Diagnosis and Evaluation of PsA

Introduction

The diagnostic evaluation of psoriatic arthritis (PsA) can be challenging, as there are often no specific laboratory or clinical findings. As with most other medical conditions, the proper diagnosis depends on a combination of history, clinical exam, laboratory findings and imaging.

History

A careful medical history will often identify a likely case of psoriatic arthritis (PsA) even before the physical exam. One of the first tasks in making a diagnosis of PsA is establishing a diagnosis of psoriasis. Most patients will present with skin disease long before they develop joint disease, but one must always remember that up to 10% of patients will present with joint symptoms before developing skin psoriasis. Patients may never have had a specific diagnosis of psoriasis, so careful questioning for any history of scaly rash or nail changes is important.

A history of severe dandruff may be indicative of scalp psoriasis that has never been formally diagnosed. Obtaining a full family history is also important; the CASPAR criteria identify a family history of psoriasis as an important element in the diagnosis of PsA. Finally, a personal or family history of other spondyloarthropathy features, including uveitis or colitis, may be helpful in identifying a potential diagnosis of PsA in a patient with inflammatory joint symptoms.

The patient’s history of musculoskeletal symptoms may provide helpful clues to a diagnosis. Application of the CASPAR criteria begins by establishing a history of inflammatory joint disease, but this history may include peripheral, axial or entheseal involvement. As with other spondyloarthropathies, enthesitis is common feature of PsA; patients may present with enthesitis alone, such as plantar fasciitis or Achilles tendonitis, with no other evidence of arthritis. PsA may occasionally present with chest wall pain, with the pain presumably arising from entheseal insertions in the spine, sternum or ribs. The synovitis of PsA may be described similarly to other types of inflammatory arthritis, but PsA patients may have fewer joints involved than in RA, and they may have asymmetrical or predominantly lower extremity involvement. As with any inflammatory arthritis, morning stiffness, either peripheral or axial, is an important component of PsA and should be queried.

Joint Exam

Evaluation of PsA should include an objective assessment of joint and entheseal involvement. Joint counts may be assessed by examining either 28 joints or 66/68 joints for swelling and tenderness; these are the same joint counts that are used in the evaluation of rheumatoid arthritis. Such joint counts are used commonly in clinical trials but are also useful in clinical practice to provide an objective measurement of joint involvement. Joint counts also form an important component of the composite outcome measurements.

The 28-joint count, which includes the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, wrists, elbows, shoulders and knees, is the most practical joint count to use in clinical practice (Figure 5-1). It may be easily performed with the patient sitting in the exam room rather than laying down on an exam table, and it does not require that they remove their shoes although examination of the feet is appropriate for patients who report lower extremity symptoms.

It should be remembered that the standard 28-joint count used in disease activity scores does not include the distal interphalangeal (DIP), which may be involved in PsA and should be assessed separately. The 66/68-joint count, which includes the DIP joints, is more commonly used in clinical trials than in clinical practice (Figure 5-2); in addition to the DIP joints, it adds temporomandibular, acromioclavicular, sternoclavicular, hip, ankle, MTP and the interphalangeal joints of the feet, although hips are assessed only for tenderness and not swelling.

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Entheseal Exam

A careful examination for the presence of entheseal tenderness should be part of the evaluation of a patient with psoriatic arthritis (PsA). Common locations for entheseal tenderness include the Achilles tendon insertions, the plantar fascia, the medial and lateral epicondyles, the inferior patella and tendon insertions at the trochanters.

While a general examination of entheseal sites may suffice in clinical practice, there have been efforts to quantify this evaluation for use in clinical trials. The two commonly used assessments are the Mander Enthesitis Index (MEI) (Figure 5-3) and the Maastricht AS Entheses Score (MASES) (Figure 5-4), both originally developed for assessing enthesitis in ankylosing spondylitis. The MEI involves evaluating for tenderness on a semiquantitative scale at 66 entheseal insertions on the trunk, pelvis, upper extremity and lower extremities. This is obviously a time-consuming examination and not practical for clinical practice. The MASES is a modification of the MEI that eliminates difficult to reach or closely positioned areas; it focuses on just the sternoclavicular region, the pelvis and the Achilles insertions.

