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Objective: The aim of the study is to assess the performance of the DACTOS (DACtylitis glObal Sonographic) score in a PsA dactylitis clinical setting. In particular, we evaluated the ability of DACTOS to identify the affected fingers, its sensitivity to change after treatment, the correlations between DACTOS and clinical parameters, and the capacity of the score to identify the treatment responders., Methods: Forty-six consecutive patients with symptomatic PsA hand dactylitis were enrolled. A total of seventy-three dactylitic digits were evaluated clinically and sonographically before and after treatment in this observational and prospective study. Clinical assessment included the Leeds Dactylitis Index-basic (LDI-b) score and visual analogue scales for pain (VAS-p) and functional impairment (VAS-FI). Sonographic lesions were investigated using high-frequency ultrasound with grey scale and power Doppler features according to the DACTOS score. Correlations between the DACTOS score and the clinical parameters were assessed at baseline, 1 month (T1) and 3 months (T3)., Results: We observed significant improvements in all of the assessed clinical parameters and the DACTOS scores after dactylitis treatment. There was a statistically significant correlation between the variation of all clinical parameters (VAS-p, VAS-FI and LDI-b) and the DACTOS score at T1 and T3 evaluations. We found statistically significant differences in the DACTOS score between clinical responder and non-responder groups (P < 0.001) and between clinical remission and non-remission groups (P < 0.001)., Conclusion: The DACTOS score performs well in real-life clinical settings in terms of sensitivity to change and correlations with clinical features in PsA dactylitis., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To assess the effectiveness of steroid injection (local treatment, LT) into the digital flexor tendon sheath of dactylitis in psoriatic arthritis (PsA) patients as compared with systemic treatment (ST)., Methods: Forty-six PsA patients with a total of 73 dactylitic fingers were assessed in an observational, multicentre, prospective study by the Leeds Dactylitis Index basic (LDI-b) score and evaluated for local pain (visual analogue scale-VAS pain) and functional impairment (VAS-FI). Steroid injection was proposed to all patients. Patients refusing LT were treated with oral NSAIDs. Both the groups continued baseline csDMARDs and/or corticosteroids therapy. The clinical outcomes were measured at baseline, 1 month (T1) and 3 months (T3)., Results: The reduction of VAS-pain, VAS-FI and LDI-b values was statistically significant higher in the LT group (24 patients, 38 dactylitic fingers) as compared with the ST group (22 patients, 35 dactylitic fingers), both at T1 (p < 0.001, p < 0.001 and p = 0.008, respectively) and at T3 (p < 0.001, p < 0.001 and p < 0.001, respectively). A clinically meaningful treatment response (defined as a contemporary reduction of at least 5 points in VAS-pain and VAS-FI or as values of VAS-pain and VAS-FI were both ≤ 2) was observed at T1 in 33 (87%) digits in LT group and in 6 (17%) digits in ST group (p < 0.001). At T3, clinical response improved significantly in both the groups, with significant difference (94% vs 31%, p < 0.001)., Conclusions: For the first time, we show the effectiveness of steroid injection into the digital flexor tendon sheath in improving clinical aspects of hand psoriatic dactylitis. Key Points • Therapy with steroid injection (local treatment, LT), into the digital flexor tendon sheath for the treatment of active dactylitis in psoriatic arthritis patients, is more effective when compared with systemic treatment (ST) alone. • The reduction of VAS-pain, VAS-functional impairment (VAS-FI) and Leeds Dactylitis Index basic values was statistically significant higher in the LT group as compared with the ST group, both at T1and at T3. • A clinically meaningful response was observed at T1 in 87% of digits of patients treated with steroid injection and in 17% of digits of the systemic treatment group (p < 0.001). At T3, clinical response improved significantly in both the groups, with significant difference. • For the first time, findings from this study show that the use of steroid injections into the digital flexor tendon sheath for psoriatic dactylitis could be an effective and safe first-line therapy for psoriatic dactylitis.

Objectives: The aim of this study was to explore the link between specific sonographic findings and Leeds Dactylitis Index basic (LDI-b) score in psoriatic arthritis (PsA) patients with hand dactylitis., Methods: Ninety-one hand dactylitis were evaluated in a multicentre study for the presence of pain, functional limitation and tenderness (2-point scale) and LDI-b score. Dactylitic fingers were investigated using high-frequency US in grey scale (GS) and power Doppler (PD). According to median LDI-b score value of 12, fingers were then divided into two groups and categorised into quartiles on the basis of the value of ratio of circumference., Results: Dactylitic fingers with a LDI-b score >12 showed a significantly higher prevalence of GS flexor tenosynovitis (p=0.015), PD flexor tenosynovitis (p=0.001) and soft tissue oedema (p=0.004), when compared with those with those with LDI-b score <12. GS synovitis at proximal interphalangeal (PIP) level (p=0.003) showed more frequent in dactylitic fingers with a LDI-b score <12, than those with a higher LDI-b value. Fingers in the fourth quartile showed a significantly higher prevalence of GS flexor tenosynovitis of grade ≥2 (p=0.046) and joint synovitis of grade ≥2 at PIP level (p=0.028)., Conclusions: We found that high values of LDI are associated with US flexor tenosynovitis and soft tissue oedema in PsA dactylitis. Results suggest a potential role of PIP joint synovitis in the genesis of hand digital swelling and of extra-articular structures alterations in determining the LDI score.

