724 CLINICAL REPORT
ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Risk of Non-melanoma Skin Cancer in Patients with Atopic Dermatitis Treated with Oral Immunosuppressive Drugs
Floor M. GARRITSEN 1, Jorien VAN DER SCHAFT 1, Juul M. VAN DEN REEK 2, Klaziena POLITIEK 3, Harmieke VAN OS- MEDENDORP 1, Marijke VAN DIJK 4, Dirk J. HIJNEN 1, Marlies DE GRAAF 1, Carla A. BRUIJNZEEL-KOOMEN 1, Elke M. DE JONG 2, 5, Marie-Louise A. SCHUTTELAAR 3 and Marjolein S. DE BRUIN-WELLER 1 Departments of Dermatology, 1 University Medical Center Utrecht, Utrecht, 2 University Medical Center Nijmegen, Nijmegen, 3 University Medical Center Groningen, Groningen, 4 Department of Pathology, University Medical Center Utrecht, Utrecht, and 5 Radboud University, Nijmegen, The Netherlands
There is uncertainty about the risk of developing nonmelanoma skin cancer( NMSC), including basal cell carcinoma and squamous cell carcinoma( SCC), in patients with atopic dermatitis( AD) treated with oral immunosuppressive drugs. A total of 557 patients with AD treated with these drugs in the University Medical Center Utrecht and Groningen, the Netherlands, were analysed. NMSC after oral immunosuppressive treatment was reported in 18 patients( 3.2 %). The standardized incidence ratio for developing SCC was 13.1( 95 % confidence interval( CI) 6.5 – 19.7). Patients developing NMSC were older at the start of therapy( p < 0.001) and data lock( p < 0.001) compared with patients without NMSC. No significant differences were found in sex, cumulative days of oral immunosuppressive drugs and follow-up between these groups( p = 0.42, p = 0.88, and p = 0.34, respectively). In interpreting these results it is important to include other factors, such as lack of association between treatment duration and tumour development and the long interval between treatment discontinuation and tumour development in some patients.
Key words: atopic dermatitis; oral immunosuppressive drugs; non-melanoma skin cancer.
Accepted Feb 20, 2017; Epub ahead of print Feb 20, 2017 Acta Derm Venereol 2017; 97: 724 – 730.
Corr: Floor M. Garritsen, Department of Dermatology and Allergology, University Medical Center Utrecht, Room G02.124, Post Box 85500, NL- 3508 GA Utrecht, The Netherlands. E-mail: f. m. garritsen @ umcutrecht. nl
Atopic dermatitis( AD) is a chronic inflammatory skin disease with a prevalence of 1 – 3 % in adults( 1). Although AD can be controlled adequately with topical treatment and / or ultraviolet( UV) light therapy in the majority of patients, a subgroup of severe and difficultto-treat patients remains. Furthermore, in some patients it is impossible to taper topical corticosteroid treatment to a safe maintenance scheme. Oral immunosuppressive drugs are indicated in all of these patients.
Oral immunosuppressive drugs that are regularly used in the management of AD are cyclosporin A( CsA), azathioprine( AZA), methotrexate( MTX), mycophenolate mofetil( MMF), enteric-coated mycophenolate sodium( EC-MPS),( extended-release) tacrolimus and systemic glucocorticosteroids.
Clinical efficacy and safety have been proven in clinical trials for most of these drugs( 2 – 5). However, treatment duration in clinical trials is limited. Due to the chronic nature of AD, long-term treatment with oral immunosuppressive drugs is often necessary to maintain adequate disease control. Recent drug survival studies demonstrate that oral immunosuppressive drugs are regularly used for many years in daily practice( 6 – 8).
An important barrier to long-term use of oral immunosuppressive drugs in patients with AD is the possible increased risk of development of malignancies, especially non-melanoma skin cancer( NMSC), including basal cell carcinoma( BCC) and squamous cell carcinoma( SCC).
Most data on the risk of developing malignancies in patients treated with oral immunosuppressive drugs are derived from transplant patients( 9, 10). Immunosuppressive agents may increase the risk of cancer development by causing DNA damage and diminishing DNA repair mechanisms. Tumour angiogenesis may be promoted and the susceptibility to viral infections may be increased. Finally, immune surveillance, which normally prevents the growth and development of malignancies, may be inhibited by immunosuppressive drugs( 9, 11, 12). Recent studies also report an increased risk of NMSC and lymphoma in patients using AZA for autoimmune diseases, such as inflammatory bowel disease( IBD) and other non-rheumatic autoimmune diseases( 13 – 15).
To date, there has been a lack of data regarding the risk of NMSC in patients with AD using oral immunosuppressive drugs.
The aim of this study was to estimate the incidence of NMSC in a large cohort of patients with AD treated with oral immunosuppressive drugs in the Netherlands and to compare these findings with those for the Dutch general population.
MATERIALS AND METHODS Design
This retrospective cohort study was approved by the Medical Ethics Committee of the University Medical Center Utrecht, The Netherlands. Data were collected from the Departments of Dermatology of the University Medical Center Utrecht and the University Medical Center Groningen, The Netherlands, in the period from 1989 to 1 January 2014. doi: 10.2340 / 00015555-2637 Acta Derm Venereol 2017; 97: 724 – 730
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica.