RESUMO
BACKGROUND AND AIMS: Contrast-enhanced ultrasonography (CEUS) is a potential interesting method for assessing accurately Crohn's disease (CD) activity. We compared the value of intestinal ultrasonography (US) coupled with contrast agent injection with that of magnetic resonance enterography (MRE) in the assessment of small bowel CD activity using surgical histopathology analysis as reference. METHODS: Seventeen clinically active CD patients (14 women, mean age 33 years) requiring an ileal or ileocolonic resection were prospectively enrolled. All performed a MRE and a US coupled with contrast agent injection (CEUS) less than 8 weeks prior to surgery. Various imaging qualitative and quantitative parameters were recorded and their respective performance to detect disease activity, disease extension and presence of complications was compared to surgical histopathological analysis. RESULTS: The median wall thickness measured by US differed significantly between patients with non-severely active CD (n = 5) and those with severely active CD (n = 12) [7.0 mm, IQR (6.5-9.5) vs 10.0 mm, IQR (8.0-12.0), respectively; p = 0.03]. A non-significant trend was found with MRE with a median wall thickness in severe active CD of 10.0 mm, IQR (8.0-13.7) compared with 8.0 mm, IQR (7.5-10.5) in non-severely active CD (p = 0.07). The area under the ROC curve (AUROC) of the wall thickness assessed by US and MRE to identify patients with or without severely active CD on surgical specimens were 0.85, 95% CI (0.64-1.04), p = 0.03 and 0.80, 95% CI (0.56-1.01), p = 0.07, respectively. Among the parameters derived from the time-intensity curve during CEUS, time to peak and rise time were the two most accurate markers [AUROC = 0.88, 95% CI (0.70-1.04), p = 0.02 and 0.86, 95% CI (0.68-1.04), p = 0.03] to detect patients with severely active CD assessed on surgical specimens. CONCLUSION: The accuracy of intestinal CEUS is close to that of conventional US to detect disease activity. A thickened bowel and shortened time to peak and rise time were the most accurate to identify CD patients with severe histological disease activity.
Assuntos
Doença de Crohn , Adulto , Meios de Contraste , Doença de Crohn/complicações , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , UltrassonografiaRESUMO
BACKGROUND: Epidermolysis bullosa simplex generalized severe (EBS-gen sev) is a genetic disorder caused by mutation in the KRT5 or KRT14 genes. Although it is usually considered a mechanical disease, recent data argue for additional inflammatory mechanisms. OBJECTIVES: To assess the inflammation in the skin of patients with EBS-gen sev. METHODS: A first immunohistochemical retrospective study was performed on frozen skin samples from 17 patients with EBS-gen sev. A second multicentre prospective study was conducted on 10 patients with severe EBS-gen sev. Blister fluid and epidermis were processed for immunochemical analysis and quantitative real-time polymerase chain reaction. Cytokine expression was analysed in blister fluid and compared with that in controls. RESULTS: Histological analysis showed a constant dermal perivascular CD4+ lymphocyte infiltrate in skin biopsies of both blister (n = 17) and rubbed skin (n = 5), an epidermal infiltration of neutrophils and eosinophils in 70% of cases, and increased immunostaining for CXCL9 and CXCL10 in blistering skin. High levels of T helper 17 cytokines were detected in lesional skin. Three adult patients with EBS-gen sev were treated with apremilast, with a dramatic improvement of skin blistering and good tolerance. CONCLUSIONS: Our study demonstrates the importance of inflammation in patients with EBS-gen sev and underlines the key role for T helper 17 cells in its pathogenesis. In addition, this study provides promising new therapeutic approaches for this disabling disorder.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Epidermólise Bolhosa Simples/imunologia , Pele/efeitos dos fármacos , Células Th17/imunologia , Talidomida/análogos & derivados , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Criança , Pré-Escolar , Epidermólise Bolhosa Simples/tratamento farmacológico , Epidermólise Bolhosa Simples/genética , Feminino , Humanos , Lactente , Recém-Nascido , Queratina-14/genética , Queratina-5/genética , Masculino , Pessoa de Meia-Idade , Mutação , Projetos Piloto , Estudos Retrospectivos , Pele/citologia , Pele/imunologia , Células Th17/efeitos dos fármacos , Talidomida/farmacologia , Talidomida/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Ivermectin (IVM) is widely used in both human and veterinary medicine to treat parasitic infections. Recent reports have suggested that IVM could also have anti-inflammatory properties. METHODS: Here, we investigated the activity of IVM in a murine model of atopic dermatitis (AD) induced by repeated exposure to the allergen Dermatophagoides farinae, and in standard cellular immunological assays. RESULTS: Our results show that topical IVM improved allergic skin inflammation by reducing the priming and activation of allergen-specific T cells, as well as the production of inflammatory cytokines. While IVM had no major impact on the functions of dendritic cells in vivo and in vitro, IVM impaired T-cell activation, proliferation, and cytokine production following polyclonal and antigen-specific stimulation. CONCLUSION: Altogether, our results show that IVM is endowed with topical anti-inflammatory properties that could have important applications for the treatment of T-cell-mediated skin inflammatory diseases.
