Allergol Immunopathol (Madr). 2018;46(6):557---564 Allergologia et immunopathologia Sociedad Espa ˜nola de Inmunolog´ıa Cl´ınica, Alergolog´ıa y Asma Pedi ´atrica www.elsevier.es/ai ORIGINAL ARTICLE Fungal Allergy: Pattern of sensitization over the past 11 years a a,∗ a R. Fernández-Soto , E.M. Navarrete-Rodríguez , B.E. Del-Rio-Navarro , b a a J.J. Luis Sienra-Monge , N.A. Meneses-Sánchez , O.J. Saucedo-Ramírez a Servicio de Alergia e Inmunología Clínica Pediátrica, Hospital Infantil de México Federico Gómez, Mexico City, Mexico b Subdirección de Pediatria Ambulatoria. Hospital Infantil de México Federico Gómez, Mexico City, Mexico Received 16 November 2017; accepted 25 January 2018 Available online 5 May 2018 KEYWORDS Abstract Fungi; Introduction and objectives: Although the prevalence of sensitization to fungi is not precisely known, it can reach 50% in inner cities and has been identified as a risk factor in the development Skin test; Alternaria; of asthma. Whereas the prevalence of allergic diseases is increasing, it is unclear whether the Aspergillus; same occurs with sensitization to fungi. Cladosporium; Patients and methods: A retrospective study was performed at the ‘‘Hospital Infantil de Méx- Penicillium ico Federico Gómez’’. From skin tests taken between 2004 and 2015, information was gathered about Alternaria alternata, Aspergillus fumigatus, Candida albicans, Cladosporium herbarum, Mucor mucedo and Penicillium notatum. The participating patients were 2---18 years old, pre- sented some type of allergic condition, and underwent immediate hypersensitivity tests to the fungi herein examined. Descriptive analysis and chi-squared distribution were used. Results: Of the 8794 patients included in the study, 14% showed a negative result to the entire panel of environmental allergens. The remaining 7565 individuals displayed sensitization to at least one fungus, which most frequently was Aspergillus, with a rate of 16.8%. When the patients were divided into age groups, the same trend was observed. The highest percentage of sensitization (58%) toward at least one type of fungus was found in 2014, and the lowest percentage (49.8%) in 2008. Conclusion: The rate of sensitization to at least one type of fungus was presently over 50%, higher than that detected in other medical centers in Mexico. This rate was constant over the 11-year study, and Aspergillus exhibited the greatest frequency of sensitization among the patients. © 2018 SEICAP. Published by Elsevier Espana,˜ S.L.U. All rights reserved. ∗ Corresponding author. E-mail address: [email protected] (E.M. Navarrete-Rodríguez). https://doi.org/10.1016/j.aller.2018.01.005 0301-0546/© 2018 SEICAP. Published by Elsevier Espana,˜ S.L.U. All rights reserved. 558 R. Fernández-Soto et al. Introduction de México Federico Gómez’’. Skin tests were carried out by physicians and chemists to detect the presence of A. alter- Fungi are eukaryotic organisms that live as saprophytes, nata, A. fumigatus, C. albicans, C. herbarum, M. mucedo parasites or symbionts in their plant or animal hosts. and P. notatum. All patients included herein were 2---18 These ubiquitous organisms, which grow in intra- and extra- years old and presented asthma, rhinitis and/or eczema, domiciliary environments and in almost any substrate, which require a skin-prick test (SPT) in compliance with cur- exhibit optimal growth at a temperature between 18 and rent guidelines. After the clinical history was reviewed by a ◦ 1 32 C. Of the more than 100,000 existing species, there certified allergist and immunologist, subjects who met the are more than 80 genus (especially in the Ascomycota and criteria had a skin-prick test performed against inhalants Basidiomycota phyla) known to cause type 1 allergies in sus- (with previously signed consent and assent). The aforemen- 2 ceptible individuals. tioned indoor allergens were included. Patients were mainly Penicillium, Aspergillus, Cladosporium and Alternaria from Mexico City and the surrounding metropolitan area. For are reportedly the most prevalent fungal aeroallergens each patient, both demographic information and the refer- 3 worldwide. Spores from the former two genera are present ring diagnosis were reviewed. The protocol was approved by 4 all year round, whereas Cladosporium and Alternaria tend the Ethics, Research and Biosafety Committees at the hos- to show seasonal peaks, primarily during the rainy season pital (protocol number HIM/2015/045) and complied with 5 and from April to October. institutional and international guidelines. Although the prevalence of sensitization to fungi is not During the entire study, skin prick tests were carried out ® precisely known, it is estimated to vary between 3% and 10% with IPI Assac extracts. These have been standardized in among the general population (depending to a large extent the same way since 1999 and commercialized as A. alternata 4 on the climatic conditions of the area under study), and can UBE/ml (equivalent biologic unit), A. fumigatus PNU/ml 6 reach 50% in the inner cities. (protein nitrogen units), C. albicans