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1.
Dermatol Online J ; 26(2)2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32239898

RESUMO

A 60-year old man developed skin hardening and edema on his extremities. Although he had been treated with oral prednisolone at another hospital, skin stiffness relapsed during tapering of prednisolone. At the initial visit to our department, physical examination showed skin hardening of the extremities and also symmetric erythematous macules on the back. Histological examination revealed fasciitis on the forearm and morphea on the back. Eosinophilic fasciitis is occasionally associated with morphea. However, cases of concurrent eosinophilic fasciitis and generalized morphea are rare. In the present case, CD34 was differentially expressed in both lesions, suggesting eosinophilic fasciitis and morphea are separate diseases with different origin of mesenchymal cells.


Assuntos
Eosinofilia/complicações , Fasciite/complicações , Escleroderma Sistêmico/complicações , Adulto , Idoso , Antígenos CD34/metabolismo , Eosinofilia/tratamento farmacológico , Eosinofilia/patologia , Fasciite/tratamento farmacológico , Fasciite/patologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/patologia
2.
Harefuah ; 159(1): 34-37, 2020 Jan.
Artigo em Hebraico | MEDLINE | ID: mdl-31930806

RESUMO

AIMS: This study aims to critically review the pros and cons of biological drugs as treatments and triggers of eosinophilic dermatoses. BACKGROUND: Eosinophilic dermatoses syndromes are rare diseases with a prominent eosinophilic infiltration mechanism. These syndromes have several known treatments with limited success. Several physicians worldwide suggested possible advantages of using specific biological drugs, which are different from eosinophil targeted biotherapies as treatments for eosinophilic dermatoses syndromes. Others considered these drugs as possible triggers. METHODS: Articles published in the last 30 years containing relevant key words were reviewed using PubMed and Medline. Associations between Infliximab, Adalimumab, Etanercept, TNF alpha inhibitors and Ustekinumab to Eosinophilic Dermatoses syndromes were reviewed. RESULTS: Our search revealed an association between 17 eosinophilic dermatoses patients and the drugs of interest. Out of 5 Wells' syndrome cases, four patients had an outbreak of the disease following treatment and one improved by the treatment. Six cases of Eosinophilic Fasciitis mostly had a positive reaction to the treatment. More associations were found among 4 cases of Churg-Strauss syndrome, one case of Granuloma Faciale and 1 case of Eosinophilic Pustular Folliculitis. CONCLUSIONS: TNF alpha inhibitors and Ustekinumab may have a role in the treatment of eosinophilic dermatosis syndromes. These drugs may act as triggers among Wells' syndrome patients. Further investigation is needed.


Assuntos
Eosinofilia/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa , Ustekinumab/uso terapêutico , Etanercepte , Humanos
3.
BMJ Case Rep ; 12(10)2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31604720

RESUMO

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe adverse drug reaction driven by eosinophilia. Treatment is focused on withdrawal of medication, supportive care and immunosuppression such as high-dose corticosteroid therapy. Here we report a 56-year-old male patient who initially presented with breathlessness and eosinophilia, subsequent development of respiratory failure and admission to ITU for non-invasive ventilation. The patient continued to deteriorate despite high-dose prednisolone and methylprednisolone. Other causes of hypereosinophilia were normal. He was diagnosed with DRESS syndrome secondary to pregabalin and was treated with subcutaneous mepolizumab. We observed the rapid resolution of eosinophilia and clinical improvement; the patient was discharged home within a month of administration. This represents the successful use of mepolizumab in the acute setting of pulmonary failure secondary to DRESS. A similar approach could be adopted in other acute conditions with refractory eosinophilic inflammation where standard steroid therapy has failed.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome de Hipersensibilidade a Medicamentos/complicações , Eosinofilia/complicações , Eosinofilia/tratamento farmacológico , Pneumonia/tratamento farmacológico , Pneumonia/etiologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Pregabalina/efeitos adversos
4.
Dermatol Online J ; 25(8)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31553865

RESUMO

Eosinophilic fasciitis is a rare connective tissue disorder characterized by inflammation of the fascia that leads to painful, indurated skin. Because of its variable clinical presentation and overlap with conditions, such as morphea, the diagnosis of eosinophilic fasciitis can be challenging and relies on clinical presentation, histopathologic and laboratory analysis, and response to therapy. Herein, we present an unusual, solitary, isolated plaque with pathologic features and response to therapy most consistent with eosinophilic fasciitis.


