Short Communication Dermatologica 150: 316-319 (1975)
Photochemotherapy of Psoriasis with 4,5',8-Trimethylpsoralen V.N. Sehg al , V.L. R ege , V.N. K harangate and M. R eys Department of Venereology and Dermatology and Department of Pathology, Goa Medical College, Panaji
Recently the value of topical psoralens has been demonstrated [1, 2] in cases of resistant psoriasis. Accordingly we were interested to know if systemic 4,5',8-trimethylpsoralen (TMP, supplied by Mac Laboratories Ltd.) may be of assistance in such cases.
Materials and Methods All 11 psoriasis patients, comprising 9 males and 2 females, were inducted to the trial. Their age ranged from 18 to 64 years, with duration varying from 3 months to 20 years. Each patient was orally administered 40 mg of the drug biweekly, 2 -2.5 h before the sun exposure, on a full stomach for 9-12 sittings (4-6 weeks). The exposure of the psoriatic lesions to midday sunshine (between 11 a.m. and 3 p.m.) for 20 min was enough to cause erythema. The weekly follow-up of the patients w'as ensured throughout the period of study. The reduction of scales and flattening of lesions characterised a favourable clinical response. The illustration of the morphological changes was done by serial photographic records. The documentation of microscopic regression of psoriasis was achieved by repeated histopathological examination, preferably the tissue sections prepared from biopsy taken from the vicinity of the initial biopsy.
Observations
Received: March 3, 1975; accepted: May 14, 1975.
Downloaded by: King's College London 137.73.144.138 - 3/7/2018 3:37:43 AM
The response to treatment is shown in table I. There was a gradual reduction of scales right from the start of therapy (fig. 1-3). The duration of complete or partial clearance of the lesions marked by flushing to the skin
317
Sehgal/R ege/K harangate/R eys
Table I. Response to treatment Patient Age years No.
Sex
9 9
100 100
scalp, extremities, trunk
12
75
m
7
m
4
scalp, legs hand, back
9 6
m m m
1 1 1
4 9 6
m m
1 2
extremities extremities extremities, back, scalp extremities
75 25 50 75
8
75 25
f
0.25
extremities, back extremities, back
3 9
3 4
29
5
35 18 38
9 I0 ‘
11
30 50 60 35
Number of Clinical improve sittings ment, %
extremities, trunk extremities
m
6‘ 7 8
Site
3 20 4
35 64 22
1 2
Duration years
m f
50
too
1 Discontinued the treatment for personal reasons.
surface was variable and directly proportional to the number of irradiations. None of the patients during the follow-up period had a recurrence of psoriasis. The histological regression of the lesions was interesting and marked by reformation of keratinised stratum corneum. In a few cases hyperkeratosis and parakeratosis was observed; the former was more marked than the latter. The regeneration of stratum granulosum and suprapapillary rete Malpighii was recorded in all the cases. There was a definite stunting of rete ridges in consequence to decrease in cellular proliferation in rete Malpighii. The reduction in the cellular inflammatory infiltrate in the dermis and the serial sections was slow but definite, synchronising with the epidermal changes.
The initial information gathered by systemic administration of TMP in psoriasis is encouraging. The innocuous nature of the drug, even in a high dosage of 40 mg biweekly, suggests further trials of the drug in this
Downloaded by: King's College London 137.73.144.138 - 3/7/2018 3:37:43 AM
Comments
Sehgal/R ege/K harangate/R eys
Fig. I. Psoriasis. Fig. 2. Two weeks treatment. Fig. J. Clearance and flattening of psoriasis after 4 weeks. Downloaded by: King's College London 137.73.144.138 - 3/7/2018 3:37:43 AM
318
Photochemotherapy of Psoriasis with 4,5',8-Trimcthylpsoralen
319
disease. Interestingly, the duration of the drug therapy is short, usually varying from 4 to 6 weeks followed by exposure to midday sunshine and facilitates considerably the patients’ inconvenience caused by conventional drugs so far in use for this condition. The suggested biweekly regime was useful because it was considered sufficient to produce the requisite erythema and descaling. Furthermore, the sun exposure should vary from temporate to tropical countries. Amongst Indians, however, the adequate exposure time for causing erythema is between 20 and 30 min. By rapid clearance of psoriasis we are convinced that TMP is invaluable for keeping psoriasis under remission and may also be useful for its maintenance. The clinical improve ment of psoriasis, however, does not seem to go hand in hand with histological regression as evident from our study. It is likely that histological reversion of psoriasis may take a longer time. We therefore surmise that it is worthwhile to study the histological details even after cessation of therapy.
References
Dr. V.N. Sehgal, MD, MAMS, Professor and Head, Department of Venereology and Dermatology, Goa Medical College, Panaji 403 001, Goa (India)
Downloaded by: King's College London 137.73.144.138 - 3/7/2018 3:37:43 AM
1 W alter, J.F. and Voorhees, J.J.: Psoriasis improved by psoralen plus black light. Acta derm.-vener., Stockh. 53: 469 (1973). 2 W illis, I. and H arris, D.R.: Resistant psoriasis. Combined methoxsalen-anthralin therapy. Archs Derm. 107: 358 (1973).
