Donatella Sangari

Remission of Behcet's disease with anti-tumor necrosis factor monoclonal antibody therapy: a case report

BackgroundBehcets disease (BD) is a chronic relapsing multisystem inflammatory disorder with mucocutaneous, ocular, articular, vascular, gastrointestinal and central nervous system manifestations. Tumor necrosis factor (TNF)-alpha is believed to play a pivotal role in BD. Therapeutic blockade of the activity of TNF has been successfully given in a short course of therapy with favorable effects in patients with BD refractory to conventional immunosuppressive drugs. We aimed to find out whether a 12-month treatment with infliximab, a chimeric monoclonal antibody to TNF-alpha, had any beneficial effect in reducing relapses of a patient with long-standing BD refractory to conventional immunosuppressive drugs.Case presentationA 54 year-old-woman with a 35-year history of BD with orogenital ulcerations, arthritis in the right knee and retinal lesions compatible with vasculitis received infliximab, 5 mg/kg by a two-hour intravenous infusion. Symptoms improved within 24 hours and eight days later the genital and oral ulcers healed as well as the arthritis in the right knee subsided. The retinal infiltrates completely resolved within 10 days. The infusions were repeated at weeks 2, 6, 14, 22 and then every 8 weeks. The patient was able to return to her domestic daily life. No exacerbation of the mucocutaneous ocular or arthritic symptoms occurred during the treatment period.ConclusionsPrevious studies have suggested that infliximab given in a short course of treatment is effective in inducing remission of severe mucocutaneous, gastrointestinal and ocular manifestations of BD. Our patient received a 12-month infliximab treatment showing a favorable effect on remission of BD manifestations.The long-term infliximab treatment appears as a new therapeutic option for patients with active BD who failed to respond to conventional immunosuppressive agents.

Bone Mineral Density, Bone Turnover Markers and Fractures in Patients with Systemic Sclerosis: A Case Control Study

Objective The aim of our study was to elucidate the pathophysiology of systemic sclerosis-related osteoporosis and the prevalence of vertebral fragility fracture in postmenopausal women with systemic sclerosis (SSc). Methodology Fifty-four postmenopausal women with scleroderma and 54 postmenopausal controls matched for age, BMI, and smoking habits were studied. BMD was measured by dual energy-x-ray absorptiometry at spine and femur, and by ultrasonography at calcaneus The markers of bone turnover included serum osteocalcin and urinary deoxypyridinoline. All subjects had a spine X-ray to ascertain the presence of vertebral fractures. Results bone mineral density at lumbar spine (BMD 0.78±0.08 vs 0.88±0.07; p<0,001), femoral neck (BMD: 0.56±0.04 vs 0.72±0.07; p<0,001) and total femur (BMD: 0.57±0.04 vs 0.71±0.06; p<0,001) and ultrasound parameter at calcaneus (SI: 80.10±5.10 vs 94.80±6.10 p<0,001) were significantly lower in scleroderma compared with controls; bone turnover markers and parathyroid hormone level were significantly higher in scleroderma compared with controls, while serum of 25(OH)D3 was significantly lower. In scleroderma group the serum levels of 25(OH)D3 significantly correlated with PTH levels, BMD, stiffness index and bone turnover markers. One or more moderate or severe vertebral fractures were found in 13 patients with scleroderma, wherease in control group only one patient had a mild vertebral fracture. Conclusion Our data shows, for the first time, that vertebral fractures are frequent in subjects with scleroderma, and suggest that lower levels of 25(OH)D3 may play a role in the risk of osteoporosis and vertebral fractures.

Correction: Propylthiouracil prevents cutaneous and pulmonary fibrosis in the reactive oxygen species murine model of systemic sclerosis

Introduction Recent advances suggest that the cellular redox state may play a significantrole in the progression of fibrosis in systemic sclerosis (SSc). Another,and as yet poorly accounted for, feature of SSc is its overlap with thyroidabnormalities. Previous reports demonstrate that hypothyroidism reducesoxidant stress. The aim of this study was therefore to evaluate the effectof propylthiouracil (PTU), and of the hypothyroidism induced by it, on thedevelopment of cutaneous and pulmonary fibrosis in the oxidant stress murinemodel of SSc.

