A study of psoralen photochemotherapy with topical tar in the management of psoriasis vulgaris

Introduction

Photochemotherapy using oral 8-methoxypsoralen and subsequent exposure to long wave ultra- violet light radiation (PUVA) or sunlight exposure (PUVASOL) has been reported as a satisfactory treatment for psoriasis. PUVASOL can be combined with topical tar, dithranol or topical corticosteroids. The tar and PUVASOL combination has the advantage of saving the number of light exposures, reducing the treatment time and reducing the cumulative psoralen dose required for clearing of psoriatic lesions.[4] We present the study of combined use of PUVASOL and 10% liquor picis carbonis (coal tar solution) in ointment base in the treatment of psoriasis vulgaris. The present study had two objectives: Firstly, to determine whether there is any benefit or problem arising from combining conventional topical agent with PUVASOL. Secondly to assess whether addition of topical tar treatment to PUVASOL would reduce total cumulative psoralen dose.

Materials and Methods

Clinically diagnosed 310 cases of psoriasis vulgaris patients who had attended the skin centre at a service hospital between Jan 98 to Jun 99 were included in the study. The diagnosis of psoriasis was confirmed by histopathological examination. The patients having pustular, erythrodermic and flexural psoriasis and the lesions involving axillae, groins and genitals were excluded from study. The study was limited to patients with psoriasis vulgaris who were not being treated with systemic corticosteroids or cytotoxic agents. Pregnancy was additional contra-indication to treatment. The area of skin involved by the disease ranged from 10% to 90% with average involvement of 40% for the both groups (rule of 9 for large areas and palm equals 1% body surface area for small areas). At the time of evaluation 68% of the patients had psoriasis of the scalp. Patients whose disease state and motivation made them acceptable for this study were randomly allocated to one of the treatment groups.

Design of the study

One hundred and fifty patients who completed the study were divided into two groups. In group I, 75 patients received PUVASOL therapy. Liquor picis carbonis 10% and salicylic acid 2% in vaseline base were applied on the lesions over the skin and a cream base containing 10% liquor picis carbonis and salicylic acid 2% was applied to the scalp at night. All patients with scalp involvement used 3% cetavelon lotion as shampoo for cleaning the scalp. In group II as control 75 patients were treated with PUVASOL therapy alone. Except for the use of lubricants as required to relieve dryness of the skin lesions the patients of this group received no topical treatment.

PUVASOL Therapy

8-methoxypsoralen (0.6 mg/ kg body wt) was ingested by the patients in both groups 2h before sunlight exposure on alternate day. Patients were exposed to sunlight starting from 15 minutes daily in the first week and increasing by 5 minutes to gradually 30 minutes. Eyes were protected by dark sunglasses while exposure to sunlight and also advised to put it throughout day. The above regimen were continued for a period of 8 weeks in both groups.

Laboratory investigations

Before starting therapy, all patients had a complete blood count, LFT, SGOT, SGPT, alkaline phosphatase and routine urinalysis RE. In addition a pre-treatment ophthalmologic examination was performed, to be repeated at six months interval.

Evaluation

Each patient was evaluated at weekly intervals and assessment of progress of treatment was carried out in each patient. The degree of scaling, palpability and redness of the lesions were recorded [Table - 3]. Erythematous reactions and pigmentation of uninvolved skin were assessed according to 1 to 3 scale as slight (+), moderate (+ +) and marked (+ + +),

Follow up

Patients were followed up monthly for 6 months. Once the psoriasis had cleared maintenance treatments were commenced at the final clearance dose of PUVASOL on a schedule of 4 treatments at weekly intervals followed by 4 treatments at fortnightly intervals. A relapse of psoriasis was defined as psoriasis involving > 5% body surface during the maintenance period.

Results

There was no significant difference between any of the treatment group or the control group in terms of age, sex, skin type , extent of psoriasis , previous systemic cytotoxic therapy and previous

systemic cytotoxic therapy and previous hospitalisation. Out of 13200 patients attending skin OPD during the above period, a total number of 310 (2.3%) patients had psoriasis. In this study, 150 completed 8 weeks of therapy and follow up. Out of 150 cases 108 were males and 42 were females between 18 and 65 years of age [Table - 1]. Duration of disease varied from 2 months to 16 years [Table - 2].

