Olga Kaloudi

Digital ulcers in scleroderma: staging, characteristics and sub-setting through observation of 1614 digital lesions

OBJECTIVE To evaluate in SSc, the frequency of digital lesions and the morphology, characteristics, natural course and time to healing of 1614 digital ulcers (DUs). METHODS One hundred SSc patients were followed up for 4 years. In the first step, the digital lesions were observed and classified at the time of presentation [digital pitting scar (DPS); DU; calcinosis; gangrene]. In the second step, DUs were divided into subsets according to their origin and main features. In the third step, the time to healing was recorded for each DU and the influence of DU main characteristics on time to healing was also evaluated. RESULTS In the first step, 1614 digital lesions were observed: DPS, 712 (44.1%) lesions; DU, 785 (48.6%); calcinosis, 110 (6.8%); and gangrene, 7 (0.8%). In the second step, DUs were subsetted as follows: DU developed on DPS (8.8%), pure DU; DU developed on calcinosis (60%); DU derived from gangrene. In the third step, the mean time to healing was 25.6 (15.6) days in DPS, 76.2 (64) days in pure DU, 93.6 (59.2) days in calcinosis ulcers and 281.1 (263.3) in gangrene. CONCLUSIONS In SSc, digital lesions are represented by DPS, DU, calcinosis and gangrene, and provide an evidence-based DU subsetting according to their origin and main characteristics. Subsetting may be helpful for a precise DU evaluation and staging, and in randomized controlled trials for a precise identification of those DUs that are to be included in therapeutic studies.

Psoriatic arthritis: a systematic review.

Psoriatic arthritis is an inflammatory rheumatic disorder of unknown etiology occurring in patients with psoriasis. The Classification Criteria for Psoriatic Arthritis study group has recently developed a validated set of classification criteria for psoriatic arthritis with a sensitivity of 91.4% and a specificity of 98.7%. Three main clinical patterns have been identified: oligoarticular (≤ 4 involved joints) or polyarticular (≥ 5 involved joints) peripheral disease and axial disease with or without associated peripheral arthritis. In this context distal interphalangeal arthritis and arthritis mutilans may occur. According to other reports, also in our centre, asymmetric oligoarthritis is the most frequent pattern at onset. Axial disease has been estimated between 5% and 36% of patients. It is characterized by an irregular involvement of the axial skeleton with a predilection for the cervical spine. Recurrent episodes of enthesitis and dactylitis represent a hallmark of psoriatic arthritis. In around 20% of cases distal extremity swelling with pitting edema of the hands or feet is observed. Unilateral acute iridocyclitis, usually recurrent in alternate fashion, is the most frequent extra‐articular manifestation, and accelerated atherosclerosis is the prominent comorbidity. The clinical course of peripheral and axial psoriatic arthritis is usually less severe than rheumatoid arthritis and ankylosing spondylitis, respectively. Local corticosteroid injections and non‐steroidal anti‐inflammatory drugs are recommended in milder forms. Sulphasalazine and methotrexate are effective in peripheral psoriatic arthritis. Recent studies have provided evidence on the efficacy of anti‐tumor necrosis factor‐α drugs to control symptoms and to slow or arrest radiological disease progression.

Ultrasound Elastography Assessment of Skin Involvement in Systemic Sclerosis: Lights and Shadows

