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1.
Allergy ; 77(3): 946-955, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34287950

RESUMO

BACKGROUND: The pathophysiology of the underlying paroxysmal permeability disturbances in angioedema (AE) is not well understood. METHODS: To identify clinical and laboratory parameters specific for a certain AE subtype, 40 AE patients were prospectively enrolled: 15 hereditary (HAE), 13 ACE-inhibitor induced (ACE-AE), and 12 mast cell-mediated without wheals in chronic spontaneous urticaria (CSU-AE). Ten healthy subjects served as controls. Serum levels of markers indicating activation of the ficolin-lectin pathway, of endothelial cells, or those indicating impairment of vascular integrity or inflammation were assessed by enzyme-linked immunosorbent assay. RESULTS: New routine clinical diagnostic criteria could not be identified, not even for distinguishing bradykinin-mediated (BK-) AE (ie, HAE and ACE-AE) from mast cell-/histamine-mediated CSU-AE. However, FAP-α and tPA were significantly increased in all AE compared to controls. In HAE, FAP- α, tPA, uPAR, pentraxin-3, Tie-2, sE-selectin, and VE-cadherin were significantly increased compared to controls. In HAE compared to CSU-AE and ACE-AE, sE-Selectin, Tie-2, and VE-Cadherin were significantly increased, whereas for Ang-2 the difference was significant compared to CSU-AE only. Tie-2 correlated strongly negatively with C4, C1-INH activity, and C1-INH function. CONCLUSIONS: This study is the first to compare HAE, ACE-AE, and CSU-AE. Although significance is limited by small sample size, Tie-2 was identified as a new promising biomarker candidate for HAE. FAP- α and tPA might serve as a marker for AE in general, whereas sE-selectin and Ang-2 were increased in BK-AE only. Our results add information to the role of endothelial dysfunction and serine proteases in different AE subtypes.


Assuntos
Angioedema , Angioedemas Hereditários , Urticária Crônica , Angioedema/diagnóstico , Angioedemas Hereditários/diagnóstico , Biomarcadores , Bradicinina/metabolismo , Proteína Inibidora do Complemento C1 , Células Endoteliais/metabolismo , Histamina/metabolismo , Humanos , Mastócitos/metabolismo , Selectinas/metabolismo , Fatores de Transcrição/metabolismo
2.
Allergy ; 77(3): 734-766, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34536239

RESUMO

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.


Assuntos
Angioedema , Asma , Urticária , Angioedema/diagnóstico , Angioedema/etiologia , Angioedema/terapia , Doença Crônica , Humanos , Prevalência , Qualidade de Vida , Urticária/diagnóstico , Urticária/epidemiologia , Urticária/etiologia
3.
BMC Ophthalmol ; 22(1): 341, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948879

RESUMO

BACKGROUND: The aim was to evaluate the safety and efficacy of a trifocal intraocular lens (IOL) for the correction of presbyopia and to assess patient satisfaction. METHODS: Records from three centres were reviewed to select presbyopic patients having undergone bilateral refractive lens exchange and implantation of the AT LISA tri 839MP multifocal IOL. Postoperatively, monocular and binocular distance, intermediate and near visual acuities, corrected and uncorrected, and subjective refraction were measured. Patients also completed a quality of life questionnaire. Safety evaluation included IOL stability and postoperative complications. RESULTS: 72 eyes (36 patients) were analysed. No clinically significant difference between pre- and postoperative corrected distance visual acuity (CDVA) was found for monocular or binocular measurements. Mean postoperative monocular CDVA was 0.02 ± 0.04 logMAR. Mean refractive values all improved statistically significantly compared with preoperative baseline (p ≤ 0.0064). Overall, 82.4% of eyes had spherical equivalent within ± 0.5 D and 97.1% within ± 1.0 D of emmetropia with a mean accuracy of -0.10 ± 0.41 D. Spectacle independence for distance, intermediate and near visual acuity was 87.5%, 84.4% and 78.1% respectively, and 78.1% of patients were satisfied with their postoperative, spectacle-free vision. Eight eyes received Nd:YAG laser treatment. No other IOL-related safety issues were reported. CONCLUSION: AT LISA tri 839MP multifocal IOL bilaterally implanted in presbyopic patients provided excellent distance, intermediate and near visual outcomes with very accurate correction of refraction. These results were associated with a high level of spectacle independence and patient satisfaction. TRIAL REGISTRATION: Trial registered on https://clinicaltrials.gov/ under the identification NCT03790592 (31/12/2018).


