F. Bandinelli

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.

Ultrasound discloses entheseal involvement in inactive and low active inflammatory bowel disease without clinical signs and symptoms of spondyloarthropathy

OBJECTIVE To investigate the presence of lower limb entheseal abnormalities in IBD patients without clinical signs and symptoms of SpA and their correlation with IBD clinical variables. METHODS A total of 81 IBD patients [55 Crohns disease (CD) and 26 ulcerative colitis (UC), 43 females and 38 males, mean age 41.3 (12.4) years, BMI 24 (2)] with low active (12) and inactive (67) disease were consecutively studied with US (LOGIQ5 General Electric 10-MHz linear array transducer) of lower limb entheses and compared with 40 healthy controls matched for sex, age and BMI. Quadriceps, patellar, Achilleon and plantar fascia entheses were scored according to the 0-36 Glasgow Ultrasound Enthesitis Scoring System (GUESS) and power Doppler (PD). Correlations of GUESS and PD with IBD features [duration, type (CD/UC) and activity (disease activity index for CD/Truelove score for UC)] were investigated. The intra- and inter-reader agreements for US were estimated in all images detected in patients and controls. RESULTS Of the 81 patients, 71 (92.6%) presented almost one tendon alteration with mean GUESS 5.1 (3.5): 81.5% thickness (higher than controls P < 0.05), 67.9% enthesophytosis, 27.1% bursitis and 16.1% erosions. PD was positive in 13/81 (16%) patients. In controls, US showed only enthesophytes (5%) and no PD. GUESS and PD were independent of duration, activity or type (CD/UC) of IBD. The intra- and inter-reader agreements were high (>0.9 intra-class correlation variability). CONCLUSIONS US entheseal abnormalities are present in IBD patients without clinical signs and symptoms of SpA. US enthesopathy is independent of activity, duration and type of gut disease.

Clinical and radiological evaluation of sacroiliac joints compared with ultrasound examination in early spondyloarthritis

OBJECTIVE To compare clinical and X-ray examinations with US findings of SI joints (SIJ) in early SpA patients. METHODS Twenty-three early SpA patients, diagnosed according to Assessment of SpondyloArthritis international Society criteria, were investigated clinically [sacral sulcus tenderness, BASMI, BASFI, BASDAI, pain and fatigue visual analogue scale (VAS), morning stiffness and sleep disturbance], with SIJ X-rays (New York score) and with My Lab70 US 7-10 MHz US (Esaote, Genoa, Italy), evaluating the width of the SIJ capsule and posterior sacroiliac (PSL) and sacrotuberosus (STL) ligament thickness and comparing the results with 23 healthy controls. RESULTS SIJ width [right 2.2 (0.6) and left 2.3 (0.7) in SpA vs 1.6 (0.1) and 1.7 (0.2) in healthy controls, respectively, expressed as mean (s.d.)] and STL thickness [right 3.9 (1.3) and left 3.4 (1.0) vs 1.8 (0.1) and 1.8 (0.1), respectively, expressed as mean (s.d.)] were higher in SpA patients than in controls (P < 0.001 and P < 0.05, respectively). PSL thickness was similar in patients and controls. Only STL thickness was higher when SIJ was tender at clinical examination (P < 0.01) and correlated with pain VAS (P < 0.001) and BASFI (P < 0.05). Furthermore, SIJ US results were unrelated to X-ray findings (similar when X-ray sacroiliitis was present and not). CONCLUSION Our exploratory study suggested that in early SpA patients US might be a promising method, complementary to other imaging techniques, to study articular and soft tissue periarticular involvement of SIJ, independent of clinical and X-ray examination.

