Dr Aizad Mumtaz and Prof Oliver FitzGerald of the Department of Rheumatology at St Vincent’s University Hospital, Dublin examine the latest management options for psoriatic arthritis
Psoriasis is a common skin disorder affecting about 3 per cent of the population in Ireland. Somewhere in the range of between 5 per cent and 40 per cent of individuals with psoriasis may develop psoriatic arthritis (PsA), depending on the population studied.
Classification
Initially, PsA was thought to be a variant of rheumatoid arthritis with co-existant psoriasis. Following the pioneering work by Moll and Wright, PsA was established as a separate clinical entity by the American College of Rheumatology in 1964. The differences between PsA and rheumatoid arthritis (RA) are now well established on the basis of clinical, genetic and immuno-histochemical features.
More recently, a new classification criteria was proposed by the Group for Research and Assessment in Psoriasis and Psoriatic Arthritis (GRAPPA).The ClASsification of Psoriatic ARthritis (CASPAR) criteria consist of established inflammatory articular disease with at least three points from the following features: current psoriasis (assigned a score of 2; all other features were assigned a score of 1), a history of psoriasis (unless current psoriasis was present), a family history of psoriasis (unless current psoriasis was present or there was a history of psoriasis), dactylitis, juxta-articular new bone formation, rheumatoid factor negativity, and nail dystrophy. The sensitivity and specificity was 0.914 and 0.987 respectively.
Clinical features
PsA presents with peripheral joint involvement, with or without inflammatory back pain (IBP), enthesitis, dactylitis and extra-articular features common to the HLA-B27-associated spondyloarthropathies. Erosive and deforming arthritis occurs in 40-60 per cent and is progressive from within the first year of diagnosis. The heterogeneity of PsA is such that the term psoriatic disease (PD) has been suggested to more accurately reflect how patients may be affected.
Skin: The most common form of psoriasis in PsA patients is psoriasis vulgaris; however the pustular, erythrodermic and guttate variety are also reported. It is interesting to note that there is no correlation between the extent of skin involvement and the severity of arthritis.
Psoriasis usually precedes the onset of arthritis in 70 per cent of cases; arthritis is diagnosed concomitantly with psoriasis in another 15 per cent, while joint involvement occurs before the skin symptoms in around another 15 per cent of cases.
There are many objective instruments available but the PASI (Psoriasis Area and Severity Index) is the most widely used and includes assessment of area and severity, with measurement of erythema, induration and desquamation in each area. The presence of arthritis in patients with psoriasis may go unrecognised and the results from the recent PRESTA study are of interest in this regard, as a mean of 13 swollen and 19 tender joints were found in psoriasis patients attending dermatology clinics.
Nail: Psoriasis nail involvement is observed in up to half of patients with psoriasis. Typical features include: pitting, nail-plate crumbling, leuconychia, onycholyis, red spots in the lunula, splinter haemorrhages and oil drop discolouration. The extent of nail involvement can be quantified by using several measures like the NAPSI (Nail Psoriasis Severity Index). Nail dystrophic changes occur more frequently in PsA and may be a measure of disease severity.
Joint: The assessment of joint tenderness and swelling, representing articular inflammation, is critical to the evaluation of PsA. Moll and Wright initially described five patterns of joint involvement in PsA: oligo-articular (up to four joints), distal inter-phalangeal (12 per cent), polyarticular, arthritis mutilans and asymmetric sacroiliitis.
The presence of polyarticular involvement, whether at baselines or during follow up, is an important prognostic indicator of PsA. It is now increasingly being recognised as the most common form of joint involvement in PsA.
Arthritis mutilans is a characteristic feature of PsA. It is a severe and destructive form of arthritis resulting in fused and flail joints. It can affect up to 10 per cent of PsA patients.
The ACR (American College of Rheumatology) 66/68 joint counts provide adequate assessment of all of the involved joints in PsA and it has also been demonstrated to provide good inter- and intra-observer variability. A reduced count involving 28 joints has been proposed to assess PsA patients; however it may underestimate the extent of arthritis in a disease which frequently involves joints below the knee.
Enthesitis
Enthesitis is considered to be an important feature of PsA. It involves inflammation at tendon or ligament insertion into the bone. The most common sites to be involved in PsA are the Achilles insertion and the plantar fascia insertion. However, many other sites like the lateral and medial epicondyles of humerus, insertion of quadriceps and patellar tendons, iliac crest and insertion of the rotator cuff may be involved. This is the site of an erosive inflammatory infiltrate composed of lymphocytes and plasma cells and occasionally polymorphonuclear cells. The erosive process is followed by fibrous tissue proliferation leading to the formation of cartilage and subsequently bone.
A more recent immuno-histochemistry study of entheses in elderly patients with spondyloarthropathy undergoing total knee joint replacement demonstrated oedema with an inflammatory infiltrate in the bone marrow underlying an enthesis.
