Understanding Psoriatic Arthritis: A Comprehensive Overview

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Psoriatic arthritis (PsA) is a chronic inflammatory disease that is part of the spondyloarthritis family and is associated with psoriasis. The classic presentation is with inflammatory arthritis, dactylitis, and enthesitis. The pathogenesis of PsA is incompletely understood, but both genetic and environmental factors are believed to play a role. Recent years have brought novel insights into the disease through both imaging and biomarker studies. There are several tools that are available to help diagnose PsA, including classification criteria, such as the CASPAR criteria, and the MDA and DAPSA scores. A multidisciplinary approach is required for the management of PsA. Several treatment options are available, including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologic DMARDs, and targeted synthetic DMARDs. The treatment that is used should be tailored to the individual patient and their specific disease phenotype.

Psoriatic arthritis is a chronic inflammatory disease that is part of the spondyloarthritis family and is characterized by inflammatory arthritis, enthesitis, and distinct psoriatic skin and nail lesions. It is important for both dermatologists and rheumatologists to have a good understanding of psoriatic arthritis, the disease, and its different presentations, as well as the tools that are available to help diagnose and manage it. In this review, we will provide an overview of psoriatic arthritis, including the clinical features, pathogenesis, diagnosis, and the available treatment options, with a specific focus on the roles of the dermatologist and rheumatologist in managing this disease.

Epidemiology and Risk Factors

Psoriatic arthritis (PsA) is a chronic inflammatory disease that belongs to a group of conditions known as seronegative spondyloarthropathies. PsA usually develops in individuals who have cutaneous psoriasis, a chronic immune-mediated skin disease that is characterized by the presence of thick, red scaly lesions. PsA affects connective tissue in the body and is clinically heterogeneous in presentation; it can affect peripheral joints with symptoms of synovitis, as well as other joint structures including enthesitis (inflammation at the site of insertion of ligaments and tendons into bone), dactylitis (inflammation of a whole digit), and the spine. PsA can also cause nail dystrophy and can have extra-articular manifestations, including inflammatory eye disease. Data from the US National Psoriasis Foundation suggest that up to 30% of individuals with psoriasis may develop PsA. Since psoriasis affects approximately 2-3% of the population, this represents a large number of affected individuals, with considerable impact on quality of life and on healthcare resource utilization.

Psoriatic arthritis: A comprehensive overview. Psoriatic arthritis (PsA) is a chronic inflammatory disease that usually develops in individuals who have cutaneous psoriasis, a chronic immune-mediated skin disease that is characterized by the presence of thick, red scaly lesions. PsA affects connective tissue in the body and is clinically heterogeneous in presentation; it can affect peripheral joints with symptoms of synovitis, as well as other joint structures including enthesitis, dactylitis, and the spine. PsA can also cause nail dystrophy and can have extra-articular manifestations. The goals of treatment in PsA are to manage pain, to control inflammation, to preserve joint function and prevent structural damage, and to address other aspects of the disease, including skin and nail involvement, and extra-articular manifestations. Several pharmacologic agents are available to address the different aspects of PsA, and individuals with PsA often benefit from a multidisciplinary approach that includes rheumatologists, dermatologists, and other health professionals.

Clinical Features and Diagnosis

PsA can occur at any age, but usually occurs in the third to fifth decades of life, which is later than other inflammatory arthritides. Men and women are affected equally. The HLA antigens most strongly associated with PsA are HLA-B27, HLA-Cw0602, and HLA-B38. Other HLA antigens, which have been associated with psoriasis in general, are HLA-B17, HLA-B13, HLA-B39, HLA-DR7, and HLA-DQ3. The diagnosis of PsA is predominantly a clinical one, based on recognition of characteristic features by a physician. There are no widely accepted diagnostic tests or tissue findings to confirm the diagnosis of PsA. Rather than there being a single diagnostic criterion for PsA, there are different classification criteria, which have been developed for purposes of research and include the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria. These criteria require inflammatory articular disease (asymmetric arthritis, or arthritis, or spondylitis, or enthesitis), usually identified by a rheumatologist, in addition to known characteristic skin, nail, and/or radiographic findings.

PsA is an inflammatory arthritis associated with psoriasis and characterized by an array of clinical features. It affects both the skin and the musculoskeletal system and has a heterogeneous disease presentation. The primary manifestations of PsA include dactylitis, enthesitis, and synovitis; less common are spinal inflammation and severe destructive, erosive disease. The course of PsA can range from mild and non-progressive synovitis to severe and deforming arthritis. It usually develops insidiously, occurring years after skin disease onset, which might not have been diagnosed or treated. It commonly affects the distal joints of the fingers and toes and has a predilection for asymmetrical joint involvement. The nails are affected in up to 80% of PsA patients, and changes include pitting, ridging, onycholysis, and the presence of oil spots in the nail bed. The eyes can also be affected, causing inflammatory ocular conditions.

