Regístrese
¿Aún no está registrado?
Información relevante

Consulte los artículos y contenidos publicados en este medio, además de los e-sumarios de las revistas científicas en el mismo momento de publicación

Máxima actualización

Esté informado en todo momento gracias a las alertas y novedades

Promociones exclusivas

Acceda a promociones exclusivas en suscripciones, lanzamientos y cursos acreditados

Crear Mi cuenta
Buscar en
Revista Médica del Hospital General de México
Toda la web
Inicio Revista Médica del Hospital General de México Allergic bronchopulmonary aspergillosis in teenager with bronchial asthma
Información de la revista
Vol. 81. Núm. 3.Julio - Septiembre 2018
Páginas 107-176
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Visitas
436
Vol. 81. Núm. 3.Julio - Septiembre 2018
Páginas 107-176
Clinical case
DOI: 10.1016/j.hgmx.2017.05.001
Open Access
Allergic bronchopulmonary aspergillosis in teenager with bronchial asthma
Aspergilosis broncopulmonar alérgica en adolescente con asma bronquial
Visitas
436
C.I. Urquiza-Ramírez
Autor para correspondencia
dr.urquizaramirez@gmail.com

Corresponding author at: Dr. Balmis 148, Cuauhtémoc, Doctores, 06726 Mexico City, Mexico.
, G.A. Eliosa-Alvarado, S. González-Flores, J.C. Fernández de Córdova-Aguirre, A.A. Velasco-Medina, G. Velázquez-Sámano
Servicio de Alergia e Inmunología Clínica, Hospital General de México “Dr. Eduardo Liceaga”, Mexico City, Mexico
Este artículo ha recibido
436
Visitas

Under a Creative Commons license
Información del artículo
Resumen
Texto Completo
Bibliografía
Descargar PDF
Estadísticas
Figuras (3)
Mostrar másMostrar menos
Tablas (3)
Table 1. Pulmonary aspergillosis clinical syndromes.
Table 2. Criteria for the diagnosis of ABPA in patients with asthma.
Table 3. Stages of ABPA.
Mostrar másMostrar menos
Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder caused by hypersensitivity mechanisms against antigens released by Aspergillus species, colonizing the airways.

We present the case of a 16-year-old male with a history of asthma and allergic rhinoconjunctivitis with a history of 15 months of cough with purulent sputum, intermittent fever and dyspnea. Thoracic tomography showed bronchiectasis accompanied by mucus impaction. He was treated with different antibiotics and steroid regimens, without a favorable clinical response. The presence of eosinophilia in the peripheral blood, immunoglobulin E Total, skin tests for Aspergillus positive guided the diagnosis of ABPA. Treatment with prednisone plus itraconazole was started, with remission of symptoms.

ABPA should be suspected in patients with asthma with poor response to treatment and alteration in radiologic studies. Treatment includes systemic steroids and avoiding exposure to Aspergillus.

Keywords:
Allergic bronchopulmonary aspergillosis
Hypersensitivity mechanisms
Asthma
Bronchiectasis
Resumen

La aspergilosis broncopulmonar alérgica (ABPA) es un trastorno pulmonar causado por mecanismos de hipersensibilidad contra antígenos liberados por especies de Aspergillus, que colonizan las vías respiratorias.

Presentamos el caso de un varón de 16 años con antecedentes de asma y rinoconjuntivitis alérgica con historia de 15 meses de tos con esputo purulento, fiebre intermitente y disnea. La tomografía torácica reporto bronquiectasias acompañadas de impactación de moco. Se le trató con diferentes regímenes de antibióticos y esteroides, sin tener una respuesta clínica favorable. La presencia de eosinófilia en la sangre periférica, inmunoglobulina E Total elevada y pruebas cutáneas para Aspergillus positivo guiaron el diagnóstico de ABPA. Se inició tratamiento con prednisona más itraconazol, con remisión de los síntomas.

