Urticaria pigmentosa
Encyclopedia
Urticaria pigmentosa is the most common form of cutaneous mastocytosis
. It is a rare disease
caused by excessive numbers of mast cells in the skin that produce hives or lesions on the skin when irritated.
s in the skin. Red or brown spots are often seen on the skin, typically around the chest and forehead. These mast cells, when irritated (e.g. by rubbing the skin, heat exposure), produce too much histamine
, triggering an allergic reaction that leads to hives localized to the area of irritation, sometimes referred to as Darier's sign
. Severe itching usually follows, and scratching the area only serves to further symptoms. Symptoms can range from very mild (flushing, hives, no treatment needed) to life-threatening (vascular collapse).
at amino acid
816 of the proto-oncogene c-kit. c-kit is a transmembrane protein which, when bound to Mast Cell Growth Factor (MCGF), signals the cell to divide. Mutations in position 816 of c-kit can result in a constant division signal being sent to the mast cells, resulting in abnormal proliferation. Different mutations have been linked to different onset times of the disease.
For example, the Asp816Phe and Asp816Val mutations (the aspartate normally at position 816 in the c-kit protein has been replaced with phenylalanine
or valine
respectively) have been associated with early manifestation of the disease (mean age of onset: 1.3 and 5.9 months respectively).
The classification of NSAIDs can be disputed. Aspirin
, for example, causes the mast cells to degranulate
, releasing histamines and causing symptoms to flare. However, daily intake of 81 mg aspirin may keep the mast cells degranulated. Thus, while symptoms may be worsened at first, they can get better as the mast cells are unable to recharge with histamine.
are useful because they reduce the mast cell's ability to react to histamine.http://dermnetnz.org/colour/urticaria-pigmentosum.html
At least one clinical study suggested that nifedipine
, a calcium channel
blocker used to treat high blood pressure, may reduce mast cell degranulation in patients with urticaria pigmentosa. A 1984 study by Fairly et al. included a patient with symptomatic urticaria pigmentosa who responded to nifedipine at dose of 10 mg po tid. However, nifedipine has never been approved by the FDA for treatment of urticaria pigmentosa.
Another Mast cell stabilizer
Gastrocrom, a form of Cromoglicic acid has also been used to reduce mast cell degranulation.
, affecting fewer than 200,000 people in the United States
.
Mastocytosis
Mastocytosis is a group of rare disorders of both children and adults caused by the presence of too many mast cells and CD34+ mast cell precursors in a person's body.- Classification :Mastocytosis can occur in a variety of forms:...
. It is a rare disease
Rare disease
A rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population.Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear...
caused by excessive numbers of mast cells in the skin that produce hives or lesions on the skin when irritated.
Signs and symptoms
Urticaria Pigmentosa is characterized by excessive amounts of mast cellMast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...
s in the skin. Red or brown spots are often seen on the skin, typically around the chest and forehead. These mast cells, when irritated (e.g. by rubbing the skin, heat exposure), produce too much histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
, triggering an allergic reaction that leads to hives localized to the area of irritation, sometimes referred to as Darier's sign
Darier's sign
Darier's sign is a change observed after stroking the skin of a person with systemic mastocytosis or urticaria pigmentosa.In general, the skin becomes swollen, itchy and red. This is a result of compression of mast cells, which are hyperactive in these diseases. These mast cells release...
. Severe itching usually follows, and scratching the area only serves to further symptoms. Symptoms can range from very mild (flushing, hives, no treatment needed) to life-threatening (vascular collapse).
Cause
The majority of urticaria pigmentosa cases are caused by a point mutationPoint mutation
A point mutation, or single base substitution, is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic material, DNA or RNA. Often the term point mutation also includes insertions or deletions of a single base pair...
at amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
816 of the proto-oncogene c-kit. c-kit is a transmembrane protein which, when bound to Mast Cell Growth Factor (MCGF), signals the cell to divide. Mutations in position 816 of c-kit can result in a constant division signal being sent to the mast cells, resulting in abnormal proliferation. Different mutations have been linked to different onset times of the disease.
