Case report

A 37-year-old man with severe skin and nail psoriasis and asymmetric polyarthritis presented to our department in June 2008. He had had psoriasis and polyarthritis since the ages of 21 and 27, respectively, and several episodes of dactylitis 4 years before. His grandfather had had severe psoriasis. He had been sequentially treated with methotrexate, leflunomide, ciclosporin, etanercept, adalimumab and infliximab, all withdrawn due to inefficacy or toxicity. At admission, he had polyarthritis involving the shoulders, elbows, wrists, hands, knees, ankles and feet, and extensive skin lesions with severe involvement of the nails. The erythrocyte sedimentation rate was 84 mm/h and C-reactive protein was 166 mg/l. Rheumatoid factor and anticitrullinated proteins/peptide antibodies were negative. X-rays showed multiple erosions and juxta-articular new bone formation in the hands and feet. Knee synovial fluid (SF) showed 23 000 leucocytes/mm³ (85% neutrophils).

Arthroscopy of the left knee showed multiple thin fibrinoid membranes and synovitis with enlarged erythematous villae and marked vessels (figure 1A). Synovial biopsies were obtained for immunohistochemistry, which showed abundant extravascular CD15+ neutrophils predominantly in the lining, CD68+ lining and sublining macrophages and abundant vessels. CD3+ T lymphocytes were scarce, with a predominance of CD8 cells (84%). A low proportion of CD20+ B cells and CD79+ plasma cells was identified, without significant lymphoid aggregation (figure 1B).5

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Figure 1

(A) Arthroscopic view of left knee at baseline and after 24 weeks of abatacept therapy showing very active synovitis with marked vascularisation and inactive villae without vascularisation, respectively. (B) Microscopic analysis of synovial infiltrate at baseline and 24 weeks after abatacept therapy. Representative images of HE staining (vessels/mm²) and immunostaining for CD15+ neutrophils, CD68+ macrophages, CD3+ T cells and CD20+ B lymphocytes. The whole area of each section was systematically counted by Digital Image Analysis (Olympus), with a total area between 16 and 20 mm² analysed for each marker. The numbers of vessels/mm² and cells/mm² at baseline and after 24 weeks of abatacept therapy are shown. L, lining; SL, sublining. Original magnification ×200.

Abatacept was started in July 2008 at 10 mg/kg at days 1, 15, 30, and every month thereafter, with excellent tolerability. Joint pain and swelling progressively improved and skin and nail lesions decreased. Pre/post-treatment (at 6 months) psoriasis area and severity index and disease activity 66/68 scores were 16.9/4.8 and 7.6/2.09, respectively. Only mild joint symptoms in the left knee persisted and SF cell count showed 200 leucocytes/mm³, with lymphocyte predominance. Arthroscopy showed resolution of synovitis with non-vascularised, inactive white villae (figure 1A). A dramatic reduction in neutrophils, sublining macrophages and T cells was observed, with a predominance of CD4 T cells (60%) (figure 1B). A Luminex bead assay was used to assess levels of cytokines in SF at baseline and 6 months (Procarta; Panomics Inc, Fremont, California, USA).6 A significant reduction in the levels (units pg/ml) of IL-6 (35 362 vs <1.2), IFNγ (3.1 vs 0.2), TNFα (25.7 vs 7.5), IL-1β (4.5 vs 2.8) and IL-10 (4.4 vs 2.5) was observed, whereas IL-4 and IL-12 were unchanged, and IL-7, IL-17 and IL-23 were undetectable in both samples.

Our results suggest that abatacept can be effective in PsA refractory to TNFα antagonists. Regression of synovial cell infiltration and downregulation of T helper type 1 and pro-inflammatory cytokines, remarkably IL-6, were observed in parallel with an excellent clinical response. Consistent with previously identified tissue biomarkers of response, neutrophil and macrophage synovial infiltration were efficiently reduced by abatacept therapy, supporting its pathogenetic role.7 Similar changes have been observed in skin psoriasis lesions treated with abatacept together with clinical improvement.3 We also observed an improvement of nail psoriasis, a difficult-to-treat manifestation.

Immunopathological changes in response to the lymphocyte function-associated antigen 3 antagonist alefacept or TNFα blockade in PsA have also shown a significant reduction of synovial T cells and macrophages in parallel to the clinical response.8 9 Interestingly, in rheumatoid arthritis patients treated with abatacept, a significant reduction of synovial IFNγ messenger RNA was only observed in responders.10 This is consistent with our results and points to IFNγ as a potential T-cell marker of response to abatacept.

In conclusion, we report the first case of clinical and biological response to abatacept in a patient with refractory PsA.