Debe sospecharse ABPA en pacientes con asma con mala respuesta al tratamiento y alteración en los estudios radiológicos. El tratamiento incluye esteroides sistémicos y evitar la exposición a Aspergillus.

Palabras clave:
Aspergilosis broncopulmonar alérgica
Mecanismos de hipersensibilidad
Asma
Bronquiectasias
Texto Completo
Introduction

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder caused by a hypersensitivity mechanisms type I, III and IV against antigens released by Aspergillus species, colonizing the airways of patients mainly with asthma and cystic fibrosis (CF).1,2

In predisposed individuals, disease occurs following colonization of the bronchi by Aspergillus conidia. The fungal hyphae extend, and allergens are released, leading to persistent airway inflammation resulting in excessive viscous mucous production and impaired mucociliary function. ABPA is clinically characterized by poorly controlled asthma, recurrent pulmonary infiltrates, and bronchiectasis, in some cases can leading to pulmonary fibrosis.3

In Mexico, its prevalence is unknown, however different case reports have been published.4 It is estimated that ABPA affects 12.9% (2–32%) of the asthmatic population; in steroid-dependent asthmatics the prevalence is thought to be 7–14%.5,6 It occurs with equal frequency in both sexes. Most patients are less than 35 years old at the time of diagnosis.7

Clinical case presentation

A 16 year old male patient with a previous diagnosis of asthma and allergic rhinoconjunctivitis since he was 6 years old, is evaluated in our department of allergy and immunology having history of 15 months of cough with purulent sputum, intermittent fever, progressive dyspnea and acrocianosis. Six months after onset of symptoms he was hospitalized in pediatric unit for 2 months with diagnosis of pneumonia, treated with different antibiotics. The chest X-rays showed a reticular pattern accompanied by images suggesting bronchiectasis, computed tomography of the lungs confirmed central bronchiectasis, accompanied by mucoid impaction and reticular infiltrates (see Figs. 1–3).

Figure 1.
(0,07MB).

X-ray chest shows right posterior basal segmental atelectasis, the lungs present diffuse interstitial reticulum infiltrates, inflammatory infiltrates in the left lung base, bronchiectasis in principal and segmental bronchi, associated right pleural effusion. In addition, right subdiaphragmatic intestinal loops (Chilaiditi syndrome).

Figure 2.
(0,11MB).

Computed tomography of the chest, axial section with a window for pulmonary parenchyma in which atelectasis with mucus impaction is observed in the lower right lobe (segments 7, 8 and 10). Cystic bronchiectasis with mucus impaction in the left lower lobe (segments 9 and 10).

Figure 3.
(0,07MB).

Coronary reconstruction with window for pulmonary parenchyma in which consolidation is observed in the right upper lobe and parenchymal bands. Atelectasis with mucus impaction in the right lower lobe. In the lower left lobe there is consolidation, thickening of the wall of the main bronchus.

Due to poor response to treatment, were performed multiple studies among them: sputum smear microscopy in 3 determinations negative, tuberculin test negative, Chlorine test in the sweat (Chlorimetry and conductivity) two determinations negative, the flow cytometry and the nitroblue tetrazolium test were within normal limits, the immunoglobulins were not compatible with some pattern of Immunodeficiency, so it was ruled out that it was pulmonary tuberculosis, cystic fibrosis or some primary immunodeficiency.

An attempt was made to perform fiberoptic bronchoscopy but patient presented significant desaturation during the procedure, which impeded the conclusion of the procedure and take samples.

He was discharged with mild clinical improvement and oxygen dependence, Nine months after discharge was evaluated in our service of allergy and immunology, were performed the following studies: Blood peripheral eosinophils 9.1% (absolut # 700), total IgE: 455IU/mL (NV: <150), specific IgG for Aspergillus fumigatus 4.19mgA/L (NV: <2.0), sputum cytology studies reported polymorphonuclear cells 3+, eosinophils 3+, negative sputum culture for fungi, positive skin prick tests for Aspergillus fumigatus, Chenopodium album, Prosopis spp., Fraxinus americana, Dermatophagoides spp.

