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Psoriatic arthritis

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Definition

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease associated with psoriasis of the skin and/or nails (1).

Frequency and incidence

There is no difference in the incidence of psoriatic arthritis between men and women (2), with an incidence of approximately 6 per 100,000 per year (3). Estimates of the prevalence of psoriatic arthritis within patients with psoriasis range from 4 to 30 per cent.

Diagnosis

The occurrence of inflammatory joint swelling in patients with psoriasis makes the diagnosis of psoriatic arthritis likely. However, the diagnosis of PsA is made more difficult as patients with psoriasis can also suffer from rheumatoid arthritis or chronic inflammatory bowel disease at the same time, for example. There are no generally accepted classification criteria. Based on the CASPAR study, which included 588 patients with PsA and 536 patients with other inflammatory joint diseases, the following classification criteria can be used (4):

Occurrence of inflammation of the musculoskeletal apparatus (arthritis, enthesitis or sacroiliitis)

  • Occurrence of inflammation of the musculoskeletal system (arthritis, enthesitis or sacroiliitis)

and three of the following

  • Psoriasis (current, previously documented or a positive family history)
  • Nail changes
  • Dactylitis
  • Negative rheumatoid factor
  • Radiological changes

Clinic

PsA is characterised by involvement of the peripheral joints and also the axial skeleton. Peripheral joint involvement can be similar to that of rheumatoid arthritis (RA) with symmetrical involvement of the metacarpophalangeal and interphalangeal joints, but can also affect the distal interphalangeal joints (DIPs) and is then often asymmetrical and characterised by diffuse swelling of entire phalanges ("dactylitis", "sausage finger/toe"). DIPs can be affected in isolation or together with other joint regions such as proximal interphalangeal joints or metacarpophalangeal joints. The tendency towards joint destruction is less pronounced than is the case with RA, but joint destruction similar to RA does occur, particularly in the symmetrical type of disease. In addition to destruction, PsA is often characterised radiologically by bone formation. Taking all these aspects into account, the treatment of PsA must be considered in a more differentiated way than that of RA, especially as the skin involvement must also be taken into account.

Therapy

  • Therapy after joint infestation
    In mild cases, such as pure infestation of the DIPs, mild measures such as the administration of NSAIDs are usually sufficient. In the oligoarthritic and polyarthritic forms, synthetic basic therapeutics are usually effective; if they are not sufficiently effective, biologics should be used. In arthritis mutilans, i.e. the rapid-destructive form of PsA, the need to use biologics should be assessed very soon after starting MTX or other basic therapies. If the axial skeleton is affected, the same approach should be taken as for ankylosing spondylitis: administration of NSAIDs in adequate doses and, if they are ineffective, application of TNF inhibitors.
  • Symptomatic therapy
    Non-steroidal anti-inflammatory drugs and glucocorticoids
    In mild joint involvement, particularly isolated distal interphalangeal joint involvement without evidence of joint destruction, non-steroidal anti-inflammatory drugs (NSAIDs), including Cox-2 inhibitors, can not only significantly reduce pain and swelling, but can also be sufficiently effective to prevent progression. For many patients, this treatment measure is completely sufficient. Glucocorticoids, both systemically and intra-articularly applied, can lead to a significant improvement in joint symptoms, but massive exacerbations of cutaneous psoriasis have been described after discontinuation of steroids, which also initially lead to an improvement in the skin condition.
  • Basic therapeutics
    Methotrexate (MTX) is effective for both joint and skin infections. Due to its good success on the skin as well, MTX is usually the drug of first choice if NSAIDs are not sufficiently effective. However, it is reported that the adverse hepatic effects of MTX are greater in PsA than in RA. Therefore, similar to RA, it should be clarified whether pre-existing liver damage (including hepatitis B and C) exists before using MTX and alcohol abstinence should be strictly adhered to. In any case, MTX reduces the clinical symptoms and probably also the joint destruction in PsA. Sulfasalazine (SSZ), cyclosporine A and leflunomide can also be considered as further basic therapeutic agents. However, SSZ has no effect on the skin infestation. Cyclosporin A improves both arthritis and cutaneous psoriasis, but the adverse effects, particularly renal, are limiting when using this drug. Leflunomide, on the other hand, has similar efficacy on joints and skin without the renal side effects and is therefore also a drug of choice for the treatment of PsA today. In a controlled study, approximately 60% of PsA patients treated with leflunomide met the response criteria compared to 30% of controls. Antimalarials such as chloroquine and hydroxychloroquine are also effective in PsA, although cutaneous exacerbations have been described. None of these drugs has a proven effect on axial skeletal involvement in psoriasis (nor in ankylosing spondylitis)
  • Biologics
    In PsA, similar to RA, the concentrations of inflammatory cytokines such as TNF, IL-1 and IL-6 are significantly increased in the joint. Accordingly, all three currently available TNF inhibitors, adalimumab, etanercept and inflixmab, are clearly effective in PsA. These effects affect the peripheral joint involvement as well as that of the axial skeleton, the tendon set complaints that can occur with PsA (enthesiopathy) and also dactylitis. In addition, all three TNF blockers also improve psoriasis.
  • TNF inhibitors

