RESUMEN
Recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) with a predominant Th2 endotype of inflammation, including associated with bronchial asthma and/or allergic rhinitis, aspirin triad, refers to diseases with an insufficient level of control, despite the use of a wide range of options for conservative and surgical treatment. OBJECTIVE: To analyze our own experience, clinical and organizational features of the application of the method of biological therapy in patients with severe forms of recurrent CRSwNP. MATERIAL AND METHODS: 25 patients with severe and moderate forms of CRSwNP were examined, who, in a round-the-clock hospital (model CSG 36.018) was treated with Dupilumab, in the form of subcutaneous injections of 300 mg/2 ml 1 every two weeks. The diagnosis was confirmed on the basis of anamnestic data, SNOT-22 quality of life questionnaires, visual endoscopic examination, evaluation of CT data (Lund-Mackay scale), laboratory data. The effectiveness of treatment was monitored after 16 weeks, based on endoscopic examination data, evaluation of CT and SNOT-22 data. In 3 observations, a study of pathomorphological material for tissue eosinophilia was performed. RESULTS: The duration of the course of treatment ranged from 10 to 56 weeks. The most striking clinical effect was observed for signs such as sense of smell and nasal breathing (in some cases-after the first injection). The degree of regression of polyps according to CT and endoscopic examination was more prolonged in time, the same dynamics was observed in the level of total IgE. In a number of patients, the phenomenon of eosinophilia growth was observed against the background of treatment (with regression of clinical symptoms). Pathomorphological examination confirmed a high level of tissue eosinophilia as one of the fundamental signs of Th2 inflammation. One patient with concomitant chronic tubar dysfunction had an improvement in hearing. All patients with AD noted a subjective improvement in disease control (a decrease in the frequency and severity of choking attacks). The cancellation (break in treatment) of treatment was accompanied by a gradual return of symptoms in all patients at various times. CONCLUSIONS: Patients who have not achieved an acceptable level of control of CRSwNP,that meets the criteria of Th2 inflammation can be considered as candidates for the use of targeted biological therapy. With strict compliance with the selection criteria, there is a good clinical effect, primarily in relation to nasal symptoms (sense of smell and nasal breathing) and improved control of asthma symptoms.
Asunto(s)
Asma , Eosinofilia , Pólipos Nasales , Rinitis , Sinusitis , Humanos , Pólipos Nasales/complicaciones , Pólipos Nasales/diagnóstico , Pólipos Nasales/tratamiento farmacológico , Calidad de Vida , Rinitis/complicaciones , Rinitis/diagnóstico , Rinitis/tratamiento farmacológico , Sinusitis/complicaciones , Sinusitis/diagnóstico , Sinusitis/tratamiento farmacológico , Eosinofilia/complicaciones , Eosinofilia/diagnóstico , Eosinofilia/tratamiento farmacológico , Inflamación , Terapia Biológica , Atención a la Salud , Enfermedad CrónicaRESUMEN
Eosinophilic fasciitis (EF) is a rare condition in children that is typically treated with systemic corticosteroids. We present the case of a 9-year-old boy with biopsy-proven EF, refractory to systemic corticosteroids and methotrexate. The tyrosine kinase inhibitor imatinib was added as adjuvant therapy, leading to improvement in joint function and skin laxity. Our case is the first to suggest the anti-fibrotic properties of imatinib may benefit EF patients.
Asunto(s)
Eosinofilia , Fascitis , Corticoesteroides , Niño , Eosinofilia/tratamiento farmacológico , Fascitis/diagnóstico , Fascitis/tratamiento farmacológico , Humanos , Mesilato de Imatinib/uso terapéutico , MasculinoRESUMEN
RATIONALE: Sparganosis is an infectious disease caused by a larval tapeworm of the genus Spirometra, which commonly invades subcutaneous tissues. Pulmonary and pleural involvement due to sparganum has been rarely reported previously. PATIENT CONCERNS: We herein described a case of recurrent eosinophilic pleuritis in a 24-year-old woman. She was admitted with persistent cough and shortness of breath for more than 1 month. Initial chest computed tomography scan suggested right pleural effusion and diffuse pleural thickening. Slightly elevated eosinophil counts were found in both the peripheral blood and pleural fluid. She underwent right pleurectomy but histological examination failed to obtain an etiological diagnosis. Moreover, eosinophilic pleural effusion re-appeared in the contralateral thoracic cavity one month later. After re-admission, we reviewed her medical history meticulously and found she had a history of ingesting raw snake gallbladders before hospitalization. The final diagnosis was confirmed by the markedly positive reaction against sparganum antigen in both serum and pleural fluid sample. DIAGNOSIS: Eosinophilic pleuritis caused by sparganum infection. INTERVENTIONS: After the diagnosis, the patient was treated with praziquantel at 75âmg/kg/d for 3 days. OUTCOMES: Pleural effusion absorbed completely and eosinophil count in peripheral blood returned to normal range. No evidence of recurrent pleural effusion had been observed in over one year of follow-up. LESSONS: Clinicians need to be aware the possibility of sparganum infection in cases of eosinophilic pleuritis. The specific enzyme-linked immunosorbent assay remains a useful method in acquiring a rapid diagnosis, especially when histological examination is unable to detect the larvae in the thoracic cavity.
