Psoriatic arthritis (PsA) is a form of progressive inflammatory arthritis that is often associated with psoriasis. The prevalence of PsA in the United States is 0.16%, and PsA has been reported to affect up to 30% of patients suffering from psoriasis [1, 2]. Both physician assistants and nurse practitioners play a critical role in the early identification and diagnosis of PsA, helping to ensure that patients receive proper treatment to improve their quality of life (QoL), mostly pain and activities of daily living and long-term health.

Although it can affect patients at any age, PsA is typically diagnosed in patients who are 30–50 years old [3]. Frequently, PsA develops within 10 years after the appearance of psoriasis. Nearly 85% of patients develop psoriasis before PsA; however, 5–10% of patients display signs of PsA concomitantly with psoriasis, and PsA precedes psoriasis in 5–10% of patients [4, 5].

While the disease can range from mild and monoarthritic to polyarthritic, the rapid rate of progression associated with PsA makes early diagnosis and treatment imperative to positive long-term health outcomes [3]. Within 2 years of disease onset, 47% of patients have at least one joint erosion, and more than half of patients followed for 10 years or more have at least five deformed joints [5]. An estimated 20% of all patients receiving a PsA diagnosis will eventually develop a disabling form of the disease [5].

To achieve minimal disease activity and improve QoL, patients need to be treated aggressively [6]. In a recent study, the disease burden (health impact in terms of disease activity and patient-reported outcomes) of PsA was shown to be similar to that of rheumatoid arthritis and axial spondyloarthritis [7]. A separate study revealed that patients with psoriasis and PsA have a poorer QoL compared with patients with only psoriasis, as demonstrated by lower scores on the 36-item Short Form Health Survey (SF-36) and the Health Assessment Questionnaire (HAQ; 42.2 vs. 49.7, respectively) [8].

PsA can be challenging to differentiate from other forms of autoimmune arthritis due to its heterogeneous clinical presentation and unpredictable manifestation across six different domains, including peripheral arthritis, axial disease, enthesitis, dactylitis, skin disease, and nail dystrophy. Additionally, the most common domain of inflammatory peripheral arthritis can display symptoms that are seemingly related to rheumatoid arthritis or osteoarthritis. This article will discuss identification of PsA symptoms across different clinical domains, as well as conventional and biologic treatments options for PsA.

This review is based on previously conducted studies and does not contain any studies with human participants or animals performed by the author.

Diagnosing PsA: A Careful Look at Patient History and Identification of Symptoms

More than a decade ago, the ClASsification criteria for Psoriatic ARthritis (CASPAR) Study Group developed a set of criteria to standardize classification of patients with PsA for research purposes, which are presented in Table 1. Using these criteria, patients are scored based on the presence or absence of current psoriasis or personal or family history of psoriasis, nail dystrophy; negative blood test for rheumatoid factor, current or previous dactylitis, and radiographic evidence of juxta-articular new bone formation. While these criteria were not developed specifically for use in the differential diagnosis of PsA, many clinicians find it useful to consider these criteria when evaluating patients with suspected PsA [9, 10].

Table 1 CASPAR criteria for classification of PsA

Patient History and Family Background

Given the importance of personal or family history of psoriasis in the CASPAR criteria [9, 10], proper records indicating a history of psoriasis are very useful for distinguishing between PsA and other forms of inflammatory arthritis. Specifically, up to 30% of patients presenting with psoriasis are also affected with PsA [1]. There is also a strong genetic basis for the development of PsA, with significant familial aggregation predominantly associated with human leukocyte antigen alleles within the major histocompatibility complex [11]. Due to genetic associations, first-degree relatives of patients with PsA are 49 times more likely to develop PsA than the general population [12]. A patient’s susceptibility to PsA (realized by either a personal or family history of psoriasis, or a family history of PsA or other autoimmune disorders) is, therefore, valuable in making an informed diagnosis.

Patient history of failed arthritis treatment, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, or the presence of arthritis in the absence of trauma should also be considered for diagnosis. For example, degenerative joint disease (osteoarthritis) is often caused by the frequent use of, or injury to, a particular joint. PsA can also be triggered by trauma when an individual is genetically predisposed to psoriasis, but trauma itself is not a hallmark of the disease [13]. Therefore, patients who develop arthritic symptoms without a history of trauma should be carefully examined for other symptoms of PsA.

