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. 2013 May 1;6(1):9.
doi: 10.1186/1939-4551-6-9.

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

Jill D Jacobson  1 , Angela L Turpin, Scott A Sands
Affiliations

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

Jill D Jacobson et al. World Allergy Organ J. .

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.

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Figures

Figure 1
Figure 1
Diagram depicting the method of measurement of the sums of wheal and flare (Σ of flare) responses to histamine skin testing.
Figure 2
Figure 2
Vertical dot plot depicting the sum of flare (Σ of flare) responses to histamine skin testing on the back in control participants and in patients with MAS. * A significantly higher histamine response is seen in MAS patients compared to controls (n = 11 per group; p = 0.004).
Figure 3
Figure 3
Vertical dot plot depicting the sum of wheal (Σ of wheal) responses to histamine skin testing on the back in control participants and in patients with MAS. Each group included one patient whose wheal measurement was not recorded. *A significantly higher histamine response is seen in MAS patients compared to controls (p = 0.01).
Figure 4
Figure 4
Whisker plot of Gαs mRNA and Gαq mRNA in controls versus MAS participants. Sufficient quantities and quality of mRNA were available on 9 to 11 participants per group. Although no differences are seen in Gαs mRNA, * Gαq mRNA is significantly higher in MAS patients compared to controls (p = 0.039). The solid lines within the boxes represent median values.
Figure 5
Figure 5
Regression analysis demonstrating a direct, positive correlation between Tanner stage and the maximum sum of flare responses to histamine skin testing irrespective of anatomical site in patients with MAS (n = 11; Spearman r = 0.67; p = 0.02) and in healthy control participants (n = 9; Spearman r =0.64; p = 0.03).
See this image and copyright information in PMC

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