Objectives: Dactylitis is one of the most typical features of psoriatic arthritis (PsA), with a high lifetime prevalence and inclusion in PsA clinical indices. Musculoskeletal ultrasonography (Msk-US) can readily detect inflammatory involvement of finger anatomical structures particular to dactylitis and monitor therapeutic effects. In this study, we aim to identify the characteristic lesions in PsA dactylitis of the hands, assess the reliability of Msk-US in scoring those lesions and develop a DACTylitis glObal Sonographic (DACTOS) score., Methods: After a systematic literature review on the use of Msk-US in PsA dactylitis, 12 rheumatologists participated in a three-round Delphi procedure and consensus meeting to agree on the sonographic elementary lesions characterising dactylitis and on the composition of a global sonographic score. Then, a web-based and a patient-based intra-rater and inter-rater reliability exercise was performed to assess those lesions included in the score., Results: DACTOS score was obtained by summing the scores of each lesion selected in the Delphi survey: subcutaneous soft tissue oedema, flexor tenosynovitis, peritendon extensor inflammation and synovitis. The DACTOS score ranges from 0 to 25. In the reliability exercises, we obtained moderate-to-excellent agreement for the sonographic lesions included in the score., Conclusions: The novel DACTOS score is a reliable measure to interpret the multiple characteristic sonographic features of dactylitis. The DACTOS score provides a useful global analysis of dactylitis of the hand and can represent a support to clinical diagnosis as well as a useful tool for the management and research in patients with PsA with dactylitis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The digital accessory pulleys are highly mechanically stressed mini-entheses that are thickened in patients with a history of PsA-related dactylits. This study explored whether these pulleys are involved in PsA dactylitis as assessed by intra-pulley US power Doppler changes., Methods: Fifty-eight PsA patients with dactylitis had US of the second to fourth digits for pulleys of the dactylitic and contralateral digits. The Leeds Dactylometer was used for thickness measurement. The presence of digital pain, tenderness, and swelling in the dactylitis finger and in the contralateral side was evaluated., Results: We recruited 34 patients with acute and 24 patients with chronic dactylitis, 45/58 (77%) of which had tenderness on clinical assessment. Intra-pulley power Doppler was more frequently found in the dactylitic digits compared with contralateral sides and linked to A1, A2 and A4 pulleys thickening [power Doppler signals in A1 pulley (51%), A2 (22%) and A4 (12%) in dactylitic digit; compared with 1 A1, A2 and A4 pulleys each in the contralateral side (1.7%)]. Almost all cases had peri-tendinous oedema, and 82.6% of dactylitic digits had flexor tenosynovitis with power Doppler signals in 65.2% of flexor tendons., Conclusion: Despite their small size and relatively avascular, the accessory pulleys exhibit power Doppler change in active Psoriatic dactylitis, supporting a pivotal role in dactylitis-related tenosynovitis and extra-tendinous disease., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Despite diffuse digital swelling, dactylitis may sometimes be asymptomatic. The objective of this study was to compare the clinical and ultrasonographic features of symptomatic with asymptomatic psoriatic arthritis (PsA) dactylitis., Methods: One hundred and twenty-five hand dactylitis were evaluated in a multicenter cross-sectional study for the presence of pain, subjective functional limitation, and tenderness (4-points scale) with the calculation of a Leeds Dactylitis Index (LDI) score. Fingers were subsequently investigated using high-frequency ultrasound (US) both in gray-scale (GS) and power Doppler (PD), for the presence and grading of flexor tenosynovitis, soft tissue edema, subcutaneous PD signal (PDUS), extensor tendon involvement, and joints synovitis. Clinical and US characteristics of symptomatic dactylitic fingers were compared with the asymptomatic dactylitic ones., Results: Symptomatic fingers (n = 80) had a significantly lower dactylitis duration compared to asymptomatic fingers (n = 36) (p < 0.001). Values of LDI, patient VAS-pain, and VAS-functional score were significantly higher in fingers with symptomatic dactylitis (p < 0.001 and p = 0.010, respectively). Symptomatic dactylitis had a higher prevalence of flexor tenosynovitis of grade > 2, soft tissue edema and subcutaneous PDUS signal (p < 0.001). Asymptomatic dactylitis showed a greater prevalence of joint synovitis (both in GS and in PD) than symptomatic dactylitis (p < 0.001)., Conclusions: Digital tenderness and pain are linked to US tenosynovitis of grade > 2 and extra synovial abnormalities and conversely asymptomatic dactylitis is associated with joint-based synovitis.Key Points• Digital tenderness and local pain in psoriatic arthritis dactylitis are strongly associated with flexor tenosynovitis of grade> 2, soft tissue edema, and subcutaneous PD signal.• In psoriatic arthritis, asymptomatic dactylitis showed a greater prevalence of joint synovitis than symptomatic dactylitis.• In psoriatic arthritis, ultrasound inflammatory abnormalities are present in about 70% of cold dactylitis which is linked for disease chronicity.• In psoriatic arthritis, the flexor tendon and adjacent soft tissues play a significant role in symptomatic dactylitis.