Asunto(s)
Eosinofilia/parasitología , Pleuresia/parasitología , Esparganosis/diagnóstico , Antihelmínticos/uso terapéutico , Diagnóstico Diferencial , Ensayo de Inmunoadsorción Enzimática , Eosinofilia/tratamiento farmacológico , Femenino , Humanos , Medicina Tradicional China/efectos adversos , Pleuresia/tratamiento farmacológico , Praziquantel/uso terapéutico , Recurrencia , Esparganosis/tratamiento farmacológico , Adulto JovenRESUMEN
Eosinophilic inflammation is a component of many atopic diseases such as asthma, and biologics targeting eosinophils have been shown to be effective in subsets of these patients. However, there also are conditions in which eosinophils are the key inflammatory cells responsible for driving tissue damage. In these eosinophilic diseases such as hyper-eosinophilic syndrome, eosinophilic esophagitis, and eosinophilic granulomatosis with polyangiitis (EGPA), the development of biologics inhibiting eosinophilic inflammation have offered targeted therapeutic strategies for patients that have not responded well to typical first line drugs, which often have significant adverse side effects with poor disease modification or recurrent relapse with significant morbidity. IL-5 has long been recognized as the key inflammatory cytokine involved in the priming and survival of eosinophils and their proliferation and maturation in eosinophilic disease. There are a number of trials and case series demonstrating the immunomodulatory benefits of anti-IL-5 therapies in these diseases with good clinical responses. Yet, due to the heterogeneity and rarity of these conditions, anti-IL-5 therapies have not resulted in disease remission for all patients. Clearly, further research into the use of anti-IL-5 therapies in various eosinophilic diseases is needed and ongoing investigation into other immune mechanisms underlying chronic eosinophilic diseases may provide alternative therapies for these challenging conditions.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Eosinofilia/tratamiento farmacológico , Síndrome Hipereosinofílico/tratamiento farmacológico , Interleucina-5/antagonistas & inhibidores , Terapia Molecular Dirigida , Anticuerpos Monoclonales/farmacología , Biomarcadores , Ensayos Clínicos como Asunto , Diagnóstico Diferencial , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Eosinofilia/diagnóstico , Eosinofilia/etiología , Eosinofilia/metabolismo , Humanos , Síndrome Hipereosinofílico/diagnóstico , Síndrome Hipereosinofílico/etiología , Síndrome Hipereosinofílico/metabolismo , Pronóstico , Resultado del TratamientoRESUMEN
S-Allyl cysteine (SAC) is an active component in garlic and has various pharmacological effects, such as anti-inflammatory, anti-oxidant, and anti-cancer activities. In this study, we explored the suppressive effects of SAC on allergic airway inflammation induced in an ovalbumin (OVA)-induced asthma mouse model. To induce asthma, BALB/c mice were sensitized to OVA on days 0 and 14 by intraperitoneal injection and exposed to OVA from days 21 to 23 using a nebulizer. SAC was administered to mice by oral gavage at a dose of 10 or 20â¯mg/kg from days 18 to 23. SAC significantly reduced airway hyperresponsiveness, inflammatory cell counts, and Th2 type cytokines in bronchoalveolar lavage fluid induced by OVA exposure, which was accompanied by reduced serum OVA-specific immunoglobulin E. In histological analysis of the lung tissue, administration of SAC reduced inflammatory cell accumulation into lung tissue and mucus production in airway goblet cells induced by OVA exposure. Additionally, SAC significantly decreased MUC5AC expression and nuclear factor-κB phosphorylation induced by OVA exposure. In summary, SAC effectively suppressed allergic airway inflammation and mucus production in OVA-challenged asthmatic mice. Therefore, SAC shows potential for use in treating allergic asthma.
