RESUMO
Summary: The hunt for the causes and pathogenic mechanisms involved in chronic spontaneous urticaria (CSU) has engaged clinicians and scientists for decades. Although not all aspects of the disease are defined, our knowledge has now improved to the point that we can consider CSU as an umbrella clinical phenotype under which several different endotypes probably exist. The present article will briefly summarize the fascinating history of the progress in our knowledge of this disease.
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Urticária Crônica , Urticária , Humanos , Urticária/diagnóstico , Urticária/etiologia , Doença Crônica , Causalidade , FenótipoRESUMO
The consensus panel 2 (CP2) of the 11th International Workshop on Waldenström's macroglobulinemia (IWWM-11) has reviewed and incorporated current data to update the recommendations for treatment approaches in patients with relapsed or refractory WM (RRWM). The key recommendations from IWWM-11 CP2 include: (1) Chemoimmunotherapy (CIT) and/or a covalent Bruton tyrosine kinase (cBTKi) strategies are important options; their use should reflect the prior upfront strategy and are subject to their availability. (2) In selecting treatment, biological age, co-morbidities and fitness are important; nature of relapse, disease phenotype and WM-related complications, patient preferences and hematopoietic reserve are also critical factors while the composition of the BM disease and mutational status (MYD88, CXCR4, TP53) should also be noted. (3) The trigger for initiating treatment in RRWM should utilize knowledge of patients' prior disease characteristics to avoid unnecessary delays. (4) Risk factors for cBTKi related toxicities (cardiovascular dysfunction, bleeding risk and concurrent medication) should be addressed when choosing cBTKi. Mutational status (MYD88, CXCR4) may influence the cBTKi efficacy, and the role of TP53 disruptions requires further study) in the event of cBTKi failure dose intensity could be up titrated subject to toxicities. Options after BTKi failure include CIT with a non-cross-reactive regimen to one previously used CIT, addition of anti-CD20 antibody to BTKi, switching to a newer cBTKi or non-covalent BTKi, proteasome inhibitors, BCL-2 inhibitors, and new anti-CD20 combinations are additional options. Clinical trial participation should be encouraged for all patients with RRWM.
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Antineoplásicos , Macroglobulinemia de Waldenstrom , Humanos , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética , Fator 88 de Diferenciação Mieloide/genética , Consenso , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico , Antineoplásicos/uso terapêuticoRESUMO
Summary: The autologous serum skin test (ASST) has been used in patients with chronic spontaneous urticaria (CSU) as a means to detect an autoreactivity state for thirty-five years now. Nonetheless, several aspects of this old diagnostic test are still insufficiently defined. Particularly, the nature of the factor(s) responsible for the appearance of the wheal-and-flare skin reaction is still poorly characterized. This article will review our current knowledge about the clinical significance of the ASST and the factors possibly associated with the occurrence of the skin reaction following the intradermal administration of autologous serum that are known so far.
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Urticária Crônica , Urticária , Humanos , Doença Crônica , Pele , Testes Cutâneos , Urticária/diagnósticoAssuntos
Oncologia/normas , Recidiva Local de Neoplasia/terapia , Medicina de Precisão/normas , Sociedades Médicas/normas , Macroglobulinemia de Waldenstrom/terapia , Assistência ao Convalescente/métodos , Assistência ao Convalescente/normas , Idade de Início , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças Assintomáticas/terapia , Medula Óssea/patologia , Europa (Continente) , Humanos , Incidência , Oncologia/métodos , Fator 88 de Diferenciação Mieloide/genética , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Plasmaferese/métodos , Plasmaferese/normas , Medicina de Precisão/métodos , Receptores CXCR4/genética , Transplante de Células-Tronco/métodos , Transplante de Células-Tronco/normas , Sobrevivência , Transplante Autólogo/métodos , Transplante Autólogo/normas , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/epidemiologia , Macroglobulinemia de Waldenstrom/patologiaRESUMO
BACKGROUND: Erythema-directed digital photography is a novel method for evaluating the efficacy and tolerability of topical acne treatments. Here, we describe three case reports in which erythema-directed digital photography was used to evaluate acne before and after up to 12 weeks of treatment with clindamycin 1%/tretinoin 0.025% (Clin-RA). MATERIALS AND METHODS: Erythema-directed digital photography was used to evaluate acne in three patients with mild-to-moderate facial acne, two of whom had refused to continue previous topical acne treatment (benzoyl peroxide 5% and clindamycin 1%/benzoyl peroxide 5%) due to persistent irritation. Acne lesions and erythema were evaluated using standard clinical photography and erythema-directed digital photography (VISIA-CR™ system) before and after 8-12 weeks of treatment with Clin-RA. RESULTS: Erythema-directed digital photography revealed background erythema from previous topical acne treatments that was not evident from standard clinical photographs and allowed a better visualization of both inflammatory and non-inflammatory lesions. In all patients, there was a clear improvement in background erythema and a reduction in acne lesions following treatment with Clin-RA. CONCLUSION: This study has demonstrated for the first time that erythema-directed digital photography can enhance the evaluation of the efficacy and tolerability of topical acne treatments. These cases show that Clin-RA was associated with improved efficacy and tolerability vs previous treatments with topical monotherapy (benzoyl peroxide 5%) or a topical fixed-dose combination (clindamycin 1%/benzoyl peroxide 5%).
