# Pollen-Food Allergy Syndrome: Allergens, Clinical Insights, Diagnostic and Therapeutic Challenges
## 1 Introduction
In recent decades, food allergies have emerged as an alarming \"second wave\" of the allergy epidemic, particularly in westernized societies [27; 28]. The increasing prevalence of food allergies is particularly concerning due to their potential for life-threatening reactions, especially in children and adolescents [29; 30]. This trend places a growing burden on healthcare systems, many of which are ill-prepared to address the challenges posed by the allergy epidemic. The association between respiratory allergies and food allergies, exemplified by conditions like pollen-food allergy syndrome (PFAS), highlights the complex interplay between different allergic conditions. Cross-reactivity between pollen allergens and plant-derived foods is a key mechanism driving PFAS, as this phenomenon occurs due to structural similarities between proteins found in pollens and those present in certain fruits, vegetables, nuts, and seeds [31]. These shared protein epitopes, known as panallergens, are mistakenly recognized by the immune system as identical, triggering an allergic response in sensitized individuals [32]. Key panallergen families involved in PFAS include pathogenesis-related protein class 10 (PR-10) proteins, profilins, lipid transfer proteins (LTPs), and gibberell-regulated proteins (GRPs), each contributing to distinct patterns of cross-reactivity [31]. Clinically, PFAS presents a spectrum of symptoms, ranging from mild oral irritation, such as itching or tingling in the mouth and throat, to more severe reactions. These may include angioedema, gastrointestinal discomfort, or in rare cases, systemic anaphylaxis, which can be life-threatening [33]. The allergens involved in PFAS are typically labile, losing their allergenity with heat or enzymatic digestion, which explains the mild symptoms in most cases. However, when symptoms are severe, they may reflect primary sensitization to stable, genuine food allergens that retain their immunogenic properties even after processing, blurring the distinction between PFAS and classical IgE-mediated food allergies [34]. Environmental and individual factors can further modulate the clinical presentation of PFAS. Cofactors such as physical exercise, alcohol consumption, or the use of nonsteroidal anti-inflammatory drugs (NSAIDs) can exacerbate symptoms, potentially tipping mild reactions into severe systemic responses [35]. Understanding these cross-reactive mechanisms is critical for accurate diagnosis and effective management of PFAS, highlighting the need for personalized therapeutic approaches and patient education to mitigate risks. This clinical entity was first described in 1942 as the connection between pollinosis and reactions to labile allergens in fresh vegetables and termed oral allergy syndrome (OAS) [36]. This initial understanding emphasized the localized oral and pharyngeal symptoms caused by cross-reactivity between pollen allergens and homologous proteins in raw fruits, vegetables, and nuts. In 1987, the term pollen-food allergy syndrome was proposed to provide a more comprehensive descriptor of this condition, recognizing its broader clinical implications and relationship with pollen-associated food allergies [37]. OAS is still a term sometimes used interchangeably with PFAS, but is now typically reserved for allergic reactions confined to the orophnx after the ingestion of certain foods [38]. However, OAS can occur as the initial symptom of both class I and class II food allergies [31]. Therefore, the confusion between OAS and PFAS poses a clinical risk. Patients with primary food allergies (sensitized to class I allergens) may exhibit mild oral symptoms to small allergen doses but are at risk of progressing to systemic reactions or anaphylaxis. Misdiagnosing these patients as having PFAS may result in inadequate management, including failure to prescribe life-saving epinephrine auto-injectors, thereby increasing the risk of severe outcomes [34].