Asunto(s)
Antiasmáticos/uso terapéutico , Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Cisteína/análogos & derivados , Eosinofilia/tratamiento farmacológico , Alérgenos , Animales , Antiasmáticos/farmacología , Antiinflamatorios/farmacología , Asma/inmunología , Asma/patología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Cisteína/farmacología , Cisteína/uso terapéutico , Citocinas/inmunología , Modelos Animales de Enfermedad , Eosinofilia/inmunología , Eosinofilia/patología , Femenino , Inmunoglobulina E/sangre , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Ratones Endogámicos BALB C , Moco/metabolismo , OvalbúminaRESUMEN
Zizyphus jujuba Mill, a famous oriental traditional medicine, has been reported to exhibit diverse activities in biological systems including the respiratory system. However, a little information is available on its antiasthmatic activity. Jujuboside B (JB) is a natural saponin and one of the active constituent of fruits of Zizyphus jujuba. In the present investigation, JB was isolated from ethanolic extracts of fruits of Zizyphus jujuba (EZJF). EZJF and JB were then evaluated for anti-asthmatic activity using various screening methods. JB was additionally evaluated using ovalbumin (OVA) -induced allergic asthma in mice. Results obtained in the present study showed that EZJF and JB significantly inhibited clonidine-induced catalepsy, milk-induced leucocytosis and eosinophilia, clonidine-induced mast cell degranulation, and passive paw anaphylaxis. The number of inflammatory cells in bronchoalveolar lavage (BAL) fluid was considerably lowered and the severity of pulmonary inflammation was alleviated in the mice pretreated with JB. The high-level expression of T-helper type 2 (TH2) cytokines was markedly reduced in the serum, BAL fluid, and lung homogenates. Thus EZJF and JB showed potent anti-asthmatic activity. Hence EZJF and JB possess a potential role in the treatment of asthma.
Asunto(s)
Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Saponinas/uso terapéutico , Ziziphus/química , Animales , Antiasmáticos/farmacología , Asma/inducido químicamente , Catalepsia/inducido químicamente , Catalepsia/tratamiento farmacológico , Clonidina/farmacología , Clonidina/uso terapéutico , Citocinas/metabolismo , Modelos Animales de Enfermedad , Eosinofilia/tratamiento farmacológico , Leucocitosis/inducido químicamente , Leucocitosis/tratamiento farmacológico , Pulmón/patología , Mastocitos/efectos de los fármacos , Medicina Tradicional China , Ratones , Leche/toxicidad , Ovalbúmina/toxicidad , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Saponinas/farmacologíaRESUMEN
BACKGROUND: The interaction of IL-5 with its receptor on eosinophils increases the activation and maintenance of eosinophils; blocking this interaction reduces asthma symptoms in patients with the eosinophilic phenotype. Reslizumab, which binds to IL-5, and benralizumab, which targets the IL-5 receptor α subunit, have not been compared in head-to-head trials. OBJECTIVE: To indirectly compare reslizumab with benralizumab in similar patient populations using a network meta-analysis. METHODS: A systematic literature review was conducted and a network meta-analysis was performed on eligible studies using the Markov Chain Monte-Carlo simulation method and a Bayesian statistical framework. RESULTS: Eleven studies were identified, 4 of which evaluated clinically relevant doses and had outcomes at similar time points. To control for population differences, subgroups were selected for the base-case efficacy analysis: a benralizumab subgroup with blood eosinophil levels of greater than or equal to 300 cells/µL (n = 1537) and a reslizumab subgroup in Global Initiative for Asthma step 4/5 with 2 or more previous exacerbations and greater than or equal to 400 eosinophils/µL (n = 318). Safety was analyzed in the full population (N = 3462). Reslizumab significantly improved Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) scores compared with benralizumab once every 4 weeks and there were reasonably high posterior probabilities that reslizumab is superior to benralizumab once every 4 weeks and once every 8 weeks for ACQ score, AQLQ score, FEV1, and clinical asthma exacerbations. CONCLUSIONS: This indirect comparison suggests that reslizumab may be more efficacious than benralizumab in patients with eosinophilic asthma in Global Initiative for Asthma step 4/5 with elevated blood eosinophil levels (benralizumab, ≥300/µL; reslizumab, ≥400/µL) and 2 or more exacerbations in the previous year.
Asunto(s)
Antiasmáticos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/tratamiento farmacológico , Eosinofilia/tratamiento farmacológico , Eosinófilos/inmunología , Teorema de Bayes , Terapia Biológica , Progresión de la Enfermedad , Humanos , Interleucina-5/antagonistas & inhibidores , Subunidad alfa del Receptor de Interleucina-5/antagonistas & inhibidores , Recuento de Leucocitos , Metaanálisis en Red , Calidad de VidaRESUMEN
Some patients with chronic obstructive pulmonary disease (COPD) have eosinophilic inflammation which may be evaluated via the measurement of fractional exhaled nitric oxide (FeNO) like asthma. The aim of this prospective study was to assess whether FeNO levels can be used to identify patients with COPD with eosinophilic inflammation who may respond to inhaled corticosteroid (ICS) therapy.This study included patients (Nâ=â112) with COPD (age >18 years) who were divided into 4 groups depending upon whether they had high (≥25 parts per billion [ppb]) or low (<25 ppb) pretreatment (baseline) FeNO and if they were treated with either ICS plus long-acting ß-agonist (ICSâ+âLABA) or a long-acting muscarinic antagonist (LAMA). The 4 groups were: high FeNO/ICSâ+âLABA, high FeNO/LAMA, low FeNO/ICSâ+âLABA, and low FeNO/LAMA. Outcomes assessed included FeNO, COPD assessment test (CAT), and pulmonary function.The high FeNO/ICSâ+âLABA group had the greatest reduction from baseline in FeNO levels (-25.80 ppbâ±â27.14) compared with the high FeNO/LAMA, low FeNO/ICSâ+âLABA, and low FeNO/LAMA groups (range, -4.45 to 1.31 ppb; Pâ<â.001). The high FeNO/ICSâ+âLABA group also showed the greatest improvement in CAT (-7.20), which was statistically larger than the low FeNO/ICSâ+âLABA and low FeNO/LAMA groups (-1.72 and -2.03, respectively). No difference in pulmonary function following treatment was observed across the 4 groups.This study found that patients with high FeNO showed the greatest reduction in FeNO and improvement in CAT with ICSâ+âLABA therapy, supporting the use of FeNO to identify patients who would benefit from ICS use.