Two other indices have been proposed for measuring entheseal involvement in PsA. The Spondyloarthritis Research Consortium of Canada (SPARCC) has developed an index of 16 sites identified as commonly involved in spondyloarthropathies by ultrasound and magnetic resonance imaging (MRI) imaging (Figure 5-5). Finally, the Leeds Enthesitis Index (LEI) is the only one developed specifically for PsA (Figure 5-7). Focusing on bilateral evaluation at just six sites (lateral epicondyles, medial femoral condyles, Achilles insertion), the LEI is more practical for use in following patients in clinical practice.

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Dactylitis

Examination for the presence and extent of dactylitis should be part of the initial evaluation of psoriatic arthritis (PsA) for tenderness, and these findings can be followed during the course of the disease. The finding of tenderness in a dactylitic digit may be more indicative of active disease than the chronic, nontender swelling that can sometimes occur. The Leeds Dactylitis Index (LDI) is a validated instrument for assessing dactylitis that assesses circumference of involved digits. The LDI is a time-consuming evaluation that is not practical for clinical practice and may even prove difficult in clinical studies. Most clinical trials to date have simply measured the presence and number of involved digits.

Axial Evaluation

There are no specific tools for the evaluation of axial disease in psoriatic arthritis (PsA). As with enthesitis, outcomes developed for use in ankylosing spondylitis (AS) may be applied to PsA. In particular, mobility measurements used in AS may be helpful for following axial disease in PsA.

The Schober’s test is used to measure mobility at the lumbar spine (Figure 5-7). To perform a Schober’s test, the patient is asked to stand, and a mark is made over the spine at the lumbosacral junction, identified by the midline between the dimples of Venus or the posterior superior iliac crests, and a second mark is made 10 cm above the first. When the patient bends over, the distance between the two marks is measured again. With normal lumbar flexion, the distance between the two marks should extend to 15 cm as the skin stretches over the spine. In patients with limited mobility, from AS, axial PsA or other axial spondyloarthropathies, the distance will be <14 cm.

A second measure of axial mobility is the occiput to wall test, where the distance between the posterior occiput and the wall is measured in a patient standing with their back to the wall and their heels up against the wall. Patients with normal cervical extension should be able to touch their occiput to the wall easily; the distance is increased as cervical mobility diminishes. Occiput to wall distance is generally increased only in late-stage AS.

Finally, chest expansion can be measured as an indication of axial involvement, although this has not been specifically studied in PsA. In patients with a normal spine, chest circumference increases during inspiration, as the ribs rotate at their articulations with the spine. When mobility is reduced at these joints, chest expansion decreases correspondingly. Chest expansion may be measured with a measuring tape at the xiphisternum level. There is a great deal of variability and no validated normative values for this measurement, but it has been used to show change with response to therapy in AS.

In addition to measures of mobility, the clinical outcome measurements used in AS may be used in the evaluation of PsA patients with axial involvement. The most commonly used measurements are the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the ASAS response criteria. The BASDAI uses patient-completed visual analog scales to assess disease activity and impact (Table 5-1). Patients mark their current status on a series of 10-cm visual analog scales (VAS) and the scores are averaged to give a composite score that ranges from 0 to 10.

The ASAS response criteria were designed to function similarly to the ACR response criteria in RA. They also use a series of VAS querying pain, stiffness, global status and function (using the Bath Ankylosing Spondylitis Functional Index, BASFI); the scales are measured from 0 to 100 (Table 5-2). ASAS20 responders must have at least 20% and 10 units of improvement in three of the measured domains, and no more than 20% worsening in the fourth. An ASAS40 response, correspondingly, represents 40% and 20 units of improvement in the same domains, while an ASAS partial remission is defined by have a VAS score of <2/10 in all four domains of global disease activity, pain, function and stiffness.