Objective. To assess skin elasticity in systemic sclerosis (SSc) by using a new imaging modality, ultrasound elastography (UE). Methods. Our study included 18 consecutive patients with SSc and 15 healthy controls. Modified Rodnan skin score, physical examination, and assessment of organ involvement were performed. UE was carried out on the middle forearm and on the fingers of the dominant arm. The echo signals recorded in real time during freehand operations of probe compression and relaxation produced images representing tissue elasticity, consisting of translucent colored bands superimposed on the B-mode ultrasonographic images. The color scale varied within a large band spectrum from red, indicative of soft and highly elastic tissue, to blue, which denoted hard and barely elastic tissue. Results. On the forearm of all patients, UE showed a homogeneous blue area corresponding to the dermis visualized in a B-mode ultrasonographic image; in controls, a blue pattern was never detected and a predominance of green with sporadic areas of pale blue was observed. At sequential evaluations, UE of fingers produced inconstant and changeable colored areas. Conclusion. The imaging pattern observed in the forearm of patients with SSc may represent the reduction of strain in the dermis due to loss of elasticity. The variable pattern obtained by finger evaluation demonstrated that UE can assess skin involvement in SSc only in those areas where the dermis is known to be thicker and where the bone hyperreflection is minimal. Further studies are needed to confirm our results and determine the validity of this new imaging modality.

High frequency ultrasound measurement of digital dermal thickness in systemic sclerosis

Background Currently, assessment of dermal thickness in systemic sclerosis (SSc) is performed by palpation and assessment using the modified Rodnan skin score (mRSS). Objective To verify whether high frequency ultrasound (US) may be a reliable and a reproducible method to measure digital dermal thickness. Methods In 70 patients with SSc, skin thickness was evaluated with US by 2 observers at 2 different sites on the second digit of the dominant limb to determine the interobserver variability. Patients and controls were examined twice by the first observer for intraobserver variability. Patients were divided into three subgroups according to the phase of the disease (oedematous, fibrotic or atrophic). Results At both examined areas, US showed a significant dermal thickening (p<0.001) in the whole group of patients with SSc. A low intraobserver and interobserver variability was found. A highly significant correlation between the global mRSS and the local dermal thickness at the two examined sites (p=0.032, p=0.021) was detected. Skin thickness was significantly higher in the oedematous than in the fibrotic group (p<0.001) and significantly higher in the fibrotic and the oedematous group (p<0.001) than in the atrophic group (p<0.002). Conclusions US is a reliable tool giving reproducible results, and is able to detect digital dermal thickening in SSc.

Sustained maintenance of clinical remission after adalimumab dose reduction in patients with early psoriatic arthritis: a long-term follow-up study

Purpose: The primary purpose of this study was to evaluate the proportion of psoriatic arthritis (PsA) patients maintaining clinical remission after adalimumab (ADA) dose reduction compared with patients with rheumatoid arthritis. Secondary purposes include evaluating the proportion of PsA patients who achieve remission, the duration of remission after ADA dose reduction, time to relapse, psoriasis course, and the frequency of adverse events at the end of follow-up. Methods: This was a single-center, prospective, follow-up, case-control study of 76 consecutive patients (35 females, 41 males; mean age 46 ± 10.2 years) who met the classification criteria for psoriatic arthritis and required anti-tumor necrosis factor therapy according to Group for Research and Assessment of Psoriasis and Psoriatic Arthritis recommendations. The 76 patients were compared with 55 patients (40 females, 15 males; mean age 50 ± 11.6 years) who satisfied the American College of Rheumatology criteria for rheumatoid arthritis and received the same treatment. Case patients and controls were recruited from January 2008 to December 2010. At baseline, PsA patients and controls received 40 mg of ADA every other week, usually with methotrexate (10 to 20 mg/weekly). In the presence of clinical remission, ADA dose was reduced to 40 mg every 4 weeks in both groups. Results: Fifty-three of the 76 (69.7%) PsA patients and 17 of the 55 (30.9%) rheumatoid arthritis (P < 0.019) controls achieved remission after a mean time of 5.1 ± 1.2 and 6.3 ± 1.6 months, respectively (P = nonsignificant). After halving the dose of ADA, 47 of the 53 (88.6%) PsA patients and three of the 17 (17.6%) controls maintained remission (P = 0.016) over a mean follow-up period of 28.9 ± 8.4 and 24.2 ± 6.4 months, respectively. No significant changes in Psoriatic Arthritis Severity Index scores were observed. The mean time to relapse was 8.3 ± 3.4 months in six case patients and 7.2 ± 4.2 in 14 controls (P = not significant). No serious adverse events occurred in either group. Conclusion: Clinical remission is possible in a high percentage of patients with early PsA receiving ADA. Such remission is maintained in a high proportion of subjects after ADA dose halving, with relevant advantages in terms of patient compliance, drug-exposure risk, and economic burden.

