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1.
Artigo em Inglês | MEDLINE | ID: mdl-31472293

RESUMO

BACKGROUND: Chronic spontaneous urticaria (CSU) is characterized by the degranulation of skin mast cells and the influx of basophils and eosinophils to affected skin sites. Blood basopenia has been linked to severe antihistamine-resistant CSU and type IIb autoimmunity, whereas the role of eosinophils in CSU is largely unknown. OBJECTIVE: We analyzed data from 1,613 CSU patients from two centers to study the prevalence, role and relevance of eosinopenia in CSU. METHODS: Peripheral blood eosinophil and basophil counts were measured by automated hematology analyzers. Patient files were screened for clinical characteristics, results of laboratory tests, the autologous serum skin test (ASST), the serum-induced basophil histamine release assay (BHRA), and response to second-generation H1-antihistamines (sgAHs) and omalizumab. RESULTS: Ten percent of CSU patients had eosinopenia. Eosinopenia was associated with female gender, high disease activity, ASST and BHRA positivity, low total IgE, and high levels of C-reactive protein and IgG-anti-TPO (P≤0.007). Non-responders to sgAHs or omalizumab had significantly lower eosinophils as compared to responders (P<0.05 and P<0.01, respectively). Blood eosinophil counts correlated with basophil counts (r=0.396, P<0.001), and 81% of CSU patients with undetectable eosinophils had basopenia. The combination of eosinopenia and basopenia is a better predictor of non-response to sgAHs than eosinopenia alone (odds ratio of 9.5 vs 4.8). CONCLUSION: Eosinopenia, in CSU patients, is associated with type IIb autoimmunity, high disease activity and poor response to treatment. Eosinophils should be explored as biomarkers and investigated for their contribution to the pathogenesis of CSU.

2.
Allergy ; 2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31494963

RESUMO

BACKGROUND AND OBJECTIVES: Urticaria is a frequent skin condition, but reliable prevalence estimates from population studies particularly of the chronic form are scarce. The objective of this study was to systematically evaluate and summarize the prevalence of chronic urticaria by evaluating population-based studies worldwide. METHODS: We performed a systematic search in PUBMED and EMBASE for population-based studies of cross-sectional or cohort design and studies based on health insurance/system databases. Risk of bias was assessed using a specific tool for prevalence studies. For meta-analysis we used a random effects model. RESULTS: 18 studies were included in the systematic evaluation and 11 in the meta-analysis including data from over 86,000,000 participants. Risk of bias was mainly moderate, whereas the statistical heterogeneity (I2 ) between the studies was high. Asian studies combined showed a higher point prevalence of chronic urticaria (1.4%, 95%-CI 0.5-2.9) than those from Europe (0.5%, 0.2-1.0) and Northern American (0.1%, 0.1-0.1). Women were slightly more affected than men, whereas in children <15 years we did not find a sex-specific difference in the prevalence. The four studies that examined time trends indicated an increasing prevalence of chronic urticaria over time. CONCLUSIONS: On a global level, the prevalence of chronic urticaria showed considerable regional differences. There is a need to obtain more sex-specific population-based and standardized international data particularly for children and adolescents, different chronic urticaria subtypes and potential risk and protective factors. This article is protected by copyright. All rights reserved.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31369803

RESUMO

Mast cells (MCs) are capable of executing powerful inflammatory response programs triggered by surface IgE cross-linking or through pattern recognition receptors. The question of how MCs contribute to human disease has been intensely investigated and stimulated much controversy. Correlative evidence comes from human studies, pointing to pathogenetic or protective MC functions in patients with atopic conditions, autoimmune disorders, type 2 diabetes, chronic urticaria, mastocytosis, and cancer. Experiments in MC-deficient mice underpinned key roles for MCs in patients with IgE-mediated allergic conditions. Important pathogenetic MC contributions to other inflammatory and neoplastic conditions were suggested by studies in traditional KIT mutant MC-deficient mouse strains. However, many of these findings were not reproduced in more recently developed improved mouse models of MC deficiency, largely ruling out roles for MCs in mouse models for autoimmune disease, diabetes, and cancer. We discuss limitations of studies in mice and human subjects and provide suggestions for how they can be overcome, such as through the development of specific and selective MC-targeted treatments.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31374358