Assuntos
Alérgenos/imunologia , Dermatite Atópica/imunologia , Ivermectina/administração & dosagem , Administração Tópica , Animais , Antígenos de Dermatophagoides/imunologia , Linhagem Celular , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Modelos Animais de Doenças , ELISPOT , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Ativação Linfocitária/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Receptores Purinérgicos P2X4/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismoRESUMO
Heparin is widely used as an anticoagulant and is indicated in the prevention and treatment of thromboembolic disorders. Heparin-induced delayed-type hypersensitivity presents as eczematous lesions, either at the injection site or generally, and affects 7.5% of patients on heparin. This poses diagnostic and therapeutic issues, since an alternative anticoagulant treatment is essential and the risk of cross-reactivity may be as high as 80%, depending on the type of heparin used. If delayed-type hypersensitivity is suspected, heparin-induced thrombocytopenia must first be ruled out, and heparin should be stopped. Fondaparinux is currently the first-line alternative, with a risk of cross-reactivity estimated at only 10%. The switch from a low-molecular-weight heparin (LMWH) to another LMWH is no longer recommended. The use of unfractionated heparin, danaparoid or hirudin may be warranted in the event of recurrence with fondaparinux, and an immuno-allergological work-up is needed to specify the exact profile of cross-allergies.
Assuntos
Anticoagulantes/efeitos adversos , Heparina/efeitos adversos , Hipersensibilidade Tardia/induzido quimicamente , Árvores de Decisões , Diagnóstico Diferencial , Humanos , Hipersensibilidade Tardia/diagnóstico , Hipersensibilidade Tardia/terapiaRESUMO
Adverse drug reactions (ADR) can result from immune-mediated (drug allergy) and nonimmune-mediated mechanisms. In both types of reaction, conclusive diagnosis and appropriate management remain major problems in daily clinical practice. This review summarizes the potentials and shortcomings of the currently available in vitro tests in the diagnosis of immediate (mostly IgE mediated) and nonimmediate (mostly T-cell mediated) drug allergy, particularly quantification of specific IgE, flow-assisted analysis of in vitro activated lymphocytes and basophils and the enzyme-linked immunosorbent spot.
Assuntos
Hipersensibilidade a Drogas/diagnóstico , Especificidade de Anticorpos/imunologia , Basófilos/imunologia , Biomarcadores , Citocinas/imunologia , Hipersensibilidade a Drogas/imunologia , Humanos , Imunoensaio , Imunoglobulina E , Ativação Linfocitária/imunologia , Linfócitos/imunologiaRESUMO
BACKGROUND: Delayed allergic skin reactions to drugs are common iatrogenic diseases mediated by activation of specific T cells in the skin. METHODS: To better understand the role of T cells in these diseases, we developed a mouse model of drug allergy induced by skin sensitization to amoxicillin (amox), a penicillin antibiotic frequently involved in delayed drug allergy. RESULTS: Whereas wild-type mice could not be sensitized to amox, CD4+ T-cell-deficient mice developed an amox-specific allergic skin response, mediated by IFN-gamma-producing CD8+ T cells. Amox-specific CD8+ T cells, induced in lymphoid organs at a high frequency during sensitization, were recruited in the skin upon challenge. CD8+ T cells were effectors of the allergic skin reaction to amox as in vivo treatment with depleting anti-CD8 mAbs abrogated the skin inflammatory reaction and as purified CD8+ T cells could adoptively transfer the allergic response to naive recipients. CONCLUSION: CD8+ T cells mediate penicillin skin allergy.
