Introduction

Polysensitization refers to a state where an individual is sensitized to multiple allergens from unrelated sources.¹ This condition is more common than monosensitization in the general populations of Europe and the USA.^2,3 Spain’s diverse climate and geography contribute to varying allergen profiles across different regions, complicating the diagnosis and treatment of these patients.⁴ In Spain, according to epidemiological data, 23.3% of patients are sensitized to at least two types of allergens and 10.1% to three or more.⁵ Polysensitization escalates the likelihood of developing allergic diseases, including allergic asthma, with the severity of the allergic disease being directly linked to the number of sensitizations.^6,7 The identification of allergen IgE binding molecules responsible for allergic manifestations, known ascomponent-resolved diagnosis (CRD) has expanded in clinical practice, enhancing the precision of the diagnostic process and the specific prescription of allergen immunotherapy (AIT).^8,9 AIT, the only treatment currently available that targets the root cause and potentially modifies the disease, is recommended for patients with allergic rhinitis (AR) who exhibit moderate-to-severe symptoms despite regular and/or avoidance strategies and show evidence of IgE sensitization to one or more clinically relevant allergens.¹⁰ In Europe, the typical treatment approach for polysensitized patients involves one or more allergens deemed most clinically relevant.^7,11,12 The CONDOR consensus project in Spain advised that a maximum of three allergen sources could be combined in the same AIT vaccine for polysensitized patients and that AIT treatments should be supported by their own safety and efficacy studies.⁴

Nonetheless, the ongoing need to conduct new consensus efforts specifically for pediatric polysensitized patients and their management with AIT is recognized. This article presents the findings of the second part of the Delphi consensus on the management of polysensitized children (CAPP study), the first part of which is also available in this issue.

Materials and Methods

Study design

The CAPP project was a nationwide Spanish multicenter, two-round Delphi study to seek expert opinion on the clinical management of polysensitized children in Spain to guide the indication for and prescription of AIT. The study was started as an initiative of the Spanish Society of Pediatric Allergy, Asthma, and Clinical Immunology (SEICAP).

The approval of the Institutional Review Board (IRB) or by the equivalent ethics committee(s) was not required as this Delphi study does not involve research with human subjects. No patient data were collected, and this study was based entirely on experts’ feedback and opinions.

For a detailed description of the Delphi process, see the “Methods” section in Part I of this issue.

Delphi process

Selection of Delphi participants

The scientific expert committee comprised 10 specialists experienced in managing polysensitized patients and AIT and recognized experts in the field, who are also members of the SEICAP AIT group. For a detailed description of the functions of the scientific expert committee, see the “Methods” section in Part I of this issue.

A total of 46 specialists from 40 hospitals distributed across Spain were invited to participate in the project as Delphi panel experts (panelists) in Rounds 1 and 2 of the Delphi process. The expert panel consisted of allergists and pediatric allergists with at least 10 years of full-time dedication to allergology and extensive experience in prescribing AIT. Participants were selected, with representation from all Spanish regions, from members of the SEICAP and Spanish Society of Allergology and Clinical Immunology (SEAIC), the two most influential allergology societies in Spain. Most panelists worked in the Public Health Service and had participated in clinical trials and studies, with publications and/or communications to conferences related to AIT. This selection process aimed to ensure a diverse group of experts with varied backgrounds and perspectives while maintaining a high level of expertise in managing polysensitized pediatric patients and AIT.

The purpose of the expert panel was to reach a consensus based on the current clinical evidence and their daily practice and knowledge on AIT management for polysensitized children. For a detailed description of the Delphi process, see the “Methods” section in Part I of this issue.

Selection of Delphi questionnaire dimensions and items

The scientific expert committee carried out a systematic literature review regarding the main topics, focusing on current controversial and unresolved topics.

Delphi rounds

The members of the Delphi expert panel were asked during March 2022 (Round 1) and between July and September 2022 (Round 2) to rate their level of agreement with each questionnaire item on a 9-point Likert scale from 1 (completely disagree) to 9 (completely agree). Each item was categorized according to the scores as rejected (scores 1–3), undetermined (scores 4–6), or accepted (scores 7–9). Panelists were also encouraged to provide comments after scoring each item using open-text comment fields included in the online survey.

