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MRGPRX2 in Drug Allergy

MRGPRX2 in Drug Allergy

True or classic drug allergy is mediated by the drug activating the allergic protein (IgE) which in turn causes Mast cells in the skin and throughout the body to release histamine.  However, it has been known for quite some time that some drug reactions are not mediated by IgE.  These have been referred to as pseudo-allergic reactions or anaphylactoid (as opposed to anaphylaxis). 

Then comes the discovery of Mas-related G protein – coupled receptor X2 (MRGPRX2) which sits on the surface of Mast cells (primarily Mast cells in the skin).  When this receptor is stimulated it too causes Mast cells to release histamine.  The most common drugs that do this are:  Leupron, Firazyr, Cetrotide, neuromuscular blocking agents (used in anesthesia), opiates, fluoroquinolones and vancomycin. 

The one good thing about MRGPRX2 receptor is it is “low-affinity” i.e., it requires a high concentration of drug to be activated.  This is in contrast to the IgE receptor which is high affinity.  A practical example is opiate.  If the dose is kept low enough many people can tolerate these drugs without reaction. 

Drug hypersensitivity genetic?

Drug hypersensitivity genetic?

The most common cause for drug allergy is from IgE-mediated (allergic) reactions, such as having hives from penicillin. New research is discovering a second mechanism for drug reaction being called “drug hypersensitivity,” as it is mediated by T-lymphocytes. The reactions are different from the arch-typical “allergy” in that they tend to be somewhat delayed and different types of rashes. Examples are measles-type bumps, the life-threatening skin condition Steven-Johnson Syndrome or liver irritation.

Of great interest is that there seems to be a genetic predisposition to react to certain individual drugs. Following is a list of certain HLA (genetic) types and the drug that reacts:


Genetic Type


HLA A 31:01


HLA   A 33:03


HLA   A 68:01


HLA   A 02:06

Cold Medicines

HLA   B 56:02


HLA   B 58:01


HLA   DRB 1 11:01


HLA   DRB 1 13:02


HLA   C 04:01



Because this research is new there are lots of uncertainties. Genetic testing is expensive, and everyone with the implicated gene won’t react to the medicine. It’s too early to recommend across-the-board testing, but an awareness of possibilities, along with finding less expensive ways to do this testing, may soon lead to “genetic profiling” of all of us.

Slow dosage start more prudent?

Slow dosage start more prudent?

Questioning whether the starting dosage of a medication might influence the likelihood of hypersensitivity reactions, research scientists at the Medical University in New Zealand conducted a study using a time-honored therapy for gout.

Unfortunately this medication, Allopurinol, has a predilection to cause hypersensitivity reactions that can be troublesome because, in addition to an allergic skin rash, there also may be inflammation of the liver and kidneys.

The study was simple, comparing two groups starting Allopurinol. One group started with the usual full dose and maintained that dose; the other with half the usual dose. This dose was maintained for several months and only then was gradually increased to full strength.

Fifty-four patients developed drug allergy and almost all of them were among the full-dose starters. The scientists editorialized that they understood why full-dose starting is the usual approach as both the patient suffering the gout and the physician treating it want as speedy improvement as possible. But perhaps slow, gradual – and therefore safe – improvement is the better route.