Key Domains to Consider in PsA Diagnosis

PsA manifestations are divided into six different domains: peripheral arthritis, axial disease, enthesitis, dactylitis, skin disease, and nail dystrophy [14]. Although patients with PsA may not present with all disease characteristics, it is advantageous to identify disease manifestations that are included in CASPAR criteria and that are important for early detection, such as patient or family history of psoriasis and the presence of dactylitis, nail dystrophy, and radiographic bone changes [15]. Questions that patients can be asked to help identify symptoms of PsA and evaluate response to treatment are provided in Table 2.

Table 2 Questions to identify symptoms and evaluate response to treatment by PsA domain

Peripheral Arthritis

An estimated 95% of patients with PsA experience inflammation, pain, and/or tenderness in peripheral joints of the hands and/or feet [3]. Affected joints may also display purplish discoloration [16]. While all joints of a digit can be affected, swelling of the distal interphalangeal joints is the most common presentation. Polyarticular patterns of involvement are more common than oligoarticular patterns [3]. Roughly 60% of patients with peripheral arthritis have symmetric, polyarticular (> 4) joint involvement, usually in the hands, feet, and larger weight-bearing joints [17]. Asymmetric oligoarthritis is more common in men and often involves the distal interphalangeal joints, larger joints, and feet [17]. About 5% of patients with peripheral arthritis develop a severe, destructive form of PsA known as arthritis mutilans, which is associated with telescoping digits, bone destruction and deformity, and profound functional disability [18].

Axial Disease

Isolated axial joint involvement affects roughly 5% of patients [3]. However, involvement is a common secondary feature to peripheral arthritis in up to 50% of patients with PsA. Axial PsA typically presents as asymmetric sacroiliitis or spondylitis. Axial PsA can cause symptoms of morning stiffness and/or immobility; however, axial disease can be asymptomatic in some patients [3]. On physical examination, lateral spinal flexion, cervical rotation, and chest expansion is often restricted in patients with axial disease. Limitations in spinal mobility correlate with radiographic disease progression [19].


Enthesitis, defined as inflammation adjacent to joints at tendon, ligament, or joint-capsule insertions, is present in 60–80% of patients with PsA [20]. Body areas commonly affected by enthesitis in patients with PsA include insertion sites of the plantar fascia and Achilles tendons, as well as ligamentous attachments to the spine, pelvis, and ribs [3]. Enthesitis is more common in lower than in upper extremities, and generally only one or two body sites are simultaneously affected [21, 22]. Symptoms of enthesitis can include soreness or pain at entheses, along with redness and swelling at insertion sites. Risk factors for developing enthesitis among patients with PsA include more actively inflamed joints, higher body mass index, and younger age [21]. Patients with enthesitis generally have poorer prognosis than patients without this PsA manifestation. Additionally, enthesitis significantly reduces patients’ QoL, functional status (due to chronic pain and altered gait, for example) and sleep quality [23].


Dactylitis, or “sausage digits,” is a common feature of PsA that usually occurs asymmetrically and results in swelling of an entire digit [16, 24]. Such digits can be identified by swelling and pain along the flexor tendons with limited ranges of motion [25]. When dactylitis affects fingers, swelling can extend to the palm, ulnar bursa, or radial bursa [26, 27]. Dactylitis affects roughly half of all patients with PsA, and is more commonly observed in toes than fingers and on the right versus the left side [19, 28, 29]. Acute dactylitis presents as swollen, hot, erythemic, painful digits; in chronic cases, swelling is present without inflammation [19, 28]. Dactylitis is typically the first clinical sign of PsA; it may be months or years before other manifestations develop [29]. Often dactylitis recurs in the same digit several times over a patient’s lifetime, and digits affected by dactylitis are significantly more likely to have erosive joint damage than non-affected digits. Interestingly, dactylitis has been shown to be an independent risk factor for cardiovascular morbidity in patients with PsA [29].

Skin Disease

Psoriasis, characterized by skin erythema, thickening, and scaling, precedes development of PsA in about 70% of patients and develops simultaneously with PsA in about 15% of patients [19, 30]. Almost all patients with PsA will have symptoms of psoriasis at some point in their disease course [28]. Development of psoriatic lesions on the scalp and in intergluteal or perianal regions is associated with increased risk of PsA [30]. For example, in a population-based cohort study, the risk of developing PsA was almost four times higher in patients with scalp psoriasis and was more than doubled in patients with intergluteal/perianal lesions compared with patients without these psoriasis features [31].