Importantly, clinical appearance of lesions make up the basis by which psoriasis is objectively measured in clinical trials. The two most commonly used measures are the physician global assessment (PGA) and Psoriasis Area and Severity Index (PASI). The PGA is usually a static, that is, measurement at a single time, where the erythema, induration and scale of all the lesions present at a given time are considered. The evaluator then takes what they consider to be the average of these lesions and classifies the severity on a 0 to 5 or 0 to 6 scale. In general, a patient is considered to have a clinically significant response in psoriasis when their PGA is a 0 or 1 or “clear” or “almost clear.” This scale is weakened significantly by the fact that it does not consider BSA. A patient with one small, but very erythematous, indurated and scaly lesion will be considered to have more severe psoriasis than a patient who has 50% of their BSA covered with lesions that have less redness, scale and thickness.

The PASI is a measure that incorporates both the activity of lesions and the BSA involved. Lesion quality is evaluated over different body parts and then the area involved in each of those parts is evaluated. Through a rather complicated calculation (Figure 5-8), an absolute PASI score between 0 and 72 is derived. Typically, a score of <5-10 is considered mild disease, 10-20 is considered moderate to severe, and >20 is considered to be quite severe. Evaluation of psoriasis in clinical trials is often dynamic with measures of improvement being used. The general standard of improvement used is a 75% improvement in the PASI, also called a PASI 75. PASI 50, PASI 90 and PASI 100 are also frequently used as measures of efficacy of interventions for psoriasis.

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Nail Changes

Nail changes are common in psoriasis but are particularly common in psoriatic arthritis (PsA). Evaluation of a patient with PsA should include documentation of specific nails involved, in both hands and feet. In addition, there is an objective assessment of nail involvement, the Nail Psoriasis Severity Index (NAPSI) that may be useful when a quantifiable measurement is desired, such as in clinical trials or registries (Table 5-3).

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Laboratory Testing

Rheumatoid factor (RF) is usually negative in psoriatic arthritis (PsA) – a negative RF is one element of the CASPAR criteria – but a positive RF may be seen in as many as 10% of patients. Antibodies to cyclic citrullinated peptide (anti-CCP or anti-citrullinated protein antibodies) may help distinguish polyarticular rheumatoid arthritis (RA) from PsA, as they are generally considered to be more specific for RA than RF. However, anti-CCP antibodies have been reported in patients with PsA, so their presence does not completely rule out the diagnosis. Anti-CCP antibodies are more often present in PsA patients with polyarticular disease, although there is as yet no data to suggest that, as in RA, they are associated with more structural damage.

Elevated acute phase reactants, either erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), nonspecific indicators of inflammation, may be seen in one third of patients with PsA, less frequently than in RA. As a consequence, these tests are generally not as helpful as biomarkers of disease activity in PsA as they are in RA.

HLA-B27 positivity may be seen in patients with PsA. It is more common in those with axial disease, less frequent in patients with strictly peripheral disease, although still more common than in the general population. Psoriatic skin disease without PsA is not associated with an increased prevalence of HLA-B27 positivity.

Composite Disease Activity Scores

In clinical trials, composite measures of disease outcome are commonly used as end points to identify response to therapy. The first outcome developed specifically for psoriatic arthritis (PsA) clinical trials was the Psoriatic Arthritis Response Criteria (PsARC) (Table 5-4). The PsARC, which uses a combination of patient and physician assessment and joint counts, was developed as a consensus criteria for response in the VA cooperative sulfasalazine trials during the 1980s. Achieving a PsARC response is comparatively easy, which can lead to very high response rates with active drugs in clinical trials and even relatively high placebo response rates. This may make it a challenge to use the PsARC to estimate the real clinical efficacy of a drug with any degree of precision.

The ACR20 response rate has also been used in clinical trials in PsA (Table 5-5). This outcome assessment adds both function and a measure of acute phase reactants to the components of the PsARC. While useful, the ACR response is an imperfect measurement of response in PsA. Improvement in swollen and tender joints may be difficult to assess in patients with only a few active joints, and the utility of acute phase reactants is limited in a disease in which as many as two thirds of patients do not have an elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP).