Objective: To use ultrasonography to study whether the duration of psoriatic dactylitis was associated with different patterns of extracapsular and synovial-based involvement., Methods: One hundred cases of hand dactylitis from 85 patients with psoriatic arthritis (PsA) were consecutively enrolled in a multicenter cross-sectional study and divided into 2 groups according to dactylitis duration (shorter or longer than the median: 20 weeks). All dactylitis fingers were investigated using high-frequency ultrasound both in greyscale (GS) and power Doppler (PD), evaluating the presence of flexor tenosynovitis, soft tissue edema, subcutaneous PD signal (PDS), extensor tendon involvement, and joint synovitis., Results: Cases with a shorter dactylitis duration (< 20 weeks) had a significantly higher prevalence of GS flexor tenosynovitis of grade > 2, PD flexor tenosynovitis, soft tissue edema, and subcutaneous PDS (p = 0.001, p < 0.001, p < 0.05, and p = 0.001, respectively). However, the presence of synovitis in GS and PD mode (in both cases at proximal interphalangeal level) was more frequent in patients with longer dactylitis duration (p < 0.001). When detected in the chronic form, flexor tenosynovitis was grade 2 or lower., Conclusion: In a large cohort of PsA hand dactylitis, we found a predominant extracapsular inflammation (flexor tenosynovitis and soft tissue edema) in early cases and a high prevalence of joint synovitis at proximal interphalangeal level in the chronic form. However, longitudinal imaging studies are needed to clarify these aspects.

Aim: To define and score finger soft tissue oedema in psoriatic dactylitis by ultrasound., Material and Methods: A systematic literature review (SLR) on ultrasound-detected finger soft tissue oedema was performed. Subsequently, based on the SLR, a Delphi survey was developed and circulated among a group of 13 expert sonographers, in order to obtain agreement on detection, definition and scoring of finger oedema by B-mode and power Doppler ultrasound. Agreement was considered achieved when each statement was approved by >75% of participants., Results: At the first Delphi round, 91 % agreement was obtained for the scanning technique to adopt, including the most appropriate area to evaluate. At the second round, 76% agreement was achieved on the definition of soft tissue finger oedema. At the third round, 76% agreement was obtained for B-mode and power Doppler scores. The volar aspect of the finger and comparisons with the contralateral side were agreed to be the most appropriate in terms of scanning technique. Agreed ultrasound definition of finger soft tissue oedema was "abnormal hypoechoic/anechoic areas, diffused or localized within the subcutaneous tissue between the epidermidis and the tendon-related anatomic structures (i.e. flexor tendon sheath, peritenonium, tendon pulleys), with local thickening, with or without local abnormal Doppler signal, visualised in two perpendicular planes and not evident on the contralateral side". Semiquantitative (0-3) scores for both B-mode and power Doppler were agreed to be the most appropriate to be used., Conclusion: Our work produced, for the first time, technical indications, definition and scoring for the ultrasound assessment of soft tissue oedema in psoriatic dactylitis.

