*Review* **Heiner Syndrome and Milk Hypersensitivity: An Updated Overview on the Current Evidence**

**Stefania Arasi 1,\* ,†,‡, Carla Mastrorilli 2,†,‡, Luca Pecoraro 3,4,‡, Mattia Giovannini 5,‡, Francesca Mori 5,‡ , Simona Barni 5,‡, Lucia Caminiti 6,‡, Riccardo Castagnoli 7,‡, Lucia Liotti 8,‡, Francesca Saretta 9,‡ , Gian Luigi Marseglia 7,‡ and Elio Novembre 10,‡**


**Abstract:** Infants affected by Heiner syndrome (HS) display chronic upper or lower respiratory tract infections, including otitis media or pneumonia. Clinically, gastrointestinal signs and symptoms, anemia, recurrent fever and failure to thrive can be also present. Chest X-rays can show patchy infiltrates miming pneumonia. Clinical manifestations usually disappear after a milk-free diet. The pathogenetic mechanism underlying HS remains unexplained, but the formation of immune complexes and the cell-mediated reaction have been proposed. Patients usually outgrow this hypersensitivity within a few years. The aim of this review is to provide an updated overview on the current evidence on HS in children, with a critical approach on the still undefined points of this interesting disease. Finally, we propose the first structured diagnostic approach for HS.

**Keywords:** allergy; anemia; cow's milk; children; immunology; non-IgE-mediated food allergy; pneumonia; pulmonary hemosiderosis; pulmonary infiltrates
