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

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.

Children with Heiner Syndrome: A Single-Center Experience

“…If a patient has pulmonary symptoms and pulmonary infiltrate on chest x-ray or pathology-confirmed pulmonary hemosiderosis, which resolves after milk removal, then he or she “probably” has Heiner syndrome. Additionally, if the symptoms recur after milk reintroduction, then there is higher likelihood of Heiner syndrome; thus, the patient’s findings that are “convincing” suggest Heiner syndrome, but the provocation or reintroduction is not mandatory for the diagnosis [ 7 ]. The authors here emphasize the importance of the differential diagnosis of Heiner syndrome as the prognosis and management are different from those of IPH.…”

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - III - Cow's milk allergens and mechanisms triggering immune activation

“…111 It is characterized by enhanced susceptibility to infections in ear (recurrent otitis media) and respiratory tract (pneumonia and pulmonary hemosiderosis), as well as gastrointestinal symptoms (vomiting, diarrhea, colic, and hematochezia), which resolve after a milk-free diet. Despite iron-deficiency anemia in the blood, 112,113 accumulation of iron can occur in tissues and cells, eg, in macrophages. 111,112 In rare cases, also hematemesis can occur.…”

“…Despite iron-deficiency anemia in the blood, 112,113 accumulation of iron can occur in tissues and cells, eg, in macrophages. 111,112 In rare cases, also hematemesis can occur. 114 The pathophysiology so far is descriptive, and the mechanism is not revealed yet.…”

Pediatric hypersensitivity pneumonitis: literature update and proposal of a diagnostic algorithm

“…A peculiar form of HP is represented by Heiner’s syndrome, caused by the intake of cow’s milk (CM). Sixty-one cases have been published in the literature, all in the pediatric age [ 27 ]. It is characterized by recurrent respiratory symptoms with pulmonary infiltrates at the chest radiography, poor growth, gastrointestinal symptoms, iron deficiency anemia, and occasionally pulmonary hemosiderosis.…”

“…Moreover, the reintroduction of milk caused a reoccurrence of the disease. Overall, this syndrome is so rare that it can be almost defined as anecdotal [ 27 ].…”