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1.
Br J Dermatol ; 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39418120

RESUMO

BACKGROUND: Bullous pemphigoid affects elderly individuals with multiple comorbidities, making conventional treatments unsuitable. OBJECTIVE: Evaluate the effectiveness and safety of dupilumab in the treatment of bullous pemphigoid. METHODS: A multicenter ambispective cohort study was conducted in 34 hospitals. Patients with bullous pemphigoid treated with Dupilumab were included. Most of patients (97.1%) received an initial 600 mg dose followed by 300 mg every two weeks. OUTCOMES AND MEASURES: The primary outcome was the proportion of patients achieving complete remission within 4 weeks, defined as Investigator Global Assessment score of 0 or 1. Complete remission at weeks 16, 24, and 52, adverse events, reductions in peak pruritus numerical rating scale, and systemic glucocorticoid use were also assessed. RESULTS: The study included 103 patients with a median age of 77.3 years, 58.0% male. Complete remission was achieved by 53.4% within 4 weeks and 95.7% by week 52. Peak pruritus scale reduced by 70.0% by week 4 and was completely controlled by week 24. Thirteen patients presented adverse events, most of which were mild. Systemic glucocorticoid use reduced by 82.1% by week 52. Shorter disease duration and exclusive cutaneous involvement predicted better response at 16 weeks. No differences in response rates to dupilumab were observed between drug-associated bullous pemphigoid and idiopathic cases. No significant difference in response rates was observed between patients treated with dupilumab in monotherapy and those receiving dupilumab with concomitant treatments. CONCLUSIONS: Dupilumab is effective, rapid, and safe in managing bullous pemphigoid, reducing the need for corticosteroids and other treatments. Early initiation and exclusive skin involvement predict better outcomes.

2.
Int J Mol Sci ; 25(16)2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39201262

RESUMO

Interleukin (IL)-9 is present in atopic dermatitis (AD) lesions and is considered to be mainly produced by skin-homing T cells expressing the cutaneous lymphocyte-associated antigen (CLA). However, its induction by AD-associated triggers remains unexplored. Circulating skin-tropic CLA+ and extracutaneous/systemic CLA- memory T cells cocultured with autologous lesional epidermal cells from AD patients were activated with house dust mite (HDM) and staphylococcal enterotoxin B (SEB). Levels of AD-related mediators in response to both stimuli were measured in supernatants, and the cytokine response was associated with different clinical characteristics. Both HDM and SEB triggered heterogeneous IL-9 production by CLA+ and CLA- T cells in a clinically homogenous group of AD patients, which enabled patient stratification into IL-9 producers and non-producers, with the former group exhibiting heightened HDM-specific and total IgE levels. Upon allergen exposure, IL-9 production depended on the contribution of epidermal cells and class II-mediated presentation; it was the greatest cytokine produced and correlated with HDM-specific IgE levels, whereas SEB mildly induced its release. This study demonstrates that both skin-tropic and extracutaneous memory T cells produce IL-9 and suggests that the degree of allergen sensitization reflects the varied IL-9 responses in vitro, which may allow for patient stratification in a clinically homogenous population.


Assuntos
Dermatite Atópica , Enterotoxinas , Interleucina-9 , Células T de Memória , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Humanos , Interleucina-9/metabolismo , Feminino , Masculino , Adulto , Enterotoxinas/imunologia , Células T de Memória/imunologia , Células T de Memória/metabolismo , Pele/imunologia , Pele/metabolismo , Pyroglyphidae/imunologia , Animais , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Pessoa de Meia-Idade , Antígenos de Diferenciação de Linfócitos T/metabolismo , Adulto Jovem , Alérgenos/imunologia , Adolescente , Glicoproteínas de Membrana
3.
Clin Exp Dermatol ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093288