Efficacy of infliximab in refractory Behçet’s disease-associated and idiopathic posterior segment uveitis: a prospective, follow-up study of 50 patients

Purpose To evaluate the long-term efficacy of infliximab in patients with refractory Behçet’s disease (BD)-associated and idiopathic posterior uveitis (PU). Methods Single center, prospective, 6-year duration, follow-up study on 50 consecutive patients (20 [40%] males and 30 [60%] females with a mean age of 37.5 ± 12.3 years) with refractory BD-associated PU (36 patients) and idiopathic PU (14 patients) who had failed at least one immunosuppressive drug. At baseline, patients received prednisone 1 mg/kg/day with rapid tapering and infliximab infusions (5 mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter. Nonresponders after the third infusion withdrew from the study. Primary outcome measures were visual acuity (VA) value improvement compared to baseline. Secondary outcome measures were proportion of patients with VA improvement from baseline; proportion of patients achieving disease remission; number of PU flare-ups; and incidence of adverse events. Results At the final follow-up, mean right and left eye VA respectively increased from 0.57 ± 0.31 at baseline to 0.68 ± 0.33 (P = 0.048) and from 0.67 ± 0.28 to 0.76 ± 0.27 (P = 0.047). None of the patients had VA worsening and new onset ocular complications. A complete response of PU was recorded in 34/50 (68%) patients and partial response in 11/50 (22%). Five patients were nonresponders and withdrew from the study after the third infusion. A significant reduction of ocular attacks and of the proportion of patients with cystoid macular edema was observed. No differences in infliximab efficacy was recorded between patients with BD-associated and idiopathic PU. No serious adverse events occurred. The mean follow-up duration was 36.8 months. Conclusion Long-term infliximab therapy was equally effective and safe with a significant VA gain in refractory BD-associated and idiopathic PU.

Anti-hnRNP and other autoantibodies in systemic sclerosis with joint involvement

OBJECTIVES To investigate joint involvement in SSc and its relationship with autoantibody to the hnRNP and to anti-cyclic citrullinated peptide (anti-CCP). METHODS Sera from 55 SSc patients were investigated. Joint involvement was determined by clinical, radiological and ultrasonographical evaluation. Anti-hnRNP proteins A1 and A2 (anti-hnRNP-A1/A2) antibodies were determined by immunoblotting. Anti-CCP, ACA, anti-topo I (ATA), Sm, U1-RNP, ribosomal RNP, Ro/SSA, La/SSB autoantibody and RF were determined. RESULTS Six patients were positive for anti-hnRNP-A2 autoantibody and two were anti-A1 positive. Eight patients had joint erosions: seven of the eight patients positive for anti-hnRNP-A2 or A1 presented articular involvement (P < 0.04) and five of the eight erosive patients were positive for either of the two autoantibodies (P < 0.02). Of the four patients positive for anti-CCP, none had anti-hnRNP but three had erosive aspects. ATAs were found in 10 patients, six of which were also positive for anti-hnRNP (P < 0.05). RF was positive in 16 patients and in seven among those with articular involvement (P < 0.04). RF was significantly associated with anti-hnRNP in patients with erosive arthritis (P < 0.02), but not with the presence of anti-hnRNP alone. Epitope mapping of the three strongest anti-hnRNP-A2-positive sera recognized the same major epitope as patients with RA. SSc patients have higher incidence of erosions and anti-hnRNP-A2/A1 positivity. RF test and anti-hnRNP had a statistically significant diagnostic value for articular involvement. CONCLUSIONS These parameters might suggest that autoantibody to both hnRNP antigens might become a non-specific but useful marker for joint involvement in SSc patients and identify SSc patients prone to develop joint damage.