Photochemotherapy of Psoriasis with 4,5',8-Trimethylpsoralen V.N. Sehg al , V.L. R ege , V.N. K harangate and M. R eys Department of Venereology and Dermatology and Department of Pathology, Goa Medical College, Panaji
Recently the value of topical psoralens has been demonstrated [1, 2] in cases of resistant psoriasis. Accordingly we were interested to know if systemic 4,5',8-trimethylpsoralen (TMP, supplied by Mac Laboratories Ltd.) may be of assistance in such cases.
Materials and Methods All 11 psoriasis patients, comprising 9 males and 2 females, were inducted to the trial. Their age ranged from 18 to 64 years, with duration varying from 3 months to 20 years. Each patient was orally administered 40 mg of the drug biweekly, 2 -2.5 h before the sun exposure, on a full stomach for 9-12 sittings (4-6 weeks). The exposure of the psoriatic lesions to midday sunshine (between 11 a.m. and 3 p.m.) for 20 min was enough to cause erythema. The weekly follow-up of the patients w'as ensured throughout the period of study. The reduction of scales and flattening of lesions characterised a favourable clinical response. The illustration of the morphological changes was done by serial photographic records. The documentation of microscopic regression of psoriasis was achieved by repeated histopathological examination, preferably the tissue sections prepared from biopsy taken from the vicinity of the initial biopsy.
Observations
Received: March 3, 1975; accepted: May 14, 1975.
Downloaded by: King's College London 137.73.144.138 - 3/7/2018 3:37:43 AM
The response to treatment is shown in table I. There was a gradual reduction of scales right from the start of therapy (fig. 1-3). The duration of complete or partial clearance of the lesions marked by flushing to the skin
317
Sehgal/R ege/K harangate/R eys
Table I. Response to treatment Patient Age years No.
Sex
9 9
100 100
scalp, extremities, trunk
12
75
m
7
m
4
scalp, legs hand, back
9 6
m m m
1 1 1
4 9 6
m m
1 2
extremities extremities extremities, back, scalp extremities
75 25 50 75
8
75 25
f
0.25
extremities, back extremities, back
3 9
3 4
29
5
35 18 38
9 I0 ‘
11
30 50 60 35
Number of Clinical improve sittings ment, %
extremities, trunk extremities
m
6‘ 7 8
Site
3 20 4
35 64 22
1 2
Duration years
m f
50
too
1 Discontinued the treatment for personal reasons.
surface was variable and directly proportional to the number of irradiations. None of the patients during the follow-up period had a recurrence of psoriasis. The histological regression of the lesions was interesting and marked by reformation of keratinised stratum corneum. In a few cases hyperkeratosis and parakeratosis was observed; the former was more marked than the latter. The regeneration of stratum granulosum and suprapapillary rete Malpighii was recorded in all the cases. There was a definite stunting of rete ridges in consequence to decrease in cellular proliferation in rete Malpighii. The reduction in the cellular inflammatory infiltrate in the dermis and the serial sections was slow but definite, synchronising with the epidermal changes.
The initial information gathered by systemic administration of TMP in psoriasis is encouraging. The innocuous nature of the drug, even in a high dosage of 40 mg biweekly, suggests further trials of the drug in this
Downloaded by: King's College London 137.73.144.138 - 3/7/2018 3:37:43 AM
Comments
Sehgal/R ege/K harangate/R eys
Fig. I. Psoriasis. Fig. 2. Two weeks treatment. Fig. J. Clearance and flattening of psoriasis after 4 weeks. Downloaded by: King's College London 137.73.144.138 - 3/7/2018 3:37:43 AM
318
Photochemotherapy of Psoriasis with 4,5',8-Trimcthylpsoralen
319
disease. Interestingly, the duration of the drug therapy is short, usually varying from 4 to 6 weeks followed by exposure to midday sunshine and facilitates considerably the patients’ inconvenience caused by conventional drugs so far in use for this condition. The suggested biweekly regime was useful because it was considered sufficient to produce the requisite erythema and descaling. Furthermore, the sun exposure should vary from temporate to tropical countries. Amongst Indians, however, the adequate exposure time for causing erythema is between 20 and 30 min. By rapid clearance of psoriasis we are convinced that TMP is invaluable for keeping psoriasis under remission and may also be useful for its maintenance. The clinical improve ment of psoriasis, however, does not seem to go hand in hand with histological regression as evident from our study. It is likely that histological reversion of psoriasis may take a longer time. We therefore surmise that it is worthwhile to study the histological details even after cessation of therapy.
References
Dr. V.N. Sehgal, MD, MAMS, Professor and Head, Department of Venereology and Dermatology, Goa Medical College, Panaji 403 001, Goa (India)
Downloaded by: King's College London 137.73.144.138 - 3/7/2018 3:37:43 AM
1 W alter, J.F. and Voorhees, J.J.: Psoriasis improved by psoralen plus black light. Acta derm.-vener., Stockh. 53: 469 (1973). 2 W illis, I. and H arris, D.R.: Resistant psoriasis. Combined methoxsalen-anthralin therapy. Archs Derm. 107: 358 (1973).