For example, the Asp816Phe and Asp816Val mutations (the aspartate normally at position 816 in the c-kit protein has been replaced with phenylalanine
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
or valine
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
respectively) have been associated with early manifestation of the disease (mean age of onset: 1.3 and 5.9 months respectively).
Irritants
The following can worsen the symptoms of urticaria pigmentosa:- Emotional stress
- Physical stimuli such as heat, friction, and excessive exercise
- Bacterial toxins
- Venom
- Eye drops containing dextranDextranDextran is a complex, branched glucan composed of chains of varying lengths...
- NSAIDs
- AlcoholAlcoholic beverageAn alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
- MorphineMorphineMorphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
The classification of NSAIDs can be disputed. Aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
, for example, causes the mast cells to degranulate
Degranulation
Degranulation is a cellular process that releases antimicrobial cytotoxic molecules from secretory vesicles called granules found inside some cells...
, releasing histamines and causing symptoms to flare. However, daily intake of 81 mg aspirin may keep the mast cells degranulated. Thus, while symptoms may be worsened at first, they can get better as the mast cells are unable to recharge with histamine.
Diagnosis
The disease is most often diagnosed as an infant, when parents take their baby in for what appears to be bug bites. The bug bites are actually the clumps of mast cells. Doctors can confirm the presence of mast cells by rubbing the baby's skin. If hives appear, it most likely signifies the presence of urticaria pigmentosa.Treatments
There are no permanent cures for urticaria pigmentosa. However, treatments are possible. Most treatments for mastocytosis can be used to treat urticaria pigmentosa. Many common anti-allergy medicationsAntihistamine
An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
are useful because they reduce the mast cell's ability to react to histamine.http://dermnetnz.org/colour/urticaria-pigmentosum.html
At least one clinical study suggested that nifedipine
Nifedipine
Nifedipine is a dihydropyridine calcium channel blocker...
, a calcium channel
Calcium channel
A Calcium channel is an ion channel which displays selective permeability to calcium ions. It is sometimes synonymous as voltage-dependent calcium channel, although there are also ligand-gated calcium channels.-Comparison tables:...
blocker used to treat high blood pressure, may reduce mast cell degranulation in patients with urticaria pigmentosa. A 1984 study by Fairly et al. included a patient with symptomatic urticaria pigmentosa who responded to nifedipine at dose of 10 mg po tid. However, nifedipine has never been approved by the FDA for treatment of urticaria pigmentosa.
Another Mast cell stabilizer
Mast cell stabilizer
Mast cell stabilizers are cromone medications used to prevent or control certain allergic disorders. They block a calcium channel essential for mast cell degranulation, stabilizing the cell and thereby preventing the release of histamine and related mediators. One suspected pharmacodynamic...
Gastrocrom, a form of Cromoglicic acid has also been used to reduce mast cell degranulation.
Epidemiology
Urticaria pigmentosa is an orphan diseaseRare disease
A rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population.Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear...
, affecting fewer than 200,000 people in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
.
See also
- MastocytosisMastocytosisMastocytosis is a group of rare disorders of both children and adults caused by the presence of too many mast cells and CD34+ mast cell precursors in a person's body.- Classification :Mastocytosis can occur in a variety of forms:...
- Mast CellsMast cellA mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...
- UrticariaUrticariaUrticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
- Dermatographic urticariaDermatographic urticariaDermatographic urticaria is a skin disorder seen in 4–5% of the population and is one of the most common types of urticaria, in which the skin becomes raised and inflamed when stroked, scratched, rubbed, and sometimes even slapped.-Presentation:The symptoms are thought to be caused by mast cells in...
- Generalized eruption of cutaneous mastocytosis (adult type)Generalized eruption of cutaneous mastocytosis (adult type)Generalized eruption of cutaneous mastocytosis is the most common pattern of mastocytosis presenting to the dermatologist, with the most common lesions being macules, papules, or nodules that are disseminated over most of the body but especially on the upper arms, legs, and trunk.- See also :*...