1. General introduction 12 physical symptoms, and is also associated with depression.16 For this reason, keloids are a heterogenous group of fibroproliferative scars. Several genetic factors play a role in the development of keloids. A Japanese genome-wide association study (GWAS) was the first to reveal four single-nucleotide polymorphisms (SNPs) in three chromosomal regions: 1q41, 3q22.3-23 and 15q21.3.17 Subsequently, another study found that these SNPs, specifically the rs8032158 SNP, may influence clinical keloid severity and may be a used as a biomarker for the prevention and treatment of keloidal scars.18 Recently, also other genes such as TFCP2L1 have been identified by machine learning and RNA-sequence that may serve as potential biomarker for keloid development.19 Other risk factors for keloid development include local factors (e.g. tension on scar and local infection), systemic factors (e.g. hypertension and rheumatism) and lifestyle factors (e.g. smoking).20-22 With regards to the phenotypes of keloids, a distinction has been made between ‘mild’ and ‘severe’ keloids.9 Severe keloids are defined as multiple or large (>10 cm2)) keloids.23 The heterogeneity among keloids is often not considered in clinical studies and may explain differences in results between studies. Besides genetic factors, keloid severity and treatment response may be influenced by the location-, thickness-, and treatment history of keloids.22,24 Therefore, the ‘standard keloid’ patient does not exist. However, especially in the severely affected patient group the burden of disease seems very high. Keloid treatment Several factors limit the risk of developing keloidal scars. Preventive measures include minimalizing tension on wounds (e.g. with z-plasty), infection prevention, hydration of wounds with silicon gels or - plasters, and of course minimalizing trauma to the skin as much as possible.12,22,25 However, up to date, clinicians face difficulties in the treatment of keloidal scars. Several anti-inflammatory treatments have been used to improve keloidal scars, including intralesional treatment with corticosteroids, or chemotherapeutics e.g. bleomycin and 5-fluorouracil.26 Yet, unfortunately no ‘holy grail’ to treat this heterogeneous group of fibroproliferative scars has been found. Especially severe keloids are challenging to treat in clinical practice, which can severely affect
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