Nail Dystrophy

Nail lesions are particularly important in diagnosing PsA because they occur in 66% of patients with PsA [32]. Signs of disease in the nail matrix include pitting, leukonychia (i.e., white discoloration), nail plate crumbling, red patches on the lunula, and onychorrhexis (i.e., nail ridging). When the nail bed is affected, oil spots, onycholysis, subungual hyperkeratosis, and splinter hemorrhages are the most commonly observed nail changes [32]. Additionally, when the tip of the nail becomes inflamed, the nail plate can become detached [32]. Nail changes in PsA are thought to result from progression of entheseal inflammation in the distal interphalangeal extensor tendon to nail [33].

Differentiating PsA from Other Arthropathies

The heterogeneous presentation of PsA requires that practitioners evaluate patients across multiple domains to differentiate PsA from other conditions, such as rheumatoid arthritis, ankylosing spondylitis (AS), and osteoarthritis. PsA, much like other arthritides, leads to stiffness and a limited range of motion in affected joints, including large joints—especially those of the lower extremities, distal joints of the fingers and toes, the back, and sacroiliac joints. Inflammatory back pain that worsens during inactivity and morning back stiffness lasting for longer than 1 h differentiates PsA from osteoarthritis [16]. Inflammation of the sacroiliac joint occurs in roughly 50% of patients with PsA, but is virtually absent in those with rheumatoid arthritis or osteoarthritis [34]. Asymmetric involvement of sacroiliac joints is indicative of PsA and can help physician assistants and nurse practitioners differentiate PsA from AS [34]. Patients with PsA are also much more likely to have peripheral distribution of arthritis (96%) compared with patients presenting with AS (25%) [34].

Symptoms that can distinguish PsA from rheumatoid arthritis and osteoarthritis include plantar fasciitis, Achilles tendon pain, and general heel pain, which can all be signs of enthesitis [3, 12]. The pattern of disease involvement in peripheral joints can help differentiate between PsA and rheumatoid arthritis. Affected joints usually occur symmetrically in patients with rheumatoid arthritis, whereas PsA often affects the distal interphalangeal and proximal interphalangeal joints, and sometimes all joints on 1 digit, leading to a ray pattern of joint involvement [16]. Dactylitis and enthesitis are hallmark features of PsA that are uncommon in other types of arthritis; thus, the presence of these manifestations can often be used to exclude a diagnosis of rheumatoid arthritis, osteoarthritis, and reactive arthritis [19, 28]. Lastly, physical examinations and patient-reported outcomes questionnaires, such as SF-36, HAQ, and Routine Assessment of Patient Index Data 3, are important tools for detection of PsA signs and symptoms (Table 3) [16, 35, 36], and can be critical for identifying back pain, morning stiffness, and undiagnosed psoriatic skin lesions, nail dystrophy, and dactylitis, all of which are indicative of PsA versus rheumatoid arthritis or osteoarthritis [12]. Figure 1a provides an overview of key body areas that should be included in physical examinations, and Fig. 1b gives a visual example of the hand of a patient showing signs of psoriasis, dactylitis, and peripheral arthritis.

Table 3 Physical examination and questionnaires to detect PsA
Fig. 1
figure 1

Reproduced with permission from: 76

Clinical features of PsA. a Areas of the body affected by the different clinical domains of PsA. DIP distal interphalangeal, PIP proximal interphalangeal, GRAPPA Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, PsA psoriatic arthritis. b The hand of a patient with PsA [76]. Psoriatic lesions and the involvement of peripheral joints are indicative of PsA.

Treatments for PsA

Once PsA has been diagnosed, treatment is necessary to improve the patient’s QoL (joint pain and swelling, physical activity, and quality of sleep if caused by joint pain) and prevent future bone remodeling (erosion and formation) [37,38,39]. In 2016, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the European League Against Rheumatism (EULAR) both issued updated treatment recommendations for PsA [14, 40]. Given the breadth of available treatments for PsA and the significant heterogeneity in disease presentation, current guidelines provide treatment recommendations specific to each PsA domain (Fig. 2) [14]. Available treatments often vary in consistency and response across PsA domains. Table 4 summarizes differences in efficacy results from clinical trials of biologics and small-molecule inhibitors for the specific domains of enthesitis and dactylitis; however, because there is no consensus on the best tools for measuring enthesitis and dactylitis in clinical trials, it is not possible to compare many of the results across trials of different targeted therapies. Table 5 shows nail dystrophy efficacy results from clinical trials of targeted therapies in psoriasis and PsA, and Fig. 3 shows results for peripheral arthritis and psoriatic skin disease domains. Considering all differences across therapies, choice of treatment should be optimized to target the PsA domain(s) that are considered to be most severe by the individual patient and healthcare practitioner. Treatment goals should focus on maximizing patients’ long-term health-related QoL by preventing structural damage, controlling symptoms, and improving patients’ daily functioning [14, 40].

