Background: Allergen immunotherapy (AIT) is the only known causative treatment for Alternaria allergy, but the difficulty in standardizing Alternaria extracts hampers its effectiveness and safety. Summary:Alternaria, a potent airborne allergen, has a high sensitization rate and is known to trigger the onset and exacerbation of respiratory allergies, even inducing fungal food allergy syndrome in some cases. It can trigger a type 2 inflammatory response, leading to an increase in the secretion of type 2 inflammatory cytokines and eosinophils, which are the culprits behind allergic symptoms. Diagnosing Alternaria allergy is a multistep process, involving a careful examination of clinical symptoms, medical history, skin prick tests, serum-specific IgE detection, or provocation tests. Alt a1, the major component of Alternaria, is a vital player in diagnosing Alternaria allergy through component-resolved diagnosis. Interestingly, Alternaria can reduce the protein activity of other allergens like pollen and cat dander when mixed with them. In order to solve the problems of standardization, efficacy and safety of traditional Alternaria AIT, novel AIT methods targeting Alt a1 and innovative vaccines such as epitope, DNA, and mRNA vaccines seem promising in bypassing the standardization issue of Alternaria extracts. But these studies are in early stages, and most researches are still focused on animal models, calling for more evidence to validate their use in humans. Key Messages: This review delves into the various aspects of Alternaria allergy, including characteristics, epidemiology, immune mechanisms, diagnosis, clinical manifestations, and the application and limitations of Alternaria AIT, aiming to provide a foundation for the management of patients with Alternaria allergy.

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