|Year : 1992 | Volume
| Issue : 1 | Page : 15-19
Methotrexate-puvasol combination in treatment of psoriasis
Source of Support: None, Conflict of Interest: None
Patients with severe psoriasis were divided into 2 groups. In group A, consisting of 30 patients, remissions were induced by short term use of combination therapy consisting of methotrexate (5 mg every 12 hours x 3 doses per week) + psoralen (30 mg on alternate days) and sun exposure (PUVASOL). Thereafter, remission was maintained by use of minimal possible PUVASOL treatment alone. However, flare-ups during maintenance-phase were controlled by short term addition of methotrexate. Remission was induced in all these cases after a mean of 5.1 weeks (range, 3 - 9 weeks) of treatment using a mean total dose of 74.6 mg of methotrexate along with PUVASOL. During maintenance phase, recurrence was observed in 19 of these patients after a mean of 4.6 months. These recurrences were again controlled by clearance courses of methotrexate. On an average 1 - 6 (mean, 4) clearance courses were required during a period of 2 years.
In group B, consisting of 10 patients, remission was induced by use of methotrexate alone and after achievement of remission methotrexate was withdrawn. Comparatively I did not find any significant advantage of adding PUVASOL for clearance of the lesions. However, during follow-up all patients in group b reported with recurrence much earlier. I recommend the use of methotrexate alone for clearance of lesions in severe psoriasis and PUVASOL alone in maintenance phase to prevent relapse.
Keywords: Psoriasis, Methotrexate, PUVASOL.
|How to cite this article:|
Talwar S. Methotrexate-puvasol combination in treatment of psoriasis. Indian J Dermatol Venereol Leprol 1992;58:15-9
| Introduction|| |
Effectiveness of methotrexate observed as early as 1958  provided hope of cure in psoriasis. Roenigk et al  suggested that methotrexate does not cure but offers only control in psoriasis like insulin in diabetes. However, side effects associated with its long term use along with the need of doing repeated liver biopsies when used in large doses, prevented it in attaining the status of drug of choice in psoriasis. With PUVA, recurrence rate of 93% has been observed in first year.  Reports of dose dependant squamous cell carcinoma of skin with PUVA therapy has prompted workers to keep the cumulative dose of PUVA as low as possible. Various combination therapies were tried to evolve a most suitable method of treatment in psoriasis. ,, For treatment of unpredictable and inveterate disease like psoriasis `guerilla campaign' tactics are said to be more successful than a frontal attack. 
This study was designed to induce remission with short term use of methotrexate and PUVASOL and thereafter maintain remission with minimum possible PUVASOL treatment alone. However, flare-ups during maintenance phase were controlled by short term use of methotrexate. To have comparison another group was treated with methotrexate alone and no drug was given after achieving the remission.
| Materials and Methods|| |
Forty patients of extensive and refractory psoriasis were inducted into the study. Mean body area involvement of more than 40 percent was regarded as extensive involvement. Six cases with body area involvement of less than 40 percent were also included in the refractory category as they failed to respond to an average of 45 PUVASOL treatment. These cases were divided into two groups:
Group A - This included 30 patients treated by methotrexate - PUVASOL combination. This group included 3 categories of patients; (a) 10 patients who had not responded to PUVASOL therapy given for more than 3 months (45 treatments) were labelled as PUVASOL failures (b) 8 patients who had responded to PUVASOL therapy but reported with recurrence while on irregular maintenance treatment (c) 10 fresh cases who had not received any treatment earlier.
All patients were given test dose of 2.5 mg methotrexate to rule out idiosyncratic reactions, which was not observed in any of the patients. One week later they were given methotrexate in doses of 5 mg every 12 hours x 3 doses per week. Simultaneously they were also given 30 mg of psoralen on alternate day. Two hours after taking psoralens patients were exposed to sunrays for 15 - 30 minutes between 0900 hrs to 1200 hours as there is not much variation in UVA received from sun during this period.  After clearance of skin lesions (involved area being less than 1% of the body surface area), methotrexate was given for 1 more week and then stopped. Thereafter, patients were put on tapering doses of PUVASOL alone. The frequency of PUVASOL was reduced to once every 3rd day for 2 weeks followed by once every 4th day for 2 weeks and later once a week. Patients were followed-up for 2 years. Recurrence/ flare-up of the disease (body surface area involvement being more than 5 percent) was treated by another clearance course consisting of methotrexate and PUVASOL.
Group 3 : To have comparison 10 new cases of severe psoriasis were treated with methotrexate alone to induce remission and after induction of remission methotrexate was stopped and patients were observed for flare-ups/remission. Flare-ups during maintenance in this group were also controlled by methotrexate.