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Acne Vulgar/diagnóstico por imagem , Eritema/diagnóstico por imagem , Fotografação , Acne Vulgar/tratamento farmacológico , Administração Cutânea , Adolescente , Peróxido de Benzoíla/efeitos adversos , Clindamicina/efeitos adversos , Clindamicina/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Combinação de Medicamentos , Eritema/induzido quimicamente , Feminino , Humanos , Masculino , Resultado do Tratamento , Tretinoína/uso terapêutico , Adulto JovemRESUMO
INTRODUCTION: Patients with haemophilia B who develop factor IX (FIX) neutralizing antibodies (inhibitors) after FIX infusion are at high risk of hypersensitivity reactions upon FIX re-exposure, but the underlying mechanisms are incompletely understood. AIM: To investigate biomechanisms of FIX hypersensitivity. METHODS: A cellular antigen stimulation test (CAST) was employed to evaluate leukotriene C4 (LTC4) release from basophils stimulated by FIX in three treated children with haemophilia B, one of whom developed FIX inhibitor and experienced anaphylaxis following FIX re-exposure. Anti-FIX IgE and IgG antibodies and markers of complement activation (C5b9, C3d and iC3b) were measured in plasma, the last also after FIX infusion. Ten healthy children served as controls. RESULTS: The patient who developed anti-FIX inhibitors and anaphylaxis had a nonsense mutation in FIX gene (p.Arg298Stop) and, compared to controls, had higher plasma levels of specific anti-FIX IgE (2.285 vs 0.084 OD492 nm ), with marked LTC4 release from his FIX-stimulated basophils (519.8 vs 39.9 pg/mL). Further, he had higher plasma levels of anti-FIX IgG of all the four subclasses (total IgG 1.180 vs 0.120 OD492 nm ) with FIX neutralizing activity (1.5 BU); mild complement activation occurred during FIX-induced anaphylaxis (C5b9 increased from 258.5 to 351.1 ng/mL). The same parameters were normal in the two patients who tolerated FIX infusion. CONCLUSION: In the patient with haemophilia B who experienced anaphylaxis after FIX, but not in the patients with haemophilia B who tolerated FIX, the CAST assay showed FIX-induced LTC4 release, which was associated with high plasma levels of specific anti-FIX IgE and IgG antibodies.
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Anafilaxia/complicações , Anticorpos Neutralizantes/imunologia , Basófilos/imunologia , Ativação do Complemento , Fator IX/imunologia , Hemofilia B/imunologia , Imunoglobulina E/imunologia , Pré-Escolar , Hemofilia B/complicações , Humanos , MasculinoAssuntos
Anemia Hemolítica Autoimune/etiologia , Antineoplásicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/etiologia , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Adenina/análogos & derivados , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Ensaios Clínicos Fase III como Assunto , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Piperidinas , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: Functionally active autoantibodies to IgE and to the high-affinity IgE receptor (FcεRI) can be detected in serum in about 40% of patients with chronic spontaneous urticaria (CSU). Recent studies showed that serum from patients with CSU can induce activation of mast cells, irrespective of whether they carry high-affinity IgE receptors. To evaluate mast cell activation induced by factors in the serum of CSU patients with a molecular weight lower than that of autoantibodies. METHODS: Eight CSU patients and 5 healthy controls were evaluated. Whole serum and serum fractionated at 100, 50, and 30 kDa were used to stimulate in vitro LAD2 mast cells. The enzymatic activity of ß-hexosaminidase was evaluated in supernatants and cell pellets as a measure of mast cell degranulation. RESULTS: Mean (SEM) release of mast cell ß-hexosaminidase induced by whole serum from CSU patients was higher than that induced by serum from the healthy controls (14.4 [2.7%] vs 5.1 [2.4%]; P=.027). In addition, serum fractions below 100 kDa and below 50 kDa from CSU patients induced mast cell degranulation that was significantly higher than that induced by the corresponding fractions in sera from healthy controls (10.2% [1.4%] vs 3.8% [1.9%] [P=.024] and 10.1% [1.2%] vs 3.9% [1.7%] [P=.012], respectively). In 4 CSU patients, we evaluated serum fractions <30 kDa, which retained their capacity to activate mast cells (11.0% [0.7%]). CONCLUSIONS: This study shows that sera from CSU patients may contain low-molecular-weight mast cell-activating factors other than autoantibodies. These factors could be an additional mechanism contributing to the pathogenesis of CSU.