Item selection was based on the acceptance of questionnaire items by ≥66.7% of the expert panel and the agreement of the scientific committee. Statements not achieving 66.7% agreement were removed or modified according to the feedback provided by the expert panel. After completion of Round 1 and summarization of expert comments, amendments were made to some questionnaire items. The updated questionnaire was redistributed to the panelists for Round 2. After analysis of the responses described for Round 1, the statements that did not meet expert agreement were retained for discussion.

Concluding round

The concluding round comprised a teleconference meeting among the scientific committee experts to assess the nonconsensus items in Round 2 until an agreement was reached to retain or eliminate them from the final consensus guidelines.

Statistical analysis

A descriptive statistical analysis of the characteristics of the Delphi expert and the data obtained from the expert panel assessment of the Delphi questionnaire items in Rounds 1 and 2 was conducted. For a detailed description of the statistical analysis conducted, refer to the “Methods” section in Part I of this issue.

Results

Panel experts

The characteristics of the 46 and 44 Delphi panel experts who participated in Rounds 1 and 2, respectively, are summarized in Table 1 of the article detailing Part 1 of this study (see in the current issue).

Overview of the Delphi study

Global results of the Delphi study are illustrated in Figure 1 of the article detailing Part 1 (see in the current issue). As commented there, due to the scope of the project and the volume of results, the scientific expert committee decided to split the work into two publications. The first part included the results related to diagnosis, therapeutic management, and pollen allergy (dimensions 1–3); while this second part (present article) includes the results related to AIT in pediatric patients polysensitized to mites, molds, animal dander, Hymenoptera venom, and the use of allergen mixtures (dimensions 4–8).

Figure 1 Consensus achievement and key recommendations emerging from the consensus in Dimension 4 (Dust mites). AIT, allergen immunotherapy.

Results from dimensions 4–8

Tables S1–S5 summarize the results from the Delphi process and the level of agreement after the two rounds for the statements related to the management of the polysensitized child with dust mites (Table S1), mold (Table S2), animal dander (Table S3), Hymenoptera venom (Table S4) allergies, and the AIT mixing allergens from multiple sources (Table S5).

Dimension 4: Dust mites

Consensus was reached for 14 items (56%; Figure 1). A total of 13 and 1 statements reached agreement in Rounds 1 and 2, respectively. Eleven statements did not achieve consensus in Round 2.

With an agreement of 100%, it was established that house dust mites (HDM) of the genus Dermatophagoides (including D. pteronyssinus or D. farinae) are the most important source of indoor allergens. The need for SPT and determination of total and specific IgE to the whole complete extract and its components in patients with suspected HDM sensitization by clinical history reached 100 and 84.8% agreement, respectively. In addition, 71.7% of panel experts agreed that it is necessary to know the component profile before prescribing AIT in the case of Dermatophagoides species sensitization. On the other hand, there was no sufficient agreement to recommend the identification of Der p 1, Der p 2, Der p 23, and/or Der p 10 by molecular diagnosis for the correct diagnosis of mite allergy in a polysensitized pediatric population (statements 8–10). Besides, panelists did not accept that sensitization to a single group (1 or 2) predicts lower severity of disease and worse response to AIT (statement 2, 47.7%; statement 12, 15.9%).

No consensus was reached among the panelists on whether the sublingual or subcutaneous AIT route of administration is superior in the treatment of mite allergy-related rhinitis (statement 13, 43.2%). A total of 73.9% of panel experts considered it advisable to indicate AIT early in case of progressive sensitization to avoid asthma and/or rhinitis or increased severity of symptoms. The mixing of Lepidoglyphus and Dermatophagoides AIT is recommended if sensitization to both species is shown to be clinically relevant by 91.3% of panelists, as well as the use of mixtures of mites from nonhomologous families, which was acceptable to 89.1% of panel experts.

If after 1 year of AIT treatment with mite extracts, there is no evidence of the efficacy of the therapy, panelists agreed (97.8%) in assessing compliance with treatment. In contrast, no agreement was reached regarding whether to discontinue treatment (54.5%), consider a change of product (61.4%), or increase the dose (45.5%).

Dimension 5: Molds

Consensus was reached for 10 items (83.3%; Figure 2). A total of eight and two statements reached an agreement in Rounds 1 and 2, respectively. Two statements did not achieve consensus in Round 2.

Figure 2 Consensus achievement and key recommendations emerging from the consensus in Dimension 5 (Molds). AIT, allergen immunotherapy; IgE, immunoglobulin E.

