Azathioprine as a therapeutic modality for the treatment of severe adult atopic dermatitis

Introduction

Atopic dermatitis is a common, intensely pruritic, chronic eczematous dermatosis. The severity of the disease varies from patient to patient and in the same patient also it varies from time to time. Therefore, most of these patients experience significant morbidity in terms of infections, occupational disability, disturbance in daily activities, sleep, social life and emotional upsets. Long term therapy is thus often required. Treatment is usually conservative and most patients have relief with corticosteroids.[1] However, in severe disease higher doses of corticosteroids may be required for longer durations leading to serious side effects.[2] Azathioprine has been shown to be a very effective and safe corticosteroid-sparing agent in corticosteroidresponsive dermatoses even when used for long periods.[3],[5] A few reports suggest that azathioprine may be effective in the treatment of atopic dermatitis.[6],[7],[8] We, therefore, in a preliminary study evaluated its role in adult atopic dermatitis, not adequately controlled with conventional therapy.

Case Report

Case 1: A 53-year-old housewife presented with a 4-year history of serverely itchy papules involving mainly the flexures of the extremities, neck and axillae. The lesions used to exacerbate during every summer from April to June. She was being treated with emollients, various preparations of topical corticosteroid and antihistamines with inadequate control. There was no family history of atopy. Cutaneous examination revealed 0.5mm-1mm erythematous, symmetrically distributed papules on the antecubital and popliteal fossae, inframammary areas, axillae and neck. There were no other lesions. Systemic examination was within normal limits. The routine baseline investigations consisting of haemogram,liver and renal function tests, blood sugar, urinalysis, stool examination, chest X-ray and electrocardiogram done before starting the therapy and every one month during the treatment period to determine the biochemical side effects, were normal.

She was diagnosed as a patient of adult atopic dermatitis and treated with azathioprine 50mg twice daily orally. Hydroxyzine 25 mg twice daily orally and topical betamethasone valerate 0.12% were used at the initiation of therapy. The patient was evaluated every month to record the therapeutic response and to monitor the side effects of the therapy. After 2 months of treatment, the lesions in all areas except axillae subsided. She continued the treatment for another 2 months. At the end of 4 months of therapy she had complete remission without any side effects of the therapy. Now she gets occasional lesions only, which are controlled by topical betamethasone valerate.

Case 2: A 20-year-old school teacher had severely itchy, exudative papules on flexures of the extremities and face since 7 years. There had always been an aggravation of lesions in summers. The patient was a known case of bronchial asthma since early childhood. She had been using emollient and topical as well as oral corticosteroids in a dose of 12 mg per day with moderate improvement only. Cutaneous examination revealed lichenified plaques and erythematous, 0.5-2mm papules on the flexures and extensor aspects of both upper and lower extremities, face and neck. Systemic examination and routine baseline as well as monthly investigation as in case I were within normal limits. She was diagnosed as a patient of atopic dermatitis and treated with azathioprine 50 mg twice daily orally, betamethasone dipropionate (0.05%) topically twice daily and cetirizine 10 mg per daily orally. There was 50% reduction in her itching within one week of therapy with minimal improvement in the lesions and in another 8 weeks all lesions had almost completely subsided leaving behind hyperpigmentation. In the third month of therapy the azathioprine had to be withdrawn due to reduction in total leucocyte count to 2500/mm3 which returned to normal values after 2 weeks. There were no other side effects of the therapy. Now the patient is on emollients only and she stays in remission for the last 10 months.

Case 3: A 30-year-old female presented with severely itchy hyperpigmented plaques on the flexures of the extremities, neck and trunk for 7 years. There used to aggravation of disease during summer and monsoon periods. She was being treated with variable doses of topical and oral corticosteroids and antihistamines with significant improvement in the lesions. But the lesions used to relapse soon after stoppage of oral corticosteroids therapy. There was history of atopy in the family. On cutaneous examination she had lichenified, mildly erythematous papules and plaques on the popliteal fossae, forearms, neck, abdomen and lower back with excoriation marks. Systemic examination and all routine baseline and periodic investigations as in the previous cases were within normal limits. A diagnosis of adult atopic dermatitis was made and she was treated with azathioprine 50 mg twice daily along with cetirizine 10mg daily orally and topical betamethasone dipropionate. In 3 weeks of therapy the itching had completely subsided with some improvement in the skin lesions. After 3 months of therapy almost all the lesions had cleared with about 75% reduction in the lichenification. The azathioprine was stopped after 3 months while she continued betamethasone dipropionate for the lichenified lesions which also subsided in another 6 weeks. There were no side effects of the therapy. Now she is in almost complete remission for the last one year with only occasional lesions which are controlled with topical corticosteroids.

Case 4: A 28-year-old female presented with severely itchy papular lesions on upper and lower extremities, neck and trunk since 3 years. There was history of recurrent bacterial infections in these lesions. She had a history of bronchial asthma since 4 years. The previous treatment with indigenous drugs, topical corticosteroids and antihistamines was ineffective. On cutaneous examination she had erythematous,0.5-1.0 mm papules on both the antecubital and popliteal fossae, neck and chest. Many of the papules were excoriated. Systemic examination and all routine baseline as well as monthly investigations as in the previous cases were within normal limits. She was diagnosed as a patient of atopic dermatitis and treated with azathioprine 50 mg along with hydroxyzine 25 mg thrice daily orally and topical batamethasone. There was almost complete control in itching after 3 weeks of therapy however she continued to develop occasional new lesions with only minimal improvement in the existing lesions even till 2 months. But she continued the treatment and after 3.5 months of therapy all the lesions completely subsided with hyperpigmentation. The patient did not experience any side effects of the therapy. Now for the last about 8 months she gets only occasional lesions which are controlled with emollients.

Discussion

There is no entirely satisfactory treatment for atopic dermatitis. Conservative treatment often fails in severe disease. Corticosteroids, although frequently effective cannot be used continuously for long period because of potentially severe side effects.[2] Azathioprine has been found to be a better alternative in corticosteroid-responsive dermatoses particularly in situation where long term therapy is required.[3],[4],[5] It may also be a better therapeutic option where corticosteroids are contraindicated. Azathioprine acts by inhibiting the purine base synthesis thereby inhibiting DNA and RNA synthesis. It is a potent T-cell suppressor and thus suppresses the cell mediated immunity.[9],[10] However, its machanism of action in atopic dermatitis is unclear. Probably there also it acts by its effect on T lymphocytes. All four patients in our study were symptomatic and had active dermatitis which was not sufficiently controlled with conservative measures and oral corticosteroids were only temporarily effective. After starting them on azathioprine there was significant improvement in their disease within 4-8 weeks and all of them had almost complete remission in 3-4 months. There were no significant side effects of therapy. Laboratory parameters also remained within normal range. Therefore, we suggest that azathioprine can be a better and safer alternative drug in adult atopic dermatitis, not adequately controlled with conservative therapeutic measures. A regular monitoring of the patients for side effects and laboratory parameters is however essential to detect any such effect occurring in an odd patient.