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Psoriatic arthritis in focus

Discussion

Psoriatic arthritis (PsA) is a member of the spondyloarthropathy family and may be diagnosed when there is evidence of an inflammatory arthropathy associated with psoriasis and usually negative for rheumatoid factor (RF). The Classification Criteria for Psoriatic Arthritis (CASPAR), which should not be used for diagnosis but for case consistency in clinical studies or controlled trials, require the presence of inflammatory articular disease (of joints, spine or enthesis) with at least three points from the following features:

  • Current psoriasis (assigned a score of 2)
  • A history of psoriasis (in the absence of current psoriasis; assigned a score of 1)
  • A family history of psoriasis (in the absence of current psoriasis and history of psoriasis; assigned a score of 1)
  • Dactylitis (assigned a score of 1)
  • Juxta-articular new bone formation (assigned a score of 1)
  • RF negativity (assigned a score of 1)
  • Nail dystrophy (assigned a score of 1)

Epidemiologic studies have supported the concept that PsA is a unique disease entity separate from RA. The prevalence of inflammatory arthritis is increased among patients with psoriasis, ranging from 7 per cent to 25 per cent, compared with a general population estimate of 2-to-3 per cent.

The prevalence of psoriasis among subjects with arthritis also is increased, at 2.6-to-7 per cent compared with a general population estimate of 0.1 per cent-to-2.8 per cent. Among patients with psoriasis, 7-to-42 per cent develop arthritis.

Disease domains

Peripheral arthritis

There are four clinical patterns of peripheral arthritis:

Symmetric polyarthritis

Symmetrical polyarthritis involves the small joints of the hands and feet, in addition to lager joints. It affects males and females equally and can be clinically indistinguishable from RA. It tends to evolve over time, has longer disease duration and tends to be associated more with erosive disease.

Asymmetric oligoarthritis

Asymmetrical oligoarthritis is the most common presentation of PsA. It occurs more commonly in males, and lower-limb involvement is common. A high proportion of patients with this type will, however, progress to polyarthritis.

Predominant DIP joint involvement

Involvement of the DIP joints in PsA is considered a distinctive disease phenotype. DIP joints are involved more frequently in patients with PsA than in patients with inflammatory arthritis without psoriasis. DIP joint involvement is thought to be associated more with dactylitis and nail dystrophy.

Arthritis mutilans

Arthritis mutilans is a rare, destructive, erosive arthropathy affecting peripheral joints, especially of the hands and feet. Clinical criteria include shortening of digit, digital telescoping and/or flail joint not due to subluxation. Radiographic criteria include erosion involving entire articular surfaces on both sides of the joint and/or pencil-in-cup change; osteolysis is considered a defining feature. Involvement of one joint is sufficient to include patients in this group.

Treatment of peripheral arthritis in PsA varies, depending on the course of the disease. It ranges from NSAIDs for mild, mono-articular disease, to systemic treatment with short courses of oral steroids at the lowest effective dose, csDMARDs (eg, methotrexate (MTX), leflunomide, sulfasalazine), and biological DMARDs (bDMARDs), including anti-TNF therapies that are approved for the treatment of PsA (eg, etanercept, adalimumab, infliximab, certolizumab and golimumab), as well as treatments targeting the IL-23 pathway, such as ustekinumab.

As advised in the EULAR guidelines, for patients with peripheral arthritis, particularly in those with many swollen joints, structural damage in the presence of inflammation, high ESR/CRP and/or clinically relevant extra-articular manifestations, csDMARDs should be considered at an early stage, with MTX preferred in those with relevant skin involvement. Patients with an inadequate response to at least one csDMARD should be commenced on a bDMARD, usually a TNF inhibitor. In patients who fail anti-TNF therapy, biologics targeting IL12/23 (ustekinumab) may be considered. The PDE-4 inhibitor apremilast has recently received approval for treatment of PsA but is not yet generally available. It is likely that IL-17 inhibitors, now available for skin psoriasis, will be licensed for PsA over the next year.