Assuntos
Eosinofilia/patologia , Fasciite/patologia , Administração Cutânea , Administração Oral , Adolescente , Clobetasol/uso terapêutico , Eosinofilia/tratamento farmacológico , Fasciite/tratamento farmacológico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Prednisona/uso terapêutico , Coxa da Perna
5.
BMJ Case Rep ; 12(9)2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527200

RESUMO

A 57-year-old man presented for an elective pacemaker upgrade, complicated by the discovery of device infection. He had a background of complex congenital heart disease, including replacement of heart valves, and was treated for presumed infective endocarditis that was later confirmed by echocardiography. Antibiotic treatment, with intravenous vancomycin, was given as per the tissue sample sensitivities. On day 24 of treatment he deteriorated clinically, with the evolution of recurrent fever, epigastric pain, diarrhoea, widespread pruritic rash, lymphadenopathy and severe hypoxia over the subsequent 7-10 days. Blood tests revealed development of a marked eosinophilia, transaminitis and rising inflammatory markers. Further radiological imaging was non-diagnostic. On the basis of these clinical and biochemical features a diagnosis of drug reaction with eosinophilia and systemic symptoms syndrome was made. This led to the cessation of vancomycin, the offending agent and the referral for specialist immunology advice. He was subsequently treated with oral prednisolone and made a full recovery.


Assuntos
Endocardite Bacteriana/tratamento farmacológico , Eosinofilia/induzido quimicamente , Doenças das Valvas Cardíacas/tratamento farmacológico , Marca-Passo Artificial/efeitos adversos , Vancomicina/efeitos adversos , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Síndrome de Hipersensibilidade a Medicamentos , Eosinofilia/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Infecções Relacionadas à Prótese/tratamento farmacológico , Valva Tricúspide/microbiologia , Vancomicina/uso terapêutico
6.
Korean J Gastroenterol ; 74(3): 163-167, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554032

RESUMO

Eosinophilic gastrointestinal disorder (EGID) is an uncommon disease that is accompanied by intestinal eosinophil infiltration without a secondary cause of eosinophilia. Eosinophilic enteritis is a secondary portion of EGID that can present a range of gastrointestinal symptoms according to the affected depth of the intestinal layer. The subserosal type of eosinophilic enteritis presenting as ascites is relatively rarer than the mucosal type. In general, eosinophilic enteritis occurs in patients with food allergies, but its mechanism is unclear. The authors experienced a 29-year-old female patient with a large amount of ascites with diarrhea and abdominal pain. The patient was diagnosed with an influenza A infection one week earlier. Peripheral eosinophilia (absolute eosinophil count: 6,351 cells/mm3) and eosinophilic ascites (97% of white blood cells in the ascites are eosinophil) were present. Abdominal CT revealed a large amount of ascites and edematous changes in the ileum and ascending colon wall. A diagnosis of eosinophilic enteritis was confirmed as eosinophilic ascites by paracentesis, with eosinophil infiltration of the bowel wall by an endoscopic biopsy. The patient's symptoms improved rapidly after using steroids. To the best of the author's knowledge, this is the first report of eosinophilic enteritis with massive ascites after an influenza A virus infection in a Korean adult.


Assuntos
Enterite/diagnóstico , Eosinofilia/diagnóstico , Gastrite/diagnóstico , Influenza Humana/diagnóstico , Adulto , Antivirais/uso terapêutico , Ascite , Colonoscopia , Ciclopentanos/uso terapêutico , Enterite/tratamento farmacológico , Enterite/etiologia , Eosinofilia/tratamento farmacológico , Eosinofilia/etiologia , Eosinófilos/citologia , Feminino , Gastrite/tratamento farmacológico , Gastrite/etiologia , Guanidinas/uso terapêutico , Humanos , Vírus da Influenza A/isolamento & purificação , Influenza Humana/complicações , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Esteroides/uso terapêutico , Tomografia Computadorizada por Raios X
7.
Medicine (Baltimore) ; 98(28): e16382, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305439