Objective: The purpose of the ULISSE study was to evaluate the prevalence of clinical and ultrasonographic (US) entheseal involvement in patients with psoriatic arthritis (PsA), psoriasis, and fibromyalgia syndrome (FMS)., Methods: In this cross-sectional multicenter study, patients with PsA and psoriasis (not taking systemic therapy) and FMS underwent a clinical evaluation of the entheses, and a B-mode and power Doppler examination of 6 pairs of entheses., Results: The study analyzed 140 patients with PsA, 51 with psoriasis, and 51 with FMS. Clinical and US examinations were performed in 1960 and 1680 entheses in the PsA group, and 714 and 612 entheses both in the psoriasis group and in the FMS group. In both per-patient and per-enthesis evaluation, the frequency of entheseal tenderness was higher in patients with FMS (92% of the patients and 46% of the entheses, compared with 66%/23% in the PsA group and 59%/18% in the psoriasis group). With US examination, signs of entheseal involvement were more frequent in both the per-patient and per-enthesis evaluation in PsA and psoriasis (about 90% of patients in both the PsA and psoriasis groups and 75% of patients in the FMS group had at least 1 site affected, and 54%, 41%, and 27% of the pairs of entheses in, respectively, PsA, psoriasis, and FMS patients showed at least 1 enthesis involved)., Conclusion: The ULISSE study indicated that enthesitis is a common feature in patients with PsA, those with psoriasis, and in those with FMS if only clinical examination is used. US entheseal assessment showed findings more consistent with the 3 disorders.

Objectives: To explore the link between ultrasonographic features of dactylitis in psoriatic arthritis (PsA) and symptoms, digital tenderness and duration of dactylitis., Methods: Forty-eight cases of PsA dactylitis were investigated using high frequency ultrasound (US) both in grey scale (GS) and Power Doppler (PD), evaluating the presence and the degree of flexor tenosynovitis, peri-tendinous oedema, subcutaneous PD, extensor tendon involvement, GS synovitis and intra-articular PD signal (PDS) of the involved digits. Patients were compared according to the presence of local pain and digital tenderness, the duration of dactylitis and the concomitant treatment., Results: The presence of pain/tenderness was positively associated with US GS flexor tenosynovitis of grade > 2 (p < 0.001), PD-flexor tenosynovitis (p < 0.001), peri-tendinous oedema (p < 0.001) and subcutaneous PDS (p < 0.001); moreover, it was negatively associated with GS synovitis (p < 0.001) and intra-articular PD (p < 0.001). The same positive and negative association with US findings were found comparing patients with duration of dactylitis shorter or longer than the median (24 weeks) (p < 0.001 for all comparisons)., Conclusions: Pain and digital tenderness are linked to dactylitis duration and earlier lesions are associated with extra synovial inflammatory changes. These findings suggest a hitherto unappreciated extra synovial basis for symptoms in PsA dactylitis.

Objectives: To determine whether a detailed sonographic evaluation of the hand flexor tendon compartment could help differentiate between psoriatic arthritis (PsA) and rheumatoid arthritis (RA)., Methods: Thirty-seven patients with PsA, 47 with RA and 10 healthy controls (HC) had flexor tendon (FT) compartment imaging of the dominant hand 2nd to 4th tendons using grey scale (GS) and power Doppler (PD) ultrasound (US) with evaluation for tenosynovitis, peri-tendinous lesions, soft tissue oedema and bony changes at FT insertions. 24/37 PsA and 19/47 RA cases had morning stiffness and 19/37 PsA and 10/47 RA had swollen and/or tender fingers., Results: Tenosynovitis was more common in PsA (25/37) despite higher DAS28 scores in RA (25/37 versus 10/45; p<0.001). Peri-tendinous dermal soft tissue oedema with associated PD signal was evident in one third of PsA patients but in no RA patients (p=0.003). Flexor tendon enthesopathy including new bone formation at the insertional site was significantly more common in PsA (p=0.001). Considering a total inflammatory score per patient summing up the three modifications of the flexor tendon (tenosynovitis, peri-tendinous oedema and insertional enthesophytes) the difference between PsA and RA remained statistically significant (p<0.001)., Conclusions: Our study adds to the growing body of literature that high resolution US of the hand FT compartment may help differentiate between RA and PsA, which needs assessment in the diagnostic setting.

Objectives: Skin and joint involvement in psoriasis (PsO) and psoriatic arthritis (PsA) are thought to relate to the so-called Koebner response. Given that dactylitis is non-randomly distributed in the digits, this study tested the hypothesis that the accessory pulleys linked to the flexor tendons were thickened in PsA and thus exhibited koebnerisation., Methods: Ninety-six subjects (27 PsA, 27 rheumatoid arthritis (RA), 23 PsO and 19 healthy controls (HCs)) were enrolled. The A1, A2 and A4 pulley thickness was measured using a high-resolution probe (22 MHz). All patients were in remission or low disease activity with current dactylitis being excluded., Results: Within 864 pulleys investigated, patients with PsA had thicker pulleys in every digit compared with both RA (P<0.001 and P=0.003) and HCs (P<0.001). RA and PsO groups had some pulleys in some digits thicker than HCs whereas some others were comparable. The second digit A1 pulley thickness was higher in patients with PsA with previous dactylitis (P=0.020). More pulleys were thickened in the PsA group (165/243, 68%) than RA (41/243, 17%; P<0.001) and HCs (13/171, 7.6%; P<0.001)., Conclusions: In established PsA, the accessory pulleys are thickened compared with RA, PsO or HCs and especially in subjects with a history of dactylitis. These findings implicate the involvement of pulleys in PsA-related tenosynovitis and dactylitis supporting the idea of deep koebnerisation in dactylitis and sites of high physical stress., Competing Interests: Competing interests: DMG received grants and/or honoraria from Abbvie, Celgene and Janssen. SZA received grants and/or honoraria from Abbvie, Novartis, UCB, Sanofi and Pfizer., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