RESUMO

BACKGROUND: Moderate-to-severe atopic dermatitis (AD) can be difficult to manage in paediatric patients, with few licensed treatments in this age group. Dupilumab is approved for AD in children older than 6 months. OBJECTIVES: To assess the effectiveness and safety of dupilumab in a real-life cohort of paediatric AD patients in Spain. METHODS: A multicentre, retrospective real-life study on the effectiveness and safety of dupilumab in patients aged 2 to 18 years old with moderate-to-severe AD was conducted. Demographic and clinical characteristics were analysed, and effectiveness (EASI, IGA, DLQI, NRS itch), safety, and drug survival measures were assessed. A comparison of our results with other real-world outcomes and with clinical trials was made. RESULTS: Data from 243 patients from 19 centres was collected, with a mean follow-up of 85 weeks. Dupilumab exhibited significant effectiveness, with marked reductions in severity scores from week 4. By week 16, 79.4% of patients reached EASI75 and 40.5% reached EASI90. Mean percentage reduction in EASI was 79.7%. Increasing improvements were observed until week 52, with 85.8% and 49.6% achieving EASI75 and EASI90, respectively. Forty-three patients developed adverse events (AE) (43/243, 17.7%), being the most frequent ocular surface diseases (20/243, 8.2%), injection site reactions (8/243, 3.3%) and facial redness (7/243, 2.9%). Drug survival was high (96.9% and 93.1% after 1 and 2 years of follow-up, respectively), with only 19 (19/243, 7.8%) patients interrupting treatment: 7 (7/243, 2.9%) due to AE, 2 (2/243, 0.82%) due to secondary failure, 5 (5/243, 2.1%) were lost to follow-up and 5 (5/243, 2.1%) entered remission and stopped treatment. CONCLUSION: Real-life use of dupilumab in paediatric AD showcased sustained effectiveness, high drug survival, and acceptable safety profiles. Longer-term studies are crucial for AE surveillance and how to manage disease remission.

4.
Clin Exp Dermatol ; 49(9): 1002-1006, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-38430106

RESUMO

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Most patients are older and have associated multiple comorbidities. Topical and systemic corticosteroids are considered the first-line treatment for BP, and immunosuppressants are used as steroid-sparing treatments. However, both have side-effects and contraindications, which are even more common in this older population. New treatments targeting interleukins and receptors related to BP pathogenesis have been proposed to decrease these side-effects while achieving equal or better effectiveness and response rates. Omalizumab is a monoclonal antibody that targets IgE and has been proposed for the treatment of BP due to the evidence that IgE autoantibodies play an essential role in BP pathogenesis. OBJECTIVES: To assess the efficacy and safety of omalizumab for the treatment of BP. METHODS: We carried out a multicentre, retrospective, observational study including patients diagnosed with BP who received omalizumab for ≥ 3 months from 15 tertiary hospitals in Spain. IgE levels prior to treatment were measured, and we evaluated the possible correlation with clinical response. We excluded patients treated with omalizumab for < 3 months, as we consider this duration to be insufficient for a comprehensive assessment of its efficacy. To evaluate the effectiveness of the treatment, we used the percentage of body surface area improvement. RESULTS: We included 36 patients. The vast majority had associated multiple comorbidities, and all patients had used other systemic therapies apart from corticosteroids before omalizumab. In total, 83% experienced some kind of treatment response and 42% of all patients treated achieved complete response. We did not find any correlation between higher IgE levels and a better response (P = 0.2). All patients tolerated omalizumab without reported side-effects. CONCLUSIONS: Omalizumab is a good therapeutic alternative for BP as it provided clinical response in most patients, and nearly one-half of the cases achieved complete response. It showed no side-effects, which is crucial in older patients with BP.