RESUMO

Omalizumab is an effective treatment for patients with chronic spontaneous urticaria (CSU). In routine clinical practice, physicians often face complex cases of CSU and need to decide whether patients are suitable for omalizumab treatment and how to manage this therapy. Here, we provide evidence and experience-based answers to the most common and important questions on omalizumab treatment of CSU. At 4 large urticaria centers, questions on the use of omalizumab in the treatment of patients with CSU were collected and then ranked by frequency and importance and grouped into top 5 domains using an interactive consensus approach. We suggest that omalizumab can be used to treat patients with CSU with any of the 3 CSU phenotypes (wheals only, angioedema only, wheals and angioedema), with comorbid chronic inducible urticaria, with cancer, who receive other biologics or cyclosporine, or who are pregnant or want to become pregnant, or are breast-feeding. Omalizumab treatment should be started with 300 mg every 4 weeks, monitored with validated patient-reported outcome measures, and maintained, in responders, until remission of CSU. Finally, partial responders or non responders can benefit from omalizumab updosing or adding or switching to cyclosporine. We believe our suggestions on the use of omalizumab in CSU will help to inform clinical decision making. Follow-up efforts should increase, systematically review, and profile the data available and provide evidence-based recommendations on how to best use omalizumab in CSU.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31446134

RESUMO

OBJECTIVE: Chronic urticaria (CU) is a common, heterogeneous and debilitating disease. Antihistamines and omalizumab are the mainstay therapies of CU. Additional treatment options are needed. Here, we review the off and beyond label use of licensed drugs, novel treatments that are currently under development, and promising new targets. DATA SOURCES: and Study Selection: We performed a thorough search of the recent literature on reports of the successful use of treatments in CU and promising targets for the development of novel treatment options. Also, we searched clinicaltrials.gov for recent and ongoing randomized controlled trials in CU. RESULTS: Omalizumab, the treatment of choice in patients with antihistamine-resistant chronic spontaneous urticaria (CSU), should be explored for the use in chronic inducible urticaria, in children <12 years old with CSU, and at higher doses. The off label use of dupilumab, reslizumab, mepolizumab and benralizumab can be effective in CU. Ligelizumab and UB-221, two novel anti-IgE monoclonal antibodies are in clinical trials for CU. Other promising drugs that are currently under development for CU are a CRTh2 antagonist, a monoclonal antibody to Siglec-8 (AK002), Bruton's tyrosine kinase inhibitors (Fenebrutinib and Lou064), a Syk inhibitor and dupilumab. Promising targets of future therapies include the Mas-related G-protein coupled receptor X2, the H4 receptor, C5a and its receptor, inhibitory mast cell receptors other than Siglec-8, Interleukin-33/Interleukin-25/TSLP, and SCF. CONCLUSION: Novel and better treatments for CU are very much needed. Some are in clinical trials already, and additional ones should be developed, making use of the many promising targets recently identified and characterized.

8.
Sci Rep ; 9(1): 10878, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350436

RESUMO

As a first host barrier, the skin is constantly exposed to environmental insults that perturb its integrity. Tight regulation of skin homeostasis is largely controlled by the aryl hydrocarbon receptor (AhR). Here, we demonstrate that Henna and its major pigment, the naphthoquinone Lawsone activate AhR, both in vitro and in vivo. In human keratinocytes and epidermis equivalents, Lawsone exposure enhances the production of late epidermal proteins, impacts keratinocyte differentiation and proliferation, and regulates skin inflammation. To determine the potential use of Lawsone for therapeutic application, we harnessed human, murine and zebrafish models. In skin regeneration models, Lawsone interferes with physiological tissue regeneration and inhibits wound healing. Conversely, in a human acute dermatitis model, topical application of a Lawsone-containing cream ameliorates skin irritation. Altogether, our study reveals how a widely used natural plant pigment is sensed by the host receptor AhR, and how the physiopathological context determines beneficial and detrimental outcomes.

9.
Acta Derm Venereol ; 99(10): 905-906, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31233177

RESUMO

is missing (Short communication).