An agreement of 97.8% was reached for the statement indicating that Alternaria is responsible for the clinical manifestations in the majority of the pediatric patients (statement 1). In addition, 93.5% of panelists agreed that pediatric patients sensitized to Alternaria have a higher risk of developing severe asthma (compared to other aeroallergens) and asthma exacerbations (statements 2 and 3). The optimal diagnostic strategy in polysensitized patients with suspected mold allergy is the prick test, total and specific IgE, and molecular diagnosis with Alt a 1 with an agreement of 95.7% (statement 8). However, prick tests and specific IgE as optimal diagnostic strategies did not achieve consensus (statement 5, 52.3%). Finally, the administration of subcutaneous AIT form was advisable in this patient profile, according to the consensus reached (statement 11, 76.1%). In contrast, no agreement was made on the acceptance of mixing different types of molds in the same AIT preparation (statement 12, 18.2%).

Dimension 6: Animal dander

Consensus was reached for nine items (60%) (Figure 3). A total of nine statements reached an agreement in Round 1, while no statements reached consensus in Round 2. Six statements did not achieve consensus in Round 2.

Figure 3 Consensus achievement and key recommendations emerging from the consensus in Dimension 6 (Animals). AIT, allergen immunotherapy.

Regarding sensitization to major cat (Fel d 1) and dog (Can f 1) allergens during childhood, panelists agreed with 84.8 and 73.9%, respectively, that increased the risk of development of respiratory allergy symptoms in adolescence. On molecular diagnostics, panel experts agreed that Fel d 1, Can f 1, and Can f 5 sIgE are better predictors than specific IgE determination to cat or dog entire extracts (82.6%) and should be performed in case of suspected cat and dog allergy in polysensitized patients (89.1%). In contrast, no agreement was reached regarding the acceptance of AIT with mixtures of different animal extracts (15.9%).

Dimension 7: Hymenoptera venom

Consensus was reached for 28 items (82.3%; Figure 4). A total of 27 and 1 statements reached agreement in Rounds 1 and 2, respectively. Six statements did not achieve consensus in Round 2.

Figure 4 Consensus achievement and key recommendations emerging from the consensus in Dimension 7 (Hymenoptera venom). AIT, allergen immunotherapy; µg, micrograms.

The main accepted factors that can be highlighted for the therapeutic decision on AIT initiation in the pediatric polysensitized population with Hymenoptera allergy, were have suffered a generalized reaction limited to the skin but at high risk of exposure to Hymenoptera (100% of consensus), and other risk factors such as geographical location (95.7% of consensus).

The expert panelists agreed that IgE determination against entire extract complemented by molecular diagnostics improve the correct decision on the AIT to be administered (statement 16, 100% of agreement). In this way, panelists agreed that Api m 2 sIgE is a marker of cross-reactivity in children with Vespid and Apis mellifera IgE (88.9% of agreement), and Api m 4 sIgE has been identified as a marker for systemic reaction with AIT in Apis mellifera venom allergies (91.1%).

Finally, agreement was reached on the high dependency of the efficacy of Hymenoptera AIT on the venom used as a maintenance dose (100 µg) (91.3% of consensus). Panelists also agreed that mixtures of Apis and Vespid venom extracts are not recommended (86.7% of agreement).

Dimension 8: AIT with mixtures of multiple allergen sources

Consensus was reached for 15 items (65.2%; Figure 5). A total of 15 statements reached an agreement in Round 1, while no statement reached a consensus in Round 2. Eight statements did not achieve consensus in Round 2.

Figure 5 Consensus achievement and key recommendations emerging from the consensus in Dimension 8 (Mixtures). AIT, allergen immunotherapy; SCIT, subcutaneous immunotherapy; SLIT, sublingual immunotherapy.

When preparing mixtures of allergen extracts for AIT, agreement was reached regarding several factors (statements 2–7). Panelists also agreed with 80.4% of the consensus that SCIT is more suitable than SLIT in the case of mixtures. In addition, agreement was achieved on the possible dilution effect of the concentration of the individual allergen components, since maybe the final mixture is less concentrated than the individual allergens (statement 5, 84.8%).