A third composite outcome assessment has also been studied in a post-hoc analysis of clinical trials in PsA, although not yet used in the primary analysis of these trials. The Disease Activity in Psoriatic Arthritis (DAPSA) scale is based on the Disease Activity in Reactive Arthritis (DAREA) scale, developed and validated for disease assessment in reactive arthritis. The DAPSA is a simple summation of the numerical measurements of tender and swollen joint counts (66/68 joints), patient global assessment, patient pain assessment and CRP in mg/dL. Outside of the potential contribution of these features to the patient and physician global assessments, none of these composite measurements specifically assess the skin, nail or entheseal components of PsA.

With the limitations of the PsARC, the DAPSA, and the ACR response rate in mind, the Group for the Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), in conjunction with the group Outcomes Measures in Rheumatology (OMERACT), is working to develop a composite measurement of disease activity that is specific to PsA. Two composite measures that have received some attention are the Psoriatic Arthritis Disease Activity Score (PASDAS) and the Composite Psoriatic Disease Activity Index (CPDAI), both of which include assessments of enthesitis and dactylitis in addition to synovitis, and, in the case of the CPDAI, skin disease. While still a work in progress, the goal of these instruments is to assess both the unique manifestations of the joint involvement in PsA and the non-joint manifestations, including skin and entheses.

In clinical practice, where a simple, practical outcome measure is desired, the Routine Assessment of Patient Index Data 3 (RAPID3), has been shown to be a useful outcome measure in PsA. Finally, stringent criteria for minimal disease activity (MDA) have been proposed for use in both clinical trials and clinical practice; these are intended to indicate remission, or at least effective control, of the various manifestations of psoriatic disease. To be considered meet MDA criteria, a patient must meet five of the following seven criteria: tender joint count ≤1; swollen joint count ≤1; PASI ≤1 or body surface area involvement ≤3%; visual analog scale (VAS) score of ≤15 on patient‘s assessment of pain; VAS score of ≤20 on patient’s global assessment of disease activity; HAQ DI score of ≤0.5; and ≤1 tender entheseal point.

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Radiographic Evaluation

Radiographic changes are not always seen in early psoriatic arthritis (PsA) but, when present, may be diagnostically useful. The radiographic changes seen in rheumatoid arthritis (RA) are those of destructive bony lesions and cartilage loss with periarticular erosions and joint space narrowing, while radiographs in osteoarthritis (OA) show osteophytes or evidence of new bone production. PsA has a unique radiographic picture, as both destructive and productive bony changes may be seen in the same individual.

Hand and foot radiographs may be useful as part of the baseline evaluation, along with radiographs of other involved joints. Erosive disease may be seen as in RA; involvement of the distal interphalangeal (DIP) joints may help distinguish PsA from RA. In addition, unique radiographic features that may be seen in PsA include periostitis, distal tuft resorption and soft tissue swelling in digits with dactylitis (Figure 5-9). Progressive changes may be seen as new bone formation develops at entheseal insertions; in severe cases, this may produce a “pencil-in-cup” deformity, as new bone formation at the base of the distal phalanx surrounds the distal end of the more proximal phalanx that has been eroded away (Figure 5-10). In clinical trials, a modified version of the Sharp radiographic scoring system that adds distal interphalangeal joints has been used (Figure 5-11).

Axial radiographic changes can be seen as well, including the typical syndesmophytes seen in spondyloarthropathies. Pelvic radiographs may show unilateral sacroiliitis rather than the bilateral changes typically seen in ankylosing spondylitis (AS); radiographic evidence of lumbar spine involvement is less common than in classic AS. The modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) may be used to follow syndesmophyte formation and ankylosis in the cervical and lumbar spine over time.

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Other Imaging Modalities

Beyond plain radiographs, other imaging technologies have been used in psoriatic arthritis (PsA). Ultrasound imaging may be used to evaluate enthesitis, as well as synovial joint involvement (Figure 5-12). Computed tomography (CT) may be useful in evaluation of joints, such as the sternoclavicular joints or the sacroiliac joints, that may be difficult to properly evaluate with plain radiographs. MRI may be useful in identifying early changes in peripheral joints, but is particularly useful at identifying sacroiliitis; MRI abnormalities in the sacroiliac joints may be present years before they can be seen on plain radiographs. Bone marrow edema on MRI, an indication of active inflammation, may be seen even without the use of gadolinium contrast, so that contrast imaging is not generally necessary.

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