Skin and Joint Symptoms

Psoriatic arthritis and psoriasis are both associated with a number of comorbidities, including cardiovascular disease, metabolic syndrome, and depression. Careful dermatological evaluation of patients with inflammatory joint symptoms in the absence of overt skin disease may raise the suspicion of early PsA. Management of these patients typically involves a dermatologist and a rheumatologist. The dermatologist can perform a skin biopsy if there are diagnostic concerns, and joint symptoms can be addressed with disease-modifying antirheumatic drugs (DMARDs) as initiated by a rheumatologist. Although the pathophysiology of PsA is incompletely understood, dysregulation of the immune system, genetic factors, and environmental triggers all play a role. The development of monoclonal antibodies and fusion proteins that target specific components of the immune system have helped to change the management and outlook of the disease.

Psoriatic arthritis (PsA) is a chronic inflammatory disease that manifests as joint inflammation, structural damage, and new bone formation, which are associated with psoriasis – a chronic skin disease that causes skin cells to grow too quickly, resulting in thick, white, silver, or red patches of skin. Current evidence suggests that PsA may occur together with psoriasis, manifesting in the joints prior to the skin, or develop in the absence of any apparent skin disease. Ten to fifteen percent of patients develop joint symptoms before the onset of skin psoriasis, forty to fifty percent have skin psoriasis first, and in up to thirty percent of patients, PsA develops in the absence of cutaneous psoriasis. However, the presence of subtle nail changes in these patients may provide important clues, as there is significant concordance between nail psoriasis and the development of PsA.

Diagnostic Criteria

Countless classification criteria have been identified, and with good justification, many have been heavily criticized. High sensitivity to encompass all patients in clinical and research settings has led to the inclusion of patients with rheumatoid and other seronegative spondyloarthropathies into “atypical” cohorts. On the other hand, specificity was considered essential in some studies to make comparisons with disease-modifying anti-rheumatic drugs used in rheumatoid arthritis and TNF-α. For the clinician seeing patients in everyday practice, sensitivity is of utmost importance in order not to miss the diagnosis and delay therapy. With a sensitivity of 91% and specificity of 98%, the CASPAR criteria strike what is, in our opinion, the best balance and have been validated in multiple cohorts, including early disease, established disease, and primary care populations.

The diagnostic diagram for psoriatic arthritis is presented in Figure 3. Dermatology is frequently the point of entry into the healthcare system. Due to pain and functional impairment, patients may seek care in dermatology or other primary care specialties. Periodic examinations after a diagnosis of psoriasis have led to the discovery of accompanying joint disease. Conversely, a patient diagnosed first with peripheral arthritis may have psoriasis disclosed during a joint examination or may develop psoriasis years after the joint diagnosis. For patients with back pain, psoriasis is rarely disclosed. However, in a patient with inflammatory back pain, the presence of heel pain plus or minus dactylitis increases the likelihood of psoriatic arthritis.

Pathophysiology and Underlying Mechanisms

There are several genetic, immunological, and environmental mechanisms that specifically drive the disease process in psoriatic arthritis and distinguish it from other arthritides. From the genetic point of view, association with HLA-B27 is weaker but with HLA-C increased. Genome-wide association studies identified some non-MHC loci shared with other seronegative spondyloarthritides. Unique to PsA is the association with SNPs at the IL-23 receptor locus, Th17 cells being a key immune cell subset with a role in the pathogenesis of both skin and joint disease, reinforcing the interest in the IL23/Th17 immune pathway as a target for therapy. Other identified pathways include TNF, the family of receptor activator of nuclear factor kappa-B (RANK), its ligand (RANKL) and osteoprotegerin, the Notch signalling pathway, autoinflammatory pathways, and shared with the other spondyloarthritides, the toll-like receptor and antigen presentation pathways. The adipokine pathway has also been shown to have an important role in PsA. A ‘multidomain hypothesis’ states that amidst systemic dysregulation, several pathways, be it immunological, genetic, or related to adipokines and bone signalling, all have a ‘domain’ in the joint or enthesis, the interplay among these pathways driving the heterogeneous disease phenotype. Despite these data, more work is needed to dissect out the precise molecular circuits driving the pathophysiology of psoriatic arthritis, including identifying additional genetic or epigenetic factors and possible microbial triggers, characterizing the immune responses taking place in the joint and other affected tissues, and interpreting biomarker data in PsA.