In general, no agreement was achieved regarding the recommendation to mix the following allergens (statements 11–15): pollen and mites (25%); pollen and molds (40.9%) (although the mixture of Alternaria and pollen in the same SCIT preparation was accepted, statement 19: 67.4%); pollen and animal dander (61.4%); mites and molds (36.4%); and mites and animal danders (54.5%). The use of AIT mixtures of animal dander and other allergen sources (mites, molds or pollens) was not accepted by 80.4% of panelists (statement 23). In contrast, agreement was achieved on the statement indicating that mixing pollen allergens and animal dander is possible if mixture stability, safety and efficacy are demonstrated (statement 16, 71.7% of consensus).

Discussion

Polysensitization is common in Spain and other Mediterranean regions, and it has impacts on allergic disease management.^1,7 The decision-making process is complicated by the lack of scientific evidence.¹¹ With that in mind, the Delphi approach assists in gathering expert perspectives, reaching consensus, encouraging reflection, and ensuring the dependability of conclusions.^13–15

Overall, consensus was reached respectively in 14 (56%), 10 (83.3%), 9 (60%), 28 (82.3%), and 15 (65.2%) of the statements for AIT management in pediatric patients allergic to HDM, molds, animal dander, Hymenoptera venom allergy management, as well as AIT with mixtures of multiple allergen sources. To simplify the interpretation of the results, a set of recommendations was developed with the most relevant items that reached expert consensus in the Delphi process (Table 1).

Dust mites

Regarding HDM allergy management, no sufficient agreement was reached to recommend the identification of Der p 1, Der p 2, Der p 23, and/or Der p 10 by molecular diagnosis for the correct diagnosis in a polysensitized pediatric population (statements 8–10). tt This conclusion may be attributed, in part, to the continuous discovery of novel molecular markers whose clinical relevance remains uncertain. Furthermore, the limited availability of these newly identified molecules for diagnostic purposes in many healthcare facilities complicates their selection and implementation in routine clinical practice. The data on sensitization to Der p 1, Der p 2, and Der p 23 allergens are clinically significant as early sensitization to these allergens is related to bronchial asthma development.^16,17 There is also evidence that patients with allergic rhinitis respond to a larger number of HDM allergens and are more often sensitized to Der p 23 and Der p 7.^18–20

The panel experts agreed that it is necessary to know the component profile before prescribing AIT in the case of Dermatophagoides species sensitization. Studies have shown that molecular profiling of sensitization to HDM is an important aspect for predicting AIT efficiency.²¹ Current EAACI pediatric guidelines indicate the importance of knowledge on the specific epidemiology of each geographic region and assessment of the patient’s sensitization status (monoallergic or polyallergic).²⁰ Recent research on AIT efficacy in individuals with diverse sensitization profiles suggested that the treatment elicited protective IgG, primarily to Der p 1 and Der p 2, but not to other allergens such as Der p 5, Der p 7, and Der p 21.²² This suggesting that AIT has a higher therapeutic efficacy in patients who are sensitized to Der p 1 and/or Der p 2 when compared to patients who are sensitized to additional allergens.

Overall, 91.3 and 89.1% of panelists recommended the mixing of Lepidoglyphus and Dermatophagoides AIT (if sensitization to both species is shown to be clinically relevant) and the use of mixtures of mites from nonhomologous families, respectively. The Delphi consensus study previously conducted in Spain indicated that in circumstances where the sensitization to Dermatophagoides and minor mites coexists and clinical relevance for both types of mites is suspected, AIT containing both species could be suitable.⁴ When preparing allergen extract mixtures, the prescribing physician must consider the possibility of allergen degradation caused by proteolytic enzymes.²³ In previous studies, mite allergens were found to be resistant to insect and fungal proteases when stored in ≥ 10% glycerin. After mixing grass pollen with mite extracts from various manufacturers at concentrations equivalent to current immunotherapy practices, no detectable loss of allergen reactivity was observed.²⁴ However, the majority of the studies demonstrating AIT efficacy have used a single allergen, with little data to support multiallergen AIT.²⁵ An important recommendation, included in the current guidelines, would be to conduct specific studies in pediatrics to confirm the safety and efficacy of AIT products already used in adults.²⁰

