Targeting extra-articular manifestations in PsA: a closer look at enthesitis and dactylitis

Enthesitis and dactylitis are cardinal manifestations of psoriatic arthritis (PsA), but a limited understanding of underlying pathophysiologic mechanisms has hindered development of targeted therapies. This gap is of clinical relevance because these manifestations are clinically relevant to patients. Herein, we discuss new exciting findings in animal models with enthesitis and dactylitis, summarize developments in clinical and imaging assessments and review recent clinical trial data on the efficacy of targeted therapies for enthesitis and dactylitis.

Several different animal models reveal that cytokines in the interleukin-23/Th17 pathway and mechanical stress are key events in the development of enthesitis and dactylitis. Elevated levels of interleukin-23, generated in the gut, joint or skin, trigger subsequent tissue inflammation. Both enthesitis and dactylitis involve heterogeneous tissues, associate with specific Class I Major Histocompatibility Complex alleles, and enthesitis may be critical for the development of PsA, although a causal pathway remains unproven. Diagnosis is based on clinical and imaging assessments; however, Power Doppler ultrasound (PDUS) is more sensitive for diagnosis and longitudinal follow-up of enthesitis. Agents targeting tumor necrosis factor, interleukin-12/23, interleukin-17, interleukin-17 receptor (interleukin-17R) and PDE4 are effective therapies for psoriatic enthesitis and dactylitis.

Novel preclinical models established, for the first time, the importance of the interleukin-23/Th17 pathway and mechanical stress in pathogenesis of dactylitis and enthesitis. Advances in imaging, particular (PDUS), may improve sensitivity and specificity for diagnosis and longitudinal assessments. Many targeted therapies are effective for enthesitis and dactylitis.