Respiratory Functional Tests demonstrated a very severe flow obstruction without response to bronchodilator (Albuterol) with data suggesting pulmonary distention and increased resistance and severely decreased diffusion. With the clinical and laboratory data, we concluded that the patient had allergic bronchopulmonary aspergillosis stage 1. Treatment was started with prednisone at 1mg/kg/day for 2 weeks then 0.5mg/kg/day for 12 weeks and tritrated to 5mg/day.

He was kept with prednisone 5mg/day for a year, combined with itraconazole 200mg/day for 6 months, salmeterol/fluticasone 50/500μg bid. The patient was evaluated in a month and then every 2 months, at 6 months follow-up had significant clinical improvement. He had suspended supplemental oxygen and returned to normal activities at home and at school.

Discussion

ABPA should be suspected in patients with asthma who have a poor response to usual treatment since an appropriate management can cause an impact on quality of life because ABPAs symptoms may be severe and leading to pulmonary fibrosis.

Aspergillus-related pulmonary disorders may be classified into four clinical categories depending on whether the host is atopic, non-atopic or immunosuppressed (see Table 1),7 Invasive aspergillosis (IA) is seem in patients with severe neutropenia, allogeneic bone marrow transplantation, prolonged use of systemic steroids, treatment with immunosuppressants and primary immunodeficiency, our patient did not have any of these conditions.8

Table 1.

Pulmonary aspergillosis clinical syndromes.

Invasive aspergillosis  Allergic or hypersensitivity reactions  Saprophytic colonization  Mycotoxicosis 
- Generalized or disseminated  - Allergic asthma  Aspergilloma (mycetoma or fungus ball)  Chemical pneumonitis 
a. Aspergillosis pneumonia  - Allergic bronchopulmonary aspergillosis     
b. Angioinvasive aspergillosis  - Extrinsic allergic alveolitis     
c. Lung abscess and multiple cavities  - Bronchocentric granulomatosis     
d. Aspergillosis bronchitis/tracheobronchitis       
e. Infarction       
f. Pleural effusion and empyema       
- Localized or limited       
a. Chronic necrotizing pulmonary aspergillosis       

ABPA is commonly caused by A. fumigatus, an ubiquitous mold common in indoors and frequently found around farm buildings and compost heaps. It is a Th2 hypersensitivity lung disease caused by bronchial colonization with A. fumigatus, characterized by asthma exacerbations, recurrent transient chest radiographic infiltrates, peripheral and pulmonary eosinophilia, especially during an exacerbation. Diagnosis is based on clinical and immunologic criteria for ABPA, standardized by Greenberger and Patterson: (1) asthma or CF with deterioration in lung function, (2) Aspergillus species immediate skin test reactivity, (3) total serum IgE level of 1000ng/mL (417IU/mL) or greater, (4) increased specific IgE and IgG antibodies for Aspergillus species-, and (5) chest radiographic infiltrates. Additional criteria modified might include peripheral blood eosinophilia, Aspergillus species serum precipitating antibodies, central bronchiectasis, and Aspergillus species-containing mucus plugs9–11 (see Table 2). The case that we presented complied with the 5 criteria according to original criteria of Greenberger and Patterson, complying for both central bronchiectasis and for seropositive ABPA.

Table 2.

Criteria for the diagnosis of ABPA in patients with asthma.