RESUMO

RATIONALE: Type I monoclonal cryoglobulinemia is usually associated with lymphoproliferative disorders, such as monoclonal gammopathy of undetermined significance (MGUS), myeloma, chronic lymphocytic leukemia (CLL) and lymphoplasmocytic lymphoma (LPL). Clinical symptoms related to Type I cryoglobulin (CG) isotype often include skin, neurological and renal manifestations. PATIENT CONCERNS: A 42-year-old woman who initially presented urticaria, palpable purpura in both her upper extremities and legs, eosinophilia and Raynaud phenomenon. Skin biopsy revealed eosinophil infiltration. Monoclonal immunoglobulin (Ig) G-κprotein was detected and CG was also positive. DIAGNOSES: The patient was finally diagnosed as MGUS related Type I CG. INTERVENTIONS: Cyclophosphamide-dexamethasone-thalidomide (CDT) therapy was initiated. OUTCOMES: The treatment relieved the skin symptoms efficiently. LESSONS: To our knowledge, this is a rare case of Type I cryoglobulinemic vasulitis with eosinophilia complicated by MGUS, and the effective treatment of cyclophosphamide combined with thalidomide and prednisone may provide a new therapeutic option for cryoglobulinemic vasulitis.


Assuntos
Crioglobulinemia/complicações , Eosinofilia/complicações , Gamopatia Monoclonal de Significância Indeterminada/complicações , Vasculite/complicações , Adulto , Crioglobulinemia/diagnóstico , Crioglobulinemia/tratamento farmacológico , Diagnóstico Diferencial , Eosinofilia/diagnóstico , Eosinofilia/tratamento farmacológico , Feminino , Humanos , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/tratamento farmacológico , Vasculite/diagnóstico , Vasculite/tratamento farmacológico
8.
Ann Hematol ; 98(9): 2187-2195, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273420

RESUMO

Organizing pneumonia (OP) is a poorly understood complication of hematopoietic stem cell transplant (HSCT). We identified 15 patients diagnosed with OP following HSCT and described their clinical course. CT chest findings were remarkable for multifocal infiltrates that were predominantly consolidating or ground glass opacities. Bronchoalveolar lavage (BAL) was performed on 14 patients with five having lymphocytosis (> 25% lymphocytes), three with eosinophilia (> 5% eosinophils), three with neutrophilia (> 30% neutrophils), and three with normal cell counts. Flow cytometry was analyzed on BAL fluid in 13 patients with 11 having a CD4/CD8 of < 0.9. Initial treatment with 0.3-1.0 mg/kg prednisone resulted in improvement in symptoms, in radiographic findings, and in pulmonary function testing for the majority of patients. Six patients had recurrence of OP after completing treatment. Eleven patients had evidence of extra-pulmonary graft-versus-host disease prior to diagnosis of OP, and seven patients were diagnosed with an upper respiratory tract infection (URI) within 8 weeks of OP diagnosis. Most patients respond well to prednisone with significant improvement in pulmonary function, but risk of recurrence is high after cessation of steroid treatment. Risk factors for the development of OP may include prior URI.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Pulmão , Pneumonia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Líquido da Lavagem Broncoalveolar , Eosinofilia/diagnóstico por imagem , Eosinofilia/tratamento farmacológico , Eosinofilia/fisiopatologia , Eosinófilos , Feminino , Doença Enxerto-Hospedeiro/diagnóstico por imagem , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/fisiopatologia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Neutrófilos , Pneumonia/diagnóstico por imagem , Pneumonia/tratamento farmacológico , Pneumonia/etiologia , Pneumonia/fisiopatologia , Testes de Função Respiratória
9.
Korean J Parasitol ; 57(3): 249-256, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31284347

RESUMO

Steroids are commonly used in patients with eosinophilic meningitis caused by A. cantonensis infections. The mechanism steroids act on eosinophilic meningitis remains unclear. In this mouse experiments, expressions of 14-3-3 isoform ß and γ proteins significantly increased in the CSF 2-3 weeks after the infection, but not increasedin the dexamethasone-treated group. Expression of 14-3-3 ß, γ, ε, and θ isoforms increased in brain meninges over the 3-week period after infection and decreased due to dexamethasone treatment. In conclusion, administration of dexamethasone in mice with eosinophilic meningitis decreased expressions of 14-3-3 isoform proteins in the CSF and in brain meninges.