PUVASOL therapy with or without topical agents, achieved clearance of psoriasis to less than 10% body involvement in 87.3% of the 150 patients. [Table - 4] outlines the results of the individual treatment groups. Group I patients who received topical therapy responded with fewer treatments at a lower final PUVASOL dose as compared to the control patients. This required a mean of 16 PUVASOL treatments over a period of 8 weeks. The control group receiving PUVASOL alone, their skin lesions cleared with 22 mean PUVASOL doses.

The response to the therapy of psoriatic involvement of the scalp and nails in patients who cleared to less than 1% body involvement was better in patients using topical therapy along with PUVASOL [Table - 4]. 90% of the 51 patients using topical therapy on their scalp cleared the psoriasis in this area by the time their body psoriasis had cleared. In the control group only 2 of the 45 (4.4%) patients with scalp involvement cleared. Those two patients had only minimal scalp involvement limited to the margins. When reviewed 6 months later, the psoriasis of their scalp had remained clear in 46% patients without any topical therapy. The remaining 54% continued to use topical therapy for the scalp. Nail disease poorly responded to treatment in both groups and was slower to respond than psoriasis of the skin.

Nail disease was classified according to the predominant type present in each patient (pitting, onycholysis, dystrophy) but no significant difference was seen with response rates of the different types. The response of the nail disease did not differ between the treatment groups. All 7 patients with psoriatic arthritis cleared psoriasis but none of them noted any symptomatic alteration with severity of their arthritis during the course of treatment in both groups. Nausea, erythema and pruritus [Table - 5] were seen in some patients receiving PUVASOL therapy. All the laboratory investigations were within normal limit in all patients.

Discussion

The combination of tar with UV light (Goeckerman regimen) has long been known to be helpful in psoriasis.[6] Laboratory studies have shown that tar plus UV light reduces epidermal DNA synthesis.[7] This may be related to the formation of cross links between opposite strands on the DNA double helix.[8] The effectiveness of oral 8-methoxypsoralen and UV radiation (UVA) in resolving plaque psoriasis led to coining of the terms photochemotherapy and PUVA.[1] PUVA and PUVASOL have now been established as an effective out patient therapy in the management of psoriasis.[3] Photochemotherapy of psoriasis is safe. Several large,long-term follow up studies have shown, no increased incidence of skin tumours.[9] No cataract unequivocally attributable to PUVA has been reported in humans.[10]

The present study was designed to explore the interaction between PUVASOL therapy and existing topical treatments for psoriasis in terms of the benefits and the problems that may result from such combination therapy.

PUVASOL therapy has not been found to be useful in the treatment of scalp psoriasis because hairs scatter and absorb most of the incident UV-A. This study clearly shows that adjunctive topical tar with PUVASOL is better than PUVASOL therapy alone for the treatment of the scalp psoriasis. Furthermore at the 6 months follow up, 46% of the patients who had cleared their psoriasis on the scalp were still clear without any further topical therapy. It is possible that the small amount of radiation penetrating the hair, while being insufficient to clear the disease, may be adequate for maintenance of a clear state on the scalp.

Psoriatic nail disease cleared in 36% of the affected patients by the time of the 6 months post clearance follow up. Disease at that site takes longer to clear than psoriasis elsewhere and possibly more patients would have cleared with a longer follow up. Psoriatic arthritis did not alter during therapy but this is not surprising as little UV-A would be expected to reach the synovium of most joints.

Nausea affected about 13.3% of the patients receiving psoralen, and pruritus about 20% cases. Pigmentation was the commonest (29.3%) of cutaneous changes observed in our study which was diffuse type. Similar side effects have been observed by various workers.[2] Topical tar therapy in psoriasis is safe.[11],[12] No increase in malignancy of skin, bladder or any other organ was found in psoriasis patients using intermittent topical tar therapy over that of general population.[13]

This study has indicated that adjunctive topical tar therapy has a place in combination with PUVASOL in the treatment of scalp psoriasis. In addition it may have a place in the treatment of resistant localised plaques.