Asunto(s)
Corticoesteroides/uso terapéutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Eosinofilia/tratamiento farmacológico , Eosinofilia/fisiopatología , Óxido Nítrico/análisis , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Administración por Inhalación , Anciano , Anciano de 80 o más Años , Pruebas Respiratorias , Femenino , Flujo Espiratorio Forzado , Humanos , Masculino , Flujo Espiratorio Medio Máximo , Persona de Mediana Edad , Estudios Prospectivos , Capacidad VitalRESUMEN
BACKGROUND: Asthma is a chronic inflammatory airway disease in which innate and adaptive immune cells act together to cause eosinophilic inflammation, goblet cell metaplasia (GCM), and bronchial hyperreactivity (BHR). In clinical trials using biologicals against IL-4 receptor (IL-4R) α or IL-5, only a subset of patients with moderate-to-severe asthma responded favorably, suggesting that distinct pathophysiologic mechanisms are at play in subgroups of patients called endotypes. However, the effect of multiple cytokine blockade using bispecific antibodies has not been tested. OBJECTIVE: We sought to target simultaneously the IL-4, IL-13, and IL-5 signaling pathways with a novel IL-4Rα/IL-5-bispecific antibody in a murine house dust mite (HDM) model of asthma. METHODS: Two mAbs neutralizing IL-4Rα and IL-5 were generated by using a llama-based antibody platform. Their heavy and light chains were then cotransfected in mammalian cells, resulting in a heterogeneous antibody mixture from which the bispecific antibody was isolated by using a dual anti-idiotypic purification process. C57BL/6J mice were finally sensitized and challenged to HDM extracts and treated during challenge with the antibodies. RESULTS: We successfully generated and characterized the monospecific and bispecific antibodies targeting IL-4Rα and IL-5. The monospecific antibodies could suppress eosinophilia, IgE synthesis, or both, whereas only the IL-4Rα/IL-5-bispecific antibody and the combination of monospecific antibodies additionally inhibited GCM and BHR. CONCLUSION: Type 2 cytokines act synergistically to cause GCM and BHR in HDM-exposed mice. These preclinical results show the feasibility of generating bispecific antibodies that target multiple cytokine signaling pathways as superior inhibitors of asthma features, including the difficult-to-treat GCM.
Asunto(s)
Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Neutralizantes/uso terapéutico , Asma/tratamiento farmacológico , Citocinas/antagonistas & inhibidores , Eosinofilia/tratamiento farmacológico , Animales , Anticuerpos Monoclonales/uso terapéutico , Asma/inmunología , Asma/patología , Asma/fisiopatología , Camélidos del Nuevo Mundo , Línea Celular , Citocinas/inmunología , Eosinofilia/inmunología , Eosinofilia/patología , Eosinofilia/fisiopatología , Escherichia coli , Femenino , Células Caliciformes/efectos de los fármacos , Células Caliciformes/patología , Humanos , Ratones Endogámicos C57BL , Pyroglyphidae/inmunologíaRESUMEN
BACKGROUND: We and others have shown that the gamma tocopherol (γT) isoform of vitamin E has multiple anti-inflammatory and antioxidant actions and that γT supplementation reduces eosinophilic and endotoxin (LPS)-induced neutrophilic airway inflammation in animal models and healthy human volunteers. OBJECTIVE: We sought to determine whether γT supplementation reduces eosinophilic airway inflammation and acute neutrophilic response to inhaled LPS challenge in volunteers with asthma. METHODS: Participants with mild asthma were enrolled in a double-blinded, placebo-controlled crossover study to assess the effect of 1200 mg of γT daily for 14 days on sputum eosinophils, mucins, and cytokines. We also assessed the effect on acute inflammatory response to inhaled LPS challenge following γT treatment, focusing on changes in sputum neutrophilia, mucins, and cytokines. Mucociliary clearance was measured using gamma scintigraphy. RESULTS: Fifteen subjects with mild asthma completed both arms of the study. Compared with placebo, γT notably reduced pre-LPS challenge sputum eosinophils and mucins, including mucin 5AC and reduced LPS-induced airway neutrophil recruitment 6 and 24 hours after challenge. Mucociliary clearance was slowed 4 hours postchallenge in the placebo group but not in the γT treatment group. Total sputum mucins (but not mucin 5AC) were reduced at 24 hours postchallenge during γT treatment compared with placebo. CONCLUSIONS: When compared with placebo, γT supplementation for 14 days reduced inflammatory features of asthma, including sputum eosinophils and mucins, as well as acute airway response to inhaled LPS challenge. Larger scale clinical trials are needed to assess the efficacy of γT supplements as a complementary or steroid-sparing treatment for asthma.