For assessment of body surface area, involvement of palm was taken as equivalent to 1 percent. Parameters used for assessing the skin lesions were erythema, scaling and induration graded as 0 to 3. Pretreatment assessment included history to exclude risk factors like liver or renal disease, excessive alcohol intake and pregnancy; complete blood count, live1 function tests (LFT), renal function tests and X-Ray of chest. During therapy, complete blood count was done 4 days after each course of methotrexate and LF1 was repeated 1 week after first and last methotrexate pulse.
| Results|| |
The characteristic of the patients group included a sex ratio of 23 females to 17 males; age range of 11 - 66 years (mean, 41 years); mean duration of illness being 8.6 years (range, 4 months to 30 years); mean body surface area involvement being 40 percent (range, 10-70 percent). Response during clearance phase in group A is shown in [Table - 1]. Initial response was seen in these patients after a mean of 1.5 weeks (range, 1 - 2 weeks,), while complete clearance of skin lesions was observed in all patients after a mean of 5.1 weeks (range, 3 - 9 weeks). Mean total dose of methotrexate used for clearing lesions being 74.6 mg. Induration of the skin lesions was the main factor determining the response to therapy. Patients with highly indurated areas graded as 3, took longer time to regress. Another important determinant was duration of the disease, taking longer time in patients with long duration of illness. No significant difference in response was observed in PUVASOL failure group and the other groups. Response on follow-up in group A during maintenance phase is shown in [Table - 2]. Recurrence was observed in 19 of these patients after average duration of 4.69 months after clearance. The recurrences were fully controlled with addition of methotrexate. As these recurrences were detected at initial stages, relatively low doses of methotrexate were required to control them. On an average 1 - 6 (mean, 4) clearance courses were required during a period of 2 years for control of psoriasis. In group B complete clearance was achieved in all cases after a mean duration of 5.2 weeks [Table - 3]. During follow-up, recurrences has been observed in all cases after an average duration of 3.5 months. Side effects observed were nausea and vomiting in 10 patients, anorexia in 9 patients, headache in 1 patient and burning at site of lesions in 3 patients. However, the side effects did not necessitate discontinuation of treatment. LFT and blood counts were within normal range during and after therapy.
| Comments|| |
In cooperative clinical trial  using PUVA alone success in clearance was achieved in 69 percent of cases in 10 - 15 weeks while remainder required further treatment for clearance. Roenigh et a1  using methotrexate alone achieved clearance in 61 percent of cases by 6 weeks and by prolonging the duration of therapy, higher percentage of patients achieved clearance. Combined methotrexate - PUVA therapy is reported to clear the lesions in 93 percent of cases by 5.7 weeks.  Comparatively, with combined regimen, I observed clearance in 100 percent of cases in 5.1 weeks. The response in PUVA failure group to the reduction in thickness of psoriatic plaques by methotrexate allowing increased penetration of UVA irradiation along with the possible additive effect of the 2 drugs.  However I did not observe significant advantage of combined methotrexate - PUVASOL combination as compared to methotrexate alone during clearance phase [Table - 3]. Therefore, I feel methotrexate alone is sufficient to achieve clearance in all cases. Kaur et at  in their preliminary studies with methotrexate obtained clearance using higher doses for longer periods. The flare-ups during maintenance were observed earlier in PUVASOL failure group (3.5 months) as compared to other groups (6 months). Comparatively all patients in group B who were not given PUVASOL during maintenance phase developed recurrence [Table - 3]. Thus PUVASOL has definite role in reducing the relapse during maintenance phase. However, the flare-ups responded equally well in both the groups. Intermittent use of methotrexate effectively controlled the flare-ups during maintenance phase. As patients reported earlier during recurrence, relatively low doses of methotrexate were required to control it. Kaur et al  have reported grade I changes in liver biopsies following methotrexate therapy in psoriasis. In their study, 9 out of 18 patients had shown grade I changes even in premethotrexate liver biopsies. Methotrexate can be given safely even in patients with grade I changes. Liver biopsy might provide better information about state of liver after methotrexate therapy as compared to LFT. However, liver biopsy was not performed in the present study as it is not mandatory if methotrexate is being used for short term in low doses,  and intermittent doses are supposed to be less hepatotoxic. sub Nausea and vomiting observed was well controlled with addition of metachlorpropamide. The main advantages of methotrexate - PUVASOL combination are: early clearance of skin lesions, effectiveness in PUVA resistant cases, effectiveness in prolonging remission, and that it can be instituted without hospitalisation of the patient and is safe.
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[Table - 1], [Table - 2], [Table - 3]