Evaluation on azathioprine in the treatment of parthenium dermatitis

Introduction

Airborne contact dermatitis is reported to be caused by innumerable plants encountered in nature with varying geographical distribution. The commonest plant causing airborne contact dermatitis in India is Parthenium hysterophorus, which was accidentally imported into India with wheat grains and was first detected in Pune in 1956.[1] Parthenium dermatitis involves not only exposed sites and skin folds,but can become generalised to involve widespread areas of the trunk and limbs. Parthenium dermatitis may also simulate photodermatitis.[2] The disease follows a long and protracted course with exacerbations and remissions. The management of the disease poses a challenge as avoidance of the allergen is not possible in certain areas. Various measures like sunscreens and topical corticosteroids have to be supplemented with the use of systemic corticosteroids to control the dermatitis; the use of which can lead to several complications.[3],[4] Alternatively immunosuppressive drugs could possibly bring about a change in the immunological system by suppressing the cell mediated immune reactions.[5] Azathioprine has been reported to provide encouraging results in actinic reticuloid,[6] chronic actinic dermatitis,[7] and airborne contact dermatitis[8] especially parthenium dermatitis.[9],[10],[11] This study was undertaken to further evaluate the beneficial effects of azathioprine in a larger number of patients suffering from parthenium dermatitis.

Materials and Methods

Thirty patients of airborne contact dermatitis from Parthenium hysterophorus were selected. The patient′s occupation, duration of dermatitis, seasonal variation, photosensitivity and treatment taken were recorded and patch tests were performed to confirm the diagnosis. Complete hemogram, liver function tests and renal function tests were carried out to the initiation of the therapy. The following clinical parameters were used to grade the clinical score a) Severity of itching b) Intensity of erythema c) Degree of scaling d) Degree of infiltration. Each parameter was graded as mild, moderate and and severe and were allocated clinical scores of 1,2 and 3 respectively, maximum score being 12. Azathioprine was started, in the dose of 1 mg/kg/day which was increased to 2-3 mg/kg/day in divided doses if tolerated well. Those patients who were being administered systemic corticosteroids, the does was tapered off slowly. The patients were reassessed clinically every month for a period of one year. The investigations were repeated every month. At the end of twelve months, the response to the therapy was categorised as excellent, good and poor according to the percentage reduction in the clinical score depicted as more than 90%, 60-89% and less than 60% respectively.

Results

Thirty patients of parthenium dermatitis comprised of 23 males and 7 females with a mean age of 49.53± 14.53 years. The mean duration of the disease was 5.3± 3.61 years. Seasonal aggravation in summer months was reported by 16 patients. Out of 30 patients, three patients were lost to follow up whereas treatment had to be discontinued in two patients because of leucopenia in one patient and gastrointestinal intolerance in the other one. The study was completed for a duration of one year in 25 patients.

Thirteen patients (52%) showed an excellent response with more than 90% reduction in the clinical score and 10 patients (40%) showed a good response with 60-89% reduction in the score whereas 2 patients (8%) responded poorly with less than 60% reduction in the score [Table - 1]. The mean time of onset of improvement was 8.4± 2.08 weeks. There was a progressive decrease in the average score from an initial score of 10.24 ± 1.94 to 1.88 ± 1.82 at 12 months [Figure - 1] . Mean reduction in the clinical score was seen in the range of approximately 56% at 3 months, 64% at 6 months and 82% at 12 months.

Systemic corticosteroids were tapered off in 24 patients and stopped in a period of two months of the initiation of the therapy. Out of these 24 patients, 3 patients experienced a relapse in the summers which had to be controlled with a short course of systemic corticosteroids. One patient had to be maintained on low dose corticosteroids throughout the year.

Discussion

Parthenium dermatitis has recently assumed a status of great importance in causing a lot of mor-bidity. The pathogenesis is mediated by delayed hy-persensitivity mechanisms involving the Langerhans cells and sensitised T- cells which necessitates the use of immunosuppressants in severe disease. Aza-thioprine possesses a potent immunosuppressive effect and relatively weak cytotoxic effects.[12]

The major immunosuppressive effect of aza-thioprine results from the blocking of DNA replica-tion due to incorporation of metabolite, 6 thiogua-nine nucleotide, leading to inhibition of purine syn-thesis. Azathioprine also affects the antigen present-ing capacity of the epidermal Langerhans cells.[13] In our study, 52% of the patients showed more than 90% reduction in the score. It was observed that following the initial reduction in the clinical score by 50-60% over a period of first three months, the sub-sequent improvement was relatively slower. The ear-liest time at which complete resolution was achieved was six months in the present study in contrast to earlier reports in which remission was achieved in 2-3 months.[9],[10] Patients who experienced a seasonal aggravation of the disease in the summers showed a greater reduction in the score compared to the patients who had the disease throughout the year. A significant observation made in the study was that patients suffering from the disease for a shorter du-ration responded better than those suffering for longer duration. Such patients may need a follow up for a longer period of time than that limited to one year.

Azathioprine was observed to have a considerable degree of corticosteroid sparing effect as evidenced by the withdrawal of systemic corticosteroids in most of the patients within a period of two months. Though corticosteroids had to be re-instituted in 3 patients because of replapse in summers, the duration of treatment was limited to a short period of 2-3 weeks after which these could again be discontinued. Although the drug was well tolerated by most of the patients, side effects were seen in the form of leucopenia and gastrointestinal intolerance in one patient each. It is inferred from this study that therapy with azathioprine is effective significantly in most of the patients of parthenium dermatitis requiring long term corticosteroids.