Asunto(s)
Asma/tratamiento farmacológico , Endotoxinas/efectos adversos , Eosinofilia/tratamiento farmacológico , Eosinófilos/efectos de los fármacos , Infiltración Neutrófila/efectos de los fármacos , Vitaminas/uso terapéutico , gamma-Tocoferol/uso terapéutico , Adulto , Asma/inmunología , Asma/metabolismo , Biomarcadores/metabolismo , Estudios Cruzados , Método Doble Ciego , Esquema de Medicación , Endotoxinas/administración & dosificación , Endotoxinas/inmunología , Eosinofilia/metabolismo , Eosinófilos/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mucinas/metabolismo , Esputo/efectos de los fármacos , Esputo/metabolismo , Resultado del Tratamiento , Vitaminas/farmacología , gamma-Tocoferol/farmacologíaRESUMEN
A 42 year old woman visited on our hospital because of cough, sputum, pruritus and erythema. She showed peripheral blood eosinophilia, high level of FENO, bronchial hyperresponsiveness. Diagnosis of bronchial asthma and atopic dermatitis was made, but she rejected therapy except for Saibokutou, a Kampo herbal medicine. After 1 year, her symptoms and her laboratory data were improved.
Asunto(s)
Asma/tratamiento farmacológico , Hiperreactividad Bronquial/tratamiento farmacológico , Eosinofilia/tratamiento farmacológico , Medicina Kampo , Adulto , Asma/complicaciones , Asma/inmunología , Pruebas Respiratorias , Hiperreactividad Bronquial/complicaciones , Hiperreactividad Bronquial/inmunología , Eosinofilia/etiología , Eosinofilia/inmunología , Femenino , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: Eosinophilic myocarditis encompasses a variety of etiologies and the prognosis varies. For patients with a hypersensitive response to medications, high-dose corticosteroids and discontinuation of culprit medications are the main treatments. CASE PRESENTATION: We reported a young man with biopsy-proven eosinophilic myocarditis which was possibly induced by Chinese herbal medicine. His heart failure and left ventricular hypertrophy improved soon after low-dose corticosteroid. CONCLUSION: Low-dose corticosteroid may be effective in selected patients with eosinophilic myocarditis. Early echocardiographic follow-up is mandatory for evaluation of the clinical response.
Asunto(s)
Corticoesteroides/administración & dosificación , Medicamentos Herbarios Chinos/efectos adversos , Eosinofilia/tratamiento farmacológico , Miocarditis/tratamiento farmacológico , Prednisolona/administración & dosificación , Enfermedad Aguda , Adulto , Biopsia , Ecocardiografía , Eosinofilia/inducido químicamente , Eosinofilia/diagnóstico , Eosinofilia/inmunología , Insuficiencia Cardíaca/etiología , Humanos , Hipertrofia Ventricular Izquierda/etiología , Masculino , Miocarditis/inducido químicamente , Miocarditis/diagnóstico , Miocarditis/inmunología , Inducción de Remisión , Factores de Tiempo , Resultado del TratamientoRESUMEN
Morphea, also known as localized scleroderma, encompasses a group of idiopathic sclerotic skin diseases. The spectrum ranges from relatively mild phenotypes, which generally cause few problems besides local discomfort and visible disfigurement, to subtypes with severe complications such as joint contractures and limb length discrepancies. Eosinophilic fasciitis (EF, Shulman syndrome) is often regarded as belonging to the severe end of the morphea spectrum. The exact driving mechanisms behind morphea and EF pathogenesis remain to be elucidated. However, extensive extracellular matrix formation and autoimmune dysfunction are thought to be key pathogenic processes. Likewise, these processes are considered essential in systemic sclerosis (SSc) pathogenesis. In addition, similarities in clinical presentation between morphea and SSc have led to many theories about their relatedness. Importantly, morphea may be differentiated from SSc based on absence of sclerodactyly, Raynaud's phenomenon, and nailfold capillary changes. The diagnosis of morphea is often based on characteristic clinical findings. Histopathological evaluation of skin biopsies and laboratory tests are not necessary in the majority of morphea cases. However, full-thickness skin biopsies, containing fascia and muscle tissue, are required for the diagnosis of EF. Monitoring of disease activity and damage, especially of subcutaneous involvement, is one of the most challenging aspects of morphea care. Therefore, data harmonization is crucial for optimizing standard care and for comparability of study results. Recently, the localized scleroderma cutaneous assessment tool (LoSCAT) has been developed and validated for morphea. The LoSCAT is currently the most widely reported outcome measure for morphea. Care providers should take disease subtype, degree of activity, depth of involvement, and quality-of-life impairments into account when initiating treatment. In most patients with circumscribed superficial subtypes, treatment with topical therapies suffices. In more widespread disease, UVA1 phototherapy or systemic treatment with methotrexate (MTX), with or without a systemic corticosteroid combination, should be initiated. Disappointingly, few alternatives for MTX have been described and additional research is still needed to optimize treatment for these debilitating conditions. In this review, we present a state-of-the-art flow chart that guides care providers in the treatment of morphea and EF.