Assuntos
Catarata , Lentes Intraoculares , Presbiopia , Humanos , Satisfação do Paciente , Presbiopia/cirurgia , Estudos Prospectivos , Desenho de Prótese , Qualidade de Vida , Refração Ocular
4.
J Dtsch Dermatol Ges ; 19(1): 151-168, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33491884

RESUMO

This guideline is an update from August 2020 the S2k-guideline "Atopic dermatitis" published in 2015. The reason for updating this chapter of the guideline were the current developments in the field of systemic therapy of atopic dermatitis. The agreed recommendations for systemic treatment in atopic dermatitis of the present guideline are based on current scientific data. Due to the approval of dupilumab for the treatment of moderate to severe atopic dermatitis, which cannot be treated sufficiently with topical drugs alone, this part of the guideline has now been adapted and newly consented. The indication for systemic therapy and the therapeutic response to topical and systemic treatment should be recorded and documented in a suitable form in clinic and practice. A standardized documentation of the indication for system therapy in atopic dermatitis can be recommended and is also part of the updated chapter of this guideline.


Assuntos
Dermatite Atópica , Administração Cutânea , Anticorpos Monoclonais/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Eczema , Humanos
5.
Clin Exp Allergy ; 50(5): 577-584, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31925827

RESUMO

BACKGROUND: Pruritus is a major symptom of atopic dermatitis (AD) and is transmitted by a subpopulation of non-myelinated C-type free nerve endings in the epidermis and upper dermis. Stimulation of these nerve terminals is affected by histamine, neurotrophins and physical factors. Eosinophils of patients with AD are a source of neurotrophins, including brain-derived neurotrophic factor (BDNF), levels of which correlate with disease severity. OBJECTIVE: The purpose of this study was to determine the anatomical localization of eosinophils in the skin of patients with AD with regard to peripheral nerves and to investigate whether eosinophils induce sprouting and neurite outgrowth in murine sensory neurons. METHODS: Cryosections of skin derived from AD and control (NA) patients were subjected to immunofluorescence analysis with markers for eosinophils, BDNF and neuronal cells. Stimulated eosinophil supernatants were used for the treatment of cultured peripheral mouse dorsal root ganglia (DRG) neurons followed by morphometric analysis. RESULTS: Dermal axon density and the proximity of eosinophils to nerve fibres were significantly higher in AD patients vs NA. Both neuronal projections and eosinophils expressed BDNF. Furthermore, activated eosinophil supernatants induced BDNF-dependent mouse DRG neuron branching. CONCLUSIONS AND CLINICAL RELEVANCE: Our results indicate that BDNF-positive eosinophils are also localized in close proximity with nerve fibres in AD, suggesting a functional relationship between BDNF-expressing eosinophils and neuronal projections. These observations suggest that eosinophils may have considerable impact on pruritus by supporting sensory nerve branching.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/imunologia , Dermatite Atópica , Derme , Eosinófilos , Epiderme , Células Receptoras Sensoriais , Adolescente , Adulto , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Derme/imunologia , Derme/inervação , Derme/patologia , Eosinófilos/imunologia , Eosinófilos/patologia , Epiderme/imunologia , Epiderme/inervação , Epiderme/patologia , Feminino , Humanos , Masculino , Células Receptoras Sensoriais/imunologia , Células Receptoras Sensoriais/patologia
6.
Allergy ; 75(9): 2229-2242, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32003863