To investigate the genetic variability of IL-17A, IL17-RA, IL-23A and IL-23R genes on an in-depth phenotypically characterized northern Italian Psoriatic arthritis (PsA) case-control cohort, in search for associations specific to different PsA clinical sub-phenotypes. We examined 118 patients with PsA according to CASPAR criteria (mean age 57 ± 13, female 38.4 %, mean disease duration 13.9 ± 8.6 years, peripheral disease 83.8 %, axial manifestations 34.5 %, radiological erosive disease 49 %) compared with 248 controls of the same ethnic origin matched for age and sex. The presence of axial disease was defined by the clinical axial involvement and/or the presence of radiological alteration consistent with spondyloarthropathy according to New York criteria. The presence of peripheral disease (arthritis and/or enthesitis) was defined only on clinical basis. A total of 40 SNPs, mapping within the genes mentioned above, were genotyped in both groups and used to perform association analyses by subdividing the PsA sample into subgroups according to different clinical manifestations on the basis of axial and peripheral involvements. No differences between patients and controls were found in the distribution of the IL-17A, IL17-RA, IL-23A and IL-23R genes allelic variants. Comparing patients with axial disease versus those without, we found that axial manifestations were significantly associated with the presence of IL-23R rs12401432 GG homozygosity (26.8 % vs. 5.3 %, p corr = 0.019, OR 2.63 [95 % CI 1.13-6.16]). No differences in distribution of the allelic variants were found comparing patients with versus those without peripheral disease or patients with versus without radiological peripheral erosions. In PA patients of northern Italian origin, IL-17A, IL17-RA, IL-23A and IL-23R genes allelic variants are not associated with disease susceptibility. However, a strong association with the IL-23RA rs12401432 GG genotype is associated with axial involvement of the disease.

Open prospective studies and randomized controlled trials (RCT) have shown the short-term efficacy of adalimumab (ADA) in psoriatic arthritis (PsA) and psoriasis. ADA effectively treated all varied musculoskeletal manifestations characteristic of PsA, including peripheral arthritis, spinal disease, enthesitis, and dactylitis. ADA significantly inhibited structural changes on radiographs, lessened disability, and improved quality of life in patients with active PsA. One study showed the efficacy of 24-week ADA therapy on bone marrow edema and erosions, as measured by magnetic resonance imaging. The clinical and radiographic efficacy of ADA demonstrated during short-term treatment was sustained during longterm treatment. ADA was generally well tolerated and its safety profile was similar to that reported in studies of ADA in rheumatoid arthritis. Overall, ADA has a favorable risk-benefit profile in PsA. The combination of ADA and cyclosporine seems to be more effective than ADA monotherapy in patients with active PsA and inadequate response to methotrexate; however, this observation must be confirmed in RCT.

Cyclosporin A (CsA) has been proved to be effective in the treatment of severe cutaneous psoriasis and psoriatic arthritis (PsA). In psoriasis, CsA therapy can be used as: (1) intermittent short-course therapy; (2) continuous long-term therapy; (3) crisis intervention; and (4) a combination of sequential and rotational therapy. Several open prospective studies have shown the short-term efficacy of CsA in PsA. While there were no randomized controlled trials (RCT) comparing CsA to placebo, 3 published controlled trials compared CsA to other disease modifying antirheumatic drugs (DMARD). These studies support the efficacy of CsA in patients with PsA and peripheral arthritis. However, no conclusions can be drawn on the efficacy of CsA for dactylitis and axial disease. Long-term studies have shown the persistent efficacy and safety of CsA in PsA. The beneficial effects of CsA in angiogenesis-related diseases such as PsA and cutaneous psoriasis may also be mediated by its ability to block the angiogenic effects induced by vascular endothelial growth factor.