Fig. 2
figure 2

Reproduced with permission from: Coates LC, Kavanaugh A, Mease PJ, et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for psoriatic arthritis. Arthritis Rheumatol. 2016;68:1060–71. *Light text identifies conditional recommendations for drugs that do not currently have regulatory approvals or for which recommendations are based on abstract data only

GRAPPA treatment schema for active PsA* [14].

Table 4 Enthesitis and dactylitis efficacy results from pivotal trials of targeted therapies in PsA
Table 5 Nail disease efficacy results from clinical trials of targeted therapies in psoriasis and PsA
Fig. 3
figure 3

a ACR20 and b PASI75 response rates reported at week 24 in phase 3 trials of targeted therapies approved for the treatment of active PsA [47, 56, 59, 61, 64,65,66,67,68,69,70,71]. For agents without a dose specified, results are presented for the approved dosage. Figure is for visualization purposes only and should not be used to make direct comparisons of efficacy between therapies. ACR American College of Rheumatology, BID twice daily, IV intravenous, PASI Psoriasis Area Severity Index, PsA psoriatic arthritis, Q4W every 4 weeks, Q2W every 2 weeks, QW once weekly

Conventional Non-Biologic Therapies

In the early stages of PsA, intra-articular or intra-muscular corticosteroid injections can be given to help mitigate immediate pain and swelling, and clinical benefits have been observed in patients with persistent monoarthritis and oligoarthritis [20]. NSAIDs can be used as steroid-sparing agents to alleviate musculoskeletal pain and stiffness in patients with peripheral arthritis, axial disease, enthesitis, and/or dactylitis [40,41,42]. However, corticosteroids and NSAIDs do not prevent PsA progression, so more aggressive therapies are needed in patients with erosive disease [1, 12]. Additionally, both corticosteroids and NSAIDs are associated with increased risks of adverse events and may be contraindicated for some patients [14, 40]. For patients with skin disease, topical therapies (e.g., keratolytics, steroids, vitamin D analogues, emollients, and calcineurin inhibitors), followed by phototherapy are recommended non-biologic treatment options that can be effective for mild psoriasis [14]. Co-management with a dermatologist should be considered.

Conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), such as sulfasalazine and methotrexate, are steroid-sparing agents that are recommended for use after failure of NSAIDs and to treat locally active peripheral arthritis, psoriasis, and nail dystrophy [40,41,42]. Methotrexate is usually recommended as the first-choice csDMARD for most patients, especially those with skin involvement; however, robust data on the efficacy of methotrexate are lacking, and many patients cannot tolerate methotrexate or have contraindications [1, 12]. Notably, csDMARDs can take several weeks to become effective and therefore, must be started early in disease diagnosis to maximize patient benefits [40].

Biologics and Targeted Small-Molecule Inhibitors

Tumor Necrosis Factor Inhibitors

Tumor necrosis factor (TNF) is a pro-inflammatory cytokine that is overexpressed in the synovium of patients with inflammatory arthritis, promoting synoviocyte hyperproliferation, macrophage infiltration, and synovial thickening [43]. Biologic therapies that inhibit TNF have demonstrated efficacy across all six PsA domains and are key components of current PsA treatment guidelines (Fig. 2) [14, 40]. The following TNF inhibitors are approved for the treatment of active PsA: etanercept, adalimumab, infliximab, certolizumab pegol, and golimumab. TNF inhibitors are available in formulations for subcutaneous injection (etanercept, adalimumab, certolizumab pegol, and golimumab) and for intravenous infusion (infliximab and golimumab), giving patients the option to choose their preferred route of administration based on factors such as convenience and whether they have anxiety about self-injection.

TNF inhibitors are currently a cornerstone of biologic treatment recommendations for PsA [14, 40], largely due to their established history as safe and effective treatments for both rheumatic and psoriatic disease [44]. However, TNF is an upstream modulator of PsA pathogenesis, and targeting this cytokine can have relatively non-specific effects on PsA disease features, such as osteoclastogenesis and synovial inflammation [43]. As such, some patients with PsA fail to respond to TNF inhibitors. Additionally, among individuals who do respond to initial treatment, efficacy can wane over time, resulting in failure to achieve lasting remission [44, 45].