Assuntos
Proteínas 14-3-3/genética , Angiostrongylus cantonensis/efeitos dos fármacos , Dexametasona/administração & dosagem , Eosinofilia/tratamento farmacológico , Meningite/genética , Infecções por Strongylida/genética , Proteínas 14-3-3/líquido cefalorraquidiano , Angiostrongylus cantonensis/fisiologia , Animais , Regulação para Baixo/efeitos dos fármacos , Eosinofilia/líquido cefalorraquidiano , Eosinofilia/genética , Feminino , Humanos , Masculino , Meningite/líquido cefalorraquidiano , Meningite/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Infecções por Strongylida/líquido cefalorraquidiano , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/parasitologia
10.
Medicina (Kaunas) ; 55(7)2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31277327

RESUMO

A 56-year-old man with severe asthma underwent bronchial thermoplasty (BT). However, his asthma exacerbated and hypereosinophilia developed 2 months later, thus necessitating oral corticosteroid (OCS) therapy. Six months after BT, a diagnosis of severe asthma with eosinophilic chronic rhinosinusitis (ECRS) was made and benralizumab treatment was initiated; the blood eosinophil count subsequently decreased and lung function improved, thereby permitting OCS dose tapering. Surprisingly, benralizumab both reduced nasal polyps and ameliorated ECRS. Thus, benralizumab may be a useful drug for the rapid treatment of severe asthma with ECRS, especially in patients with hypereosinophilia.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Eosinofilia/tratamento farmacológico , Sinusite/tratamento farmacológico , Anticorpos Monoclonais Humanizados/farmacologia , Asma/complicações , Termoplastia Brônquica/métodos , Progressão da Doença , Eosinofilia/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Sinusite/complicações
12.
Ann Agric Environ Med ; 26(2): 256-259, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31232056

RESUMO

INTRODUCTION: The study presents the case report of a Wells Syndrome in a 18-year -ld female. Wells Syndrome is a rare inflammatory skin disorder which seems to present an abnormal eosinophilic response to a number of triggers. OBJECTIVE: The aim of the study is to discuss several problems related to the diagnosis and treatment of Wells Syndrome. MATERIAL AND METHODS: Medical examination, blood tests, abdominal ultrasound and skin biopsy were performed. RESULTS: Medical examination revealed plaques with tense blisters on feet and erythematous lesions on trunk. Blood tests showed raised anti-streptolysin O level. Skin biopsy revealed features of eosinophilic cellulitis. Oral administration of 0.5 mg per day prednisolone and antihistaminics with local therapy resulted in good clinical response. CONCLUSIONS: Sometimes several biopsy are required to establish diagnosis. In some cases lower doses of corticosteroids with antihistaminics and local anti-inflammatory treatment can by sufficient in treatment.


Assuntos
Celulite (Flegmão)/etiologia , Eosinofilia/etiologia , Mordeduras e Picadas de Insetos/complicações , Adolescente , Celulite (Flegmão)/tratamento farmacológico , Eosinofilia/tratamento farmacológico , Feminino , Humanos , Terfenadina/análogos & derivados , Terfenadina/uso terapêutico
13.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(6): 426-431, 2019 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-31189228

RESUMO

Objective: To compare the clinical characteristics of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) by different levels of blood eosinophil (EOS) count and to investigate the predictive value of the response to glucocorticoid treatment and the readmission rate in the patients with higher blood eosinophils. Methods: A total of 120 patients with AECOPD were admitted to the Department of Pulmonary and Critical Care Medicine in The Second Xiangya Hospital of Central South University from January 01, 2017 to December 31, 2017. Patients were divided into two groups according to their admission blood eosinophil fractions. Patients with EOS%≥2% were in the EOS group (n=56) , while patients with EOS%<2% were in the Non-EOS group (n=64) . The clinical characteristics, hospitalization treatments especially the glucocorticoid treatment response were compared, and the risk of severe acute exacerbation of the two groups including the 12-month COPD-related readmission, and time to first COPD-related readmission were also compared. Results: Compared with the Non-EOS group, the EOS group had lower values of white blood cell (WBC) , neutrophil fraction (N%) , blood neutrophil-to-lymphocyte ratio (NLR) , and C-reactive protein (CRP) . The EOS group also required shorter course of antibiotic treatment [8 (6-10) and 9 (7-11) , P=0.033]. In glucocorticoid-treated patients (n=82) , the EOS group had significantly alleviated symptoms than the Non-EOS group (patients withδCAT≥2 were 86.8% and 68.2%, respectively, P=0.046) , and the duration of hospitalization of the EOS group was shorter [9 (7-11) and 10 (9 to 13) , P=0.042]. Patients with glucocorticoid treatment in the EOS group had significantly alleviated symptoms than those without glucocorticoid treatment (patients with δCAT ≥ 2 were 86.8% and 61.1%, respectively, P=0.040) . The follow-up one year after discharge showed a higher risk of severe acute exacerbation in the EOS group [Adjust OR 2.67 (1.10-6.46), P=0.030; HR: 1.57 (1.02-2.40), P=0.040]. Conclusion: The blood eosinophil levels were useful in predicting the AECOPD patients' response to glucocorticoid treatment and the risk of severe acute exacerbations.


