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 .