Objective: To evaluate the efficacy and safety of the anti-tumor necrosis factor alpha monoclonal antibody infliximab in the treatment of active psoriatic arthritis (PsA) resistant to previous symptom modifying antirheumatic drugs., Methods: Sixteen patients with peripheral active PsA with at least 6 months of methotrexate (MTX) therapy at a stable dosage were treated with infliximab administered at a dosage of 3 mg/kg at 0, 2, 6, 14, 22, and 30 weeks while continuing to receive MTX. Intake of nonsteroidal antiinflammatory drugs and corticosteroids was stable during the study period. Standard clinical assessments, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP) were determined at baseline and at weeks 2, 6, 14, 22, and 30., Results: By week 2, significant improvements were registered in the number of swollen and tender joints, visual analog scale for pain, patient and doctor global disease assessment scores, Health Assessment Questionnaire, Dougados functional index, ESR, and CRP. At week 30, the percentages of patients satisfying American College of Rheumatology (ACR) 20%, ACR 50%, and ACR 70% response rates were 64%, 57%, and 57%, respectively. In the 3 patients with active axial disease, spinal stiffness and pain resolved almost completely at week 2 and the improvement did not diminish over time. Psoriasis Area Severity Index improvement was 37% at week 2 and 86% at week 30. No patients dropped out for treatment failure. Side effects were observed in 4 of 16 patients, 2 of whom suspended the therapy due to a severe allergic reaction., Conclusion: In patients with resistant PsA, infliximab is an effective therapy without major side effects.

Objective: To compare the efficacy and tolerability of cyclosporine (CSA) with that of symptomatic therapy (ST) alone and sulfasalazine (SSZ) in the treatment of psoriatic arthritis (PsA)., Methods: Twelve rheumatology centers recruited 99 patients with active PsA in a 24 week, prospective, randomized, open, controlled study. The patients were treated with CSA (3 mg/kg/day) or SSZ (2,000 mg/day) plus ST, or ST alone (nonsteroidal antiinflammatory drugs, analgesics, and/or prednisone < or = 5 mg/day). The primary endpoint was the 6 month change in pain. Analyses were on the basis of the intention-to-treat principle., Results: In comparison with both SSZ and ST, there was a statistically significant difference in favor of CSA in terms of the mean changes in the pain score (p < 0.05), which was considered the primary response variable. A significant decrease in favor of CSA versus ST alone was also observed for swollen joint count (p = 0.05), tender joint count (p = 0.01), joint/pain tenderness score (p = 0.002), patient and physician global assessment by at least one point (p = 0.04 and 0.01, respectively), total Arthritis Impact Measurement Scale score (p = 0.002), and spondylitis functional index (p = 0.002). There was a statistically significant difference in the ACR 50% and ACR 70% response rates between the CSA and ST groups (p = 0.02, 0.05). Comparing the SSZ and ST alone groups, only the spondylitis functional index decreased significantly in the SSZ treated patients (p = 0.03). The Psoriasis Area and Severity Index was significantly lower in the CSA than in the ST and SSZ groups (p = 0.0001 and 0.01, respectively). Decrease in erythrocyte sedimentation rate was significant only in the SSZ versus the ST group (p = 0.02), whereas reduction in C-reactive protein was significant in the CSA treated patients compared with the ST group (p = 0.006). The most common adverse event in the CSA group was mild, reversible kidney dysfunction., Conclusion: The results of this open trial confirm that CSA is well tolerated by patients with PsA and suggest that it is more efficacious than ST or SSZ.

Objective: To evaluate the levels of serum chemokines in patients with psoriatic arthritis (PsA) before and during cyclosporin A (CyA) treatment., Methods: Sixteen outpatients with active PsA were followed for 6 months during low dosage CyA treatment. Serum chemokines of the C-X-C and C-C groups were determined by ELISA at the baseline. Serum RANTES levels were measured at 2 month intervals for 6 months. Serum chemokine levels were related with clinical and laboratory disease activity variables., Results: Serum interleukin 8 and macrophage inflammatory protein 1alpha levels were undetectable at baseline. Mean serum growth related gene product-alpha and monocyte chemoattractant protein 1 values were reduced and serum RANTES were elevated compared to controls. CyA treatment did not change serum RANTES levels. Patients with PsA with persistently normal serum RANTES levels (4 patients) had a more favorable clinical and laboratory response to CyA compared to patients with persistently high serum levels (6 patients)., Conclusion: Serum RANTES levels are higher in patients with PsA than in a control population. CyA treatment does not change RANTES values. Patients with PsA with persistently normal RANTES levels have a better response to CyA treatment.