RESUMO

BACKGROUND: Mas-related G protein-coupled receptor X2 (MRGPRX2) is regarded as a mast cell-specific receptor mediating non-IgE-dependent activation. We aimed to investigate whether human basophils and eosinophils express functional MRGPRX2. METHODS: Flow cytometry, immunocytochemistry, immunofluorescence, Western blot, and RT-PCR were performed in highly purified peripheral blood basophils and eosinophils of atopic and nonatopic donors. To assess functional activity, fluorescent avidin-based degranulation assay, calcium mobilization, cytokine production in supernatants, assessment of viability/apoptosis, and tricolor granulocyte activation test were used. RESULTS: MRGPRX2 was significantly expressed by basophils and eosinophils but not neutrophils. Functional capacity was shown by anti-MRGPRX2 mAb-induced calcium influx and concentration-dependent induction of degranulation. Sequential stimulation in the calcium mobilization assay gave no evidence for desensitization or receptor internalization. Anti-MRGPRX2 mAb significantly promoted survival. Inhibition of apoptosis could be due to released IL-3, IL-5, and GM-CSF found in supernatants. Short-term incubation with IL-3 dose-dependently upregulated MRGPRX2 expression in both, stimulation for 24 hours with anti-IgE, C5a, fMLP, and IL-3 in basophils and by IL-3, IL-5, and IL-33 in eosinophils. Among known mast cell MRGPRX2 agonists ciprofloxacin but not PMX-53 was functional on basophils and eosinophils. In basophils of allergic subjects, tricolor granulocyte activation test using grass pollen demonstrated MRGPRX2 upregulation associated with degranulation and CD63 expression. CONCLUSION: Unraveling the regulation and signaling mechanisms of MRGPRX2 on basophils and eosinophils might enable the development of new therapeutic strategies to prevent or inhibit allergic and nonallergic hypersensitivity. Moreover, addressing MRGPRX2 might have potential for diagnostic purposes in (drug) hypersensitivity.


Assuntos
Basófilos , Eosinófilos , Humanos , Mastócitos , Proteínas do Tecido Nervoso , Receptores Acoplados a Proteínas G/genética , Receptores de Neuropeptídeos/genética
7.
Int Arch Allergy Immunol ; 181(5): 321-333, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32224621

RESUMO

This update on chronic urticaria (CU) focuses on the prevalence and pathogenesis of chronic spontaneous urticaria (CSU), the expanding spectrum of patient-reported outcome measures (PROMs) for assessing CU disease activity, impact, and control, as well as future treatment options for CU. This update is needed, as several recently reported findings have led to significant advances in these areas. Some of these key discoveries were first presented at past meetings of the Collegium Internationale Allergologicum (CIA). New evidence shows that the prevalence of CSU is geographically heterogeneous, high in all age groups, and increasing. Several recent reports have helped to better characterize two endotypes of CSU: type I autoimmune (or autoallergic) CSU, driven by IgE to autoallergens, and type IIb autoimmune CSU, which is due to mast cell (MC)-targeted autoantibodies. The aim of treatment in CU is complete disease control with absence of signs and symptoms as well as normalization of quality of life (QoL). This is best monitored by the use of an expanding set of PROMs, to which the Angioedema Control Test, the Cholinergic Urticaria Quality of Life Questionnaire, and the Cholinergic Urticaria Activity Score have recently been added. Current treatment approaches for CU under development include drugs that inhibit the effects of signals that drive MC activation and accumulation, drugs that inhibit intracellular pathways of MC activation and degranulation, and drugs that silence MCs by binding to inhibitory receptors. The understanding, knowledge, and management of CU are rapidly increasing. The aim of this review is to provide physicians who treat CU patients with an update on where we stand and where we will go. Many questions and unmet needs remain to be addressed, such as the development of routine diagnostic tests for type I and type IIb autoimmune CSU, the global dissemination and consistent use of PROMs to assess disease activity, impact, and control, and the development of more effective and well-tolerated long-term treatments for all forms of CU.


Assuntos
Urticária Crônica , Humanos
8.
Acta Derm Venereol ; 98(8): 766-771, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-29693698

RESUMO

Bullous pemphigoid (BP) is characterized by substantial skin and blood eosinophilia as well as intensive pruritus. Since the pruritogenic cytokine interleukin (IL)-31 is increased in inflammatory skin diseases the aim of this study was to determine whether IL-31 plays a role in BP. Using immunofluorescence, IL-31 expression was analysed in eosinophils derived from blister fluids and skin from patients with BP and IL-31 levels in blister fluids, serum and culture supernatants were determined by enzyme-linked immunoassay (ELISA). High levels of IL-31 expression were observed in BP blister fluids, but they were only marginally elevated in BP serum compared with healthy controls. Eosinophils from either BP blister fluids or skin biopsies showed strong expression of IL-31. Furthermore, peripheral blood eosinophils from patients with BP, but not healthy controls, released high levels of IL-31, reflecting those in blister fluids. In conclusion, eosinophils are a major source of IL-31 in BP and this cytokine may contribute to itch in patients with BP.