Molds

A broad agreement (97.8%) was reached indicating that Alternaria is responsible for the clinical manifestations in the majority of the cases. Alternaria is a common outdoor fungus with a high prevalence in the environment because its spores are present in the air throughout the year.²⁶ With a consensus of 76.1%, the subcutaneous route is recommended for Alternaria AIT. Although Alternaria SLIT has shown efficacy in clinical trials, the product is not marketed in Spain.^27,28 A few studies have been conducted on the efficacy and safety of specific immunotherapy with allergen extracts of fungi compared with other allergen extracts.²⁹ Current pediatric guidelines agree that, based on existing evidence, there is low-quality evidence to support the effectiveness and safety of SCIT for Alternaria in the treatment of allergic respiratory symptoms.²⁰ In the case of Alternaria extracts SLIT and Cladosporium extracts SCIT, the claim is of very low quality.²⁰ Subcutaneous administration with Alt a 1 had demonstrated efficacy and safety, with reductions of rhinoconjunctivitis-associated symptoms and medication consumption, after 1 year of treatment.³⁰ In addition, the post-hoc analysis of the treated patients showed that AIT with Alt a 1 eliminated their Alt a 1 sensitization.³¹

No agreement was reached regarding the acceptance of mixing different types of molds in the same AIT preparation (18.2%). Fungal allergen extracts contain proteases that can degrade other allergens (e.g., mites and pollens) if they are combined in a single vaccine.³²

Animal dander

In the case of animal dander allergy management and, more specifically, molecular diagnostics, panel experts agreed that Fel d 1 and Can f 1 sIgE are better predictors than specific IgE for cat and dog complete allergens and that Fel d 1 and Can f 1 and Can f 5 sIgE should be performed in case of suspected cat and dog allergy in polysensitized patients. These allergens are highly prevalent in the environment and are responsible for the majority of cases of animal dander allergy. Several studies found that the levels of Fel d 1 and Can f 1 allergens in homes, cars, and schools were associated with the presence of symptoms of animal dander allergy, even in individuals who did not have detectable levels of specific IgE antibodies to these allergens.^33,34 In addition, another major allergen Can f 5 is a prostatic kallikrein found in male dog urine and is highly prevalent in the environment.³⁵ In a large study of Swedish adults, Can f 5 was the most common dog component to cause sensitization.³⁶ Another large population-based study found that Can f 5 was the most commonly recognized dog allergen across all age groups of children with cat and dog allergies, even though only about 1 in 10 of these individuals reported symptoms to dogs.³⁷ However, current literature suggests limited high-quality evidence supporting AIT for cat allergy, no clear clinical evidence of effectiveness for dog allergy, and insufficient evidence regarding the efficacy and safety of AIT for other animal allergens, such as horses.^20,38,39

Hymenoptera venom

Regarding Hymenoptera venom allergy management, panelists agreed that Api m 2 and Api m 4 sIgE are markers of Vespid and Apis mellifera cross-reactivity in children (88.9%) and systemic reaction with AIT in Apis mellifera venom allergies (91.1%), respectively. Several studies have shown that Api m 2 is implicated in cross-reactivity phenomena with Vespid venom hyaluronidases, such as Ves v 2a and its isoform Ves v 2b.⁴⁰ Other allergens, such as the dipeptidyl peptidases Api m 5 and Ves v 3, are also likely to be cross-reactive based on sequence homology.^41,42 In the case of Api m 4 sIgE, although its value as a marker allergen is limited, recent studies demonstrated a high prevalence of Api m 4 sensitization among Hymenoptera venom-allergic patients who experienced systemic reactions during the induction phase of AIT.⁴³ It is crucial to recognize that many recommendations for managing pediatric patients are extrapolated from adult studies due to the limited number of large-scale studies specifically involving children. Moreover, effectiveness data are primarily collected during AIT treatment rather than after its completion. Consequently, current guidelines emphasize the need for pediatric-specific clinical evidence on long-term effectiveness and optimal treatment duration.²⁰

Panelists also agreed that mixtures of Apis and Vespid venom extracts are not recommended (86.7%), which is in line with previously published recommendations.^23,24

Mixtures

To simplify the interpretation of the results related to mixtures, a graphical summary of the results of the Delphi process is shown in Figure 6.

Figure 6 Graphical summary of the results of the Delphi process related to mixtures. Consensus agreements are displayed in colors as shown in the key.

