Mast cells: more than just allergy

"Mast cells are most commonly associated with allergies and anaphylactic shock, but the case of Stephanie Brown reported this week in the national press has raised the profile of another condition caused by mast cells: cutaneous mastocytosis".











Mast cells, a class of white blood cell, are characterised by their large granules. They are found in most tissues of the body particularly in boundary areas near the external environment – the skin, mucosa of the lungs and the digestive tract. Mast cells play a key role in inflammatory processes, releasing the contents of their granules in response to stimulation through direct contact, antibody cross-linking or activated complement proteins. The granules contain preformed chemical modulators, such as histamine and heparin, which cause blood vessels to relax leading to swelling and redness, as well as cytokines and lipid mediators that recruit other white blood cells to the site of inflammation.

The action of mast cells is most frequently associated with allergy and they play a central role in asthma, eczema and allergic rhinitis. Allergies result from the allergen (be it pollen or food) being bound by IgE antibodies on the surface of mast cells. Binding of the allergen results in cross-linking of the antibody and the activation of the mast cell. Activation leads to the release of its granules and inflammation. In severe cases this can lead to anaphylaxis, caused by degranulation of mast cells throughout the body leading to shock. This response, though best understood in terms of allergy, is thought to have evolved originally to defend the body against intestinal parasites such as the tapeworm.

Mastocytosis is a condition involving the accumulation of mast cells in a particular organ of the body, due to increased production of these cells in the bone marrow. A condition affecting people of all ages, mastocytosis is a heterogeneous condition in that it appears to have multiple causes. Several mutations in the gene c-Kit, a gene whose product is responsible for the survival and proliferation of white blood cells such as mast cells, have been identified in many but not all patients. Mastocytosis can be systemic, affecting the whole body, or cutaneous, affecting just the skin. Paediatric mastocytosis is generally restricted to the skin and often resolves itself once children reach adulthood.

In cutaneous mastocytosis activation of the accumulated mast cells causes the development of painful blisters over the entire skin surface. These skin lesions are known as urticaria pigmentosa and can be highly disfiguring. Activation of the mast cells in the skin can be triggered by many different events including touch, exercise, alcohol, insect stings or foods. Sufferers of systemic mastocytosis experience, in addition to skin lesions, gut pains, and vomiting due to mast cell activation in the gut. The liver, kidney and joints can also be affected. The specific symptoms of individual sufferers vary due to the heterogeneous nature of the condition.

Treatment of mastocytosis is tailored to individual patients depending on their symptoms and is based on controlling the symptoms. Antihistamines are commonly given to alleviate itching and redness, while adrenaline is provided to systemic patients who suffer anaphylactic reactions. Psoralen ultraviolet A (PUVA) therapy can be used, as in the case of Stephanie Brown, to alleviate itching and provide cosmestic improval.

Psoralen is a plant compound that increases the sensitivity of skin to UVA. The combination of Psoralen UVA treatment is used to treat a range of conditions affecting the skin such as psoriasis and eczema. The exact mechanism by which exposure to UVA resolves symptoms is unknown. UV is believed to suppress the body’s immune system in a mechanism involving regulatory T cells and vitamin D, a known regulator of the immune system. The recruitment of regulatory T cells to the skin would lower the extent of mast-cell activation in mastocytosis sufferers resulting in a decrease in the number of skin lesions. This treatment does not cure sufferers but alleviates symptoms. Sufferers may need to receive repeat treatments.

While there is no cure for mastocytosis, children often grow out of the condition with symptoms usually disappearing by adulthood. Hopefully this will be the case for Stephanie Brown as well.

References
Sunbed sessions cure toddler of painful blisters 5 Mar 2010 Telegraph.co.uk
www.ukmasto.co.uk

Fuente: British Society for Inmunology.