The Role of Allergy in Chronic Rhinosinusitis. 28.08.2018
The Role of Allergy in
Chronic Rhinosinusitis
Autores:
Ashleigh A. Halderman and Laura J. Tully, Department of Otolaryngology–Head and Neck Surgery, University of Texas Southwestern
Medical Center, 5303 Harry Hines Boulevard, Dallas, TX 75390, USA
Abstract: The role of allergy in chronic rhinosinusitis (CRS) has long been debated and remains controversial. The 2 diseases frequently co-occur; however, direct causality has never been proved. The literature is largely mixed as to the manner and degree by which allergy contributes to CRS and this is in large part due to heterogeneity in the definitions of allergy and of CRS. In this review, the potential role of allergy in the disease processes of CRS without polyps, CRS with polyps, and allergic fungal rhinosinusitis is discussed.
Coordinador: Dr. Ricardo Cardona Villa
ResponderEliminarAsistentes: Jorge Mario Sánchez, Ricardo Cardona Villa, July Ospina Cantillo, Liliana Guevara, Luis Carlos Santamaría, Yurlany Gutiérrez, Susana Uribe
Relatoría: Ana María Calle
Rol de la alergia en rinosinusitis crónica (RSC).
La alergia perenne parece predisponer más a rinosinusitis crónica que la alergia estacional.
La RNC es considerada una enfermedad multifactorial en el cual factores ambientales, inmunológicos, microbiológicos, genéticos y posiblemente factores alérgicos.
Definición de RSC según las guías EPOS propone como definición una inflamación de la nariz, senos paranasales que se caracterizan por 2 o más síntomas, uno de los cuales deberían ser obstrucción, congestión, taponamiento o secreción nasal (anterior o posterior), con o sin dolor o presión facial, y/o reducción o pérdida del olfato. Además de signos endoscópicos de pólipos nasales y/o secreción mucopurulenta, obstrucción o edema de la mucosa del meato medio y/o hallazgos en la TAC como cambios en la mucosa dentro del complejo osteomeatal y/o senos nasales.
Posibles factores relacionados con la predisposición de RNS sin poliposis nasal en pacientes alérgicos:
- El proceso alérgico lleva a inflamación de la mucosa que lleva a obstrucción del ostium, esta obstrucción parece promover el crecimiento de bacterias y/o perpetuar la inflamación
- La rinitis alérgica y la eosinofilia nasal puede llevar a alteración del aclaramiento mucociliar.
- Conclusión: Los pacientes con RNC sin poliposis nasal con alergia parecen tener una enfermedad clínica más grave y posiblemente una mayor prevalencia que en aquellos pacientes no alérgicos, lo que estaría a favor de una asociación entre alergia y RSC sin poliposis nasal. Sin embargo existen estudios contradictorios que no permiten confirmar estar afirmación
En la RSC con poliposis nasal se ha logrado demostrar una mayor asociación y prevalencia de alergia que en población sin alergia, incluso puede ser mayor que en pacientes con RSC sin pólipos. De hecho el perfil inflamatorio en esta condición está caracterizado por un perfil Th2, con inflamación eosinofílica (la mayoría de los pólipos nasales son eosinofílicos (cerca del 80%), elevación de Ig E se correlaciona con la observada en inflamación alérgica.
Sin embargo existen estudios que han fallado en demostrar una asociación entre alergia y síntomas más severos y grado de poliposis en pacientes. Por lo tanto una propuesta sería realizar pruebas de provocación nasal a los pacientes con RSC con poliposis nasal, además la relevancia de sensibilización a alérgenos diferentes a ácaros como es el caso de los hongos nos debe motivar a incluir en las pruebas cutáneas un panel amplio de hongos.
Papel de la inmunoterapia en la sinusitis crónica: Se abre la puerta al uso de inmunoterapia en pacientes con RNS con sensibilización clínicamente relevante, observándose en algunos estudios mejoría clínica y radiológica con respecto a controles, aunque la evidencia actual es débil debido a la heterogeneidad de los estudios, falta de aleatorización y cegamiento.
El papel modulador de la IT en el curso de la enfermedad rinosinusal con o sin poliposis nasal aún no está determinado.
Rinosinutus fúngica alergica: rinosinusitis polipoidea recurrente, eosinofílica, no invasiva que afecta personas inmunocompetentes. En el artículo mencionan que los hongos aislados mas frecuentes son de las especies Alternaria, Bipolaris, Curvularia entre otras y una baja coexistencia de la enfermedad con la Aspergilosis broncopulmonar alérgica, sin embargo en otros estudios la especie de hongo que más se reporta es el Aspergillus, y la coexistencia de ambas enfermedades en un estudio de cohorte prospectivo fue hasta del 80% (lectura recomendada)
Lecturas recomendadas:
Eliminar- Cardona R., Duque R., Ochoa l., Acosta M. et al. Evaluación de algunos parámetros inmunológicos en pacientes con poliposis nasal unilateral de origen etmoidal Acta de Otorrinolaringología y Cirugía de Cabeza y Cuello. Diciembre 2008: 36 (4) 177-185
- Fungi-Induced Upper and Lower Respiratory Tract Allergic Diseases: One Entity. Texto completo: doi: 10.3389/fmicb.2018.00583
- European Position Paper on Rhinosinusitis and nasal Polyps 2012: http://www.ep3os.org/EPOS2012.pdf
Reduced need for surgery in severe nasal polyposis
ResponderEliminarwith mepolizumab: Randomized trial
Claus Bachert, PhD,a,b Ana R. Sousa, PhD,c Valerie J. Lund, MD,d Glenis K. Scadding, MD,d Philippe Gevaert, MD,a
Shuaib Nasser, MD,e Stephen R. Durham, MD,f Marjolein E. Cornet, MD,g Harsha H. Kariyawasam, PhD,d Jane Gilbert, MSc,h Daren Austin, PhD,c Aoife C. Maxwell, PhD,i Richard P. Marshall, PhD,c and Wytske J. Fokkens, PhDg Ghent, Belgium; Stockholm, Sweden; Uxbridge, London, and Cambridge, United Kingdom; and Amsterdam, The Netherlands
Background: Patients with eosinophilic nasal polyposis
frequently require surgery, and recurrence rates are high.