Asunto(s)
Calcitriol/análogos & derivados , Fármacos Dermatológicos/administración & dosificación , Eosinofilia , Fascitis , Glucocorticoides/administración & dosificación , Metotrexato/administración & dosificación , Esclerodermia Localizada , Tacrolimus/administración & dosificación , Administración Cutánea , Administración Oral , Algoritmos , Biopsia , Calcitriol/administración & dosificación , Diagnóstico Diferencial , Progresión de la Enfermedad , Quimioterapia Combinada , Eosinofilia/diagnóstico , Eosinofilia/tratamiento farmacológico , Eosinofilia/epidemiología , Medicina Basada en la Evidencia , Fascitis/diagnóstico , Fascitis/tratamiento farmacológico , Fascitis/epidemiología , Humanos , Fototerapia/métodos , Guías de Práctica Clínica como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Esclerodermia Localizada/clasificación , Esclerodermia Localizada/diagnóstico , Esclerodermia Localizada/tratamiento farmacológico , Esclerodermia Localizada/epidemiología , Piel/patología , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
ETHNOPHARMACOLOGICAL EVIDENCE: Peucedani Radix (PR), the root of Peucedanum praeruptorum Dunn (PPD) or Peucedanum decursivum (Miq.) Maxim. (PDM), has long been used in Korea to eliminate sputum, relieve cough, and reduce bronchus contraction. Furthermore, these therapeutic strategies are recognized as general and effective methods in western medicine as well as traditional Korean medicine. AIM OF THE STUDY: To determine and compare the anti-inflammatory effects of PPD extracts (PPDE) and PDM extracts (PDME) on allergic lung inflammation, using in vivo OVA-induced airway inflammation in mice and in vitro primary cell culture systems. MATERIALS AND METHODS: Eight-week-old female C57BL/6 mice were placed into four groups (n=4 per group): saline control, OVA-induced allergic lung inflammation with vehicle, or PPDE (200mg/kg) or PDME (200mg/kg) treatment. PR extracts (PRE) were administered from 1 week before 1st OVA sensitization to the day before sacrifice. Mice were sacrificed 18h after last OVA intra-nasal challenge followed by histological and biochemical analyses. RESULTS: Inflammatory phenotypes were alleviated with oral administration of PRE. PRE treatment decreased mucus production in airway epithelium, inflammatory cell number, eosinophilia, type 2 cytokines, and histamine in bronchoalveolar lavage fluid (BALF). Mice with PRE administration showed diminished activated CD4 T cell (CD4+CD25+ cell) and GATA-3 level in the lung. In addition, PRE treatment reduced Th2 cell activation in vitro, using Th2 polarization system. CONCLUSION: Our findings indicate that the anti-inflammatory effects of PRE arise from reduced Th2 cell activation and validate the clinical use of PR in traditional Korean medicine.
Asunto(s)
Antiasmáticos/uso terapéutico , Apiaceae , Asma/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Alérgenos/inmunología , Animales , Antiasmáticos/farmacología , Asma/inmunología , Asma/patología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Recuento de Células , Citocinas/inmunología , Eosinofilia/tratamiento farmacológico , Eosinofilia/inmunología , Eosinofilia/patología , Femenino , Factor de Transcripción GATA3/inmunología , Histamina/inmunología , Inmunoglobulina E/sangre , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Ratones Endogámicos C57BL , Moco/metabolismo , Ovalbúmina/inmunología , Extractos Vegetales/farmacología , Raíces de PlantasRESUMEN
A 57-year-old man, diagnosed with colon cancer stage III in July/2010, underwent surgery and received adjuvant chemotherapy with FOLFOX 4 (5-fluorouracil; calcium folinate and oxaliplatin), which ended in March/2011 after 12-cycles. It was then decided to maintain periodical surveillance. About 1â year later, the patient developed several episodes of diarrhoea, mainly during the night, and presented persistent peripheral eosinophilia in the blood count (range 585-1300 eosinophils/µL). Colonoscopy was performed, with the histological result showing eosinophilic infiltration of the colon, compatible with eosinophilic colitis. The patient was treated with a short course of budesonide, achieving resolution of symptoms, and has remained asymptomatic.