Musculoskeletal ultrasonography for psoriatic arthritis and psoriasis patients: a systematic literature review

Objective To systematically review the role of musculoskeletal US in patients suffering from PsA or psoriasis (Pso) in terms of prevalence, diagnosis, prognosis, monitoring and treatment. Methods A systematic literature review was conducted through medical databases (MEDLINE via PubMed, Embase) and the grey literature up to September 2015 to inform a new study of the Musculoskeletal Ultrasound Study Group of the Italian Society for Rheumatology. All articles reporting data on musculoskeletal US in PsA or Pso were included and extracted according to the underlying clinical question. Results A total of 86 publications were included. The prevalence of US abnormalities showed a wide range for each examined feature (e.g. 37-95% for entheses thickness of the lower limbs). The performance of US for diagnosis of disease or elementary lesions was variable across studies, but no study evaluated the overall performance of US in addition to clinical findings for diagnosing PsA. Considering US in defining PsA and Pso prognosis, several works focused on US of entheses of lower limbs in Pso, while for the monitoring of PsA activity five different scoring systems were identified. Last, the results of the role of US in guiding intra-articular interventions were controversial for the clinical outcomes, but in favour of US for accuracy. Conclusion despite the recognized importance of US in the management of PsA and Pso, this review clearly demonstrated the need of pivotal research in order to optimize the use of US in the diagnosis and monitoring of psoriatic disease.

Occult spondyloarthritis in inflammatory bowel disease

Spondyloarthritis (SpA) is a frequent extra-intestinal manifestation in patients with inflammatory bowel disease (IBD), although its real diffusion is commonly considered underestimated. Abnormalities in the microbioma and genetic predisposition have been implicated in the link between bowel and joint inflammation. Otherwise, up to date, pathogenetic mechanisms are still largely unknown and the exact influence of the bowel activity on rheumatic manifestations is not clearly explained. Due to evidence-based results of clinical studies, the interest on clinically asymptomatic SpA in IBD patients increased in the last few years. Actually, occult enthesitis and sacroiliitis are discovered in high percentages of IBD patients by different imaging techniques, mainly enthesis ultrasound (US) and sacroiliac joint X-ray examinations. Several diagnostic approaches and biomarkers have been proposed in an attempt to correctly classify and diagnose clinically occult joint manifestations and to define clusters of risk for patient screening, although definitive results are still lacking. The correct recognition of occult SpA in IBD requires an integrated multidisciplinary approach in order to identify common diagnostic and therapeutic strategies. The use of inexpensive and rapid imaging techniques, such as US and X-ray, should be routinely included in daily clinical practice and trials to correctly evaluate occult SpA, thus preventing future disability and worsening of quality of life in IBD patients.

Juvenile psoriatic arthritis and comorbidities: report of a case associated with enthesitis and celiac disease

The present authors report the case of a 9‐year‐old boy affected by psoriasis, juvenile psoriatic arthritis, enthesitis, and celiac disease. The signs and symptoms of the different comorbitities appeared at different times in the clinical history, complicating the overall diagnostic and therapeutic procedures. Cooperation between dermatologists and rheumatologist is mandatory in similar cases, where sophisticated technology and teams with specialized and integrated knowledge are required.

Low-dose modified-release prednisone in axial spondyloarthritis: 3-month efficacy and tolerability

Background Oral glucocorticoids (GCs) have been shown to be effective in reducing the inflammatory symptoms of rheumatoid arthritis, but their use is not supported by evidence in spondyloarthritis (SpA). Modified-release (MR) oral prednisone taken at bedtime has been shown to be more effective than immediate-release prednisone taken in the morning. The efficacy of low-dose MR prednisolone in patients with SpA is unknown. Patients and methods This single-center cohort study retrospectively assessed the effectiveness and safety of 12-week low-dose MR prednisone (5 mg daily, bedtime administration) in GC-naïve adult patients with symptomatic axial SpA. A 50% improvement of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) or a final BASDAI score of <4 according to disease activity at baseline was chosen as the primary outcome parameter after MR prednisone. Results Fifty-seven patients were evaluated; of them, 41 had an active disease (BASDAI score of ≥4) at baseline. MR prednisone significantly reduced BASDAI (from 5.5±2.6 to 3.0±2.8, P<0.001) as well as inflammatory symptoms, pain, fatigue and morning stiffness. The overall response rate after MR prednisone was 52.6% (53.7% in patients with active SpA and 50.0% in patients with low-active disease; nonsignificant). At multivariable analysis, none of the considered clinical findings independently predicted the response to MR prednisone in subjects with active SpA. Overall, seven patients (11.8%) had nonserious adverse drug reactions after MR prednisone. Conclusion In patients with symptomatic SpA and naïve to GCs, low-dose MR prednisone reduced the symptoms and clinical indexes of disease activity and showed a positive safety profile.

