Psoriativ arthritis L40.5

Immunologically triggered, rheumatoid factor-negative(mostly CCP-AK negative), eminently chronic, inflammatory polyarthritis (more rarely mono- or oligoarthritis), as a facultative manifestation of psoriasis in the musculoskeletal system. Psoriatic arthritis is characterized by an individually different expression of a typical pattern of affection of joints and bones.

Notice. Most important extracutaneous manifestation of psoriasis! S.a. Psoriasis arthropathica

Men are affected in a ratio of 1:1.3 to women. In the USA, 5-42% of patients with psoriasis vulgaris suffer from psoriatic arthritis. 40% of these patients have radiologically detectable deformities and joint damage, and 19% of patients have limitations in joint function.

• Genetic factors: twin studies prove the relevance of genetic factors. There is a concordance of 35-70% in homozygotes; first-degree relatives have a 50 times higher risk of developing psoriatic arthritis. In psoriatic arthritis, an association with HLA-Cw0602 is discussed. Associations of PsA with a heat shock protein-like transmembrane protein MICA (class I MHC chain-related) have been described; another risk is the presence of certain variants of the TNF-A gene, resulting in increased TNF-alpha expression. Connection to the PSORS1 gene locus could not be detected for psoriatic arthritis.
• Immunological factors: An increased humoral and cellular immune status could be proven. Serum IgG and IgA are usually elevated (correlation with disease activity), circulating immune complexes can be detected, the synovia contains increased IgG and IgA-producing plasma cells. Activated T cells seem to play a key role. Cytokines produced by activated T cells stimulate the proliferation and activation of keratinocytes and synovial fibroblasts in vitro. Activated CD8+ cells were detected in the synovial fluid of psoriatic arthritis patients. Skin and synovia contain mono- and oligoclonal CD8+ and CD4+ cells. Psoriatic arthritis patients show elevated serum and synovial levels of TNF.
• Environmental factors: Viral and bacterial infections can act as trigger factors. The HI-Virus has a special position here. In Zambia, in a larger study in men, 27 of 28 patients with psoriatic arthritis were tested seropositive for HIV, who suffered from newly occurring joint problems. At present it is not fully clarified whether this HIV-associated psoriasis arthritis is strictly analogous to idiopathic psoriasis arthritis, because e.g. the associations to certain HLA patterns in HIV-associated psoriasis arthritis do not occur with increased prevalence.

A lactovegetable diet should be used here, supported by the additional administration of unsaturated fatty acids (e.g. EPAMAX). If after 3 weeks a clear reduction of the complaints can be achieved, this therapy should be maintained.

Phytotherapeutically, Salix alba, willow bark from the ESCOP with a daily dose of 240 mg has been positively monographed for the treatment of psoriatic arthritis.

Also the use of the African devil's claw root (Harpagophyti radix), e.g. Rivoltan®, Doloteffin®^, is possible due to its anti-inflammatory, weak analgesic effect, positive monograph of the ESCOP, however not explicitly for psoriatic arthritis.

Frankincense, Boswella serrata H15, shows excellent effects in psoriatic arthritis. Numerous studies prove the anti-inflammatory effect by inhibiting the enzyme 5-lipoxygenase which induces the leukotriene synthesis. Frankincense has not been approved as a drug in Germany to date.

Chronic, intermittent, mutilating, seronegative, painful polyarthritis. In the foreground of the clinical symptoms are pain and synovitic swelling of the affected joints. The finger or toe end joints (distal interphalangeal joints [DIP]) are usually affected, with redness and swelling. Patients complain mainly of pain in the 2nd half of the night and morning stiffness. A typical distribution pattern is detectable (clinically or only by scintigraphy). In the case of arthritic involvement of the DIP, psoriatic involvement of the corresponding fingernail is often detectable (see Psoriasis of the nails).

• Peripheral manifestation (most common form; correlation with HLA-B 39, 18 and 5): Small, peripheral joints are affected (polyarthritis), preferably hands (mostly DIP). Characteristic are the involvement "in the beam" (so-called sausage finger, sausage toe) and the transverse involvement especially of the distal interphalangeal joints. Asymmetry of joint involvement.
• Truncal manifestation (less common; correlation with HLA-B27): Involvement of sacroiliac and vertebral joints (spondylarthritis; sacroiliitis). Clinically often severe, deforming arthritis. The pain symptoms occur in the majority of patients as nocturnal low back pain.
• Mono-arthritic type: Involvement of single joints, e.g. knee or shoulder joint (monarthritis).
• Arthritis mutilans: About 5% of patients with psoriatic arthritis suffer from aggressively destructive joint inflammation.
• Extraarticular manifestations: psoriatic nail changes (psoriatic nails), iritis, oral ulcerations, urethritis, and heel pain. Iritis is usually mild and associated with sacroiliitis and spondylitis.