UEP/ml, C. herbarum Sensitization to fungi has been identified as a risk factor PNU/ml, M. mucedo PNU/ml and P. notatum UEP/ml. 7,8 for the development of asthma. Elevated spore levels in We utilized the SPT protocol recommended by the the atmosphere correlate with an increased number of hos- Global Allergy and Asthma European Network, the European 9 pitalizations and deaths from asthma as well as a greater Academy of Allergy and Clinical Immunology, and the Amer- 10 20 risk of developing rhinitis. ican Academy of Allergy, Asthma and Immunology (AAAAI). ◦ In Mexico, several authors have investigated the rate of Allergen extracts were stored at 2 --- 8 C when not in use. The sensitization to such aeroallergens in cross-sectional stud- medications taken by patients during the weeks previous to ies, with results varying according to the particular region in the SPT were recorded with the aim of avoiding false pos- 11---18 question (Table 1). Within the 1.9 million square kilome- itive results. Tests were applied on the upper back or on ters of land area in this North American country, the average the volar surface of the forearm, at least 2 --- 3 cm away from ◦ temperatures range from 10 to 26 C (except for the most the wrist and the antecubital fossa. Histamine (10 mg/ml) 19 extreme zones representing 7% of the territory). One area and saline solutions were employed as positive and negative of special importance is Mexico City and the surrounding controls, respectively. metropolitan area. Located in a large valley at a high alti- The skin area was marked with a pen, and tests were tude, the city has a population of over 20 million people. made 2 cm apart from each other. After placing a drop The climate is sub-humid with an average temperature of of each test solution on the skin (in the same order ◦ ◦ 16 C, reaching 25 C between March and May, and descend- for all subjects), a prick was immediately made with a ◦ ing as low as 5 C in January. The rainy season is long, usually single-headed metal lancet without causing bleeding. The 19 starting in May and ending in October. outcome was registered 15 min later. The largest diameter Since the prevalence of allergic diseases is increasing, and the orthogonal diameter of the wheal were measured, it is of interest to determine whether the same pattern is and the following value was calculated: largest diame- taking place in terms of sensitization to indoor allergens such ter + perpendicular diameter/2. Wheals having a diameter as fungi. Rodriguez-Orozco et al. documented an alarming more than 3 mm larger than the negative control were 16 growth in sensitization to fungi, but to our knowledge no considered to be positive reactions. Each panel comprised other reports exist based on longitudinal studies. a total of 27 environmental allergens, which included six The objective of the current investigation, conducted types of mold (A. alternata, A. fumigatus, C. albicans, C. in a hospital of Mexico City and covering 11 years (2004 herbarum, M. mucedo and P. notatum), four animal skin dan- to 2015), was to determine the annual rate of sensitiza- der extracts (horse, cat hair, dog, and chicken feathers), tion to Alternaria alternata, Aspergillus fumigatus, Candida seven types of weeds (Ambrosia trifida, Artemisa vulgaris, albicans, Cladosporium herbarum, Mucor mucedo and Peni- Chenopodium album, Helianthus annus, Plantago lanceo- cillium notatum in children and adolescents with asthma, lata, Rumex spp and Salsola kal), three grasses (Lolium rhinitis and/or eczema. Changes in sensitization from year perenne, Phleum pretense and Cynodon dactylon) and four to year were also analyzed. trees (Fraxinus excelsior, Quercus robur, Schinus molle and Ligustrum vulgare), as well as cockroach and mite extracts. In accordance with the aims of the current investigation, Material and methods descriptive statistics were carried out to obtain the rate of sensitization and the 95% CI of hypersensitivity tests to A retrospective study encompassing an 11-year period (Jan- A. alternata, A. fumigatus, C. albicans, C. herbarum, M. uary 2004 to April 2015) was conducted in the Allergy and mucedo and P. notatum. The results were analyzed by intra- 2 Clinical Immunology Department of the ‘‘Hospital Infantil and inter-group chi-squared ( ) distribution of the rate of Fungal Table 1 Prevalence of fungi sensitization in Mexico. Allergy: Global Alternaria Aspergillus Candida CladosporiumPenicillium Climate Meza Velázquez 2000 subjects Mexico City Rhinitis, asthma orND ND 10% ND ND ND 11 et al., 1999 1---18 years old both Pattern Bedolla et al., 752 subjects Guadalajara Rhinitis 23% 10.6% 2.3% 17.4% 1.5% ND 12 2010 16---78 years old Jalisco Bedolla et al., 181 adults 16---84 Guadalajara, Rhinitis, asthma or15.6% 7.2% 1.8% 10.8% 0.9% ND 13 of 2011 years old Jalisco both sensitization Bedolla et al., 60 subjects + 60 Guadalajara, Rhinitis, asthma or21.7% 6.7% 3.3% 16.7% ND ND 14 2012 years old Jalisco both Larenas- 4169 subjects East Zone of Rhinitis, ND ND 14% ND ND ND Semi-hot, Linnemann 2---65 years old Mexico.