Vibratory urticaria is a condition in which exposing the skin to vibration, repetitive stretching, or friction results in allergy symptoms such as hives (urticaria), swelling (angioedema), redness (erythema), and itching (pruritus) in the affected area. The reaction can be brought on by towel drying, hand clapping, running, a bumpy ride in a vehicle, or other repetitive stimulation. Headaches, fatigue, faintness, blurry vision, a metallic taste in the mouth, facial flushing, and more widespread swelling (especially of the face) can also occur during these episodes, especially if the stimulation is extreme or prolonged. The reaction occurs within a few minutes of the stimulation and generally lasts up to an hour. Affected individuals can have several episodes per day.

Vibratory urticaria can be caused by a mutation in the ADGRE2 gene. This gene provides instructions for making a protein found in several types of immune system cells, including mast cells. Mast cells, which are found in many body tissues including the skin, are important for the normal protective functions of the immune system. They also play a role in allergic reactions, which occur when the immune system overreacts to stimuli that are not harmful. The specific role of the ADGRE2 protein in mast cells is not well understood.

The ADGRE2 protein consists of two parts (subunits) that interact with each other: an alpha subunit that lies on the outside surface of the cell and a beta subunit that crosses the cell membrane and extends into the cell. The ADGRE2 gene mutation that causes vibratory urticaria changes a single protein building block (amino acid) in the alpha subunit, altering the protein structure and leading to a less stable interaction between the two subunits. This fragile connection can be more easily broken; vibration, friction, or stretching of the skin can disrupt the association between subunits in mast cells. Researchers suggest that once the subunits are disconnected, the beta subunit signals the mast cells to react and produce the allergy symptoms in the skin that occur in vibratory urticaria.

Some people with vibratory urticaria do not have a mutation in the ADGRE2 gene. In these affected individuals, the cause of the disorder is unknown.

Normal Function

The ADGRE2 gene provides instructions for making a protein found in several types of immune system cells, including mast cells. Mast cells, which are found in many body tissues including the skin, are important for the normal protective functions of the immune system. They also play a role in allergic reactions, which occur when the immune system overreacts to stimuli that are not harmful. The specific role of the ADGRE2 protein in mast cells is not well understood.

The ADGRE2 protein consists of two parts (subunits) that interact with each other: an alpha subunit that lies on the outside surface of the cell and a beta subunit that crosses the cell membrane and extends into the cell.

Health Conditions Related to Genetic Changes

Vibratory urticaria

At least one mutation in the ADGRE2 gene has been identified in people with vibratory urticaria, a condition in which vibration, repetitive stretching, or friction on the skin results in allergy symptoms such as hives (urticaria), swelling (angioedema), redness (erythema), and itching (pruritus) in the affected area. The reaction can be brought on by towel drying, hand clapping, running, a bumpy ride in a vehicle, or other repetitive stimulation.

The ADGRE2 gene mutation that causes vibratory urticaria, written as Cys492Tyr or C492Y, replaces the protein building block (amino acid) cysteine with the amino acid tyrosine at position 492 of the protein sequence. The substitution alters the protein structure and leads to a less stable interaction between the two subunits. This fragile connection can be more easily broken; vibration, friction, or stretching of the skin can disrupt the association between subunits in mast cells. Researchers suggest that once the subunits are disconnected, the beta subunit signals the mast cells to react and produce the allergy symptoms in the skin that occur in vibratory urticaria.

Other Names for This Gene

• CD312
• EGF-like module-containing mucin-like hormone receptor-like 2
• EMR2

Genomic Location

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In most cases, an affected person has one parent with the condition.

Vibratory urticaria is a rare disorder; its prevalence is unknown. It belongs to a class of disorders called physical urticarias in which allergy symptoms are brought on by direct exposure to factors such as pressure, heat, cold, or sunlight. Physical urticarias have been estimated to occur in up to 5 per 1,000 people.