10.
Allergy ; 2019 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-31228881

RESUMO

BACKGROUND: Autoimmune chronic spontaneous urticaria (aiCSU) is an important subtype of chronic spontaneous urticaria (CSU) in which functional IgG autoantibodies to IgE or its high-affinity receptor (FcεRI) induces mast cell degranulation and subsequent symptom development. However, it has not been tightly characterized. This study aimed to better define the clinical and immunological features and to explore potential biomarkers of aiCSU. METHODS: This was a multinational, multicenter study of 182 CSU patients. The clinical features studied included: urticaria activity and impact (UAS7 and quality of life); autologous serum skin test (ASST); IgG anti-FcεRI and IgG anti-IgE; IgG-anti-thyroperoxidase (IgG anti-TPO); total serum IgE; and basophil reactivity (BASO) using the basophil activation test (BAT) and basophil histamine release assay (BHRA). RESULTS: Of the 182 patients, 107 (59%) were ASST+, 46 (25%) were BASO+, and 105 (58%) were IgG anti-FcεRI+/IgE+. Fifteen patients (8%) fulfilled all three criteria of aiCSU. aiCSU patients appeared more severe (UAS7 21 vs 9 P < 0.016) but showed no other clinical or demographic differences from non-aiCSU patients. aiCSU patients also had markedly lower total IgE levels (P < 0.0001) and higher IgG anti-TPO levels (P < 0.001). Of biomarkers, positive BAT and BHRA tests were 69% and 88% predictive of aiCSU, respectively. CONCLUSIONS: aiCSU is a relatively small but immunologically distinct subtype of CSU that cannot be identified by routine clinical parameters. Inclusion of BHRA or BAT in the diagnostic workup of CSU patients may aid identification of aiCSU patients, who may have a different prognosis and benefit from specific management.

13.
Acta Trop ; 194: 172-180, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30978312

RESUMO

Leishmaniasis is endemic in northern Cameroon. However, the sand fly vectors have not been incriminated. A sand fly species inventory was generated by integrating a number of techniques. Miniature light traps were used for collecting sand flies in a variety of ecotopes found across the area, and a morphological and molecular identification approach for taxonomic confirmation was undertaken. In a pilot survey conducted in September 2012, we captured 687 sand flies, 259 of which were morphologically identified to species level. They represent 14 species of the genera Sergentomyia and Grassomyia. No Phlebotomus spp. were found. A second series of collections was carried out during 2013 in five different environmental setups: two urban, two peri-urban/rural and one sylvatic; 14,036 sand flies (6665 males and 7371 females) were collected. A total of 5926 females and 98 males were morphologically identified to species level, representing 19 species of the genera Sergentomyia, Grassomyia and Phlebotomus, including Ph. duboscqi, a known vector of cutaneous leishmaniasis in the region. Two new taxa were found and are described: Sergentomyia (Sintonius) thomsoni mandarai ssp. nov. and Se. coronula sp. nov. Our study is the first to report the following species in Cameroon: Se. (Sin.) thomsoni (as ssp. nov. mandarai), Se. (Ser.) cincta, Se. (Sin.) affinis ssp. vorax, Se. (Sin.) adami, Se. (Sin.) herollandi, and Se. (Sin.) christophersi. In addition, some morphologically atypical Sergentomyia specimens (combination of Ser. x Sin. traits) were recorded. A checklist of 32 species reports from Cameroon is presented.


Assuntos
Insetos Vetores/classificação , Leishmaniose Cutânea/epidemiologia , Psychodidae/classificação , Animais , Camarões/epidemiologia , DNA/genética , Feminino , Humanos , Insetos Vetores/parasitologia , Masculino , Psychodidae/genética , Psychodidae/parasitologia , Especificidade da Espécie
14.
Front Immunol ; 10: 546, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30967871