  Minimal essential criteria 
Criteria for ABPA-central bronchiectasis
1. Asthma  Yes 
2. Central bronchiectasis  Yes 
3. Immediate cutaneous reactivity to Aspergillus species  Yes 
4. Total serum IgE concentration>417kU/L (1000ng/mL)  Yes 
5. Elevated serum IgE and or IgG to A. fumigatus  Yes 
6. Chest roentgenographic infiltrates  No 
7. Serum precipitating antibodies to A fumigatus  No 
Criteria for the diagnosis of ABPA-seropositive
1. Asthma  Yes 
2. Immediate cutaneous reactivity to Aspergillus species  Yes 
3. Total serum IgE concentration>417kU/L (1000ng/mL)  Yes 
4. Elevated serum IgE and or IgG to A. fumigatus  Yes 
5. Chest roentgenographic infiltrates  No 

CT, computed tomography.

Galactomannan (GM) detection contributes to the diagnosis of IA, even form part of the diagnostic criteria, however for ABPA Agarwal et al. suggest that serum GM estimation has a limited role in the diagnostic workup.8,12

ABPA can be divided into five stages, each stage representing a different category of presentation (Table 3). Determining the stage in which the patient is important for treatment and prognosis.13 Our patient was in stage 1 of the disease.

Table 3.

Stages of ABPA.

Stage  Description  Radiographic infiltrates  Total serum IgE 
Acute  Upper lobes or middle lobe  Sharply elevated 
II  Remission  No infiltrate and patient off prednisone for >6 mo  Elevated or normal 
III  Exacerbation  Upper lobes or middle lobe  Sharply elevated 
IV  Corticosteroid-dependent  Asthma Often without infiltrates, but intermittent infiltrates might occur  Elevated or normal 
End stage  Fibrotic, bullous, or cavitaries lesions  Might be normal 

The aim of treatment in ABPA is to reduce episodic acute inflammation, thus limiting disease progression with resultant airway destruction and both parenchymal and airway fibrosis. To achieve this, a dual treatment approach is required: corticosteroids to control immunological activity and antifungal azole agents to suppress Aspergillus colonization and proliferation, which reduce antigenic stimulation, limiting further inflammation. However, reviews have emphasized the weakness of the evidence for safety and efficacy of azoles, with only two small, short-term, randomized, double-blind, placebo-controlled trials in asthmatic ABPA, and none in cystic fibrosis ABPA. There are potential alternative approaches to antifungal treatment that avoid systemic effects, azole resistance and drugs interactions; Inhaled amphotericin B has been explored as an ABPA treatment with varying results in uncontrolled studies. Finally, the success of omalizumab (anti-IgE monoclonal antibody) in improving control of moderate–severe allergic asthma has led to great interest and rapidly increasing usage in ABPA, usually undertaken as a steroid-sparing agent, with virtually unanimous reporting of reduced steroid requirements and exacerbations in published uncontrolled studies.14–20

Our patient had a good response with combined treatment with prednisone and itraconazole, with clinical improvement. He stopped using supplemental oxygen and six months later of start treatment was able to return to previous physical activities. On last visit, we were able to stop prednisone and was only using inhaled sameterol/fluticasone 50/250μg bid.

Ethical disclosuresProtection of human and animal subjects

The authors declare that no experiments were performed on humans or animals for this study.

Confidentiality of data

The authors declare that they have followed the protocols of their work center on the publication of patient data.

Right to privacy and informed consent

The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.

Funding

No funding was received for this study.

Conflict of interest

The authors have no conflict of interests to declare.