Aims of the study to evaluate the radiologically detected progression of joint damage in patients with psoriatic arthritis (PA) treated with cyclosporin-A (CsA) and to look for clinical and/or immunological parameters that might predict outcome. Twenty-four out-patients suffering from active PA entered a 2-year open prospective study on low-dose CsA (starting dose 3 mg/kg/day). Fifteen patients completed the study. Plain radiographs of hands and feet at study entry and at the end of follow-up were compared for the number of eroded joints. Serum-soluble IL-2 receptor (sIL-2R) levels were available in 13/15 patients before CsA therapy, after 6 months and after 2 years. The mean number of eroded joints per patient increased significantly during the study period (P = 0.017). Nine patients had less than two new eroded joints (responders) while the remaining six patients had five or more new eroded joints (non-responders). Serum sIL-2R levels were in the normal range after 6 months and 2 years of CsA treatment in all the responder patients and were above the 95th percentile of the control population in the six non-responders. We did not find any other demographical, clinical, radiological or laboratory parameter predictive of outcome in conclusion. (1) CsA seems to be able to control the 2-year progression of the radiologically measured damage in peripheral joints in 60% of PA patients. (2) A normal serum sIL-2R level after 6 months of therapy seems to have a prognostic value for a good outcome in PA patients treated with CsA.

Objective: To identify isolated peripheral enthesitis and/or dactylitis as a subset of psoriatic arthritis (PsA) and to define the clinical characteristics of these patients., Methods: We examined 401 unselected patients with PsA seen in 3 Italian rheumatological centers over a 6 month period. The diagnosis of PsA was based upon the clinical experience of a rheumatologist. The clinical features of patients with PsA were assessed by clinical examination and review of the patients' charts, evaluating the presence of peripheral arthritis, spinal involvement, dactylitis, and enthesitis. A series of 483 rheumatological patients without psoriasis and spondyloarthropathy (European Spondylarthropathy Study Group criteria) seen consecutively in a one month period constituted the control group., Results: 14 patients (3.5%) presented isolated episodes of peripheral enthesitis and/or dactylitis. No patient developed peripheral arthritis and/or axial involvement during the followup period (median 30 mo; range 3-72 mo). 10/14 patients (71%) presented at least one episode of finger and/or toe dactylitis. 5 of these 10 patients (50%) had additional episodes of peripheral enthesitis (Achilles tendinitis, plantar fasciitis, and posterior tibial tendinitis). Episodes of Achilles tendinitis and/or plantar fasciitis were present in 8/14 patients (57%). 3 of these 8 patients (37%) had associated peripheral enthesitis in other sites as well: lateral epicondyle, insertion of the patella tendon into the inferior pole of the patella, femoral quadriceps, and posterior tibial tendons. An additional case had posterior tibial tendinitis and 2 episodes of toe dactylitis. None of these 14 cases presented radiological evidence of sacroiliitis and only one of the 13 typed was HLA-B27 positive. 12 patients (2.4%) of the control group had episodes of peripheral enthesitis (11 plantar fasciitis and one Achilles tendinitis). No patient had episodes of dactylitis. The frequency of isolated Achilles tendinitis and/or dactylitis was significantly higher in patients with PsA compared to controls (3.5 vs 0.2%; p = 0.001)., Conclusion: In some patients PsA can occur only with peripheral enthesitis, particularly Achilles tendinitis, and/or dactylitis. These patients may represent a subset of PsA, not defined by Moll and Wright and spondyloarthritis classification criteria, and poorly recognized in the studies on PsA.

Objective: To evaluate the prevalence of psoriatic arthritis (PsA) in Italian patients with psoriasis and to compare the Moll and Wright criteria, the European Spondylarthropathy Study Group (ESSG) criteria, and Amor criteria when applied to this patient population., Methods: We examined 205 unselected patients with psoriasis. The diagnosis of PsA was based upon the clinical experience of a rheumatologist. After, we tested these classification criteria. HLA class I and II antigens were also analyzed., Results: Thirty-six percent (75) of psoriatic patients were considered by a clinical expert to have PsA. Moll and Wright criteria identified 46 patients (22%) with PsA; 49 patients (24%) were identified by ESSG criteria and Amor criteria; 12 patients identified by Amor criteria but not by ESSG criteria presented enthesitis or dactylitis; 10 patients identified by ESSG but not by Amor criteria had peripheral synovitis. In patients with peripheral arthritis and psoriasis, the evaluation of NSAID response was critical to fulfilling Amor criteria. However, it was not easy to retrospectively evaluate NSAID response using these criteria. The sensitivity was low for each of the 3 classification criteria (from 61 to 65%), whereas the specificity was high (from 99 to 100%)., Conclusion: Our study confirms a high prevalence of PsA among an unselected population of Italian patients with psoriasis. Our data reveal the inadequacy of the existing criteria for PsA, including the ESSG criteria and Amor criteria for the classification of spondyloarthropathy.

