Red flags for clinical suspicion of eosinophilic granulomatosis with polyangiitis (EGPA).

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA), is a rare ANCA-associated systemic vasculitis. Its overlapping features with other vasculitic or eosinophilic diseases, and the wide and heterogeneous range of clinical manifestations, often result in a delay to diagnosis. OBJECTIVE: To identify red flags that raise a suspicion of EGPA to prompt diagnostic testing and to present an evidence-based clinical checklist tool for use in routine clinical practice. METHODS: Systematic literature review and expert consensus to identify a list of red flags based on clinical judgement. GRADE applied to generate a strength of recommendation for each red flag and to develop a checklist tool. RESULTS: 86 studies were included. 40 red flags were identified as relevant to raise a suspicion of EGPA and assessed by the experts as being clinically significant. Experts agreed that a diagnosis of EGPA should be considered in a patient aged ≥6 years with a blood eosinophil level >1000 cells/µL if untreated and >500 cells/µL if previously treated with any medication likely to have altered the blood eosinophil count. The presence of asthma and/or nasal polyposis should reinforce a suspicion of EGPA. Red flags of asthma, lung infiltrates, pericarditis, cardiomyopathy, polyneuropathy, biopsy with inflammatory eosinophilic infiltrates, palpable purpura, digital ischaemia and ANCA positivity, usually anti-myeloperoxidase, among others, were identified. CONCLUSION: The identification of a comprehensive set of red flags could be used to raise a suspicion of EGPA in patients with eosinophilia, providing clinicians with an evidence-based checklist tool that can be integrated into their practice.

[Nasal potential difference test to diagnose cystic fibrosis]. / Prueba de la diferencia de potencial nasal para el diagnóstico de la fibrosis quística.

Cystic fibrosis is usually diagnosed based on suspicion arising from a typical clinical picture and must be confirmed by either a finding of high chloride concentrations in sweat tests on 2 separate days or detection of 2 gene mutations. The nasal potential difference (NPD) test has been proposed to provide evidence of abnormal function of the cystic fibrosis transmembrane conductance regulator (CFTR), a receptor that forms a chloride ion channel. The test is especially useful for patients who have normal chloride concentrations in sweat tests and in whom 2 gene mutations related to cystic fibrosis have not been detected. The NPD test requires 2 electrodes connected to a voltmeter (a Tholy-Medicap device). One is placed on the nasal mucosa of the inferior turbinate and the other is placed subcutaneously on the forearm. A reading less than -40 mV is considered abnormal, as values under that cut point are never found in healthy individuals. Two abnormal NPD findings on separate days are required for a diagnosis of CFTR dysfunction. False negatives arise when the integrity of the epithelium is altered. After application of amiloride, NPD decreases more markedly in cystic fibrosis patients than in healthy individuals and applying isoproterenol or fenoterol after amiloride provokes no response in patients with the genetic defect that prevents chloride ion channel activation.

Prueba de la diferencia de potencial nasal para el diagnóstico de la fibrosis quística / Nasal potencial difference test to diagnose cystic fibrosis

En la gran mayoría de los pacientes con fibrosis quística (FQ), el diagnóstico se sospecha por unos síntomas clínicos típicos y debe confirmarse mediante la determinación en sudor de una concentración de cloro elevada en 2 días separados o mediante la identificación de 2 mutaciones en un estudio genético. Para evidenciar el anormal comportamiento de la proteína de membrana CFTR (cystic fibrosis transmembrane conductance regulator), encargada del transporte de cloro, se ha ideado la prueba de la diferencia de potencial nasal (DPN), especialmente útil en pacientes con concentraciones de cloro normales y en los que no se identifican las 2 mutaciones del gen de la FQ. Para la realización de la DPN se requieren 2 electrodos conectados a un voltímetro (dispositivo de medida Tholy-Medicap®), uno colocado sobre la mucosa nasal del cornete inferior, y otro en el tejido celular subcutáneo del antebrazo. Un valor inferior a -­40 mV se considera patológico. Los valores obtenidos en sujetos sanos no sobrepasan nunca este valor. Se precisan 2 determinaciones anormales de DPN registradas en 2 días separados para aceptar la disfunción de la CFTR. Pueden observarse falsos negativos cuando la integridad del epitelio está alterada. En la FQ, tras la aplicación de amilorida la diferencia de potencial se reduce de modo más llamativo que en sanos, y la aplicación de isoproterenol o fenoterol después de amilorida no provoca respuesta debido al defecto genético que impide la activación de los canales de cloro

