Therapeutic challenges in atopic dermatitis

Abstract

In this thesis two challenges in the treatment of patients with atopic dermatitis (AD) are investigated, safety and efficacy of treatment. Topical corticosteroids have been one of the cornerstones of treatment of AD for more than 40 years. Possible systemic side effects due to absorption of topical corticosteroids are decrease of bone mineral density (BMD) and development of glaucoma and cataract. We found that one third of 125 patients with moderate to severe AD were found to have low BMD. Surprisingly it was predominately males that had a low BMD. In our cross-sectional study there was no difference in the cumulative use of topical corticosteroids in the 5 years prior to investigation, between patients with a low BMD and normal BMD. We did find a trend towards an increased risk of low BMD with higher use of topical and oral corticosteroids. Additionally, the effect of inflammation on BMD was difficult to study but cannot be eliminated as one of the causes of low BMD. In the follow-up study we did not find a significant difference in change of BMD between patients who had used ‘low’ or ‘high’ amounts of topical corticosteroids during two year follow-up. We found only a small decrease in BMD over time. In the study evaluating glaucoma and cataract we found that the use of topical corticosteroids on the eyelids with a mean frequency of 4 days per week for several months was safe and that the use of predominantly class III (European and US classifications) topical corticosteroids with use up to 2400 grams/year did not result in glaucoma or cataract development. In patients with severe AD potent topical corticosteroids may not be sufficient, demanding additional systemic immunosuppressive drugs. The results of a randomised controlled trial comparing Enteric-Coated Mycophenolate Sodium (EC-MPS) to Cyclosporine A (CsA) as maintenance therapy in adult patients with AD show that EC-MPS is clinically effective, has a mild side effect profile and is a good alternative to CsA. At the start of therapy with EC-MPS the clinical effect is delayed, however the clinical remission after stopping EC-MPS lasts longer compared to CsA. Other factors besides disease activity probably influence quality of life (QoL) in AD is a conclusion drawn from the findings that: disease activity correlated better with QoL when disease activity was less severe, that disease extent (‘rule of nines’ score) correlated better with QoL than disease severity, and that an individual’s improvement of 10 points in disease activity was accompanied by only a small improvement in QoL. We assessed soluble CD30 and thymus and activation-regulated chemokine (TARC) as disease activity markers for AD during the use of EC-MPS and CsA. We found a positive correlation between sCD30 and disease activity (objective SCORAD) during maintenance therapy with CsA. However, during EC-MPS maintenance therapy there was no correlation between sCD30 and disease activity. We found that serum TARC levels and objective SCORAD correlated during both maintenance-therapy regimens.