Background Mast cells (MCs) and nerves can induce cutaneous inflammatory responses, both independently and by interacting with each other. However, little is known about the role of skin nerves and ...neuropeptides in the regulation of MC-mediated skin inflammation, and the contribution of MCs in neurogenic inflammation is still controversial. Objective The aim of this study was to investigate the effects of cutaneous sensory nerves on MC-driven inflammatory responses. Methods Passive cutaneous anaphylaxis, a model for type I allergic skin responses, was studied in the presence or absence of sensory nerves by using a murine model of selective cutaneous denervation. Results Passive cutaneous anaphylaxis was significantly impaired in the absence of sensory nerves. This effect was not a result of an alteration of mast cell numbers in denervated skin. Moreover, IgE-mediated activation of mast cells was markedly decreased in denervated compared with normal skin. Notably, pretreatment of mice with selective antagonists of the neuropeptides substance P and/or calcitonin gene-related peptide also resulted in decreased inflammatory responses after MC activation. Conclusion These data suggest that sensory skin nerves augment MC-driven inflammatory responses by releasing neuropeptides that increase MC degranulation.
Chronic urticaria (CU) is a debilitating skin disease that lasts for more than 6 weeks with wheals and/or angioedema, including chronic spontaneous urticaria (CSU) and chronic inducible urticaria ...(CIndU). In China, the prevalence of this disease is high, more than 1%, and on the rise. CU has a major impact on the quality of life (QoL) of patients who frequently experience sleep disturbance, depression, and anxiety. Nearly one-third of patients with CSU, in China, are resistant to second-generation H1-antihistamines (sgAHs), even at a fourfold dose (second line; off-label). Omalizumab is approved for the treatment of CSU treatment in Europe and shows remarkable efficacy and safety. In China, regulatory approval for the use of omalizumab is pending, and its use in clinical practice varies widely. Consensus on omalizumab CU treatment in China is urgently needed. The aim of this article is to propose a practical omalizumab treatment algorithm for the management of antihistamine-resistant CSU and CIndU in adults and special population including children and adolescents, and pregnant or breast feeding women, to guide daily clinical practice in China. In the development of this consensus, an expert group including mainly dermatologists, allergists, but also pulmonologists, ENTs, immunologists, and pediatricians in Allergic Disease Prevention and Control Committee, Chinese Preventive Medicine Association, reviewed the existing evidence and developed consensus on the use of omalizumab in CU patients from China. The goal of this consensus is to assist clinicians in making rational decisions in the management of refractory CU with omalizumab. The key clinical questions covered by the treatment algorithm are: 1) Omalizumab treatment routine strategy in both CSU and CIndU patients; 2) Recommended dose and treatment duration for different age stratification; 3) Treatment duration for CU patients with other allergic comorbidities; 4) Recommendation on omalizumab stopping strategy.
In 154 patients the severity of symptoms was recorded by using the weekly urticaria activity score (UAS 7), and impairment in quality of life was assessed in 156 patients by using the Dermatology ...Life Quality Index (DLQI), as described previously.6 In confirmation of previously published findings, skin reactivity to autologous serum (positive ASST result) was found in 37.5% of all 200 patients with CU tested (Fig 1), and only slightly higher numbers of patients exhibited skin reactivity to autologous plasma (positive APST result, 43.0%), which is in contrast to a previous report in which up to 86% of patients with CU were found to have positive APST results.4 The results for skin autoreactivity were found to be comparable in all 3 study centers and ranged from 42.9% to 43.8% (positive APST result) and 32% to 50% (positive ASST result).
Rationale Chronic spontaneous urticaria (csU) affects 0.5-1 % of the global population at any given time and has a considerable burden on patients, healthcare systems and society.
Patients with acquired cold urticaria (ACU) show itchy wheals during cold exposure. This disturbing condition involves histamine and platelet-activating factor in its pathogenesis. Rupatadine is a ...dual antagonist of both histamine and platelet-activating factor.
To assess rupatadine efficacy in preventing reactions to cold challenge in patients with ACU.
A crossover, randomized, double-blind, placebo-controlled study in which 21 patients with ACU received rupatadine, 20 mg/d, or placebo for 1 week each is presented. The main outcome was the critical stimulation time threshold (CSTT) determined by ice cube challenge. Secondary outcomes included CSTT and the critical temperature threshold assessed by a cold provocation device (TempTest 3.0), as well as scores for wheal reactions, pruritus, burning sensations, and subjective complaints after cold challenge.
After rupatadine treatment, 11 (52%) of 21 patients exhibited a complete response (ie, no urticaria lesions after ice cube provocation). A significant improvement in CSTT compared with placebo was observed after ice cube and TempTest 3.0 challenge (P = .03 and P = .004, respectively). A significant reduction of critical temperature threshold (P < .001) and reduced scores for cold provocation-induced wheal reactions (P = .01), pruritus (P = .005), burning sensation (P = .03), and subjective complaints (P = .03) after rupatadine treatment were also found. Mild fatigue (n = 4), somnolence (n = 1), and moderate headache (n = 1) were reported during active treatment.
Rupatadine, 20 mg/d, shows high efficacy and is well tolerated in the treatment of ACU symptoms.
Rationale Omalizumab, an anti-IgE monoclonal antibody, was evaluated in three Phase III trials (ASTERIA-I/II and GLACIAL); we report CU-Q2oL data from all three studies.
Rationale Omalizumab, an anti-IgE monoclonal antibody, was evaluated in three Phase III trials (ASTERIA-I/II and GLACIAL); we report DLQI data from all three studies.
Monitoring the effects of treatment on disease activity, impact, and control in patients with chronic spontaneous urticaria (CSU) is essential. We do not have enough information on how these features ...of CSU and its response to treatment are linked. Also, there is no information on how recurrent angioedema or coexisting chronic inducible urticaria (CIndU) affect their relation. The aim of this study was to analyse the link between disease activity, impact, and control in CSU patients and possible effects of recurrent angioedema and comorbid CIndU.
To perform these analyses, we validated the Polish version of the Urticaria Control Test (UCT) in 106 chronic urticaria patients. The relationship between CSU activity, impact, and control was assessed in regard to recurrent angioedema and coexisting CIndU.
The Polish UCT showed high levels of validity, reliability, and sensitivity to change. Disease activity, impact, and control as well as their changes, assessed by the UAS, the CU-Q2oL, and the UCT, respectively, were strongly correlated. Recurrent angioedema or comorbid CIndU did not significantly affect the link of CSU activity, impact, and control or the relation of their changes.
In CSU, there is a strong, albeit not perfect correlation of disease activity, impact, and control, which underlines the need to assess all 3 features of the disease in routine clinical practice. Recurrent angioedema and comorbid CIndU, which are both common and relevant in CSU, do not affect how disease activity, impact and control in patients with CSU are related to each other.
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