Assuntos
Eosinofilia/imunologia , Eosinófilos/imunologia , Interleucinas/imunologia , Dermatopatias Vesiculobolhosas/imunologia , Pele/imunologia , Urticária/imunologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Células Cultivadas , Eosinofilia/sangue , Eosinofilia/diagnóstico , Eosinófilos/metabolismo , Feminino , Imunofluorescência , Humanos , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Prurido/imunologia , Pele/metabolismo , Dermatopatias Vesiculobolhosas/sangue , Dermatopatias Vesiculobolhosas/diagnóstico , Regulação para Cima , Urticária/sangue , Urticária/diagnóstico
9.
Contact Dermatitis ; 78(4): 274-280, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29356000

RESUMO

BACKGROUND: The diagnostic approach to drug hypersensitivity includes a detailed medical history, clinical examination, and skin testing and/or oral challenge with a culprit or alternative drug, depending on the type of reaction and the suspected drugs. Although skin testing is considered to be rather safe, cutaneous and systemic, including fatal, reactions have been described. OBJECTIVES: To report 3 cases with generalized delayed reactions after skin testing with clindamycin, and to review the existing literature. METHODS: Thorough clinical examination, blood tests and prick, intradermal and patch tests were performed in 3 patients. RESULTS: All patients experienced generalized maculopapular exanthema after intradermal and patch testing with clindamycin and amoxicillin in the first patient, and clindamycin alone in the second and third patient. None of the patients showed immediate reactions to skin tests, while positive intradermal reactions after 24 h to amoxicillin and clindamycin were observed in the first patient, and positive intradermal reactions after 24 h to clindamycin were observed in the second and third patients. CONCLUSIONS: Skin testing with clindamycin in the diagnosis of drug hypersensitivity carries some risk of adverse reactions. A stepwise and individual diagnostic work-up, considering potential risk factors, and testing in a specialized centre with emergency equipment available is highly recommended.


Assuntos
Clindamicina/efeitos adversos , Toxidermias/etiologia , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Segurança do Paciente , Idoso , Clindamicina/imunologia , Clindamicina/farmacologia , Toxidermias/diagnóstico , Toxidermias/epidemiologia , Europa (Continente) , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Testes do Emplastro/métodos , Medição de Risco
10.
Acta Derm Venereol ; 97(4): 464-471, 2017 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-27868136

RESUMO

Bullous pemphigoid (BP) is an autoimmune blistering skin disease that is more common in elderly individuals. The aim of this study was to determine the functional activity of eosinophils in patients with BP compared with healthy donors. Blood, skin and blister-derived eosinophils were strongly activated in patients with BP, seen by increased surface expression of CD69 compared with controls. CD11b was also increased in BP blood eosinophils, which may explain the striking accumulation of eosinophils in BP (1×106 per ml blister fluid). Furthermore, CCL26 was expressed by activated eosinophils in BP skin and in blister fluid. BP eosinophils also released IL-6, IL-8 and IL-1α in BP blister fluids. Apoptosis in cultivated BP eosinophils was increased and accompanied by enhanced surface externalization of CD95. Caspase 3 positive eosinophils in lesional BP skin and blister fluid also showed the initiation of apoptosis. These results reveal novel pathophysiological aspects of BP, with a strong activation pattern and increased apoptosis of eosinophils in the peripheral blood, skin and blister fluids.


Assuntos
Apoptose , Vesícula/patologia , Eosinófilos/patologia , Penfigoide Bolhoso/patologia , Pele/patologia , Antígenos CD/sangue , Antígenos de Diferenciação de Linfócitos T/sangue , Biomarcadores/sangue , Vesícula/sangue , Vesícula/imunologia , Antígeno CD11b/sangue , Estudos de Casos e Controles , Caspase 3/metabolismo , Quimiocina CCL26 , Quimiocinas CC/metabolismo , Eosinófilos/imunologia , Eosinófilos/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lectinas Tipo C/sangue , Penfigoide Bolhoso/sangue , Penfigoide Bolhoso/imunologia , Pele/imunologia , Pele/metabolismo , Receptor fas/metabolismo
11.
J Allergy Clin Immunol ; 136(1): 96-103.e9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26044854