Understanding the pathophysiology of PsA and the mechanisms underlying its different clinical manifestations is one of the main challenges in the management of this disease. Disease understanding has grown considerably over the last years thanks to both preclinical and clinical research, including imaging studies and studies of synovial tissue and fluid. The autoinflammatory and autoimmune aspects are believed to play a key role in the development of PsA. The primary pathological lesion is enthesitis, which is unique to the seronegative spondyloarthritides, and the synovium is secondarily affected. Dactylitis is a specific clinical finding of PsA, whose exact pathogenesis is still incompletely understood.

Treatment and Management Strategies

PsA disease management can be broadly divided into 5 factors: Firstly, the tight control of disease symptoms and inflammation using the various DMARDs. The second factor is the control of pain and stiffness associated with spondylitis and sacroiliitis, which respond very well to NSAIDs and COX-2 inhibitors. In patients with severe axial disease, TNF inhibitors are highly effective and in their absence, IL-17 inhibitors are the next best option. Thirdly, local corticosteroid injections into the affected joints can provide excellent and often long-lasting relief. Being a non-systemic therapy, it can be administered safely even in patients on biological or small molecule therapy. Relatively newly identified agents known as JAK inhibitors and selective tyrosine kinase 2 inhibitors have shown promising results and are likely to play an important role in the treatment of PsA in the near future.

The primary goal in the treatment of psoriatic arthritis (PsA) is the control of peripheral and axial joint disease, as well as the suppression of the underlying inflammatory process to prevent joint damage and loss of function. The commonly used disease-modifying antirheumatic drugs for PsA include methotrexate, sulfasalazine, cyclosporine, leflunomide, apremilast, and small molecules. Biological agents used in the treatment of PsA include tumor necrosis factor inhibitors, interleukin 12/23 and 23 inhibitors, and ustekinumab that targets interleukin 12 and 23. The new kid on the block are the small molecules, such as phosphodiesterase-4 inhibitor, apremilast, that have been found to significantly improve disease activity and have a very favorable and unique tolerability profile.

Pharmacological Therapies

Oral Pharmacological Agents Retinoids, methotrexate, cyclosporine, and apremilast are oral agents that are used to treat moderate to severe psoriasis. Retinoids are members of the vitamin A family, and the prototype for retinoids is acitretin. Acitretin is an oral retinoid that is used for severe psoriasis, usually in combination with phototherapy. Acitretin is a teratogen, and pregnancy must be prevented for up to 3 years after stopping the medication. Acitretin is also associated with hyperlipidemia and abnormalities in liver function tests. Regular monitoring is needed. Retinoids are best used for palmoplantar psoriasis. Unlike methotrexate and cyclosporine, retinoids are ineffective for psoriatic arthritis.

Topical Agents The majority of patients who have skin psoriasis have mild to moderate disease localized to a few patches of psoriasis. In these patients, initial treatment with topical agents is usually effective and appropriate. There are a variety of topical agents available for the treatment of psoriasis, including corticosteroids, derivatives of vitamin D, tazarotene, anthralin, calcineurin inhibitors, and keratolytics. The most commonly used agents are corticosteroids and vitamin D analogues, with or without tazarotene. No therapy, regardless of whether it is a topical agent, phototherapy, or a systemic agent, should be used continuously and indefinitely. This is particularly true for the topical agents. High potency corticosteroids should not be used for more than 2-4 weeks at a time, particularly on the face and in sensitive areas. Topical corticosteroids and other agents may be delivered in different vehicles, such as ointments or creams. While ointments are more effective, they are messy and may cause skin irritation. Creams are more cosmetically acceptable and are less irritating, but they are less effective as well.

Introduction Management and treatment of skin psoriasis can involve the use of a variety of medications, some of which are applied topically (e.g., corticosteroids), some of which are formulated as vitamin D analogues and are applied either topically or used in combination with phototherapy (i.e., oral calcipotriol, oral hydroxyvitamin D3, oral mI-K120), and some of which can be systemic and immunosuppressive agents (e.g., methotrexate, cyclosporine, or other biologic agents) which may also be indicated in the setting of psoriatic arthritis. This overview covers pharmacological therapies used for skin psoriasis and some of which are also used in psoriatic arthritis.

Non-Pharmacological Interventions

There are several different non-pharmacologic treatment options available for patients with PsA, either self-managed or administered by health professionals. The overarching goals of these therapies are to aid pharmacologic management, help optimize physical function and quality of life, and maintain mobility and flexibility, and reduce pain. A multidisciplinary approach involving rheumatologists, dermatologists, primary care physicians, physiotherapists, occupational therapists, nurse specialists, and podiatrists is therefore key in the management of PsA.

In addition to pharmacologic treatments, several nonpharmacologic interventions play an important role in the management of PsA. The overarching goals of these therapies are to optimize function, maintain mobility, and decrease pain as a result of both the joint disease and the extra-articular manifestations of PsA.