Assuntos
Omalizumab , Penfigoide Bolhoso , Humanos , Omalizumab/uso terapêutico , Omalizumab/efeitos adversos , Penfigoide Bolhoso/tratamento farmacológico , Feminino , Masculino , Idoso , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Espanha , Resultado do Tratamento , Pessoa de Meia-Idade , Imunoglobulina E/sangue
6.
Australas J Dermatol ; 65(2): 153-162, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38058123

RESUMO

BACKGROUND: Dupilumab has shown to be an effective and safe treatment for patients with moderate-to-severe atopic dermatitis (AD). OBJECTIVE: To evaluate the predictive factors of response (PRF) in patients with moderate-to-severe AD treated with dupilumab. METHODS: Observational, retrospective and multicentre study conducted on adult patients diagnosed with moderate-to-severe AD treated with dupilumab, with a post-treatment follow-up of at least 16 weeks. The primary endpoints were EASI-75 and the IGA scale at week 52. RESULTS: A total of 198 patients were included in the analysis. Mean age was 38 ± 15.1 years and 116 (58.6%) were men. The most prevalent AD-predominant phenotypes were flexural eczema (45.3%), head-and-neck eczema (18.2%) and erythroderma (17.7%). At week 52, 140 (86.4%) patients achieved EASI-75 and 119 (93.0%) achieved an improvement in ≥2 points from baseline in IGA score. Women were 3.6 times more likely to achieve EASI-75 response than men (Odds ratio: 3.58; p = 0.020). While increased body mass index significantly reduced the probability of obtaining an improvement of ≥2 points in the IGA scale at week 52 (odds ratio: 0.88; p = 0.049). CONCLUSIONS: Dupilumab was an effective treatment in patients with moderate-to-severe AD. Additionally, sex and body mass index were significantly associated with achieving EASI-75 and an improvement of ≥2 points in the IGA scale, respectively, at week 52.


Assuntos
Anticorpos Monoclonais Humanizados , Dermatite Atópica , Eczema , Adulto , Masculino , Humanos , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/diagnóstico , Estudos Retrospectivos , Método Duplo-Cego , Índice de Gravidade de Doença , Resultado do Tratamento , Imunoglobulina A
8.
J Allergy Clin Immunol Pract ; 11(12): 3763-3771.e5, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37716526

RESUMO

BACKGROUND: Autoimmunity contributes to the pathogenesis of chronic spontaneous urticaria (CSU). The subtyping of CSU has revealed an autoimmune form of CSU. Despite autoimmune diseases having been associated with CSU, there are few prospective studies that have evaluated the characteristics and biomarkers of patients with CSU and autoimmune disease in a real-life practice setting. OBJECTIVE: To evaluate the presence of specific biomarkers for the presence of autoimmune disease in CSU and to analyze the clinical and therapeutic features of patients with CSU and autoimmune disease. METHODS: The clinical, laboratory, and therapeutic features of patients with CSU at a tertiary-level center were prospectively collected. Data obtained were compared in function of the presence/absence of autoimmune disease and typified according to IgE levels. RESULTS: Patients with CSU who had associated autoimmune disease corresponded to middle-aged women with a common pattern of blood test findings: both low baseline IgE and high-affinity receptor of IgE expression, basopenia, eosinopenia, higher baseline erythrocyte sedimentation rate and D-dimer, increased presence of antinuclear antibodies, IgG against thyroid peroxidase, and positive autologous serum skin test result. Total baseline IgE less than or equal to 43.8 IU/mL was both the optimal cutoff to predict autoimmune disease in the CSU cohort and a significant risk factor for the presence of autoimmune disease in the regression analysis. CONCLUSIONS: In real-life clinical practice, characteristics of patients with CSU and autoimmune disease share common features with type IIb autoimmune CSU. Total baseline IgE less than or equal to 43.8 IU/mL has been detected as a possible biomarker of autoimmune disease in patients with CSU.