    Adalimumab is a human monoclonal antibody that is very effective in combination with MTX in RA. In the ADEPT study, 57% of patients treated with adalimumab achieved the intended response criteria compared to 15% of patients receiving placebo, and skin involvement also improved significantly (5). With etanercept, a fusion protein consisting of the TNF receptor II and the Fc piece of an IgG1 molecule, almost 60% of PsA patients achieved the response criteria compared to 15% of controls, and skin involvement also improved (6). With infliximab, a chimeric monoclonal antibody, there were clear clinical improvements in PsA in 57% of patients compared to 11% of controls. Skin involvement improved dramatically (7). A new TNF blocker golimumab (8) has recently been approved for the treatment of psoriatic arthritis. In contrast to RA, sub-analyses have shown that in PsA, simultaneous therapy with other basic therapeutics, such as MTX, does not lead to any further improvement when TNF inhibitors are used. The TNF inhibitors also all reduce the progression of joint destruction.

References

  1. Brockbank J, Gladman D. Diagnosis and management of psoriatic arthritis. Drugs 2002;62(17):2447-57.
  2. Madland TM, Apalset EM, Johannessen AE, Rossebo B, Brun JG. Prevalence, disease manifestations, and treatment of psoriatic arthritis in Western Norway. J Rheumatol 2005;32(10):1918-22
  3. Salvarani C, Olivieri I, Cantini F, Macchioni L, Boiardi L. Psoriatic arthritis. Curr Opin Rheumatol 1998;10(4):299-305.
  4. Chandran V, Schentag CT, Gladman DD. Sensitivity and specificity of the CASPAR criteria for psoriatic arthritis in a family medicine clinic setting. J Rheumatol 2008;35(10):2069-70; author reply 2070.
  5. Mease PJ, Ory P, Sharp JT, Ritchlin CT, Van den Bosch F, Wellborne F, et al. Adalimumab for long-term treatment of psoriatic arthritis: 2-year data from the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT). Ann Rheum Dis 2009;68(5):702-9.
  6. Gottlieb AB, Kircik L, Eisen D, Jackson JM, Boh EE, Strober BE, et al. Use of etanercept for psoriatic arthritis in the dermatology clinic: the Experience Diagnosing, Understanding Care, and Treatment with Etanercept (EDUCATE) study. J Dermatolog Treat 2006;17(6):343-52.
  7. Kavanaugh A, Krueger GG, Beutler A, Guzzo C, Zhou B, Dooley LT, et al. Infliximab maintains a high degree of clinical response in patients with active psoriatic arthritis through 1 year of treatment: results from the IMPACT 2 trial. Ann Rheum Dis 2007;66(4):498-505.
  8. Kavanaugh A, McInnes I, Mease P, Krueger GG, Gladman D, Gomez-Reino J, et al. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum 2009;60(4):976-86.