Assuntos
Amoxicilina/efeitos adversos , Linfócitos T CD8-Positivos/imunologia , Hipersensibilidade a Drogas , Dermatopatias , Amoxicilina/imunologia , Animais , Modelos Animais de Doenças , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/imunologia , Feminino , Humanos , Hipersensibilidade Tardia/etiologia , Hipersensibilidade Tardia/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Pele/imunologia , Dermatopatias/induzido quimicamente , Dermatopatias/imunologia , Testes CutâneosRESUMO
Allergic contact dermatitis (ACD), one of the commonest occupational diseases, is a T-cell-mediated skin inflammation caused by repeated skin exposure to contact allergens, i.e. nonprotein chemicals called haptens. Allergic contact dermatitis, also referred to as contact hypersensitivity, is mediated by CD8+ T cells, which are primed in lymphoid organs during the sensitization phase and are recruited in the skin upon re-exposure to the hapten. Subsets of CD4+ T cells endowed with suppressive activity are responsible for both the down-regulation of eczema in allergic patients and the prevention of priming to haptens in nonallergic individuals. Therefore, ACD should be considered as a breakdown of the skin immune tolerance to haptens. Recent advances in the pathophysiology of ACD have demonstrated the important role of skin innate immunity in the sensitization process and have revisited the dogma that Langerhans cells are mandatory for CD8+ T-cell priming. They have also introduced mast cells as a pivotal actor in the magnitude of the inflammatory reaction. Finally, the most recent studies address the nature, the mode and the site of action of the regulatory T cells that control the skin inflammation with the aim of developing new strategies of tolerance induction in allergic patients.
Assuntos
Dermatite Alérgica de Contato/imunologia , Sistema Imunitário/citologia , Dermatite Alérgica de Contato/patologia , Haptenos/imunologia , Humanos , Sistema Imunitário/imunologia , Tolerância ImunológicaRESUMO
Drug allergic reactions presenting as maculo-papular exanthema (MPE) are mediated by drug-specific T cells. In this study, the frequency of circulating specific T cells was analyzed by interferon-gamma (IFN-gamma) enzyme-linked immunospot assay in 22 patients with an allergic MPE to amoxicillin (amox). Amox-specific circulating T cells were detected in 20/22 patients with frequencies ranging from 1 : 8000 to 1 : 30 000 circulating leucocytes. No reactivity was observed in 46 control patients, including 15 patients with immunoglobulin E-mediated allergy to amoxicillin, 11 patients with a history of drug-induced MPE but tolerant to amoxicillin and 20 healthy individuals. Furthermore, amox-specific T cells were still detectable several years after the occurrence of the allergic reaction even after strict drug avoidance. Finally, analysis of drug-specific T cells in one patient allergic to ticarcillin (a penicillin antibiotic distinct from amox) revealed the presence of IFN-gamma-producing T cells reactive to ticarcillin and several other betalactam antibiotics, suggesting that the IFN-gamma ELISPOT assay is able to detect T cell cross-reactivity against chemically related drugs. These findings confirm that drug-induced MPE is associated with the presence of specific T cells in blood and further suggest that the IFN-gamma ELISPOT is a sensitive assay which could improve the diagnosis of betalactam allergy.
