Background A subgroup of patients with chronic spontaneous urticaria (CU) exhibits IgE antibodies directed against autoantigens, such as thyroperoxidase (TPO). We conducted this study to investigate ...whether such patients with CU with IgE against TPO benefit from treatment with omalizumab, a humanized anti-IgE mAb licensed for the treatment of severe persistent allergic (IgE-mediated) asthma. Objectives We sought to assess the efficacy of omalizumab treatment in patients with CU with IgE autoantibodies against TPO. Methods In this multicenter, randomized, double-blind, placebo-controlled study patients with CU (male/female, 18-70 years of age) with IgE autoantibodies against TPO who had persistent symptoms (wheals and pruritus) despite standard antihistamine therapy were randomized to receive either omalizumab (75-375 mg, dose determined by using the approved asthma dosing table) or placebo subcutaneously once every 2 or 4 weeks for 24 weeks. The primary end point was the change from baseline in mean weekly urticaria activity score after 24 weeks of treatment, as calculated from patients’ diaries. The safety and tolerability of omalizumab were also assessed. Results Of the 49 randomized patients (omalizumab, n = 27; placebo, n = 22), 42 completed the study. At week 24, patients demonstrated a mean reduction in the weekly urticaria activity score from baseline of 17.8 with omalizumab and 7.9 with placebo ( P = .0089). Complete protection from wheal development was observed in 19 (70.4%) patients in the omalizumab group compared with only 1 (4.5%) patient in the placebo group. The rate of adverse events was similar in both groups. Conclusions The results of this study indicate that omalizumab is an effective treatment option for patients with CU with IgE autoantibodies against TPO who are refractory to conventional treatment.
Abstract Background Atopic dermatitis (AD) is a chronic relapsing skin disease prevalent in 1-3% of adults in Western industrialized countries. Objective To investigate the effectiveness of ...educational training in an outpatient setting on coping with the disease, quality of life (QoL), symptoms and severity in adults with AD. Methods In this German prospective, randomized controlled multi-center study, adult patients with moderate to severe AD were educated by referring to a comprehensive 12 hour training manual consented by a multi-professional study group from different centers (“ARNE=Arbeitsgemeinschaft Neurodermitisschulung für Erwachsene”). Patients were randomly allocated to the intervention group or “waiting control group”. Study visits were performed at baseline and after one year (1-year follow-up). Primary outcomes were defined as a decrease of (1) “catastrophizing cognitions” with respect to itching (JKF questionnaire), (2) “social anxiety” (MHF questionnaire), (3) subjective burden by symptoms of the disease (Skindex-29 questionnaire) and (4) improvement of disease signs and symptoms assessed by scoring atopic dermatitis (SCORAD) index at 1-year follow-up. Data was analyzed by intention-to-treat. Results At 1-year follow-up patients from the intervention group (n=168) showed a significantly better improvement compared to the waiting group (n=147) in the following defined primary study outcomes: coping behavior with respect to itching P <.001; QoL assessed by Skindex-29 questionnaire P <.001 and SCORAD index P<.001. Conclusions This is the first randomized, controlled multi-center study on patient education in adulthood AD. The ARNE training program shows significant beneficial effects on a variety of psychosocial parameters as well as on AD severity.
Background Psoriasis is a chronic inflammatory skin disease that is considered to result from activated T cells stimulated by a population of inflammatory dermal dendritic cells (DCs). The origin and ...identity of these inflammatory dermal DCs are largely unknown. Objective We previously identified slanDCs (6-sulfo LacNAc) DCs as a rich source of TNF-α and as the early major source of IL-12. Here we studied the relevance of slanDCs as inflammatory dermal DCs in psoriasis. Methods Psoriasis skin samples were stained for the presence of activated slanDCs. Functional studies were carried out to determine the cytokine production of slanDCs, their T h 17/T h 1 T-cell programming, and their migration behavior. Results Large numbers of IL-23, TNF-α, and inducible nitric oxide synthase expressing slanDCs were found in psoriatic skin samples, which can be recruited by C5a, CX3CL1, and CXCL12. SlanDCs isolated from blood produced high levels of IL-1ß, IL-23, IL-12, and IL-6. Compared with classic CD1c+ DCs, slanDCs were far more powerful in programming T h 17/T h 1 T cells that secrete IL-17, IL-22, TNF-α, and IFN-γ, yet CD1c+ DCs induced a higher IL-10 production of T cells. Self–nucleic acids complexed to cathelicidin LL37 trigger endosomal Toll-like receptor (TLR) signaling (TLR7, TLR8, TLR9) and are key factors for the activation of DCs in psoriasis. We show that slanDCs respond particularly well to complexes formed of self-RNA and LL37. Similarly, slanDCs stimulated with a synthetic TLR7/8 ligand produced high levels of proinflammatory cytokines. Conclusion Our study defines slanDCs as inflammatory dermal DCs in psoriasis and identifies their strong capacity to induce T h 17/T h 1 responses.