Assuntos
Doenças Autoimunes , Urticária Crônica , Urticária , Pessoa de Meia-Idade , Humanos , Feminino , Estudos Prospectivos , Autoanticorpos , Biomarcadores , Imunoglobulina E , Doença Crônica , Urticária/etiologia
9.
Front Immunol ; 14: 1124018, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36993985

RESUMO

Background: The role of allergen sensitization in IL-31 production by T cells and specifically in the clinical context of atopic dermatitis (AD) has not been characterized. Methods: The response to house dust mite (HDM) in purified memory T cells cocultured with epidermal cells from AD patients (n=58) and control subjects (n=11) was evaluated. AD-associated cytokines from culture supernatants, plasma proteins and mRNA expression from cutaneous lesions were assessed and related with the clinical features of the patients. Results: HDM-induced IL-31 production by memory T cells defined two subsets of AD patients according to the presence or absence of IL-31 response. Patients in the IL-31 producing group showed a more inflammatory profile, and increased HDM-specific (sp) and total IgE levels compared to the IL-31 non-producing group. A correlation between IL-31 production and patient's pruritus intensity, plasma CCL27 and periostin was detected. When the same patients were analyzed based on sp IgE and total IgE levels, an increased IL-31 in vitro response, as well as type 2 markers in plasma and cutaneous lesions, was found in patients with sp IgE levels > 100 kUA/L and total IgE levels > 1000 kU/L. The IL-31 response by memory T cells was restricted to the cutaneous lymphocyte-associated antigen (CLA)+ T-cell subset. Conclusion: IgE sensitization to HDM allows stratifying IL-31 production by memory T cells in AD patients and relating it to particular clinical phenotypes of the disease.


Assuntos
Dermatite Atópica , Animais , Alérgenos , Células T de Memória , Citocinas , Pyroglyphidae , Imunoglobulina E
10.
Biofactors ; 48(6): 1284-1294, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35927787

RESUMO

The objective of the study was to assess the pathogenic and treatment relevance of Platelet Activating factor (PAF) in chronic spontaneous urticaria (CSU). The expression and cellular location of PAF receptor (PAFR) and serum levels of PAF and PAF acetylhydrolase (PAF-AH) in patients with moderate/severe CSU (n = 45) and healthy controls (HCs, n = 17) were studied. Skin samples from the active wheal (LS-CSU, 13 samples for qPCR and 33 for immunohistochemistry) and non-lesional skin (NLS-CSU, 13 samples) of CSU patients and HCs (13 samples and 5 for immunohistochemistry) were analyzed. Serum PAF and PAF-AH levels were measured by ELISA and compared between HC (10 samples) and CSU patients (25 samples) and, among them, between those refractory and non-refractory to second-generation H1 -antihistamines (sgAH). PAFR mRNA expression was significantly higher in LS-CSU versus HCs (p = 0.014). PAFR positive staining in immunohistochemistry was mainly found in the epidermal basal layer in HCs, whereas it was broadly present along the epidermis in LS-CSU samples. Endothelial cells showed PAFR expression exclusively in LS-CSU and NLS-CSU samples. PAFR expression was observed in the nerves of HC, LS-CSU, and NLS-CSU samples. Double PAFR/CD43 expression showed that T-lymphocytes were the main cell type from the wheal inflammatory infiltrate expressing PAFR. A significantly lower PAF-AH/PAF ratio was observed in sgAH non-responders versus responders (6.1 vs. 12.6; p = 0.049). Our study confirms that PAF is a mediator of wheal pathogenesis in CSU. The significantly lower PAF-AH/PAF ratio in sgAH non-responders vs responders suggests that PAF could be a potential biomarker of sgAH refractoriness.


