 3, is Experimentally, attempts have been made to study the various structurally different psoralens in order to find the most potent. The evidence from these studies overwhelmingly indicates that psoralen, 8-methoxypsoralen and 4,5,8-trimethylpsoralen are the most active photosensitizers, 9 · 10 with equipotent activity. Considering these observations, it was decided to compare clinically the efficacy of these psoralens in treating patients with vitiligo. To our knowledge, no similar report is available.
From the Department of Venereology and Dermatology, Goa Medical College, Goa, India
lier.1.i. 14 The investigations of blood count urine and stool analysis, blood glucose level and liver function tests were performed on all patients periodically. Of the 89 patients, 37 were given trimethylpsoralen, 29 psoralen and 23 were given 8-methoxypsoralen. To each patient 10 mg of drug was administered orally in the morning after a cup of milk. The affected vitiliginous areas were exposed to morning sunshine after an interval of 2.5 hours. Initially the exposure time was 15 minutes; this was gradually increased to a stage of tolerance. The therapeutic response to the treatment was assessed by appearance of erythema and/ or repigmentation. A serial photographic record was kept of the lesions before, during and after the completion of the therapy.
Results Patients and Methods
There were 13 males and 24 females in the trimethylpsoralen group, while 9 males and 14 females were recorded in the 8-methoxypsoralen group. The details of clinical data are shown in each category in Table 1. The complete re-
Eighty-nine patients with vitiligo were treated from January 1971 through June 1973. The diagnosis in these cases was made on clinical examination. These cases were classified as outlined ear-
205
INTERN ATION A L JOURNA L OF DERM ATOLOG Y April 1975
206
Tabl e 1.
Vol. 14
Evaluation of Trimethylpsoralen, Psoralen and 8-Methoxypsoralen Trim ethylpso ralen
Improvement Parameters
Males Females
Sex
Total
Nil
Partial
Complete
Total
4(31%) 7(29%)
9(69%) 13(54%)
4(17 % )
13(35% ) 24(65 % )
11(30% )
22(60%)
4(11 % )
37(100%)
Age
M edian
26
Duration
Median
6 mo
3 yr
2.5 mo
Area ta Acrofacialis Vulgaris Zosteriform is Mucosae
2(12 % )
10(63 % )
4(25 % )
3(60%) 2(25 % )
2(40 %) 6( 75%)
5(14 % ) 8(27%)
1(20%) 3(100% )
4(80%)
5(14%) 3(8% )
20
23
of Disease Clinical type
Total Duration of Treatment
Median
11
22
4
3wk
11.5 wk
17 wk
pigmentation of vitiliginous areas were observed in 4 (11 % ) g iven tri methyl psoralen , 1 (4%) given psoralen and 3 (13%) given 8-methoxypsoralen . Incidentally, al I the patients in th is category happened to be females. In the partial improvement group there were 22 (60 % ) given trimethylpsoralen ; 21 (72%) were given psoralen therapy, while 10 (44 % ) reported a partial improvement with 8-methoxypsoralen . The over-all percentage improvement in both the sexes given psoralen and trimethylpsoralen is better than with those given 8-methoxypsoralen, although the over-all complete improvement is recorded as highest with 8-methoxypsoralen and trimethylpsoralen. In the rest
16(43 % )
37
of the patients there was no appreciable clinical improvement with any of the three psoralens. The median age was 221/2, 22 and 24 years in the complete improvement group, while this was recorded as 20, 15 and 13 years in the partial improvement group. The median duration of the disease was usually short in the complete and the partial improvement groups. There was no clear-cut association of improvement with clinical type of vitiligo in the different treatment regimens. However, a complete improvement was recorded in 4 patients with vitiligo areata who received trimethylpsoralen, while 2 other patients with vitiligo areata improved on 8-methoxypsoralens.
No. 3
VITILIGO THERAPY • Sehgal
207
Table 1. (continued)
Psoralen
8-Methoxypsorafen
Improvement
Improvement
Nil
Partial
Complete
Total
4(24 %) 3(25%)
13(77% ) 8(67% )
1(8% )
17(59%) 12(41%)
7(24%)
21 (72% )
1(4%)
29(100%)
21
15
2 yr
6mo
3(21%)
11(79% )
1(25%)
3(75%)
4(14%)
3(60%)
2(40%) 2(100%)
5(17 % ) 2(7%)
3(75%)
1(25%)
29
10
10
3
3.5 wk
20wk
26wk
3(75 %)
Nil
Partial
Complete
Total
5(56 % ) 5(36%)
4(44%) 6(43%)
3(21 %)
9(39 % ) 14(61 % )
10(44% )
10(44%)
3(13%)
23(100%)
22
19
13
28
4 mo
1 yr 3 mo
9.5 mo
3 yr
14(48%)
5(38%)
6(46%)
2(16%)
4(14%)
2(100%) 3(75%)
1(25%)
1(25%
7
21
1
4wk
9wk
18 wk
The median duration of treatment was 17 and 18 weeks with trimethylpsoralen and psoralen, respectively, in the complete improvement group, while it was 26 weeks in the 8-methoxypsoralen complete improvement group. A similar trend was recorded in the partial improvement group. There were 2 patients who complained of severe gastric disturbances with 8-methoxypsoralen. Another who took psoralen had agranulocytosis. On discontinuing the treatment, the patient recovered. The enhanced pigmentation of normal sun-exposed skin was a common phenomenon seen in some patients who did not protect their skin from the sunlight.
