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Although psoriasis and psoriatic arthritis (PsA) have been classically considered to be diseases of the skin and joints, respectively, emerging evidence suggests that a combination of innate and environmental factors creates widespread immune dysfunction, affecting multiple organ systems. A greater understanding of the pathogenesis of psoriasis and the systemic effects of psoriatic inflammation has allowed for the development of new, more effective treatments. The second portion of this two-part review series examines the comorbidities associated with psoriasis and PsA as well as the most recent advances in targeted systemic therapies for these conditions.