Psoriatic arthritis and fibromyalgia: Alsawy N et al (2021) found fibromyalgia in 38.3% of 60 patients with PsA. Other studies showed that the prevalence of fibromyalgia in PsA ranges from 17% to 64%. PsA patients with fibromyalgia are predominantly female, and are more likely to suffer from symmetric polyarthritis than patients without fibromyalgia. Fibromyalgia patients also have significantly higher scores for enthesopathies, poorer sleep quality, greater fatigue, and lower quality of life (Littlejohn GO 2021; Ulutatar F et al. 2021). However, no differences are demonstrated between groups in objective measures of disease activity, such as C-reactive protein, number of swollen joints, and number of dactylitis (Littlejohn GO 2021).

The rheumatoid factors are predominantly negative (in 5-9% of cases the RFs are positive).

10-15% of patients with psoriatic arthritis have anti-CPA antibodies (antibodies against citrullinated peptides). These are missing in psoriatic patients without arthritis.

Anti-CarP autoantibodies: Anti-CarP autoantibodies could prove to be new diagnostically relevant biomarkers for psoriatic arthritis. These are directed against the carbamylated protein (anti-CarP). In a larger French cohort study (n=720 patients) anti-CarP autoantibodies proved to be good predictors for the development of rheumatoid arthritis. In this study, anti-CarP antibodies were found in about 1/3 of the patients (32.6%) - including 23.6% of patients who were negative for both ACPA and RF. Anti-CarP antibodies are also positive for rheumatoid factor and ACPA negative psoriatic arthritis (Chimenti MS et al. 2015).

High SPA and high CRP are characteristic of psoriatic arthritis.

The SPA correlates best with clinical joint scores.

Diagnosis (see tab with CASPAR criteria) is made on the basis of history, clinic, serology and radiographic findings. Physical examination includes: number, localization, distribution of affected joints, and skin findings.

Radiology: Psoriatic arthritis shows certain features not found in rheumatoid arthritis: increased osteolysis, "pencil-in-cup" deformity, ankylosis, spur formation, calcifications at tendon insertions.

Prominent "pencil-in-cup" deformity: Pencil-in-cup lesions result from severe osteolysis. The proximal end of the phalanges or metacarpal bones bulges, and the distal end is pointed.

In the spine, there are paramarginal erosions, asymmetric sacroiliitis.

MRI may be used to evaluate for enthesiopathy.

Further diagnosis: skeletal scintigraphy.

• Traditional therapy:
• In mild cases (few joints, low clinical signs) no "disease modifying drugs" are indicated. In most cases, non-steroidal anti-inflammatory drugs are sufficient; additional physical measures; possibly intra-articular corticoid injections.
• In case of moderate to severe additional skin infections and moderate joint infections: methotrexate, mycophenolate mofetil, ciclosporin A. Methotrexate is approved in a dose of 7.5 mg to 25 mg once a week for oral or parenteral administration in PsA.
• For severe psoriatic arthritis: continuous long-term therapy. In a meta-analysis (20 randomised clinical trials), the following preparations achieved significantly better results than placebo:
• sulfasalazine
• Azathioprine
• Etretinate (low effectiveness)
• MTX parenteral. Perorally applied MTX shows better results in a study than intramuscularly applied gold preparations. No reliable evidence could be provided that MTX influences the long-term progression of arthritis.
• Ciclosporin: At least one study has shown that Ciclosporin is equivalent to MTX (but with significantly higher toxicity!).
• Sulfasalazine: Several studies prove the efficacy of (0.5 to maximum 3 g/day) in PsA, although there is no formal approval for this indication.
• Leflunomide: standard in the treatment of rheumatoid arthritis; approved for psoriatic arthritis. In studies (59% of patients treated with Leflunomid), the active ingredient showed good response within 24 weeks, as well as a reduction in PASI and quality-of-life improvement.
• Internal cortisone therapy is generally not recommended, as considerable rebound phenomena of the skin symptoms can be expected after discontinuation.
• Extended therapy:
• Etanercept: The active ingredient is approved for the monotherapy of psoriatic arthritis and plaque psoriasis (Pat. > 18 years). 2 studies have shown effectiveness in the treatment of psoriatic arthritis in active joint and skin disease. The preparation is an effective and safe alternative in the treatment of psoriatic arthritis. Cave: Cost-intensive therapy.
• Infliximab: The active ingredient shows good tolerability and is approved for the treatment of psoriatic arthritis. The combination with low-dose MTX is recommended in the treatment of rheumatoid arthritis (and psoriatic arthritis) to prevent the formation of autoantibodies against Infliximab.
• Adalimumab: The active ingredient shows good tolerability and is approved for the treatment of psoriatic arthritis. The combination with low-dose MTX is recommended to prevent the formation of autoantibodies against Adalimumab. In case of intolerance to MTX, it can also be used as monotherapy.
• Hydroxychloroquine: showed unsatisfactory clinical results in studies (dosage: 250 mg/day).
• Future therapy options:
• At present, work is underway on the development of at least 20 other biologicals for the treatment of psoriasis vulgaris and psoriatic arthritis. Another therapeutic target could be the cytokine IL-2 (stimulates T-cell growth). Daclizumab is an anti-CD25 antibody that prevents the binding of IL-2 to its receptor. In the treatment of psoriasis this leads to a significant reduction of symptoms. According to studies mostly well effective without serious adverse events.

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