Twelve patients with psoriatic arthritis (PsA) and very active articular disease resistant to conventional second line therapy entered into a 6-month open study of cyclosporine A (CsA) at a starting dosage of 3 mg/kg/day. Comparisons of phenotypic characteristics of lymphocytes and response to mitogens of peripheral blood mononuclear cells (PBMC) were made between these patients with PsA before CsA therapy, 7 patients without prior 2nd line therapy, 14 untreated patients with psoriasis alone, and 61 healthy controls. We confirmed a significant reduction of the basal percentage of CD8+ cells and an increase in the CD4/CD8 ratio in patients with PsA before CsA therapy compared to controls. These abnormalities were not present in patients with PsA without prior 2nd line therapy and in patients with psoriasis alone. Peripheral blood activated T cells (CD3+, HLA-DR+), natural killer (NK) (CD3-, CD16+ and/or CD56+), total B and CD5+ B cells were decreased only in patients with PsA before CsA therapy. The reduction of non-MHC restricted cytotoxicity T (CD3+, CD16+ and/or CD56+) was observed in all the 3 groups of patients compared to controls. After the 6 months of CsA therapy we observed a significant increase of CD3+, HLA-DR+, CD3+, CD16+ and/or CD56+, total B, and CD20+, CD5+ cells in the 11 patients with PsA compared to pretreatment values. Contrary to azathioprine, CsA does not impair the NK cell population which has a protective role against cancer and viral infections.

Twelve patients with psoriatic arthritis (PsA) were treated with low doses of cyclosporine A (CsA) (the initial dose was 3 mg/kg daily) and were entered into an open 6-month study. At the end of the study arthritis was improved in 7 patients (number of patients achieving a 50% or more reduction in the number of swollen or tender joints) and unchanged in 4 patients. Cutaneous psoriasis also improved significantly as shown by psoriasis area and severity index score. Only one patient withdrew from the study after one month because of severe nephrotoxicity. Serum creatinine fell to baseline value 6 weeks after the discontinuation of CsA. Three patients had minor side effects. CsA maintained articular improvement also in the 9 patients who are still taking this drug (mean duration of therapy of 12 +/- 0.8 months). There was no significant reduction of erythrocyte sedimentation rate during the study period. We assayed levels of soluble interleukin 2 receptors (sIL-2R) in serial serum samples obtained from 10 patients during the study period. Concentrations of sIL-2R were significantly increased in patients with PsA compared to controls. In 6 responder patients we observed a parallel decrease in joint pain/tenderness score and serum sIL-2R values. This finding was not observed in 4 nonresponders. Our results suggest that low dose CsA is a short term effective and safe therapy in patients with PsA and that serial sIL-2R levels are a useful means of measuring changes in disease activity.

The radiological changes of the cervical spine were evaluated in 57 patients with psoriatic arthritis and were correlated with clinical, radiological, and immunogenetic features of the disease. Forty patients (70%) showed radiological evidence of the cervical spine being affected by the disease. Two patterns of cervical spine abnormalities were noted. Fifteen patients (26%) had erosive and/or subluxing cervical rheumatoid like lesions; 25 patients (44%) had a more frequently reported pattern similar to ankylosing spondylitis. Although subaxial subluxations were the most frequently observed cervical abnormalities (53%) in the inflammatory subgroup, none of the patients studied had cord compression. Ankylosing cervical spine disease was the only form of axial involvement in nine (36%) of 25 patients with the ankylosing form of psoriatic arthritis. All of these patients had peripheral disease and were B27 negative. Predictors of cervical spine disease patterns were considered using clinical, demographic, and radiological features and HLA antigens. The results of a multivariate analysis showed that the best predictors of inflammatory cervical spine disease are the presence of HLA-B39 and HLA-DR4 antigens, radiocarpal erosions, and the absence of the HLA-DR5 antigen.

The frequencies of HLA antigens were studied in 101 Italian patients with psoriatic arthritis. The total group showed a significant increase in frequency of A1 and B38, and a reduction of B5 when compared to healthy controls. No association between DR and/or DQw antigens and PA were demonstrated. The comparisons between the clinical subgroups and normal controls revealed a significant association of B38 with asymmetric peripheral arthritis, B27 and B39 with spondylitis (with or without peripheral involvement). When intergroup comparison were made, the patients with spondylitis had an increase in frequency of B27 and DQw3 as compared to those with symmetric and asymmetric peripheral disease. DR4 and DRw53 were associated with earlier age of onset of arthritis. There were also significant associations between DQw3 and severe disease, and between A9, B5 and presence of erosions and joint space narrowing. No association with DR4 was showed in a subgroup of patients with symmetric polyarthritis without DIP involvement.