Disturbed iron homeostasis characterizes β-thalassemia and increases its morbidity. Our aim was to retrospectively associate β-thalassemia disease characteristics with treatment-requiring skin conditions. The files of adult β-thalassemia (including sickle β-thalassemia) patients were screened over a 10-year period for treatment-requiring skin disease episodes and their correlation with hematologic diagnoses and epidemiological and serological characteristics. Seventy-eight patients were identified, and 7 (9%) developed at least one relevant episode including cutaneous small-vessel vasculitis (CSVV), urticaria, and leg ulcers. Average ferritin serum level correlated significantly with development of a dermatosis (2,034 ± 799 μg/l in cases vs. 920 ± 907 μg/l in the overall population; p = 0.001, ANOVA). This difference relied exclusively on the high ferritin levels observed in patients with ‘generalized' dermatoses (urticaria and CSVV: 3,860 ± 1,220 μg/l) as opposed to values within the normal range in the case of ‘localized' ones (leg ulcers: 662 ± 167 μg/l). The employed iron chelation treatment influenced ferritin levels (p = 0.002, Kruskal-Wallis test) since chelation with a single agent seems to increase the risk of a skin disease (p = 0.013, likelihood ratio method). Conclusively, serum ferritin can be evaluated as risk factor for generalized dermatoses, but not for leg ulcers, in patients with the β-thalassemia genotype. This risk can be efficiently controlled with adequate chelation.

Objective: To investigate efficacy, toxicity, and drug discontinuation in patients with ankylosing spondylitis (AS) treated with infliximab. Methods: 35 patients with AS with mean (SD) age 42.5 (12.6) years and mean (SD) disease duration 14.5 (8.0) years were studied for 2 years. Patients entering the study had a negative tuberculin skin test, were fully informed about the treatment, and were followed up regularly. Infliximab, 5 mg/kg weight, was given intravenously at weeks 0, 2, 6, and every 8 weeks thereafter. Data concerning infliximab tolerability, adverse events, interval, and drug discontinuation were all recorded. Clinical improvement according to the BASDAI and the Ankylosing Spondylitis Assessment Study group (ASAS) 20%, 40%, and ASAS 5/6 response criteria were recorded. Results: After 1 year, 20 (57%) patients achieved the BASDAI 50% response criteria, 25 (71%) achieved ASAS 20%, 23 (66%) reached ASAS 40%, and 18 (51%) attained ASAS 5/6. After 2 years' treatment, 11 (31%) patients achieved BASDAI 50% response criteria, 14 (40%) ASAS 20%, 11 (31%) ASAS 40%, and 9 (26%) ASAS 5/6. Clinical improvement was associated with an improved BASFI and reduction of CRP. After 2 years' treatment, ''infliximab survival'' was 89%. Treatment was well tolerated and adverse events were mild; 3 patients discontinued the study. Conclusion: Infliximab was effective, safe, and well tolerated in patients with AS.

Rheumatoid arthritis (RA) in patients suffering from hemoglobinopathies is an important clinical problem, but the correlation between these diseases is still imperfectly known. The aim of this study was to analyze the clinical, serological and radiological characteristics of RA occurring in patients with hemoglobinopathies (thalassemia major, thalassemia intermedia and sickle-cell disease). In a single institution, in an adult cohort of 90 patients with hemoglobinopathies, we investigated retrospectively medical records of the patients. We evaluated the clinical findings, the autoantibodies and the radiological progression of patients who were diagnosed with RA according the American College of Rheumatology (ACR) criteria for RA. There were found 4 patients, with thalassemia major, who fulfilling the ACR criteria for RA. The clinical picture of the patients revealed a mild form of arthritis of the knees, shoulders, wrist and hands, while one patient had episcleritis. All patients had radiological damage compatible with RA (Larsen's score, 28.75 ± 29). All had positive rheumatoid factor, while anti-cyclic citrullinated peptide antibodies were positive in 1 patient. Three patients received steroid treatment and one immunosuppressive agent (methotrexate). True RA with low frequency of extra-articular manifestations is described. The diagnosis of RA must be suspected in patients with hemoglobinopathies picture and chronic arthritis of small joints.

