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

Jill D Jacobson,Angela L Turpin,Scott A Sands

doi:10.1186/1939-4551-6-9

Jill D Jacobson, Angela L Turpin + Show 1 more

Open Access

https://doi.org/10.1186/1939-4551-6-9

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Abstract

Background McCune 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.Objective As 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 methods After 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.Results The peak wheal and flare responses to histamine were significantly higher in MAS patients compared to controls.Conclusions This study suggests that MAS patients may be at risk for exaggerated histamine responsiveness compared to unaffected controls.

Highlights

McCune-Albright syndrome (MAS) is a rare, intriguing, genetic disorder characterized by excessive activity of multiple hormones and other mediators that signal through cAMP
The peak wheal and flare responses to histamine were significantly higher in McCune Albright syndrome (MAS) patients compared to controls
This study suggests that MAS patients may be at risk for exaggerated histamine responsiveness compared to unaffected controls

Summary

Introduction

McCune-Albright syndrome (MAS) is a rare, intriguing, genetic disorder characterized by excessive activity of multiple hormones and other mediators that signal through cAMP. The original description by Fuller Albright included the triad of precocious puberty, café-aulait skin spots, and polyostotic fibrous dysplasia [1]. The causative mutation, identified in 1991, is a missense mutation in the GNAS gene, which leads to constitutive activation of the Gsα protein [2]. Mutations in the GNAS gene occur after conception, and the individual survives with mosaicism. Endocrine features described in MAS include non-autoimmune hyperthyroidism, acromegaly, Cushing syndrome, hyperprolactinemia, and hyperparathyroidism. McCune 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). Gastroesophageal reflux, and anaphylaxis in McCune Albright patients

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