13(57%) 2(9% ) 4(17%) 4(17%) 23
Discussion The over-all therapeutic and cosmetic response observed in the series under review indicates that psoralen and 4,5,8trimethylpsoralen are superior to 8-methoxypsoralen in treating vitiligo. If the recommended dosage of 20 mg of psoralen and 8-methoxypsoralen are adapted for administration in these patients, the chances of repigmentation in vitiliginous areas may increase. The usual dosage recommended for 4,5,8-trimethoxypsoralen has been 10 mg, which is lower than the other psoralen, thus insuring a margin of safety. Laboratory investigations did not show evidence of drug toxicity in any of the patients except one, who
208
INTERNATIONAL JOURNAL OF DERMATOLOGY April 1975
had agranuiocytosis. Gastric disturbances were also observed in a couple of patients taking 8-methoxypsoralen. There was no appreciable difference observed in response to treatment in either sex with the different drugs; this also was observed in the different age groups. The duration of the disease and the clinical type had no bearing on the therapeutic response in each group. The longer the duration of treatment, the better was the response of the patients in each group. The 8-methoxypsoralen group took a longer time to show comparable results than the other two groups. Acknowledgment The authors are grateful to the Dean, Goa Medical College, for permission to publi sh this report. They express their gratitude to Mac Laboratories Pvt. Limited for supplying trimethylpsoralen (Neosoralen) and 8-methoxypsoralen (Macpsoralen) and Laboratories Grimault Pvt. Limited, for supplying psoralen (Psorline) . 8-methoxypsoralen-O xsoralen Trimethylpsoralen-Trisoralen
3. El-Mofty, A. M., A preliminary clinical report on the treatment of leucoderma with Ammi majus Linn . J. Egypt Med. Assn. 31 :651 , 1942. 4. El-Mofty, A. M., Treatment of vitili go with combination of psoralens and quinolines. Br. J. Dermatol. 76:56, 1964. 5. El -Mofty, A. M ., and Nada, M. M., On the treatm ent of vitili go. Int. J. Dermatol. 10: 262, 1971. 6.
7. 8.
9.
10.
11.
12.
References 1. Bleehen, S. S., Treatment of vitiligo with oral 4,5 ',8-trimethylpsoralen (Trisoralen). Br. J. Dermatol. 86:54, 1972. 2. Dawber, R. P. R., Oral trisoralen in vitiligo. Br. J. Dermatol. 83 :386, 1970.
Vol. 14
Kelly, E. W., Jr., and Pinkers, H., Local application of 8-methoxypsoralen in vitiligo. J. Invest. Dermatol. 25:453, 1955. Kenney, J. A., Vitiligo treated by psoralens. Arch. Dermatol. 103:475, 1971. Lerner, A. B., Denton, C. R., and Fitzpatrick, T. B., Clinical and experimental studies with 8-methoxypsoralen in vitiligo. J. Invest. Dermatol. 20:299, 1953. Pathak, M. A., Fellman, J. H., and Kaufman, K. D., Effect of structural alterations on the erythemal activity of furocoumarins: psoralens. J. Invest. Dermatol. 35:165, 1960. Pathak, M . A., and Fitzpatrick, T. B., Relationship of molecular configuration to activity of furocoumarins which increase cutaneous response following long wave ultraviolet radiation. J. Invest. Dermatol. 32 :255, 1959. Sehgal, V. N., and Dube, B., Secretary StateA positive prognostic sign in vitiligo. Dermatologica 139:168, 1969. Sehgal, V. N ., Oral trimethylpsoralen in vitiligo in children. Br. J. Dermatol. 85:454, 1971.
13 . Sehgal, V. N., Evaluation of oral trimethylpsoralen in vitiligo. Cutis 11 : 682, 1973. 14. Sehgal, V. N., A clinical evaluation of 202 cases of vitiligo. Cutis, In press. 15. Sehgal, V. N., Vitil igo and methoxypsoralen. Arch. Dermatol. 103 :343, 1971.
Erratum
In th e paper by George R. Mikhail "Chemosurgery in the Treatment of Skin Cancer," which appeared in the January / February issue, reference six should ·be: Crissey, J. T. : J. Surg. On co l. 3:387, 1971 .