1012 Background. Vascular endothelial cell activation and chronic inflammatory processes along with concomitant chronic energy deficiency characterize the steady state of sickle cell disease (SCD). Adipose tissue besides its lipid storage has also an endocrine function producing adipokines most important of which are leptin and adiponectin. These two hormones regulate food intake and energy expenditure but they are also involved in the regulation of inflammatory responses, hematopoiesis and angiogenesis. We evaluated leptin and adiponectin blood levels and determined any possible correlations with disease severity and inflammation markers in steady state SCD patients. Methods. We measured leptin and adiponectin using ELISA as well as high sensitivity C-reactive protein (hs-CRP) using nephelometry, in blood serum of 42 patients (24 male-18 female, median age 34 years, range 29–52 years) with steady state sickle cell/beta thalassemia and 40 healthy individuals matched for age, sex and body mass index (BMI) z-score who served as controls. Steady state was defined as a crisis-free period for at least 4 weeks after the previous clinical event and 3 or more months since the last blood transfusion. After natural logarithmic transformation, the measured values were investigated for correlations against hemoglobin, white blood cells, bilirubin, lactate dehydrogenase (LDH), ferritin, insulin levels, fetal hemoglobin (HbF), number of events/year (severe painful crises, transfusions, severe infections or other complications) and treatment with iron-removing agents or hydroxurea. Results. Leptin was found significantly lower in patients compared to controls (median±SD, 2.9±1.9 vs 8.5±4.9 ng/ml, p=0.006), whereas adiponectin and hs-CRP were found significantly elevated (median±SD 11.3±6.1 vs 7.5±3.1 μg/ml, p=0.003 and 2.8±1.1 mg/L vs 1.4±0.9; p=0.018, respectively). No correlations were found between adipokines and age, gender, chelation or hydroxurea treatment, ferritin, insulin, HbF, hemoglobin or clinical events. Leptin, but not adiponectin, levels were positively correlated with BMI z-score (r= 0.71, p=0.018) and negatively correlated with LDH levels (r=0.69, p=0.012). Concerning adiponectin, significant positive correlation was noted with hs-CRP levels and white blood cell number (r=0.644, p=0.015 and r=0.68, p=0.028). Conclusions. Adipokine blood levels are altered in steady state SCD possibly reflecting the effect of chronic hemolytic and inflammatory state on adipose tissue dysfunction. This could be considered as another endocrinopathy that affects SCD patients. Disclosures: No relevant conflicts of interest to declare.

4857 Background. The hemoglobin F (HbF) promoting agent hydroxyurea (HU) has been established as an effective therapy for adults with sickle cell disease (SCD) who develop frequent pain episodes, acute chest syndrome, severe vaso-occlusive events, or severe symptomatic anemia. However, concerns have been raised for long-term safety issues of HU in relation to its cytotoxic effects, which are attributed to ribonucleotide reductase inhibition. We analyzed the clinical effects of chronic use of HU in adult SCD patients treated in a referral Academic center. Methods. Medical files of 29 adult patients (10 male, median age 42 years, range 29–68 years) followed at our Thalassemia Unit for the last 17 years were retrieved, and detailed data were recorded and analyzed. Four patients had homozygous SCD and 25, sickle cell/beta thalassemia. Results. The median follow up time was 10 years (range 3–17 years), the total follow-up time was 289 patient-years and the total HU exposure period was 308 patient-years. The mean dose of HU administered was 29.3 mg/kg/day. The main clinical outcomes of HU therapy are shown in Table 1. In terms of efficacy, HU induced marked increase of HbF and substantial reduction of painful crises and transfusions needed, all outcomes designated statistically significant. HU therapy was also associated with significant increase of hemoglobin (Hb) levels, as well as with reduction of serum lactate dehydrogenase levels (LDH) and white blood cell count (WBC). In terms of toxicity, one poor HU compliant female patient died of pulmonary embolism. Disease complications observed during the long follow up time were: pulmonary hypertension in 2 patients, leg ulcers in one patient and renal impairment in one patient. Seven patients discontinued HU therapy (mean treatment duration 8.4 years) because of scheduled pregnancy (3 patients), severe neutropenia (2 patients) and non-compliance (2 patients). No patient developed cancer. Conclusions. This retrospective study, which analyzed data of most prolonged administration of HU, provides data supporting the efficacy and safety of chronic administration of HU in SCD adults. Disclosures: No relevant conflicts of interest to declare.