Cystic fibrosis is usually diagnosed based on suspicion arising from a typical clinical picture and must be confirmed by either a finding of high chloride concentrations in sweat tests on 2 separate days or detection of 2 gene mutations. The nasal potential difference (NPD) test has been proposed to provide evidence of abnormal function of the cystic fibrosis transmembrane conductance regulator (CFTR), a receptor that forms a chloride ion channel. The test is especially useful for patients who have normal chloride concentrations in sweat tests and in whom 2 gene mutations related to cystic fibrosis have not been detected. The NPD test requires 2 electrodes connected to a voltmeter (a Tholy-Medicap® device). One is placed on the nasal mucosa of the inferior turbinate and the other is placed subcutaneously on the forearm. A reading less than -40 mV is considered abnormal, as values under that cut point are never found in healthy individuals. Two abnormal NPD findings on separate days are required for a diagnosis of CFTR dysfunction. False negatives arise when the integrity of the epithelium is altered. After application of amiloride, NPD decreases more markedly in cystic fibrosis patients than in healthy individuals and applying isoproterenol or fenoterol after amiloride provokes no response in patients with the genetic defect that prevents chloride ion channel activation

[Effectiveness and efficiency of an outpatient clinic for corticosteroid-dependent asthmatics]. / Efectividad y eficiencia de una consulta externa monográfica de asma corticodependiente.

OBJECTIVE: To evaluate the efficacy and efficiency of a specialist outpatient clinic for corticosteroid-dependent asthmatics. The clinic was supervised by the respiratory medicine service of a reference hospital. MATERIAL AND METHODS: The first 20 consecutive patients (mean age 58.1+/- 9.5 years; 14 women, 6 men) treated at a specialist outpatient clinic for corticosteroid-dependent asthmatics were studied, with prospective follow-up of 12.33 +/- 4.6 months. The following variables were examined: a) forced spirometry (FS), b)corticosteroid doses, c) number and cost (NC) of visits to the outpatient clinic, d) NC of FS, e) NC of emergency room visits, f) NC of hospitalizations, g)cumulative cost of health care generated by these patients within the National Health Service of Catalonia (NHSC). The results were compared with those recorded in each patient's history. RESULTS: Findings were a) improved FEV1 (55.1 +/- 21.6% vs.60.1 +/- 21%, p = 0.02); b) decreased corticosteroid use (21.9 +/- 11.2 mg vs. 12.8 +/- 6.0 mg, p < 0.0001);c) statistically significant increase in NC to the outpatient clinic and NC of FS; d) statistically significant decrease in number of visits to emergency services and hospitalizations;e) reduced total cost of health care for these patients borne by the NHSC, which went from 4,400,070 Spanish pesetas to 1,171,157 Spanish pesetas. A hospital deficit of nearly 2,000,000 Spanish pesetas was canceled. CONCLUSIONS: Changing the system for delivering health care to these patients has led to improved care (effectiveness) and a noteworthy reduction in cost (efficiency). We conclude that medical specialists should play an important role in reorganizing the present health care system of the NHSC.