Assuntos
Urticária Crônica , Fator de Ativação de Plaquetas , Humanos , Fator de Ativação de Plaquetas/metabolismo , Transcriptoma , Células Endoteliais/metabolismo
15.
J Dermatol ; 46(6): 531-534, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31021002

RESUMO

Hypereosinophilic syndrome (HES) is often associated with cutaneous manifestations, mostly pruritic lesions, urticaria and angioedema. Mucosal lesions are rarely seen in HES but, when present, are usually the first manifestation of the disease. The clinical presentation may be heterogeneous, including erosions, aphthae or ulcers, and can be easily confused with other mucocutaneous disorders. Here, we present the case of a 64-year-old man with severe chronic erosive oral mucositis simulating pemphigus in which the finding of persistent eosinophilia and elevation of B12 vitamin serum levels raised the suspicion of HES. The FIP1L1-PDGFRA fusion gene (4q12) was detected by fluorescence in situ hybridization and the patient was treated with imatinib mesylate with complete response of the disease.


Assuntos
Síndrome Hipereosinofílica/diagnóstico , Mesilato de Imatinib/uso terapêutico , Proteínas de Fusão Oncogênica/genética , Pênfigo/diagnóstico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Estomatite/diagnóstico , Fatores de Poliadenilação e Clivagem de mRNA/genética , Diagnóstico Diferencial , Humanos , Síndrome Hipereosinofílica/tratamento farmacológico , Síndrome Hipereosinofílica/genética , Síndrome Hipereosinofílica/imunologia , Mesilato de Imatinib/farmacologia , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Proteínas de Fusão Oncogênica/antagonistas & inibidores , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Índice de Gravidade de Doença , Estomatite/tratamento farmacológico , Estomatite/genética , Estomatite/imunologia , Resultado do Tratamento , Fatores de Poliadenilação e Clivagem de mRNA/antagonistas & inibidores
17.
G Ital Dermatol Venereol ; 154(4): 444-456, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30717573

RESUMO

The second-generation H1-antihistamines (sgAH) are the first-line symptomatic treatment of patients with chronic spontaneous urticaria (CSU). Up to 50% of the patients will not respond to licensed doses of sgAH. According to the guidelines, the dose of sgAH may be increased up to 4 times the conventional dose. However, even at higher doses, there is a subgroup of patients refractory to the antihistamine treatment. The purpose of this article was to review the different treatment options of antihistamine-refractory CSU patients. This revision examines the available literature for therapies used in chronic urticaria, including omalizumab, ciclosporin A, oral glucocorticoids, leukotriene receptor antagonists, H2 antihistamines, doxepin, dapsone, hydroxychloroquine, phototherapy, methotrexate, mycophenolate mofetil, azathioprine, autohemotherapy, intravenous immunoglobulins and rituximab, between others. After the exhaustive review of the medical literature only few high-quality studies have been identified, mostly for omalizumab. Omalizumab is an anti-immunoglobulin E monoclonal antibody, approved for the treatment of CSU, that has radically changed the management of the patients without good response to sgAH, allowing to reach complete responses in a high percentage of patients. Although actually the therapeutic management of CSU is more effective and safer than before 2014, there is place even for new and more effective treatments. A good number of partial responders and slow responders to omalizumab and a little percentage still of non-responders to available therapies stimulate the development of new drugs that will also be discussed.


Assuntos
Urticária Crônica/tratamento farmacológico , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Omalizumab/administração & dosagem , Antialérgicos/administração & dosagem , Urticária Crônica/imunologia , Relação Dose-Resposta a Droga , Humanos , Resultado do Tratamento
18.
Eur J Dermatol ; 29(6): 627-635, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31903953