Assuntos
Amoxicilina/imunologia , Antibacterianos/imunologia , Hipersensibilidade a Drogas/imunologia , Penicilinas/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Criança , Pré-Escolar , Reações Cruzadas , Hipersensibilidade a Drogas/etiologia , Ensaio de Imunoadsorção Enzimática , Exantema/induzido quimicamente , Exantema/imunologia , Humanos , Lactente , Interferon gama/biossíntese , Interferon gama/imunologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Penicilinas/efeitos adversos , Dermatopatias/induzido quimicamente , Dermatopatias/imunologia , Testes Cutâneos , Linfócitos T/metabolismoRESUMO
Exposure of atopic dermatitis (AD) patients to aeroallergens or food allergens can exacerbate or maintain the disease. Atopy patch tests (APTs) are able to identify these triggering factors and consist of the epicutaneous application of allergens for 48hours with evaluation of the resulting eczematous lesions after 48 and 72hours, according to the reading criteria of the European Task Force on Atopic Dermatitis (ETFAD). APTs show a higher specificity than skin prick and specific IgE tests, since the pathophysiological mechanism of the reaction induced is very similar to what occurs in AD lesions. The standardization of APTs to aeroallergens has brought a certain degree of reliability to this method, which is not the case for food APTs, where the positive predictive value must be improved in order to avoid any unnecessary dietary restrictions. Thus, optimization of APTs and furtherance of knowledge of the pathophysiology of eczemas could help to develop new immunobiological diagnostic methods and AD-specific immunotherapy.
Assuntos
Dermatite Atópica/diagnóstico , Testes do Emplastro/métodos , Dermatite Atópica/etiologia , HumanosAssuntos
Benzoatos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Eosinofilia/patologia , Hipocalcemia/patologia , Quelantes de Ferro/efeitos adversos , Síndromes Mielodisplásicas/tratamento farmacológico , Triazóis/efeitos adversos , Idoso , Deferasirox , Eosinofilia/etiologia , Eosinofilia/metabolismo , Feminino , Humanos , Hipocalcemia/etiologia , Hipocalcemia/metabolismo , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/patologia , SíndromeAssuntos
Teste de Degranulação de Basófilos , Hipersensibilidade a Drogas/diagnóstico , Quinolonas/efeitos adversos , Adolescente , Idoso , Separação Celular , Hipersensibilidade a Drogas/imunologia , Feminino , Citometria de Fluxo , Humanos , Imunoglobulina E/imunologia , Pessoa de Meia-Idade , Diester Fosfórico Hidrolases/análise , Diester Fosfórico Hidrolases/metabolismo , Pirofosfatases/análise , Pirofosfatases/metabolismo , Quinolonas/imunologia , Sensibilidade e Especificidade , Testes CutâneosAssuntos
Anafilaxia/induzido quimicamente , Anafilaxia/diagnóstico , Anti-Inflamatórios/efeitos adversos , Teste de Degranulação de Basófilos , Metilprednisolona/efeitos adversos , Adolescente , Anafilaxia/imunologia , Anestesia Geral/efeitos adversos , Anti-Inflamatórios/imunologia , Separação Celular , Feminino , Citometria de Fluxo , Glucocorticoides/efeitos adversos , Glucocorticoides/imunologia , Humanos , Metilprednisolona/imunologia , Testes CutâneosRESUMO
Atopic dermatitis (AD) is a chronic inflammatory dermatosis due to the activation ofT-cell lymphocytes specific to protein antigens in the skin. The AD antigens come from molecules in the environment (extrinsic AD allergens associated with hyper IgE levels) or from self antigens (intrinsic AD autoantigens). The physiopathology of AD implies dendritic cells, specific T-cell lymphocytes, a network of type 1 and 2 cytokines and inflammatory chemokines. Extrinsic AD is the best known because of the existence of animal models and skin tests with allergens in humans (atopy patch tests), which reproduce eczema lesions. Although the role of the penetration of pneumo-allergens, prompted by abnormalities in the skin barrier, in inducing AD flares is established, recent works suggest that other types of allergens (trophallergens) and/or proteins derived from micro-organisms may be responsible in some patients. The ongoing studies on animal models of AD will no doubt permit rapid progression in our knowledge of the mechanisms involved in the origin of the disease and the reasons for its progressive increase in frequency.