Clinically, enthesitis may be demonstrated by application of standard pressure on the entheseal site (enough pressure to roughly blanch the nail bed). Recently a new instrument has been proposed (Leeds enthesitis Index). It involves assessment of three sites: bilateral lateral epicondyles of humerus, medial condyles of femur and Achilles insertion. It is a simple, robust and reliable clinical measure and can be applied in busy clinical settings.
Dactylitis
Dactylitis is one of the hallmark clinical features of PsA, It occurs in between 16 per cent and 48 per cent of reported cases. In an early arthritis cohort in Dublin, 29 per cent had evidence of dactylitis at presentation. Rothschild et al defined dactylitis as “uniform swelling such that the soft tissues between the metacarpophalangeal and proximal interphalangeal, proximal and distal interphalangeal, and/or distal interphalangeal joint and digital tuft were diffusely swollen to the extent that the actual joint swelling could no longer be independently recognised”.
Recent imaging studies have demonstrated that the dactylitic digits have evidence of inflammation in both joints and tendons. The involved digits show more radiographic progression. Usually feet are affected more than the hands.
Clinicians involved in the care of PsA patients should examine carefully for evidence of dactylitis as not only it helps to diagnose patients with PsA, but also serves as prognostic indicator of a more severe outcome of the disease. This should be followed by appropriate referral to specialist care.
Spinal
Spinal involvement has been reported in up to 51 per cent of PsA patients. Axial involvement is quite heterogeneous in its expression and is distinguished from that in ankylosing spondylitis (AS) by less pain, lower and often asymmetrical sacroiliac grade and less syndesmophyte formation on radiographs.
Radiologially, MRI is superior to plain x-ray in demonstrating features of sacroiliitis. The clinicians should familiarise themselves with presence of spinal symptoms, notably inflammatory back pain, tenderness, stiffness and decreased range of movement. This would facilitate appropriate diagnosis, referral and treatment with a considerable impact on the health and quality of life of patients.
Treatment
The optimal management for PD patients should be a shared care programme between the rheumatologists and dermatologists. For an adequate diagnosis, a high index of suspicion is required as the skin and joint disease may not always be apparent.
Therefore, dermatologists should incorporate validated arthritis screening questionnaires in their practice. They should also become familiar with and get training in simple joint assessment techniques.Rheumatologists need to ‘hunt’ for psoriasis when patients present with typical disease features suggestive of PsA. Often psoriasis might be missed if it involves areas like scalp, umbilicus and natal cleft.
Psoriatic arthritis poses a significant challenge to the treating physicians due to the complex array of clinical features and disease severity. It is therefore essential not only to assess individual aspects of the disease, but also the combined overall effect on the patient and quality of life as a whole.
For the treatment of peripheral arthritis, several agents like nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs) and intra-articular steroid injections are used.
There have been very few double blind, placebo controlled trials involving traditional DMARDs. Data support the utility of DMARDs, including sulfasalazine (level 1a, grade A), leflunomide (level 1b, grade A), methotrexate (level 1b-3,grade B), cyclosporine (level 1b-3, grade B) and azathioprine (level 2b, grade B) in PsA. However, it is now known that these agents do not halt radiographic progression of the disease.
Three phase III trials have demonstrated etanercept, infliximab, and adalimumab as safe and effective therapies for treatment of peripheral arthritis of PsA (1B, grade A). These agents have a significant effect in improving the symptoms and quality of life of patients. Patients on methotrexate plus an anti-TNF did not have a higher ACR response than patients on TNF antagonists alone.
Skin involvement should ideally be diagnosed and managed by dermatologists. Treatment options include topical therapy, ultraviolet light B (UVB), and psoralen ultraviolet light A (PUVA) treatment. Traditional agents like methotrexate and cyclosporine are also effective (level 1b, grade A). Adalimumab and infliximab may be more effective for treatment of psoriasis than etanercept.
There is data available that dactylitis and enthesitis improved significantly after infliximab treatment.
DMARDs are not effective in treating spondylitis. After initial screening and radiology, patients should be educated and referred to physiotherapy. Treatment of choice includes NSAIDs and the anti-TNF agents.
Conclusion
The impact of PD on joint damage, radiographic progression and quality of life is comparable to rheumatoid arthritis (RA). Therefore, like RA, early diagnosis, assessment, treatment and referral should be made by healthcare professionals involved in management of PsA patients. These measures would not only ensure improvement in quality of life and disability but also lead to significant reduction in burden on resources.
References on request.
l Dr Aizad Mumtaz, Newman Clinical Research Fellow, and
Prof Oliver FitzGerald, Newman Clinical Research Professor, Department of Rheumatology, St Vincent’s University Hospital, Elm Park, Dublin, 4.
UCD School of Medicine and Medical Science and Conway Institute of Biomolecular and Biomedical Research, UCD.
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