Genetics of Psoriasis

ABSTRACT

• Psoriasis is a chronic inflammatory skin disease. Initial disease onset typically occurs in adulthood, though it can occur in children, the elderly and any age in between. The clinical history usually consists of cycles of psoriatic flares followed by remissions. Psoriasis is common in Caucasians (2% - 3%), but is very rare in Asian populations and nearly absent from African populations.

• There are several dermal phenotypes associated with psoriasis. The most common form, psoriasis vulgaris, is characterized by scaly, inflamed plaques targeting the knees, elbows, scalp and trunk. Other less common types include inverse psoriasis, sebopsoriasis, guttate psoriasis and pustular psoriasis. These target different body regions and have varying appearance. Approximately 10-30% of psoriasis patients develop psoriatic arthritis which progressively destroys joint tissue.

• Genome-wide association studies (GWAS) have identified several loci associated with psoriasis vulgaris. The HLA class I region of the major histocompatibility complex (MHC), in particular the haplotype harboring HLA-Cw*0602 provides strongest evidence for association, and supports earlier association and linkage studies with alleles of the MHC. Other loci include those harboring genes involved in immune cell activation (IL23A, IL23R, TNFAIP3, TNIP1) and epidermal differentiation

PSORIASIS EPIDEMIOLOGY AND CLINICAL PHENOTYPE

Pathology

Psoriasis is a common, chronic inflammatory disease of the skin. Psoriatic lesions are characterized by a thickened and disorganized outer layer or stratum corneum (SC)/barrier and an inflammatory cell infiltrate in the epidermis and dermis. These are responsible for the thickened, scaly and inflamed skin lesions seen in patients experiencing a psoriatic “flare”. In psoriasis, keratinocyte development in the epidermis from basal cell to enucleated barrier cell is incomplete and accelerated such that the cells traverse from the basal layer (stratum germinativum) to the SC in 6 – 8 days instead of approximately 40 days or more in normal skin1. The incomplete development results in many cells retaining their nucleus (parakeratosis) in the SC. The increased cellularity results in thickening of the epidermis (hyperkeratosis). The increased keratinocyte proliferation also results in deeper dermal papillae. The dermal and subdermal vasculature is both more extensive and more dilated than is normal in psoriatic lesions compared to non-lesional or control skin².

CLINICAL MANIFESTATIONS

Psoriasis outbreaks are can be classified into types based on the area of the body affected and the type of lesion. These classes include psoriasis vulgaris (PV) or common plaque psoriasis, sebopsoriasis, nail psoriasis, guttate psoriasis, pustular psoriasis and inverse psoriasis. PV represents the most common psoriasis type, representing greater than 90% of all cases³. PV lesions are commonly found on the elbows, knees, scalp, and trunk. Involved skin is erythematous and scaly. Aggressive removal of the scaling leads to bleeding, as the plaques overlay living, vascular dermal tissue.

All of the other types of psoriasis are much less common, representing the remaining ...