SAT0226 Circulating Serum Levels of Cortisol Are Associated with The Pain Threshold in Systemic Sclerosis: Correlations with Depression

Background Previous studies on pain prevalence among systemic sclerosis (SSc) patients confirms its prominent role in disease outcomes1. Although pain perception is receiving more importance among patient-reported outcomes in SSc research, still its interface with mood disorders and immune system need to be further elucidated. The prevalence of clinically significant symptoms of depression or anxiety in SSc varies between 36% and 65% according to the evaluation used, and are rather associated with increased disability and altered HRQoL, than with disease-specific organ manifestations. An endocrine influence on pain perception and threshold is supported by robust evidences, more specifically related to sex, adrenal and thyroid hormones. Objectives To analyze the association between pain threshold, depression and cortisol serum levels in systemic sclerosis patients, major depression disorder patients and healthy controls. Methods Thirty SSc patients, 30 major depressive disorder (MDD) patients and 30 healthy controls completed the study. All participants underwent pressure pain threshold (PPT) assessment through an algometer in three anatomical surfaces, the ungula bed (UPPT) and the metacarpophalangeal joint (MPPT) of the second finger of the right hand and the anterior portion of the quadriceps muscle (QPPT), and depression evaluation, assessed by patient health questionnaire 9 (PHQ-9). Serum cortisol was measured in SSc and MDD patients for further analysis. Patients under treatment with corticosteroids were excluded. Results PHQ-9 values showed that 15% of SSc patients had no signs of depression, while 30% had mild and another 30% moderate signs of depression, 18% moderate/severe and 9% severe signs. Among MDD patients, PHQ-9 12% had mild depression, 45% moderate, 15 moderate to severe and 28% severe depression. PHQ-9 scores were significantly higher in SSc and MDD compared to controls (p<0.0001) and furthermore MDD patients had significantly higher than those reported by SSc patients (p<0.005). Pain threshold scores were significantly lower in SSc and MDD patients compared to healthy subjects in all sites (p<0.0001). In addition, SSc patients showed significant lower pain thresholds when compared to MDD, regardless the site of measurement (UPPT: p=0.0053; MPPT: p=0.0121; QPPT: p=0.0086). In addition, cortisol serum levels were significantly higher in MDD patients compared to SSc (17.1±5.7 vs 8.5±3.7 μg/dl; p<0.0001). Both in SSc and MDD a significant direct correlation was observed between cortisol serum levels and PPT in all sites. Conclusions The interface between pain, depression and cortisol could represent an additional complex aspect of care of patients with either SSc or MDD. References Schieir O, Thombs BD, Hudson M, Boivin JF, Steele R, Bernatsky S, Hanley J, Baron M; Canadian Scleroderma Research Group. Prevalence, severity, and clinical correlates of pain in patients with systemic sclerosis. Arthritis Care Res (Hoboken). 2010 Mar;62(3):409–17. Disclosure of Interest None declared

SAT0366 Vitamin D levels and bone mineral density in systemic sclerosis

Background Systemic sclerosis (SSc) is a chronic disease characterized by increased synthesis and deposition of collagen in skin and connective tissue, vascular alteration and immunological disturbances. Recently was demonstrated that SSc itself is a risk factor for osteoporosis. Several other studies had observed a relationship between low bone density and systemic sclerosis Objectives The aim of our study was to investigate whether SSc is arisk factor for osteoporosis, and what are the most probable causative factors that negatively regulate bone metabolism in these patients. Methods We recruited from September 2007 to March 2010 fifty-four consecutive postmenopausal women with newly systemic sclerosis (SSc) at the Unit of Rheumatology of the University of Messina, and 54 healthy postmenopausal women matched for age, body mass index (BMI), menopausal age and smoking habits served as the control group. All the patients with scleroderma met the diagnostic criteria for SSc. None of the subjects in both group were on supplementation with calcium and vitamin D. Bone mineral density was measured in all women in both groups by dual energy-x-ray absorptiometry at spine and femur, and by ultrasonography at calcaneus. Serum levels of 25-hydroxivitamin D, parathyroid hormone and bone turnover markers were examined. All patient had a spine X-ray to ascertain the presence of vertebral fractures. Results bone mineral density at lumbar spine, femoral neck and total femur and ultrasound parameter at calcaneus were significantly lower in scleroderma compared with controls; bone turnover markers and parathyroid hormone level were significantly higher in scleroderma compared with controls, while serum of 25-hydroxivitamin D was significantly lower. In scleroderma group the serum levels of 25-hydroxivitamin significantly correlated with parathyroid hormone levels, bone mineral density, stiffness index and bone turnover markers. One or more moderate or severe vertebral fractures were found in 13 patients with scleroderma, wherease in control group only one patient had a mild vertebral fracture Conclusions Vertebral fractures are frequent in patient with scleroderma. Our data shows that scleroderma is a risk factors for osteoporosis and suggest that lower levels of 25-hydroxivitamin D may play a role in the pathogenetic process underlying osteopenia in these patients. References Souza RB, Borges CT, Takayama L, Aldrighi JM, Pereira RM (2006). Systemic sclerosis and bone loss: the role of the disease and body composition. Scand J Rheumatol 35:384-387. Carbone L, Tylavsky F, Wan J, McKown K, Cheng S (1999) Bone mineral density in scleroderma. Rheumatology (Oxford) 37:1–2 Di Munno O, Mazantini M, Massel P, Ferdeghini M, Petaro N, Latorraca A, Ferri C (1995) Reduced bone mass and normal calcium metabolism in systemic sclerosis with and without calcinosis. Clin Rheumatol 14:407–412 La Montagna G, Vatti M, Valenti G, Tirri G (1991) Osteopenia in systemic sclerosis evidence of a participating role of earlier menopause. Clin Rheumatol 10:18–22 Genant HK, Wu CY, van Jujik C, Nvitt MC (1993). Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137-48 Disclosure of Interest None Declared