Anti-DFS70 autoantibodies in undifferentiated connective tissue diseases subjects: what’s on the horizon?

Objective The main objective was to determine the prevalence of anti-dense fine speckled (DFS70) antibodies in a stable population of undifferentiated connective tissue disease (UCTD) to better define their potential role. Methods Immunological and clinical records of 91 long-standing UCTD patients were studied. DFS pattern was determined using the IIF ANA test on HEp-2 cells and anti-DFS70 antibodies were tested by chemiluminescence assay and by DFS70 line immunoassay. Results Twelve (13.2%) of 91 serum samples were positive for anti-DFS70 antibodies by chemiluminescence assay and line immunoassay. There was no statistical significance between the prevalence of anti-ENA and anti-DNA autoantibodies in patients with and without anti-DFS70 antibodies. No differences were found in the clinical characteristics of both groups. The presence of the anti-DFS70 antibodies was related to the younger age class. Conclusion The high prevalence of anti-DFS70 antibodies in the UCTD patients suggested the potential role of these autoantibodies as a marker in the evolution of UCTD to CTD.

Correlation between HLA haplotypes and the development of antidrug antibodies in a cohort of patients with rheumatic diseases

Introduction The aim of this study was to investigate the correlation between human leukocyte antigen (HLA) haplotypes and the development of antidrug antibodies (ADAs) in a cohort of patients with rheumatic diseases. Patients and methods We evaluated the presence of ADAs in 248 patients with inflammatory rheumatic diseases after 6 months of treatment with anti-TNF drugs: 26 patients were treated with infliximab (IFX; three with rheumatoid arthritis [RA], 13 with ankylosing spondylitis [AS], 10 with psoriatic arthritis [PsA]); 83 treated with adalimumab (ADA; 24 with RA, 36 with AS, 23 with PsA); 88 treated with etanercept (ETA; 35 with RA, 27 with AS, 26 with PsA); 32 treated with certolizumab (CERT; 25 with RA, two with AS, five with PsA); and 19 treated with golimumab (GOL; three with RA, seven with AS, nine with PsA). Serum drug and ADA levels were determined using Lisa-Tracker Duo, the ADA-positive samples underwent an inhibition test, and the true-positive samples underwent genetic HLA typing. To have a homogeneous control population, we also performed genetic HLA typing of 11 ADA-negative patients. Results After inhibition test, the frequency of ADAs was 2/26 patients treated with IFX (7.69%), 4/83 treated with ADA (4.81%), 0/88 treated with ETA (0%), 4/32 treated with CERT (12.5%), and 1/19 treated with GOL (5.26%). The frequency of HLA alleles in the examined patients was HLA-DRβ-11 0.636, HLA-DQ-03 0.636, and HLA-DQ-05 0.727. The estimated relative risks between the ADA-positive patients and the ADA-negative patients were HLA-DRβ-11 2.528 (95% CI 0.336–19.036), HLA-DQ-03 1.750 (95% CI 0.289–10.581), and HLA-DQ-05 2.424 (95% CI 0.308–15.449). Conclusion This is the first study that shows an association between HLA and genetic factors associated with the occurrence of ADAs in patients with rheumatic diseases, but the number of samples is too small to draw any definite conclusion.