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Fatores Imunológicos/sangue , Fatores Imunológicos/imunologia , Mastócitos/imunologia , Urticária/sangue , Urticária/imunologia , Adulto , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoanticorpos/metabolismo , Doença Crônica , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de IgE/sangue , Receptores de IgE/imunologia , Urticária/metabolismo , Adulto Jovem , beta-N-Acetil-Hexosaminidases/metabolismoRESUMO
BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disease due to autoantibodies against two hemidesmosomal antigens, namely BP180 and BP230, and characterized by coagulation activation both at cutaneous and systemic levels. Skin-infiltrating eosinophils contribute to bulla formation and, upon activation, are supposed to initiate the coagulation cascade. OBJECTIVE: The aim of this study was to investigate whether the activation of eosinophils and coagulation are linked in BP. METHODS: We evaluated the correlation between eosinophil cationic protein (ECP) levels and concentrations of the prothrombotic markers F1 + 2 and D-dimer in blister fluid and blood samples of 30 BP patients. Thirty healthy subjects were used as normal controls. RESULTS: ECP, F1 + 2 and D-dimer plasma levels were significantly higher in BP patients than in normal subjects. A significant correlation was found between ECP plasma levels and blood eosinophil count (r = 0.54, P = 0.002). F1 + 2 plasma levels positively correlated with disease severity, expressed as the percentage of body surface area involved (r = 0.36, P = 0.048). A striking increase in ECP (288.8 ± 45.2 ng/mL), F1 + 2 (31 409.9 ± 2929.4 pmol/L) and D-dimer levels (342 798.3 ± 44 206 ng/mL) was found in blister fluid from BP patients. In blister fluid, ECP levels were significantly higher than in peripheral blood (P < 0.0001) and were positively correlated with the levels of both F1 + 2 (r = 0.4, P = 0.02) and D-dimer (r = 0.5, P = 0.0045). CONCLUSIONS: ECP levels are strikingly elevated in blister fluids from BP patients and correlate with markers of coagulation activation, supporting the view that eosinophils initiate the coagulation cascade at skin level.
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Vesícula/metabolismo , Proteína Catiônica de Eosinófilo/sangue , Eosinófilos , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Penfigoide Bolhoso/sangue , Fragmentos de Peptídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Protrombina , Índice de Gravidade de DoençaRESUMO
AIM: The aim of this review was to evaluate, by a thorough revision of the literature, the true efficacy of currently available topic and systemic cosmetic acne agents. METHODS: The efficacy of currently available cosmetic acne agents has been retrospectively evaluated via thorough revision of the literature on matched electronic databases (PubMed). All retrieved studies, either randomized clinical trials or clinical trials, controlled or uncontrolled were considered. RESULTS: Scientific evidence suggests that most cosmetic products for acne may enhance the clinical outcome. Cleansers should be indicated to all acne patients; those containing benzoyl peroxide or azelaic/salicylic acid/triclosan show the best efficacy profile. Sebum-controlling agents containing nicotinamide or zinc acetate may minimize excessive sebum production. Cosmetics with antimicrobial and anti-inflammatory substances such as, respectively, ethyl lactate or phytosphingosine and nicotinamide or resveratrol, may speed acne recovery. Topical corneolytics, including retinaldehyde/glycolic acid or lactic acid, induce a comedolytic effect and may also facilitate skin absorption of topical drugs. Finally, the use of specific moisturizers should be strongly recommended in all acne patients. CONCLUSION: Cosmetics, if correctly prescribed, may improve the performance of the therapy, whereas wrong procedures and/or inadequate cosmetics may worsen acne. Cosmetological recommendations may allow clinicians to make informed decisions about the role of various cosmetics and to indentify the appropriate indications and precautions. The choice of the most effective product should take into consideration the ongoing pharmacological therapy and acne type/severity as well.
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Acne Vulgar/tratamento farmacológico , Cosméticos/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Acne Vulgar/patologia , Administração Cutânea , Cosméticos/efeitos adversos , Cosméticos/farmacologia , Fármacos Dermatológicos/farmacocinética , Fármacos Dermatológicos/farmacologia , Medicina Baseada em Evidências , Humanos , Absorção CutâneaRESUMO
Chronic urticaria (CU) is a widespread skin disease, characterized by the recurrence of transient wheals and itch for more than 6 weeks. Besides autoimmune mechanisms, coagulation factors, in particular tissue factor and thrombin, might also participate in the disease pathophysiology. Tissue factor expressed by eosinophils can induce activation of blood coagulation generating thrombin which in turn can increase vascular permeability both directly, acting on endothelial cells, and indirectly, inducing degranulation of mast cells with release of histamine, as demonstrated in experimental models. D-dimer, a fibrin degradation product, generated following activation of the coagulation cascade and fibrinolysis, has been found to be increased during urticaria exacerbations; moreover, it has been proposed as a biomarker of severity and resistance to H1-antihistamines in CU patients. The possible role of coagulation in CU is also supported by case reports, case series and a small controlled study showing the efficacy of anticoagulant therapy in this disease. The purpose of this review was to summarize the available data on the possible contribution of coagulation to the pathophysiology of CU focusing on clinical aspects and possible future therapeutic developments.