AB0423 The threshold of pain in patients affected by rheumatoid arthritis correlates with ESR but not with ultrasound score

Background In clinical practice, joint synovitis is generally assessed indirectly, by collecting clinical and laboratory data. Ultrasound is a non-expensive, repeteable, non-invasive test and may help the clinician to monitor the response to the treatment with biologic and non-biologic DMARDs. Furthermore, ultrasound may detect cases of unsuspected inflammation even in those patients who have achieved clinical remission. Clinical judgment is largely based on self-assessment of disease activity, which is influenced in turn by patient’s individual perception of pain, being pain the cardinal symptom of RA. Patients with high pain threshold may refer a low disease activity, even if laboratory and ultrasound prove otherwise. In fact, patients with long-standing RA, may develop adaptationt to pain, being capable to bear a major articular inflammation with less discomfort. Objectives The aim of this study is to compare the variables used in clinical, serologic and ultrasonographic evaluation of patients with RA, including the measurement of pain threshold. Methods We randomly enrolled 13 patients (11 females, 2 males) affected by RA treated with biological and non-biological DMARDs, referring to the UOC of Rheumatology of University Hospital of Messina. Mean age was 51,6±11,9 yrs and mean duration of disease was 11,9±9,4 yrs. Patients were assessed for tender and swollen joints, ESR, CRP, GH status, VAS disease and VAS pain. Hence we calculated DAS28, CDAI and SDAI. Meanwhile we assessed the degree of synovial effusion/synovitis and of Power Doppler vascularization using a semiquantitative scale (0-3 grades) on knees, wrists, 2°-3° metacarpophalangeal and 2°-3° proximal interphalangeal joints of both hands. Finally, we determined the pain threshold by applying a modified algometer on five body sites: wrist, ear lobe, biceps, pretibial area and calcaneal enthesis of the right side. Results We do not found any correlation between the threshold of pain and the US score.On the contrary higher pain threshold was associated with an increase in ESR (p=0.04). No correlation was found between clinical evaluation and ultrasonography nor between clinical activity and algometer scores. Conclusions These preliminary data show a significative correlation between pain threshold and ESR in patients with RA, indipendently from clinical assessment. As a higher algometer score may hide a flogistic condition, every RA patient shoud be tested for pain threshold. References Aletaha D, Smolen JS. The Simplified Disease Activity Index and Clinical Disease Activity Index to monitor patients in standard clinical care. Rheum Dis Clin North Am 2009;35:759-72. Pollard LC, Ibrahim F, Choy EH et al. Pain thresholds in rheumatoid arthritis: the effect of tender point counts and disease duration. J Rheum 2012;39(1):28-31. Ozgocmen S, Ozdemir H, Kiris A et al. Clinical evaluation and Power Doppler sonography in rheumatoid arthritis: evidence for ongoing synovial inflammation in clinical remission. South Med J. 2008;101(3):240-5 Disclosure of Interest None Declared