References
[1]
S. Bains, M. Judson
Allergic bronchopulmonary aspergillosis
Clin Chest Med, 33 (2012), pp. 265-281 http://dx.doi.org/10.1016/j.ccm.2012.02.003
[2]
H. Matsuoka, T. Uzu, M. Koyama
Allergic bronchopulmonary aspergillosis presenting with cough variant asthma with spontaneous remission
Respir Med CME, 4 (2011), pp. 175-177
[3]
C. Hogan, D. Denning
Allergic bronchopulmonary Aspergillosis and related allergic syndromes
Semin Respir Crit Care Med, 32 (2011), pp. 682-692 http://dx.doi.org/10.1055/s-0031-1295716
[4]
J.C. Fernández de Córdova-Aguirre, A.A. Velasco-Medina, D.A. Cariño-Cartagena
Aspergilosis broncopulmonar alérgica
Rev Alerg México, 61 (2014), pp. 121-126
[5]
R. Agarwal, A.N. Aggarwal, D. Gupta
Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis in patients with bronchial asthma: systematic review and meta-analysis
Int J Tuberc Lung Dis, 13 (2009), pp. 936-944
[6]
I. Tillie-Leblond, A.B. Tonnel
Allergic bronchopulmonary aspergillosis
[7]
A. Amchentsev, N. Kurugundla, A. Saleh
Aspergillus-related lung disease
Respir Med CME, 1 (2008), pp. 205-215
[8]
J. Fortún, Y. Meije, G. Fresco
Aspergilosis. Formas clínicas y tratamiento
Enferm Infecc Microbiol Clin, 30 (2012), pp. 201-208 http://dx.doi.org/10.1016/j.eimc.2011.12.005
[9]
A. Knutsen, R. Bush, J. Demain
Fungi and allergic lower respiratory tract diseases
J Allergy Clin Immunol, 129 (2012), pp. 280-291 http://dx.doi.org/10.1016/j.jaci.2011.12.970
[10]
R. Agarwal, D. Maskey, A.N. Aggarwal
Diagnostic performance of various tests and criteria employed in allergic bronchopulmonary Aspergillosis: a latent class analysis
[11]
J. Schulze, U. Zissler, M. Martin Christmann
Allergic bronchopulmonary aspergillosis (ABPA) an IgE mediated disease?
Respir Med CME, 4 (2011), pp. 33-34
[12]
R. Agarwal, A.N. Aggarwal, I.S. Sehgal
Performance of serum galactomannan in patients with allergic bronchopulmonary aspergillosis
Mycoses, 58 (2015), pp. 408-412 http://dx.doi.org/10.1111/myc.12334
[13]
P.A. Greenberger
Allergic bronchopulmonary aspergillosis
J Allergy Clin Immunol, 110 (2002), pp. 685-692
[14]
R. Patterson, P.A. Greenberger, R.C. Radin
Allergic bronchopulmonary aspergillosis: staging as an aid to management
Ann Intern Med, 96 (1982), pp. 286-291
[15]
R. Agarwal, A.N. Aggarwal, S. Dhooria
A randomised trial of glucocorticoids in acute-stage allergic bronchopulmonary aspergillosis complicating asthma
Eur Respir J, 47 (2016), pp. 490-498 http://dx.doi.org/10.1183/13993003.01475-2015
[16]
R.M. Tucker, Y. Haq, D.W. Denning
Adverse events associated with itraconazole in 189 patients on chronic therapy
J Antimicrob Chemother, 26 (1990), pp. 561-566
[17]
L. Chishimba, R.M. Niven, J. Cooley
Voriconazole and posaconazole improve asthma severity in allergic bronchopulmonary Aspergillosis and severe asthma with fungal sensitization
[18]
L. Chishimba, P. Langridge, G. Powell
Efficacy and safety of nebulised amphotericin B (NAB) in severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis (ABPA)
[19]
C. Godet, J.C. Meurice, F. Roblot
Efficacy of nebulised liposomal amphotericin B in the attack and maintenance treatment of ABPA
Eur Respir J, 39 (2012), pp. 1261-1263 http://dx.doi.org/10.1183/09031936.00162311
[20]
A.L. Voskamp, A. Gillman, K. Symons
Clinical efficacy and immunologic effects of omalizumab in allergic bronchopulmonary aspergillosis
J Allergy Clin Immunol Pract, 3 (2015), pp. 192-199 http://dx.doi.org/10.1016/j.jaip.2014.12.008
Copyright © 2017. Sociedad Médica del Hospital General de México
es en pt
Política de cookies Cookies policy Política de cookies
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.