RESUMO

BACKGROUND: The subtypes of chronic urticaria (CU) share a common clinical expression, but phenotypically may show differences. OBJECTIVES: To evaluate sociodemographic and clinical differences in CU phenotypes, including: (1) isolated chronic spontaneous urticaria (CSU); (2) isolated chronic inducible urticaria (CIndU); (3) CSU with concomitant CIndU (CSU-CIndU); (4) CSU with single or multiple episodes; (5) early and late-onset CSU (<45/65 years vs ≥45/65 years); and (6) CSU with presence vs absence of serum autoreactivity. MATERIALS AND METHODS: A retrospective observational study of 997 patients with urticaria was performed, with clinical, laboratory and therapeutic comparisons between CU subtypes. RESULTS: A clear female predominance was detected for CU, mostly in patients with serum autoreactivity. CIndU patients were younger, showed less angioedema, and had a better response to antihistamines. Stress and drugs were the main triggering factors for CSU. Patients with exclusive CIndU or recurrent CSU showed less psychiatric comorbidities. Patients with concomitant CIndU and serum autoreactivity showed greater urticaria activity. CONCLUSION: Knowledge of the clinical differences between CSU subtypes may help to define an individual therapeutic strategy and improve the control of symptoms and quality of life.


Assuntos
Urticária Crônica/diagnóstico , Urticária Crônica/terapia , Idade de Início , Autoimunidade/imunologia , Urticária Crônica/etiologia , Urticária Crônica/imunologia , Comorbidade , Feminino , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Masculino , Fenótipo , Prognóstico , Estudos Retrospectivos , Fatores Sexuais
19.
Acta Derm Venereol ; 98(7): 641-647, 2018 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-29648675

RESUMO

Chronic spontaneous urticaria (CSU) is characterized by heterogeneous activity, evolution, associated comorbidities and response to treatment. The aim of this study was to identify prognostic factors in patients with CSU that predict disease course and response to standard treatments. An observational retrospective study was conducted in a cohort of 549 patients with CSU, comparing patients with isolated CSU and those with CSU with concomitant inducible urticaria (CSU-CIndU). The factors associated with a worse prognosis in terms of duration and/or CSU activity and its episodes were: multiple episodes of CSU (19.2% had more than one lifetime episode of CSU), late-onset (63.6% of patients developed first onset of CSU after the age of 45 years), concomitant CIndU (20.2%) and functional serum autoreactivity. Patients with CSU-CIndU required more frequent therapy after 5 years and higher doses of 2nd-generation H1-antihistamines. Of patients with a baseline Urticaria Activity Score 7 (UAS7) between 16 and 42, 84.6% required cyclosporine or omalizumab to achieve symptom control, compared with 15.4% of patients with a baseline UAS7 between 0 and 15 (p?=?0.0013). Baseline CSU activity is the only factor found to be predictive for refractoriness to treatment with H1-antihistamines.


Assuntos
Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Urticária/terapia , Adulto , Idade de Início , Idoso , Doença Crônica , Ciclosporina/administração & dosagem , Progressão da Doença , Resistência a Medicamentos , Feminino , Antagonistas dos Receptores Histamínicos H1/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Omalizumab/administração & dosagem , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Falha de Tratamento , Urticária/diagnóstico
20.
Acta Derm Venereol ; 97(6): 698-704, 2017 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-28303277

RESUMO

Although the efficacy of omalizumab has been clearly demonstrated in the treatment of chronic spontaneous urticaria (CSU), its mechanism of action, which results in improvement in CSU symptoms, is not entirely understood. This study investigated the effect of omalizumab on expression of the high-affinity IgE receptor (FcεRI) on blood basophils from patients with active CSU, and its association with the clinical response. Patients exhibiting significant clinical improvement showed a sharp reduction in the levels of basophil FcεRI after 4 weeks, which was maintained throughout the total duration of the treatment. Such evolution was not observed in non-responder patients. Furthermore, non-responders showed significantly lower baseline levels of FcεRI than responders. Baseline basophil FcεRI expression was found to be a potential immunological predictor of response to omalizumab (100% sensitivity and 73.2% specificity). The results of this study contribute to our knowledge of the therapeutic benefit and mechanism of action of anti-IgE therapy in CSU.


Assuntos
Antialérgicos/uso terapêutico , Basófilos/imunologia , Omalizumab/uso terapêutico , Receptores de IgE/sangue , Urticária/tratamento farmacológico , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Urticária/sangue , Urticária/diagnóstico , Urticária/imunologia
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