Interleukin-12/23 Inhibitor

Interleukin (IL)-12 and IL-23 are important cytokines in the pathogenesis of PsA and psoriasis. Upregulation of IL-12 promotes inflammation and activation of natural killer cells, and upregulation of IL-23 stimulates processes related to bone erosion and osteoclastogenesis [46]. The IL-12/23 antagonist ustekinumab is approved for the treatment of active PsA based on results from clinical trials showing that treatment with ustekinumab significantly reduces radiographic progression of joint damage and improves signs and symptoms of enthesitis, dactylitis, skin disease, and nail dystrophy [47,48,49]. Ustekinumab also improves skin and joint symptoms in patients with PsA who failed to respond to anti-TNF therapies [50].

IL-17A Inhibitors

Upregulation of IL-17A promotes angiogenesis, osteoclastogenesis, and fibrogenesis, which contribute to chronic inflammatory and bone changes that are hallmarks of PsA pathogenesis [12]. There are two IL-17A inhibitors, secukinumab and ixekizumab, approved for the treatment of active PsA based on results from pivotal randomized controlled trials showing efficacy across peripheral arthritis, dactylitis, enthesitis, skin, and nail PsA domains (Tables 4 and 5; Fig. 3). Additionally, secukinumab 150 mg was recently approved for the treatment of active AS [51] based on results of the MEASURE 1 and MEASURE 2 randomized, double-blind, placebo-controlled phase 3 trials [52, 53]. In both of these trials, secukinumab 150 mg provided ASAS20 response rates of 61% at week 16 [52]. A clinical development program evaluating ixekizumab for the treatment of active AS is ongoing (NCT02696785, NCT02696798).


Apremilast is an orally administered small-molecule inhibitor of phosphodiesterase-4, which acts to degrade cyclic adenosine monophosphate, thereby downregulating production of pro-inflammatory cytokines such as TNF-α, IL-12, and IL-23 [54]. Twice-daily treatment with apremilast demonstrated efficacy compared with placebo for treatment of the peripheral arthritis, dactylitis, enthesitis, and skin domains of PsA in the large-scale PALACE clinical studies [55, 56], and efficacy against nail disease was observed in the ESTEEM 1 and ESTEEM 2 trials in patients with psoriasis (Tables 4 and 5; Fig. 3) [57]. Axial disease was not evaluated as part of apremilast phase 3 programs.


Abatacept is a fusion protein construct that inhibits T cell activation by modulating CD28 co-stimulation associated with upregulation of pro-inflammatory cytokines [54, 58]. Abatacept is approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis, as well as PsA. In the phase 3 ASTRAEA study, abatacept demonstrated significant efficacy compared with placebo for peripheral arthritis; however, numerical improvements in dactylitis, enthesitis, and skin domains did not reach statistical significance (Table 4; Fig. 3), and nail disease was not assessed [59]. Abatacept did not appear to demonstrate significant efficacy in axial disease in patients with AS [60].


Tofacitinib is an oral Janus kinase inhibitor that preferentially targets JAK3 and JAK1, blocking signaling pathways for several inflammatory cytokines [54]. Tofacitinib is approved for the treatment of adults with moderately to severely active rheumatoid arthritis and active PsA in adults with inadequate response or intolerance to methotrexate or other non-biologic DMARDs. In the OPAL Beyond trial, tofacitinib was associated with improvements in peripheral arthritis and nail disease, but numerical improvements in dactylitis and enthesitis were not tested for statistical significance; the 10-mg dose but not the 5-mg dose was associated with significantly higher achievement of skin clearance (PASI75) compared with placebo (Tables 4 and 5; Fig. 3) [61, 62]. Results of a recently published phase 2 study of tofacitinib in patients with AS suggest it may improve axial symptoms of PsA [63].


PsA is a heterogeneous form of progressive inflammatory arthritis that is often found in patients with psoriasis. Early PsA diagnosis and initiation of treatment is necessary to prevent long-term damage associated with bone remodeling and to improve patient QoL. By recognizing each of the PsA clinical domains (peripheral arthritis, axial disease, dactylitis, enthesitis, skin disease, and nail dystrophy) and obtaining information on a patient’s personal and family history as well as administering an in-depth physical examination, physician assistants and nurse practitioners can play an important role in the early recognition, diagnosis, and treatment of PsA. Treatment choices should be tailored based on the efficacy profiles of available drugs for each PsA domain to target the clinical manifestation(s) causing the greatest burden for each patient. Newer therapies may provide effective treatment across multiple PsA clinical domains, offering alternatives to treatments emphasized in the most recent guidelines for PsA management.