Management of difficult to treat atopic dermatitis

In this thesis the management of difficult to treat atopic dermatitis (AD) is discussed. The majority of patients with AD can be adequately treated with topical therapy. Sometimes UV-light therapy is indicated, however, this is not a long-term treatment option. Long-term treatment with topical corticosteroids can be limited with respect to safety. Although the additional use of topical immunomodulators can reduce the amount of topical corticosteroids, these drugs lack potency in more severe cases of AD. Systemic immunosuppressive drugs are the second step in the treatment of AD. In patients with difficult to control AD, treatment must first be optimized before the AD can be classified as difficult to treat. Real life data from patients with AD, treated with systemic immunosuppressive drugs in daily practice provides important and essential information in addition to existing clinical trial data. In contrast to clinical trial data, data from daily practice reports long-term treatment in large unselected patient groups. This thesis describes the performance of cyclosporine A (CsA), azathioprine, enteric-coated mycophenolate sodium (EC-MPS) and methotrexate in daily practice. The performance of these drugs was analyzed with the use of drug survival analysis. Drug survival is the length of time a patient continues to take a particular drug. Drug survival analysis is based on the reason for discontinuation of the drug, which is a reflection of the balance between effectiveness and side effects. CsA has the best performance in the daily practice management of difficult to treat AD based on drug survival analysis. The performance of azathioprine and methotrexate is mainly limited owing to side effects, while the performance of EC-MPS is mainly limited owing to ineffectiveness. As there is a lack of data on the long-term safety of CsA with respect to renal function, we measured serum creatinine levels before, during and after treatment with CsA. There was a significant, but not clinically relevant, increase of serum creatinine compared to baseline levels after three weeks CsA and stabilization during maintenance phase on group level. Fifteen percent of the patients had more than 30% increase of serum creatinine (cut off point for clinically relevant change) compared to baseline level. These patients were significantly older than patients without 30% increase. During follow-up, all patients showed serum creatinine levels within 30% compared to baseline. In this thesis the first experience with extended release tacrolimus (ERT) in the treatment of patients with severe AD is described. Nine patients that were treated with ERT had to discontinue prior CsA treatment due to side effects and/or insufficient response. Surprisingly, treatment with ERT was successful in seven out of nine patients with very difficult to treat AD. In addition, treatment with ERT resulted in less side effects compared to the prior treatment with CsA. Safety monitoring including laboratory investigations during the use of oral immunosuppressive drugs is very important. In addition, it is important to ask for concomitant medication during every visit as laboratory disturbances can also be caused by the concomitant medication