Clinical and genetic stratification of childhood psoriasis

Abstract

Psoriasis is a clinically heterogeneous and common disease affecting about 2-3% of the population in Sweden. Twin and family studies have shown a strong and complex genetic background in psoriasis. The strongest known linkage association is for HLA-C*06 on chromosome 6p21.3. During the last decade several genome-wide association studies (GWAS) have independently replicated strong association with HLA-C*06 and found numerous other loci at which common single-nucleotide polymorphisms (SNPs) modestly influence the risk of developing psoriasis. Environmental factors such as infections, stressful life events and medication also contribute to disease development. Although psoriasis is such a highly heterogeneous disease most psoriasis susceptibility genes have been identified in cohorts of mixed clinical phenotypes and exploration of genes in clinical subtypes is scarce.

Age of onset is one factor that can be used for stratification. Onset of psoriasis can occur at any age in life but is most common in young adults and onset in childhood and adolescence is not uncommon. Studies stratifying for age of onset of psoriasis have in principle been limited to comparing onset before or after 40 years of age as defined by Henseler and Christophers in 1985. However, 75% of patients develop disease before 40 years of age, thus stratification for early onset of psoriasis using this definition comprises the majority of patients.

The overall aim of this thesis was to characterize the clinical phenotype and genetic background in psoriasis patients with disease onset in childhood and adolescence. Our hypothesis was that different genetic background could influence age of onset, clinical presentation and prognosis.

Within this PhD project patients with onset of psoriasis in childhood and adolescence have been included for careful clinical and genetic characterization. For stratification for age of onset patients were divided into four groups (0-9, 10-20, 21-40, > 40 years). This approach revealed different genetic variations even within the group of patients with onset before 20 years of age (0-9 vs. 10-20 years at onset) (paper I, II and IV). In paper II genetic association with IL22 in early onset psoriasis was linked to functional alterations in IL-22 responses in Tcells. In paper III we describe clinical phenotypes at onset (< 12 months after onset) in children < 16 years. Pre-pubertal children more often had genital lesions, especially boys, whereas guttate phenotype and facial lesions associated with HLA-C*06 which was more common in children with onset at puberty. Diagnosing psoriasis in potential children for inclusion was not always easy and eczema was the most common differential diagnosis.

In conclusion the data presented in this thesis stresses the importance of careful phenotypic characterization and stratification for age of onset in genetic studies in psoriasis.

Differences in genetic background could have an impact on the development of comorbidities, treatment response and prognosis. Thus, exploration of the genetic background in stratified materials may help in determining prognostic genotype and tailored biologic treatment for patients in the future.