Allergic manifestations and cutaneous histamine responses in patients with McCune Albright syndrome

Abstract

BackgroundMcCune Albright syndrome (MAS) is a rare disorder characterized by precocious puberty, café-au-lait spots, and fibrous dysplasia. Its cause is an activating mutation in the GNAS gene, encoding a subunit of the stimulatory G protein, Gsalpha (Gsα). The action of any mediator that signals via Gsα and cyclic AMP can be up regulated in MAS. We had observed gastritis, gastroesophageal reflux, and anaphylaxis in McCune Albright patients.ObjectiveAs histamine is known to signal via histamine 1 (H1) and histamine 2 (H2) receptors, which couple with stimulatory G proteins, we attempted to mechanistically link histamine responsiveness to the activating GNAS mutation. We hypothesized that responsiveness to histamine skin testing would differ between MAS patients and healthy controls.Patients and methodsAfter obtaining informed consent, we performed a systematic review of histamine responsiveness and allergic manifestations in 11 MAS patients and 11 sex-matched, Tanner-stage matched controls. We performed skin prick testing, quantifying the orthogonal diameters of wheals and erythema. We also quantitated G protein mRNA expression.ResultsThe peak wheal and flare responses to histamine were significantly higher in MAS patients compared to controls.ConclusionsThis study suggests that MAS patients may be at risk for exaggerated histamine responsiveness compared to unaffected controls.

The Clinical Meaning of Histamine Skin Reactivity

“…Various single-nucleotide polymorphisms in the human DAO gene, located on chromosome 7q35, are associated with clinical conditions, such as food allergies, and represent a potential genetic background of a reduced or accelerated histamine metabolism [14][15][16]. A peculiar and interesting case is the rare and complex McCune-Albright syndrome, which is characterized by precocious puberty and café-au-lait spots and is caused by a genetic mutation encoding a stimulatory G protein (G5alpha): all the patients with the syndrome display marked skin reactivity to histamine [17].…”