Unravelling the complexity of psoriatic arthritis on a journey towards precision medicine

Abstract

The fi rst description of psoriatic arthritis (PsA) as a distinct disease entity dates from 1956, when the British rheumatologist Professor Verna Wright described a group of patients with psoriasis and concomitant arthritis.(1) For years after its discovery PsA was considered a relatively mild form of rheumatoid arthritis (RA), with disease strictly limited to the skin and joints. However, over time it became evident that PsA is a potentially debilitating disorder characterized by signifi cant morbidity, systemic infl ammation, social stigmatization and multiple comorbidities, which substantially impacts quality of life and lifespan.(2-5) Moreover, being the second-most common form of chronic infl ammatory arthritis (global prevalence 0.05-0.25%), PsA is associated with a signifi cant economic burden in terms of psychosocial disability and productivity loss.(5-7) Axial spondyloarthritis Extra-articular manifestations Co-morbidity Arthritis Dactylitis Nail dystrophy Enthesitis Psoriasis Dactylitis Anxiety Depression Metabolic syndrome Cardiovascular disease Fatty liver disease Fatigue The importance of genetic predisposition is illustrated by the high concordance rate in twins and the strong heritability of PsA: a first-degree relative has a 30-55 times increased risk to develop the disease.(12,17,18) Genetic studies identified strong associations with class I human leukocyte antigen (HLA) susceptibility alleles.(8,19) In addition, associations in genes involved in immune activation have been observed, including interleukin (IL)-17 and interferon (IFN) signaling, the IL-23 receptor, and regulators of nuclear factor kappa B.(8,10,18) A simplified overview of the pathogenesis is shown in Figure 3. PsA may develop after an initial trigger activates stromal cells at articular, peri-articular or extra-articular sites. Chapter 1 16 Management Multidisciplinary teamFrom a dermatological perspective PsA could be considered a comorbidity of psoriasis.However, some state that psoriasis and PsA should be regarded as two phenotypes of one disease entity: psoriatic disease. (11,(37)(38)(39) The rationale of the umbrella term is that clinical care for psoriatic disease patients requires similar multidisciplinary approaches,given the great overlap in risk factors, pathophysiology, comorbidities and therapeutic options. (11,27,28,40) The concept of 'psoriatic disease' may facilitate bridging the gap between the medical specialties dermatology and rheumatology.( 38) In addition, the heterogeneous phenotype of psoriatic disease warrants expertise of additional healthcare professionals, including a general practitioner, clinical nurse specialist, ophthalmologist and gastroenterologist. Integrated multi-disciplinary treatment strategies streamline synchronous determination of formulation and dose of topical therapy, prescription of disease-modifying anti-rheumatic drugs (DMARDs), cardiovascular risk management and coping with psychosocial problems. Successful collaboration is essential to achieve the treatment goals in PsA: to contr...