Asunto(s)
Colitis/diagnóstico , Colitis/tratamiento farmacológico , Eosinofilia/diagnóstico , Eosinofilia/tratamiento farmacológico , Budesonida/uso terapéutico , Colonoscopía , Glucocorticoides/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Many plant species containing flavonoids have been widely used in traditional Chinese medicine. Naringin, a well-known flavanone glycoside of citrus fruits, possesses antioxidant, anti-inflammatory, anti-apoptotic, anti-ulcer, anti-osteoporosis, and anti-carcinogenic properties. The aim of the study was to investigate the anti-asthmatic effects of naringin and the possible mechanisms. Asthma model was established by ovalbumin. A total of 50 mice were randomly assigned to five experimental groups: control, model, and dexamethasone (2 mg/kg, orally) and naringin (5 mg/kg, 10 mg/kg, orally). Airway resistance (Raw) were measured, histological studies were evaluated by the hematoxylin and eosin (HE) staining, OVA-specific serum and BALF IgE levels and Th1/Th2 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA), and Th1/Th2 cells was evaluated by flow cytometry (FCM). T-bet and GABA3 in the lung were evaluated by Western blot. Our study demonstrated that naringin inhibited OVA-induced increases in Raw and eosinophil count; OVA-induced effects on interleukin (IL)-4 and INF-gamma levels were blunted with naringin administration. Histological studies demonstrated that naringin substantially inhibited OVA-induced eosinophilia in lung tissue and airway tissue. Flow cytometry studies demonstrated that naringin substantially inhibited Th2 cells and enhanced Th1 cells. Naringin substantially inhibited GABA3 and increased T-bet. These findings suggest that naringin may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.
Asunto(s)
Antiasmáticos/uso terapéutico , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Asma/tratamiento farmacológico , Eosinofilia/tratamiento farmacológico , Flavanonas/uso terapéutico , Balance Th1 - Th2/efectos de los fármacos , Animales , Asma/inducido químicamente , Líquido del Lavado Bronquioalveolar/química , Dexametasona/uso terapéutico , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Eosinofilia/inducido químicamente , Femenino , Inmunoglobulina E/inmunología , Interferón gamma/sangre , Interleucina-4/sangre , Pulmón/patología , Medicina Tradicional China , Ratones , Ratones Endogámicos BALB C , Ovalbúmina , Proteínas de Dominio T Box/metabolismo , Células TH1/inmunología , Células Th2/inmunología , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Eosinophilic pustular folliculitis (EPF) is a non-infectious inflammatory dermatosis of unknown etiology that principally affects the hair follicles. There are three variants of EPF: (i) classic EPF; (ii) immunosuppression-associated EPF, which is subdivided into HIV-associated (IS/HIV) and non-HIV-associated (IS/non-HIV); and (iii) infancy-associated EPF. Oral indomethacin is efficacious, especially for classic EPF. No comprehensive information on the efficacies of other medical management regimens is currently available. In this study, we surveyed regimens for EPF that were described in articles published between 1965 and 2013. In total, there were 1171 regimens; 874, 137, 45 and 115 of which were applied to classic, IS/HIV, IS/non-HIV and infancy-associated EPF, respectively. Classic EPF was preferentially treated with oral indomethacin with efficacy of 84% whereas topical steroids were preferred for IS/HIV, IS/non-HIV and infancy-associated EPF with efficacy of 47%, 73% and 82%, respectively. Other regimens such as oral Sairei-to (a Chinese-Japanese herbal medicine), diaminodiphenyl sulfone, cyclosporin and topical tacrolimus were effective for indomethacin-resistant cases. Although the preclusion of direct comparison among cases was one limitation, this study provides a dataset that is applicable to the construction of therapeutic algorithms for EPF.
Asunto(s)
Eosinofilia/tratamiento farmacológico , Foliculitis/tratamiento farmacológico , Enfermedades Cutáneas Vesiculoampollosas/tratamiento farmacológico , Adulto , Antibacterianos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Eosinofilia/clasificación , Eosinofilia/etiología , Foliculitis/clasificación , Foliculitis/etiología , Infecciones por VIH/complicaciones , Humanos , Terapia de Inmunosupresión/efectos adversos , Indometacina/uso terapéutico , Lactante , Fitoterapia , Remisión Espontánea , Enfermedades Cutáneas Vesiculoampollosas/clasificación , Enfermedades Cutáneas Vesiculoampollosas/etiología , Esteroides/uso terapéutico , Resultado del TratamientoRESUMEN
Eosinophilic fasciitis is an uncommon connective tissue disease that may mimic and overlap with other sclerosing disorders such as morphea and lichen sclerosus. Herein, we report four patients (two men and two women, aged 16-64 yeas) with eosinophilic fasciitis. There was overlap with both morphea and lichen sclerosus in 2 patients and with morphoea alone in 1 patient. Magnetic resonance imaging (MRI) was used for diagnosis in three patients and for assessing treatment response in one patient. Eosinophilic fasciitis may co-exist with morhoea and lichen sclerosus. In view of the overlapping clinical and histopathological features of these disorders, MRI may be helful in delineating the conditions by detecting involvement of fascia.