RESUMO

BACKGROUND: It has frequently been speculated that pruritus and skin lesions develop after topical exposure to aeroallergens in sensitized patients with atopic dermatitis (AD). OBJECTIVE: We sought to study cutaneous reactions to grass pollen in adult patients with AD with accompanying clear IgE sensitization to grass allergen in an environmental challenge chamber using a monocenter, double-blind, placebo-controlled study design. METHODS: Subjects were challenged on 2 consecutive days with either 4000 pollen grains/m(3) of Dactylis glomerata pollen or clean air. The severity of AD was assessed at each study visit up to 5 days after challenge by (objective) scoring of AD (SCORAD). Additionally, air-exposed and non-air-exposed skin areas were each scored using local SCORAD scoring and investigator global assessments. Levels of a series of serum cytokines and chemokines were determined by using a Luminex-based immunoassay. The primary end point of the study was the change in objective SCORAD scores between prechallenge and postchallenge values. RESULTS: Exposure to grass pollen induced a significant worsening of AD. A pronounced eczema flare-up of air-exposed rather than covered skin areas occurred. In grass pollen-exposed subjects a significantly higher increase in CCL17, CCL22, and IL-4 serum levels was observed. CONCLUSIONS: This study demonstrates that controlled exposure to airborne allergens of patients with a so-called extrinsic IgE-mediated form of AD induced a worsening of cutaneous symptoms.


Assuntos
Dermatite Atópica/imunologia , Eczema/imunologia , Prurido/imunologia , Adulto , Alérgenos/efeitos adversos , Alérgenos/imunologia , Câmaras de Exposição Atmosférica/efeitos adversos , Quimiocina CCL17/sangue , Quimiocina CCL22/sangue , Dactylis , Progressão da Doença , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Imunoglobulina E/sangue , Interleucina-4/sangue , Masculino , Pólen/imunologia , Adulto Jovem
15.
J Dtsch Dermatol Ges ; 14(1): 92-106, 2016 Jan.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-26713654

RESUMO

Atopic dermatitis (AD) represents a pruritic, non-contagious, chronic or chronically relapsing, inflammatory skin disease. The course of the disease may be complicated by bacterial or viral superinfections. The first manifestation of the disease and further flare-ups are due to genetic predisposition and also to a variety of further trigger factors. The therapy regimen should be adapted to disease symptoms that are actually present and consider individual features of the disease as reported by the patients or their parents. This short version of the German guideline on AD provides an overview of evidence-based diagnostic and treatment options. All recommendations made here are the result of a consensus of the scientific medical societies, working groups and support groups based on scientific data published to date. Abstracts and details of the studies cited are provided in the long version of this guideline (see: www.awmf.org).


Assuntos
Anti-Inflamatórios/uso terapêutico , Dermatite Atópica/diagnóstico , Dermatite Atópica/terapia , Dermatologia/normas , Guias de Prática Clínica como Assunto , Testes Cutâneos/normas , Medicina Baseada em Evidências , Alemanha , Humanos , Resultado do Tratamento
20.
J Dtsch Dermatol Ges ; 12(11): 997-1007; quiz 1008-9, 2014 Nov.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-25273223

RESUMO

Urticaria is a very common skin disease which was already described in the ancient world. Questions still remain about its pathogenesis and management remain open. Compared to other common skin diseases, the published evidence is rather low. The clinical symptoms with pruritic transient wheals and/or angioedema are caused by mediators (particularly histamine) released by activated mast cells and basophils. The mechanism of target cell activation has not been clarified in detail for most urticaria subtypes. Different urticaria subtypes should be distinguished. Spontaneous forms are more common than inducible forms. Chronic urticaria and urticaria in certain age groups (children, pregnancy) can be difficult to manage. Therefore, international consensus resulting in the regular update of urticaria guidelines can be very helpful. Currently, these updated guidelines include a three-step treatment algorithm for chronic spontaneous urticaria. Only the first step of this algorithm, second generation H1-antihistamine in standard dose, utilized approved drugs. However after omalizumab was established as a third line choice in the guideline algorithm, it has approved in many countries for chronic spontaneous urticaria without response to H1-antihistamines. The exact mechanism of action of omalizumab in urticaria has not been fully elucidated. Unrevealing this mechanism might result in a deeper understanding of urticaria pathogenesis and the development of further therapeutic strategies.


Assuntos
Anti-Inflamatórios/uso terapêutico , Dermatologia/normas , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Guias de Prática Clínica como Assunto , Urticária/diagnóstico , Urticária/tratamento farmacológico , Alemanha , Humanos
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