Efectividad y eficiencia de una consulta externa monográfica de asma corticodependiente / Effectiveness and efficiency of an outpatient clinic for corticosteroid-dependent asthmatics

OBJETIVO: Evaluar la efectividad y eficiencia de una consulta externa monográfica de asma corticodependiente centralizada en un hospital de referencia controlada por un Servicio de Neumología. MATERIAL Y MÉTODOS: Se estudian en los 20 primeros pacientes consecutivos (edad: 58,1 ñ 9,5 años; 14 mujeres y 6 varones) tratados en la consulta externa monográfica de asma corticodependiente, con un tiempo de seguimiento prospectivo de 12,33 ñ 4,6 meses, las siguientes variables: a) espirometría forzada (E); b) dosis de corticoides; c) número y coste (NC) de las visitas en consultas externas hospitalarias; d) NC de las E; e) NC de las asistencias en urgencias; f) NC de los ingresos hospitalarios en planta, y g) coste acumulado que la asistencia de estos pacientes genera para el hospital y el Servei Català de la Salut (SCS). Se comparan estos resultados con los controles históricos de cada paciente. RESULTADOS: Se han observado: a) mejoría del FEV1 (55,1 ñ 21,6 por ciento frente a 60,1 ñ 21 por ciento; p = 0,02); b) descenso de los requerimientos de corticoides (21,9 ñ 11,2 frente a 12,8 ñ 6,0 mg; p < 0,0001); c) aumento estadísticamente significativo del NC de visitas en consultas externas y NC de E; d) descenso estadísticamente significativo del número de asistencias en urgencias e ingresos en planta, y e) reducción del coste acumulado derivado de la asistencia de estos pacientes para el SCS, que pasa de 4.400.070 a 1.171.157 ptas., así como una reducción del déficit hospitalario que generan, con lo que se consigue nivelar el presupuesto, partiendo de un déficit de casi 2.000.000 de ptas. CONCLUSIONES: El cambio de la atención sanitaria de estos pacientes ha generado una mejoría asistencial (efectividad) reduciendo notablemente los costes económicos (eficiencia). Creemos que las especialidades médicas deben desempeñar un papel importante en el proceso de reorganización asistencial del actual sistema nacional de salud catalán (AU)

[Efficiency of methotrexate in the treatment of cortico-dependent asthmatic patients]. / Eficacia del metotrexato en el tratamiento de pacientes asmáticos corticodependientes.

OBJECTIVE: To evaluate the efficiency of low doses of methotrexate as corticosteroid sparing agent in asthmatic patients requiring long term corticosteroid therapy. METHODS: A prospective study was conducted with seven adult patients and one female pediatric patient suffering from corticosteroid-dependent bronchial asthma. The minimal stabilization time for each patient before initiating treatment with MTX was 3 months. The administered dose of methotrexate was 10 mg/week p.o. for adult patients and 15 mg/week for the pediatric patient. Dose tapering of methyl-prednisolone both during the stabilization and therapy periods was a 2 mg decrease every two weeks provided that no worsening in FEV1 higher than 5% occurred. RESULTS: For the group of adult patients, the stabilization time was 5.6 +/- 2.7 months. Methyl-prednisolone dose during the stabilization period could be decreased from 15.0 mg down to 25.4 +/- 12.0 mg (p = 0.013). The period of treatment of methotrexate was 7.3 +/- 3.4 months and the dose of methyl-prednisolone could be decreased from 25.4 +/- 12.0 mg down to 12.0 +/- 11.9 mg (p < 0.001). In the pediatric patient, the deflazacor dose was decreased from 60 down to 30 mg/day during treatment with methotrexate. In all patients a significant decrease could be obtained in the MP dose during treatment with methotrexate with no decrease in FEV1. No secondary effects were observed with the exception of a labial herpes in the pediatric patient. CONCLUSIONS: The administration of one single weekly dose of methotrexate 10 mg in adults and 15 in one pediatric patient allowed for a decrease of approximately 50% in the glucocorticosteroid dosage in this group of patients with corticosteroid-dependent bronchial asthma with no relevant adverse reactions during therapy.