Asunto(s)
Corticoesteroides/administración & dosificación , Imagen Eco-Planar/métodos , Eosinofilia/patología , Fascitis/patología , Liquen Escleroso y Atrófico/patología , Esclerodermia Localizada/patología , Adolescente , Biopsia con Aguja , Diagnóstico Diferencial , Eosinofilia/diagnóstico , Eosinofilia/tratamiento farmacológico , Fascitis/diagnóstico , Fascitis/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Liquen Escleroso y Atrófico/diagnóstico , Liquen Escleroso y Atrófico/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Terapia PUVA/métodos , Medición de Riesgo , Muestreo , Esclerodermia Localizada/diagnóstico , Esclerodermia Localizada/tratamiento farmacológico , Resultado del TratamientoRESUMEN
O Toxocara canis (Tc) é um parasito pertencente ao filo Nematódeo que possui como hospedeiro definitivo os cães, O homem é hospedeiro paratênico e contamina-se acidentalmente ao ingerir ovos contendo larvas infectantes (L3) do parasito, as quais são liberadas e atravessam a mucosa intestinal, atingem a circulação, Durante este processo migratório, antígenos de excreção e secreção (TES) são liberados provocando intensa reação inflamatória, do tipo Th2, caracterizando a síndrome, denominada Larva Migrans Visceral (SLMV), As principais características desta doença crônica são as eosinofilias sanguínea e tecidual persistentes, Desse modo, torna-se importante a busca por terapias que contribuam com a redução dos quadros inflamatórios com intensa eosinofilia, Assim, o uso deste bioterápico, produzido a partir do extrato antigênico de ovos e larvas de (Tc), e seu efeito no recrutamento de leucócitos totais, células mononucleares e eosinófilos no sangue, para o espaço broncoalveolar e para a cavidade peritoneal de camundongos infectados pelo (Tc) foi investigado, Foram utilizados camundongos fêmeas (Swiss), divididos nos grupos: Controle (C), Infectado (Tc), Imunizado (Im+Tc) e Tratado (Tc+Bio), Os animais Tc, Im+Tc e Tc+Bio receberam 500 ovos/animal por gavagem, Posteriormente, os animais foram eutanasiados no 18º dia da infecção e o número das células nos compartimentos foi determinado, Os resultados obtidos demonstraram que, Im+Tc, assim como nos Tc+Bio tiveram redução significativa dessas células nos compartimentos analisados quando comparados grupo Tc, Assim, sugeriu-se que a bioterapia modulou negativamente o recrutamento de células inflamatórias, principalmente eosinófilos no sangue, pulmão e intestino demonstrando um potencial anti-inflamatório desse bioterápico na SLMV experimental...
The Toxocara canis (Tc) is a parasite that belongs to the nematode phylum and has dogs as definitive host. The men can be accidentally contaminated by ingesting eggs containing infective larvae of the parasite. These larvae, when ingested, pass through the intestinal mucosa, reach the portal circulation and migrate through different tissues of the host. During this process, excretory-secretory antigens (TES) are released causing an intense inflammatory reaction, the Th2 type, characterizing the syndrome, called Visceral Larva migrans (VLMS). The main features of this chronic disease are blood and tissue eosinophilias. Thus, it is important to search for therapies that may contribute to the reduction of inflammatory conditions with intense eosinophilia. In this study, we investigated the use of a biotherapic produced from the antigenic extract from eggs and larvae (Tc) and its effect on the recruitment of total leukocyte, mononuclear cells and eosinophils in blood, bronchoalveolar space and peritoneal cavity of mice infected with (Tc). Female mice (Swiss) were used divided in three groups: control (C), Infected (Tc) Immunized (Im + Tc) and Treaty (Tc + Bio). The animals Tc, Im + Tc and Tc + Bio received 500 eggs / animal by gavage. Subsequently, the animals were euthanized on day 18 after infection and the number of cells in the compartments was determined. Our results showed that, Im + Tc, as in Tc + Bio had reduced these cells in compartments analyzed compared to Tc group. Thus, it was suggested that the biotherapy negatively modulated the recruitment of inflammatory cells, particularly eosinophils in blood, lung and intestine demonstrating an anti-inflammatory potential of the biotherapic in the experimental VLMS...