Assuntos
Eosinofilia/complicações , Eosinófilos/metabolismo , Glucocorticoides/uso terapêutico , Readmissão do Paciente , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Biomarcadores/sangue , Progressão da Doença , Eosinofilia/tratamento farmacológico , Eosinófilos/efeitos dos fármacos , Humanos , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Estudos Retrospectivos , Resultado do Tratamento
15.
J Dermatol ; 46(7): 618-621, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31144726

RESUMO

Eosinophilic dermatosis of hematological malignancy is a paraneoplastic skin eruption associated with chronic lymphocytic leukemia and other B-cell malignancies. It clinically resembles an insect bite reaction and it can precede the symptoms of the hematological malignancy or be related to a more aggressive course. Different treatments have been proposed, but partial response and recurrence are frequent. Herein, we describe a case of eosinophilic dermatosis associated with mantle cell lymphoma with remission after lenalidomide therapy.


Assuntos
Eosinofilia/tratamento farmacológico , Exantema/tratamento farmacológico , Lenalidomida/uso terapêutico , Linfoma de Célula do Manto/complicações , Síndromes Paraneoplásicas/tratamento farmacológico , Prurido/tratamento farmacológico , Eosinofilia/etiologia , Eosinofilia/patologia , Exantema/etiologia , Exantema/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/patologia , Prurido/etiologia , Prurido/patologia , Pele/patologia , Resultado do Tratamento
16.
J Investig Allergol Clin Immunol ; 29(2): 84-93, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31017107

RESUMO

Eosinophilic asthma is the most common phenotype of severe asthma. It is characterized by abnormal production and release of type 2 cytokines from T helper type 2 (TH2) lymphocytes and type 2 innate lymphoid cells, such as IL-5. This leads to a persistent increase and activation of eosinophils in blood and the airways despite treatment with high-dose inhaled corticosteroids. Eosinophil differentiation, survival, and activation are preferentially regulated by IL-5, a cytokine that binds to the IL-5 receptor (IL-5R), which is located on the surface of eosinophils or basophils and plays a critical role in the pathogenesis and severity of asthma. Benralizumab is a monoclonal antibody that binds to IL-5R via its Fab domain, blocking the binding of IL-5 to its receptor and resulting in inhibition of eosinophil differentiation and maturation in bone marrow. In addition, this antibody is able to bind through its afucosylated Fc domain to the RIIIa region of the Fcy receptor on NK cells, macrophages, and neutrophils, thus strongly inducing antibody-dependent, cell-mediated cytotoxicity in both circulating and tissue-resident eosinophils. This double function of benralizumab induces almost complete fast and maintained depletion of eosinophils that is much greater than that induced by other monoclonal antibodies targeting the IL-5 pathway, such as mepolizumab and reslizumab. This review focuses on benralizumab as an alternative to other agents targeting the IL-5 pathway in the treatment of eosinophilic asthma.


Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Basófilos/efeitos dos fármacos , Eosinofilia/tratamento farmacológico , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Asma/diagnóstico , Asma/imunologia , Basófilos/imunologia , Basófilos/metabolismo , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Eosinofilia/diagnóstico , Eosinofilia/imunologia , Humanos , Fenótipo , Pesquisa , Avaliação de Sintomas , Resultado do Tratamento
17.
J Pharmacol Exp Ther ; 369(3): 443-453, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30940692

RESUMO

This study describes the pharmacokinetic (PK) and pharmaco-dynamic (PD) profile of N-(5-(4-(5-(((2R,6S)-2,6-dimethylmorpholino)methyl)oxazol-2-yl)-1H-indazol-6-yl)-2-methoxypyridin-3-yl)methanesulfonamide (GSK2292767A), a novel low-solubility inhaled phosphoinositide 3-kinase delta (PI3Kδ) inhibitor developed as an alternative to 2-(6-(1H-indol-4-yl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole (nemiralisib), which is a highly soluble inhaled inhibitor of PI3Kδ with a lung profile consistent with once-daily dosing. GSK2292767A has a similar in vitro cellular profile to nemiralisib and reduces eosinophilia in a murine PD model by 63% (n = 5, P < 0.05). To explore whether a low-soluble compound results in effective PI3Kδ inhibition in humans, a first time in human study was conducted with GSK2292767A in healthy volunteers who smoke. GSK2292767A was generally well tolerated, with headache being the most common reported adverse event. PD changes in induced sputum were measured in combination with drug concentrations in plasma from single (0.05-2 mg, n = 37), and 14-day repeat (2 mg, n = 12) doses of GSK2292767A. Trough bronchoalveolar lavage (BAL) for PK was taken after 14 days of repeat dosing. GSK2292767A displayed a linear increase in plasma exposure with dose, with marginal accumulation after 14 days. Induced sputum showed a 27% (90% confidence interval 15%, 37%) reduction in phosphatidylinositol-trisphosphate (the product of phosphoinositide 3-kinase activation) 3 hours after a single dose. Reduction was not maintained 24 hours after single or repeat dosing. BAL analysis confirmed the presence of GSK2292767A in lung at 24 hours, consistent with the preclinical lung retention profile. Despite good lung retention, target engagement was only present at 3 hours. This exposure-response disconnect is an important observation for future inhaled drug design strategies considering low solubility to drive lung retention.


Assuntos
Indazóis/farmacologia , Indazóis/farmacocinética , /farmacocinética , Sulfonamidas/farmacologia , Sulfonamidas/farmacocinética , Pesquisa Médica Translacional , Administração por Inalação , Adulto , Animais , Lavagem Broncoalveolar , Eosinofilia/tratamento farmacológico , Feminino , Humanos , Indazóis/administração & dosagem , Indazóis/efeitos adversos , Pulmão/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Permeabilidade , /efeitos adversos , Segurança , Solubilidade , Escarro/efeitos dos fármacos , Escarro/metabolismo , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos
18.
Rev Assoc Med Bras (1992) ; 65(3): 326-329, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30994827

RESUMO

Eosinophilic fasciitis, or Shulman's disease, is a rare disease of unknown etiology. It is characterized by peripheral eosinophilia, hypergammaglobulinemia, and high erythrocyte sedimentation rate. The diagnosis is confirmed by a deep biopsy of the skin. The first line of treatment is corticotherapy. We present a rare case of eosinophilic fasciitis in a 27-year-old woman with an atypical presentation with symmetrical peripheral edema and a Groove sign. The patient responded well to treatment with corticosteroids at high doses and, in this context, was associated with hydroxychloroquine and azathioprine. After two and a half years, peripheral eosinophilia had increased, and more of her skin had hardened. At that time, the therapy was modified to include corticoids, methotrexate, and penicillamine. It is of great importance to publicize these cases that allow us to gather experience and better treat our patients.


Assuntos
Eosinofilia/patologia , Fasciite/patologia , Adulto , Biópsia , Edema/patologia , Eosinofilia/diagnóstico por imagem , Eosinofilia/tratamento farmacológico , Fasciite/diagnóstico por imagem , Fasciite/tratamento farmacológico , Feminino , Humanos , Imagem por Ressonância Magnética , Doenças Raras , Pele/patologia , Resultado do Tratamento
19.
Dig Dis Sci ; 64(8): 2231-2241, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30982212