Axial disease

Predominant spondyloarthritis is uncommon, although spinal involvement may be found in 40-to-70 per cent of PsA cases, depending on whether or not radiographs are taken. Involvement of the sacroiliac joint can be asymmetrical or symmetrical (Figure 1). Bilateral sacroiliitis occurs more commonly in patients with the HLA-B27 genotype. The cervical spine is a common site of involvement in PsA. This can occur both as part of a more widespread disease or as the sole site of axial involvement.

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Figure 1: X-ray pelvis AP view showing bilateral asymmetric sacroilitis more on the right, with evidence of subchondral sclerosis and erosions

Treatment of axial disease resembles that of AS and usually involves NSAIDs, exercise and biologic therapy. In patients with predominantly active axial disease (BASDAI ≥ 4, high CRP/ESR) and an insufficient response to NSAIDs, therapy with a bDMARD, usually anti-TNF, should be considered. It is noteworthy that csDMARDs are not effective in axial disease.

Dactylitis

Dactylitis is a feature of the seronegative arthropathies in general. It is characterised by a sausage-shaped swelling of the fingers or toes (Figure 2), and may be found in 29-to-33.5 per cent of PsA patients at first presentation, with 48 per cent having an episode of dactylitis during follow-up.

It most commonly involves one or two digits and the feet are affected more commonly than the hands. It is usually associated with DIP involvement and erosions on x-rays.

Treatment of dactylitis includes NSAIDs, local glucocorticoid injections and systemic treatment with biologic therapy, including anti-TNFs. In patients with active dactylitis and insufficient response to NSAIDs or local glucocorticoid injections, TNF inhibitors or, alternatively, bDMARDs targeting the IL12/23 pathways may be considered.

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Figure 2 (left): Showing dactylitis (white arrow) and psoriasis (black arrows). Figure 3 (right): Showing enthesitis of the right Achilles tendon

Enthesitis

Enthesitis is the inflammation at tendon and ligament insertion into bone (Figure 3). It is a feature of all of the spondyloarthropathies and can be a presenting feature in psoriatic arthritis. Enthesitis is found in 38 per cent of patients at presentation. The most common entheseal sites involved are the Achilles and plantar fascia insertions. Other sites include the insertions of the quadriceps and patellar tendons, the iliac crest, the rotator cuff, and the epicondyles at the elbow.

Treatment of enthesitis includes NSAIDs, local glucocorticoid injections and systemic treatment with biologic therapy, including anti-TNFs. In patients with active enthesitis and insufficient response to NSAIDs or local glucocorticoid injections, TNF inhibitors or, alternatively, bDMARDs targeting the IL12/23 pathways may be considered.

Skin and nail disease

Psoriasis

Plaque psoriasis or psoriasis vulgaris is the most common skin phenotype in patients with psoriatic arthritis. They usually appear as raised, inflamed, red skin covered with silvery, white scales patches. These patches may itch and burn. It can appear anywhere but commonly affects elbows, knees, scalp and lower back. Other patterns of skin involvement include guttate, inverse and pustular psoriasis.

Nail dystrophy

Psoriatic nail dystrophy mainly occurs in patients who also suffer from psoriasis of the skin. It is commonly (up to 86 per cent) seen in patients with psoriatic arthritis, particularly when the arthritis affects the DIP joints of fingers and toes. Changes include nail pitting, onycholysis and nail plate crumbling, and less frequently, beau line, leukonychia, oil spots, transverse ridging and subungual hyperkeratosis.

Treatment for skin and nail disease consists of topical creams including potent steroid creams, PUVA/UVB, and systemic treatment with DMARDs (eg, MTX, cyclosporine) and biologics in severe cases.

Treatment goals

The primary goal of treating patients with psoriatic arthritis is to maximise health-related quality of life through control of symptoms, prevention of structural damage, normalisation of function and social participation. It is important to consider extra-articular manifestations, metabolic syndrome, cardiovascular disease and other co-morbidities while managing PsA patients.

Treatment should be aimed at reaching the target of remission (absence of clinical and laboratory evidence of significant inflammatory disease activity) or, alternatively, minimal/low disease activity, by regular monitoring and appropriate adjustment of therapy.

Minimal disease activity (MDA) is defined when a patient has five of the following seven criteria: Tender joint count ≤1; swollen joint count ≤1; tender entheseal point ≤1; PASI ≤1 or body surface area ≤3 per cent; pain visual analogue score (VAS) ≤15; patient global ≤20; and Health Assessment Questionnaire ≤0.5. These criteria have been validated and can be used as a responder index in addition to a target for treatment interventions.

