Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Psoriasis induced by anti-tumor necrosis factor therapy - A paradoxical adverse reaction

Administration of anti-tumor necrosis factor (anti-TNF) agents is beneficial in a variety of chronic inflammatory conditions, including psoriasis. We describe 5 patients in whom psoriasiform skin lesions developed 6-9 months after the initiation of anti-TNF therapy for longstanding, seropositive rheumatoid arthritis (etanercept or adalimumab), typical ankylosing spondylitis (infliximab), and Adamantiades-Behcet’s disease (infliximab). In all 5 patients, the underlying disease had responded well to anti-TNF therapy. Four patients developed a striking pustular eruption on the palms and/or soles accompanied by plaque-type psoriasis at other skin sites, while 1 patient developed thick erythematous scaly plaques localized to the scalp. In 3 patients there was nail involvement with onycholysis, yellow discoloration, and subungual keratosis. Histologic findings from skin biopsies were consistent with psoriasis. None of these patients had a personal or family history of psoriasis. In all patients, skin lesions subsided either with topical treatment alone, or after discontinuation of the responsible anti-TNF agent. The interpretation of this paradoxical side effect of anti-TNF therapy remains unclear but may relate to altered immunity induced by the inhibition of TNF activity in predisposed individuals

Relationship Between Tumor Necrosis Factor-alpha (TNFA) Gene Polymorphisms and Cardiac Sarcoidosis

Identification of genetic predisposition to cardiac sarcoidosis could play a critical role in the detection of subclinical forms of the disease. The aim of this study was to investigate the possible correlations between the emergence of cardiac sarcoidosis and the -1.031T/C, -857C/T, -308G/A, and -238G/A Tumor Necrosis Factor-alpha (TNFA) polymorphisms in a well-defined Greek cohort. One-hundred and seventy-three patients of Greek origin with sarcoidosis were recruited in the present study. Cardiac sarcoidosis was determined according to established criteria. Blood samples were collected and the TNFA polymorphisms were genotyped. No significant difference was noted between the patients with cardiac involvement and those without, concerning the -1.031T/C and -238G/A TNFA polymorphisms. Regarding the -857C/T polymorphism, the TT genotype and the T allele were found to be over-represented in patients with cardiac involvement (p=0.02 and 0.012, respectively). AA genotype of the -308G/A as well as the A allele were also found significantly more frequently in patients with cardiac sarcoidosis (p= 0.014 and 0.012 respectively). From the investigated TNFA promoter polymorphisms, we were able to deduce nine main haplotypes. Haplotypes 3 and 5, including A nucleotide at position -308, and T nucleotide at position -857 respectively, were significantly over-represented in the group with cardiac involvement. We detected an increased presence of genetic polymorphisms in the TNFA gene of patients with cardiac involvement. However, the role and the clinical application of these findings need further exploration

Low disease activity—irrespective of serologic status at baseline—associated with reduction of corticosteroid dose and number of flares in patients with systemic lupus erythematosus treated with belimumab: A real-life observational study

Background: Low disease activity is a validated target of current systemic lupus erythematosus (SLE) therapy. The aim of this study was to assess the ability of belimumab to achieve low disease activity states in real-life settings. Methods: Multicentre prospective observational study of consecutive SLE patients receiving belimumab for at least 3 months, due to active disease refractory to at least one conventional immunosuppressant. Disease activity, including the recently defined lupus low disease activity state (LLDAS) and remission (clinical SLEDAI-2K = 0), accrual of organ damage, flares and side effects were documented. Results: Ninety-one patients were included [94.5% women, mean (SD) age 45.9 (12.5) years]. Most frequent manifestations were arthritis (76.7%), rash (72.5%), serologic activity (low C3/C4 and/or high anti-dsDNA; 54.9%), hair loss (47.2%) and mucosal ulcers (27.5%). Median (range) duration of treatment was 10.5 (3.0–42.1) months. Belimumab significantly decreased average SLEDAI-2K, physician global assessment (PGA) and daily prednisone dose over time, as early as 3 months after initiation, with over 20% of patients discontinuing corticosteroids. Although reduction in clinical (i.e., excluding serology) SLEDAI-2K was more pronounced in patients who were serologically active (from 8 to 1.5 at 12 months) as compared to serologically inactive (from 6 to 4) at baseline, attainment of LLDAS did not differ between the two groups and was reached by more than 40% of completer patients after 9–12 months. In addition, the number of flares and severe flares was reduced by 62% and 50%, respectively, during the first 12 months of treatment. Twenty patients (22.0%) discontinued treatment due to inadequate response and two due to side effects potentially related to the drug. Conclusions: In real-life, belimumab is efficacious in achieving low disease activity in over 40% of unselected patients, in combination with reduction of corticosteroid dosage and number of flares. Both serologically active and inactive patients respond to the drug. © 2018 Elsevier Inc