RESUMO

BACKGROUND: Eosinophilic gastroenteritis (EGE) is a rare, chronic inflammatory condition of the gastrointestinal tract. Little is known about its natural history and treatment outcomes. The aims of our analysis were to describe clinical presentation, response to current medical treatments, and to evaluate the response of refractory EGE to anti-integrin therapy. METHODS: Patients with confirmed diagnosis of EGE fulfilling the diagnostic criteria: (1) the presence of gastrointestinal symptoms, (2) dense eosinophilic infiltration of the gastrointestinal mucosa, and (3) exclusion of other conditions leading to gastrointestinal eosinophilia were included in this analysis. In patients non-responding to corticosteroids and/or anti-TNF treatment the integrin blocker vedolizumab was used. RESULTS: EGE patients (n = 22) were predominantly female (63%) with a median age at diagnosis of 41.5 years. The most frequent symptoms were abdominal pain (100%), diarrhea (59%), nausea/vomiting (36%), and bloating (27%). No pathognomonic endoscopic alterations were found. Eosinophilic infiltration was observed in the majority of patients in more than one segment. Patients were treated with systemic steroids, topical, and enteral release steroids in 21/22 (95%) patients, proton pump inhibitors in 7/22 (32%), TNFα inhibitors in 3/22 (14%), and vedolizumab in 4/22 (18%) patients. In 3/4 of steroid-refractory patients vedolizumab induced a clinical and histological improvement. CONCLUSIONS: The combination of highly variable clinical presentation, subtle endoscopic abnormalities, and involvement of several GI segments undermines the difficulty to diagnose EGE and the need for structured biopsy sampling. Corticosteroids were efficient in the majority of patients to induce remission. Response to the integrin blocker vedolizumab suggests further assessment in refractory cases.


Assuntos
Corticosteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Enterite/tratamento farmacológico , Eosinofilia/tratamento farmacológico , Gastrite/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Adolescente , Corticosteroides/efeitos adversos , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Criança , Enterite/diagnóstico , Enterite/imunologia , Eosinofilia/diagnóstico , Eosinofilia/imunologia , Feminino , Gastrite/diagnóstico , Gastrite/imunologia , Fármacos Gastrointestinais/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
Am J Gastroenterol ; 114(6): 984-994, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31008735

RESUMO

OBJECTIVES: The literature related to eosinophilic gastritis (EG), gastroenteritis (EGE), and colitis (EC) is limited. We aimed to characterize rates of diagnosis, clinical features, and initial treatments for patients with EG, EGE, and EC. METHODS: In this retrospective study, data were collected from 6 centers in the Consortium of Eosinophilic Gastrointestinal Researchers from 2005 to 2016. We analyzed demographics, time trends in diagnosis, medical history, presenting symptoms, disease overlap, and initial treatment patterns/responses. RESULTS: Of 373 subjects (317 children and 56 adults), 38% had EG, 33% EGE, and 29% EC. Rates of diagnosis of all diseases increased over time. There was no male predominance, and the majority of subjects had atopy. Presenting symptoms were similar between diseases with nausea/vomiting and abdominal pain, the most common. One hundred fifty-four subjects (41%) had eosinophilic inflammation outside of their primary disease location with the esophagus the second most common gastrointestinal (GI) segment involved. Multisite inflammation was more common in children than in adults (68% vs 37%; P < 0.001). Initial treatment patterns varied highly between centers. One hundred-nine subjects (29%) had follow-up within 6 months, and the majority had clinical, endoscopic, and histologic improvements. CONCLUSIONS: In this cohort, EG, EGE, and EC were diagnosed more frequently over time, and inflammation of GI segments outside the primary disease site co-occurrence of atopy was common with a lack of male predominance. Symptoms were similar between diseases, and initial treatment strategies were highly variable. Future investigation should assess the cause of the increased prevalence of eosinophilic GI disorders and prospectively assess outcomes to establish treatment algorithms.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/epidemiologia , Enterite/epidemiologia , Eosinofilia/epidemiologia , Eosinófilos/patologia , Gastrite/epidemiologia , Gastroenterite/epidemiologia , Fármacos Gastrointestinais/uso terapêutico , Mucosa Intestinal/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Colite/diagnóstico , Colite/tratamento farmacológico , Comorbidade/tendências , Enterite/diagnóstico , Enterite/tratamento farmacológico , Eosinofilia/diagnóstico , Eosinofilia/tratamento farmacológico , Feminino , Seguimentos , Previsões , Gastrite/diagnóstico , Gastrite/tratamento farmacológico , Gastroenterite/diagnóstico , Gastroenterite/tratamento farmacológico , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
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