Recently, Measuring Outcome in Psoriatic Arthritis (MOPSA), a new web-based tool for assessment of PsA, was developed and is freely available to use (see https://mopsa.ie).

MOPSA will calculate MDA and it also uses the Composite Psoriatic Disease Activity Index (CPDAI) to calculate disease activity across the disease domains. CPDAI assesses five domains (joints, skin, entheses, dactylitis, and spine). Within each domain a score (range 0-3) is assigned according to predefined cut-offs. The scores for each domain are then added together to give a final score range of 0–15; 0 for no disease and 15 for severe disease. If a patient has not reached MDA, further escalation of therapy should be considered.

Case report

History

A 44-year-old female with history of psoriasis for 10 years presented with joint pain and swelling affecting her fingers and toes, with early-morning stiffness lasting approximately two hours. She also reported back pain that was usually worse at night, and often woke her up from sleep. Her mother suffered from psoriasis and she had a brother with a history of ankylosing spondylitis (AS).

She took non-steroidal anti-inflammatory drugs (NSAIDs), with some symptom relief. She had been given short courses of oral corticosteroids by her GP in the past, with good short-term improvement. Her symptoms had worsened in the past few months, with reduced benefit from NSAID use. Her symptoms had impacted on her activities of daily living and her skin had interfered with sexual function.

On examination, she was found to have plaque psoriasis affecting her elbows, knees and scalp and she had a Psoriasis Area Severity Index (PASI) score of 15.6. Nail examination revealed pitting of all of her nails and onycholysis affecting the second, third and fourth fingers bilaterally. She had evidence of synovitis affecting her distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints. Her wrists were noted to be tender and swollen. She had a tender joint count (TJC) of 20/68 and a swollen joint count (SJC) of 12/66. She had dactylitis of the second and third fingers on the right, and second finger on the left. Dactylitis also affected her second and third toe on the right foot. There was evidence of enthesitis affecting the right Achilles tendon and left lateral epicondyle of the humerus. She was tender over her right sacroiliac joint and her Schober’s test measured at 3cm.

Investigations

Blood test revealed high inflammatory markers (CRP — 18, ESR 42). Rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) were both negative. Human leukocyte antigen (HLA) B27 was negative. x-rays of the hands and feet showed a deforming arthropathy with multiple erosions. Plain film of pelvis showed right-sided sacroiliitis. Ultrasound of the hands and wrists showed hyperaemia, synovitis and positive power Doppler signals.

Differential diagnosis

In summary, this patient presented with features of skin psoriasis, psoriatic nail disease, dactylitis, enthesitis, as well as axial and peripheral articular disease.

Differential diagnoses that can be considered here are rheumatoid arthritis (RA), AS and PsA.

The most likely diagnosis is PsA, as this patient’s clinical features involve domains that are typically involved in PsA, ie, peripheral arthritis, dactylitis, enthesitis, axial disease, and skin and nail disease. RA is unlikely, as patients with this condition are usually RF and/or ACPA positive, have no sacroiliac involvement, no psoriatic skin or nail disease and no evidence of dactylitis. AS is also unlikely, as patients with AS are usually HLA B27 positive, have bilateral sacroiliitis on x-ray in most cases and have no evidence of psoriasis or psoriatic nail disease.

Management

The patient started treatment on methotrexate (MTX), a conventional-synthetic, disease-modifying, anti-rheumatic drug (csDMARD), 10mg with the dose gradually increased to 20mg. As she was very symptomatic and as it would take several weeks for the MTX to take effect, a short course of oral corticosteroids was also prescribed at the start of therapy. When reassessed three months later, her symptoms had improved but they had not completely resolved. Examinations revealed TJC — 10, SJC — 4 and a PASI of 5.4. She was therefore commenced on the anti-TNF therapy adalimumab, in addition to the MTX. She was also assessed and managed by the physiotherapy department. After a further six months, her skin was clear, she had no dactylitis or enthesitis, no tender or swollen joints and her Schober’s test had improved to 7cm.

 

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