Objective: We sought to assess the efficacy and safety of
mepolizumab versus placebo for severe bilateral nasal polyposis.
Methods: This randomized, double-blind, placebo-controlled trial recruited patients aged18 to 70 yearswith recurrent nasal polyposis requiring surgery. Patients received 750 mg of intravenous mepolizumab or placebo every 4 weeks for a total of 6 doses in addition to daily topical corticosteroid treatment. The primary end point was the number of patients no longer requiring surgery at Week 25 based on a composite end point of endoscopic nasal polyp
score and nasal polyposis severity visual analog scale (VAS) score. Secondary end points included change in nasal polyposis severity VAS score, endoscopic nasal polyp score, improvement in individual VAS symptoms (rhinorrhea, mucus in throat, nasal blockage, and sense of smell), patient-reported outcomes, and safety.
Results: One hundred five patients received mepolizumab
(n 5 54) or placebo (n 5 51). A significantly greater proportion of patients in the mepolizumab group compared with the placebo group no longer required surgery at Week 25 (16 [30%] vs 5 [10%], respectively; P 5 .006). There was a significant improvement in nasal polyposis severity VAS score, endoscopic nasal polyp score, all individual VAS symptom scores, and Sino-Nasal Outcome Test patient-reported outcome score in the mepolizumab compared with placebo groups. Mepolizumab’s safety profile was comparable with that of placebo.
Conclusion: In patients with recurrent nasal polyposis recei treatment led to a greater reduction in the need for surgery anda greater improvement in symptoms than placebo. (J Allergy Clin Immunol 2017;140:1024-31.)
Texto completo: http://dx.doi.org/10.1016/j.jaci.2017.05.044
Mepolizumab or Placebo for Eosinophilic
ResponderEliminarGranulomatosis with Polyangiitis
M.E. Wechsler, P. Akuthota, D. Jayne, P. Khoury, A. Klion, C.A. Langford, P.A. Merkel, F. Moosig, U. Specks, M.C. Cid, R. Luqmani, J. Brown, S. Mallett, R. Philipson, S.W. Yancey, J. Steinfeld, P.F. Weller, and G.J. Gleich, for the EGPA Mepolizumab Study Team*
GROUND
Eosinophilic granulomatosis with polyangiitis is an eosinophilic vasculitis. Mepolizumab, an anti–interleukin-5 monoclonal antibody, reduces blood eosinophil counts
and may have value in the treatment of eosinophilic granulomatosis with polyangiitis.
METHODS
In this multicenter, double-blind, parallel-group, phase 3 trial, we randomly assigned participants with relapsing or refractory eosinophilic granulomatosis with polyangiitis who had received treatment for at least 4 weeks and were taking a stable prednisolone or prednisone dose to receive 300 mg of mepolizumab or placebo, administered subcutaneously every 4 weeks, plus standard care, for 52
weeks. The two primary end points were the accrued weeks of remission over a 52-week period, according to categorical quantification, and the proportion of
participants in remission at both week 36 and week 48. Secondary end points included the time to first relapse and the average daily glucocorticoid dose (during weeks 48 through 52). The annualized relapse rate and safety were assessed.
RESULTS
A total of 136 participants underwent randomization, with 68 participants assigned to receive mepolizumab and 68 to receive placebo. Mepolizumab treatment led to significantly more accrued weeks of remission than placebo (28% vs. 3% of the participants had ≥24 weeks of accrued remission; odds ratio, 5.91; 95% confidence interval
[CI], 2.68 to 13.03; P<0.001) and a higher percentage of participants in remission at both week 36 and week 48 (32% vs. 3%; odds ratio, 16.74; 95% CI, 3.61 to 77.56; P<0.001). Remission did not occur in 47% of the participants in the mepolizumab group versus 81% of those in the placebo group. The annualized relapse rate was
1.14 in the mepolizumab group, as compared with 2.27 in the placebo group (rate ratio, 0.50; 95% CI, 0.36 to 0.70; P<0.001). A total of 44% of the participants in the mepolizumab group, as compared with 7% of those in the placebo group, had an average daily dose of prednisolone or prednisone of 4.0 mg or less per day during
weeks 48 through 52 (odds ratio, 0.20; 95% CI, 0.09 to 0.41; P<0.001). The safety profile of mepolizumab was similar to that observed in previous studies.
CONCLUSIONS
In participants with eosinophilic granulomatosis with polyangiitis, mepolizumab resulted in significantly more weeks in remission and a higher proportion of participants
in remission than did placebo, thus allowing for reduced glucocorticoid use. Even so, only approximately half the participants treated with mepolizumab had protocol-defined remission. (Funded by GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT02020889.)
*A complete list of the members of the EGPA Mepolizumab Study Team is provided in the Supplementary Appendix,
available at NEJM.org.
Texto completo:
N Engl J Med 2017;376:1921-32.
DOI: 10.1056/NEJMoa1702079