When the use of mixtures of multiple allergen sources in AIT was addressed in detail in the present project, panelists agreed that SCIT is more suitable than SLIT in the case of mixtures (80.4%). In this sense, SLIT with multiple allergen mixtures has demonstrated efficacy, but further studies are needed to confirm its effectiveness.⁴⁴

A high consensus was reached on the concept of the dilution effect of the concentration of the individual allergen components in the final mixture (84.8%). In this sense, multiallergen immunotherapy could face formulation issues, especially in the case of more than two allergen components, with significant quality, efficacy and safety limitations.^12,45 Regarding allergen mixtures, the European Medicines Agency (EMA) recommends mixing only homologous allergens, which are typically taxonomically related.⁴⁶ Additionally, EMA advises against including allergens with enzymatic activities, such as house dust mites, in these mixtures. Conversely, the Delphi CONDOR study concluded that results from single allergen treatment studies cannot be directly extrapolated to allergen mixtures.⁴ Specifically, the study recommended ensuring the effective concentration of each allergenic source in the final mixture composition.

In general, no agreement was achieved regarding the recommendation of the following allergen mixtures: pollen and mites (25%); pollen and molds (40.9%); pollen and animal danders (61.4%); mites and molds (36.4%); and mites and animal dander (54.5%). This is justified by the fact that it has been demonstrated that the allergenic products with the highest protease activity are insect and fungal extracts.²⁴ However, the statement regarding the mixture of Alternaria and pollen in the same SCIT preparation was accepted (67.4%; Table S5, Statement 19). There is no published evidence on this, so it is an agreement derived from real-life clinical practice. Despite the lack of agreement on the mixture of pollen and animal dander, consensus was achieved on the mixing of pollen allergens and animal dander if mixture stability, safety and efficacy are demonstrated.

Limitations and strengths

The Delphi methodology is a valuable tool for gathering insights and making informed decisions in healthcare practice. One of its limitations is that, although its anonymity can mitigate biases, participants may still exhibit response predisposition. The methodology also implies that high agreement among experts does not necessarily imply that a recommendation is effective. The results of this study serve as the starting point for developing recommendation documents and management guidelines.

Due to the Delphi methodology employed in this study, a variable percentage of statements across dimensions did not reach consensus. This outcome can be attributed to several factors, particularly those related to the unique aspects of clinical experience and practice in Spain. These factors collectively contribute to this variability, highlighting the complex interplay between clinical practice, healthcare system structure, and evolving regulatory landscapes in shaping expert opinions on the management of polysensitized pediatric patients.

Firstly, most participating panelists work within the Spanish Public Health System, a context where both diagnosis and treatment are publicly funded, unlike the European average. This setting influences appointment scheduling for initial consultations and follow-ups (determined by factors such as severity, age, and waiting lists), as well as the diagnostic sequence for polysensitized patients. Secondly, while molecular diagnostics are widely used in Spain, the experience and availability vary considerably depending on the specific allergens involved.^10,47,48 Additionally, Spanish clinical practice predominantly uses SCIT over SLIT, with some exceptions as noted in the study.⁴⁹ Apart from that, chemically modified allergen extracts are frequently used in AIT in Spain and Europe.⁴⁹ The modification decreases allergenicity, maintaining the extract’s immunogenicity. However, the standardization and quality control processes for modified extracts are more complex compared to those for native allergen extracts, due to the chemical modifications involved.⁵⁰ Finally, the regulatory process for AIT in Spain is ongoing. This study reflects the current circumstances, and future consensus analyses may be necessary once the regulatory framework is fully established.

In summary, the findings of this Delphi study indicated that, while the general lines of recommendations and suggestions are consistent with established management recommendations, an adaptation to the specific characteristics of Spain polysensitized children is required.

Conclusion

When prescribing mixtures, the following are necessary: 1) to include high quality standardized extracts with proven efficacy and safety; 2) in the case of allergens without proteolytic activity between them, to include only one allergen of a homologous group; and 3) to take into account the dilution effect and the maximum dose of each allergen in the final preparation.

Given the emerging local regulations for AIT treatments and the ongoing improvement in molecular diagnosis of less common allergen sources, it is probable that the landscape will change significantly in the medium term. Consequently, future consensus-building efforts will likely be necessary to address these evolving circumstances.

In the current context, the expert consensus recommendations derived from this Delphi panel study may provide support and guidance on clinical decision-making regarding the management of polysensitized children in real-world clinical practice. Additionally, this consensus analysis may encourage discussion on controversial issues addressed in the consensus statements.