RESUMO

Schnitzler's syndrome is a rare autoinflammatory disorder characterized by interleukin-1ß-mediated and neutrophil-dominated inflammation. Neutrophil extracellular traps (NETs) are web-like structures of decondensed chromatin, histones, and antimicrobial peptides released by neutrophils. NETs were initially described in the context of pathogen defense but are also involved in autoimmune-mediated skin diseases. Here, we assessed the role of neutrophil extracellular trap formation (NETosis) in Schnitzler's syndrome. Immunofluorescence co-staining of myeloperoxidase and subnucleosomal complex was performed on lesional skin samples from patients with Schnitzler's syndrome, other neutrophilic dermatoses (cryopyrin-associated periodic syndrome, Sweet syndrome, and pyoderma gangrenosum), urticarial vasculitis and chronic spontaneous urticaria as well as healthy control skin. Blood neutrophils from patients with Schnitzler's syndrome and controls were isolated, and NETosis was induced by phorbol 12-myristate 13-acetate (PMA). Also, NETosis of control neutrophils induced by symptomatic Schnitzler's syndrome sera, cytokines and sub-threshold PMA doses was studied. Immunofluorescence co-staining revealed widespread and substantial NET formation in lesional skin of Schnitzler's syndrome patients but absence of NETs in chronic spontaneous urticaria and control skin. Neutrophils undergoing NETosis were observed in the skin of other neutrophilic diseases too. Correspondingly, blood neutrophils from Schnitzler's syndrome patients showed significantly elevated NETosis rates compared to control neutrophils following stimulation with PMA. Increased NETosis correlated well with high levels of C-reactive protein (CRP). SchS patients with the lowest NETosis rates had persistent joint and bone pain despite IL-1 blockade. Stimulation of control neutrophils and sub-threshold PMA with sera of symptomatic Schnitzler's syndrome patients disclosed enhanced NETosis as compared to control sera. Our results suggest that the induction of NET formation by neutrophils contributes to skin and systemic inflammation and may support the resolution of local inflammation in Schnitzler's syndrome.

16.
Exp Dermatol ; 28(7): 749-755, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30801834

RESUMO

In addition to their critical role in allergic disorders, mast cells (MCs) are well recognized for their protective effector functions during bacteria and parasite infections. This review describes recent advancements of our understanding of the complex role of MCs in fungal infections. Specifically, we outline key features of the contribution of MCs to infections with six fungal pathogens, namely Sporothrix, Paracoccidioides, Aspergillus, Malassezia, Candida and Dermatophytes. Evidence from studies of these pathogens suggests that MCs can function as positive regulators that detect and contain fungi at the site of infection. However, it appears that the inflammation induced by MCs following fungal infections may not always and only be beneficial to the host. MC responses during fungal infections may primarily benefit the pathogen by facilitating its spreading and contributing to a greater severity of fungal infections. This review also highlights key drivers of MCs activation and effector mechanisms that have been identified for the multidimensional function of MCs in fungal diseases and in allergic diseases combined with fungal infection.

17.
Allergy ; 74(2): 418-419, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30767264
18.
J Allergy Clin Immunol ; 143(4): 1311-1331, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30776418

RESUMO

BACKGROUND: Several treatment options for cold urticaria (ColdU) have been studied and reported, but systematic reviews and meta-analyses are limited. OBJECTIVES: We sought to meta-analyze and review the efficacy and safety of ColdU treatments. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Suitable reports were identified by searching PubMed, Scopus, and Web of Science. Our systematic review included 16 studies, 9 of which met the eligibility criteria for the meta-analysis. We analyzed the effects of treatments on critical temperature thresholds (CTTs) and critical stimulation time thresholds (CSTTs), as well as on rates of complete response and adverse events. RESULTS: Our pooled meta-analyses showed that nonsedating second-generation H1-antihistamines (nsAHs) are effective in the treatment of ColdU and that updosing of nsAHs significantly reduced CTTs relative to their own standard doses and placebos. In 4 studies involving CSTTs, updosing of nsAHs also resulted in significantly better CSTTs than their own standard doses or placebos. Omalizumab resulted in a marked reduction of CTTs in H1-antihistamine-resistant patients. Of 118 adverse events in 8 studies, standard-dose nsAHs, updosed nsAHs, and omalizumab produced lower numbers of adverse events than first-generation antihistamines. CONCLUSIONS: Our study showed that greater dosages of nsAHs were more effective than standard dosages in controlling ColdU symptoms. Increasing the dosages was not significantly associated with higher adverse event rates. Omalizumab at 150 and 300 mg every 4 weeks was shown to be effective for patients with ColdU refractory to antihistamines.

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