Frequency of iridocyclitis in patients with early psoriatic arthritis: a prospective, follow up study

The occurrence of iridocyclitis (IC) in early psoriatic arthritis (PsA) has been rarely assessed. The primary end‐point of this study was to evaluate the frequency of IC at onset in patients with early PsA.

High frequency ultrasound can detect improvement of lesions in juvenile localized scleroderma.

Abstract Background. Juvenile Localized Scleroderma (JLS) causes functional disabilities and cosmetic deformities. Evaluation and follow-up of lesions are mandatory to understand the disease evolution. The objective of this study is to evaluate the usefulness of skin ultrasonography (US) in monitoring the response to treatment in JLS. Methods. Ten patients (age: 101,7 ± 66,2 months; 7 M, 3 F) affected by juvenile onset LS underwent sequential US exams (at baseline and after 6 months). Skin thickness was measured by using high-frequency US (18 MHz). All patients were evaluated both clinically (modified Rodnan Skin Score, mRSS) and by US (dermal thickness) at baseline and at 6 months. At baseline, 6/10 patients received 3 pulses of corticosteroids (solumedrol 30 mg/kg/day for 3 consecutive days, then oral steroids (1mg/kg), and methotrexate s.c. (15 mg/mq/week). After 6 months, 1/6 was switched to mycophenolate mofetil (25 mg/kg/day) due to inefficacy of MTX; 4/10 did not receive any further therapy. Results. US showed a thicker dermis and a thinned hypodermis in the lesional skin areas in respect to the healthy ones (p < 0.05). After treatment, in seven patients a clinical improvement (decrease of mRSS) was found. In six of these patients, US showed a decrease of dermal thickness showing a correlation with clinical data. Three patients who did not receive drugs showed unmodified images and clinical findings. Conclusion. US can help the assessment of skin and hypodermis in JLS and can detect an improvement of the lesions.

Duration of remission after halving of the etanercept dose in patients with ankylosing spondylitis: a randomized, prospective, long-term, follow-up study

Background The aim of this study was to evaluate the proportion of patients with ankylosing spondylitis maintaining clinical remission after reduction of their subcutaneous etanercept dose to 50 mg every other week compared with that in patients receiving etanercept 50 mg weekly. Methods In the first phase of this randomized, prospective, follow-up study, all biologic-naïve patients identified between January 2005 and December 2009 as satisfying the modified New York clinical criteria for ankylosing spondylitis treated with etanercept 50 mg weekly were evaluated for disease remission in January 2010. In the second phase, patients meeting the criteria for remission were randomized to receive subcutaneous etanercept as either 50 mg weekly or 50 mg every other week. The randomization allocation was 1:1. Remission was defined as Bath Ankylosing Spondylitis Disease Activity Index < 4, no extra-axial manifestations of peripheral arthritis, dactylitis, tenosynovitis, or iridocyclitis, and normal acute-phase reactants. The patients were assessed at baseline, at weeks 4 and 12, and every 12 weeks thereafter. The last visit constituted the end of the follow-up. Results During the first phase, 78 patients with ankylosing spondylitis (57 males and 21 females, median age 38 years, median disease duration 12 years) were recruited. In January 2010, after a mean follow-up of 25 ± 11 months, 43 (55.1%) patients achieving clinical remission were randomized to one of the two treatment arms. Twenty-two patients received etanercept 50 mg every other week (group 1) and 21 received etanercept 50 mg weekly (group 2). At the end of follow-up, 19 of 22 (86.3%) subjects in group 1 and 19 of 21 (90.4%) in group 2 were still in remission, with no significant difference between the two groups. The mean follow-up duration in group 1 and group 2 was 22 ± 1 months and 21 ± 1.6 months, respectively. Conclusion Remission of ankylosing spondylitis is possible in at least 50% of patients treated with etanercept 50 mg weekly. After halving of the etanercept dose, remission is maintained in a high percentage of patients during long-term follow-up, with important economic implications.