Urticaria pigmentosa (also known as generalized eruption of cutaneous mastocytosis (childhood type)James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . ) is the most common form of cutaneous

mastocytosis Mastocytosis, a type of mast cell disease, is a rare disorder affecting both children and adults caused by the accumulation of functionally defective mast cells (also called ''mastocytes'') and CD34+ mast cell precursors. People affected by mas ...

. It is a

rare disease A rare disease is any disease that affects a small percentage of the population. In some parts of the world, an orphan disease is a rare disease whose rarity means there is a lack of a market large enough to gain support and resources for discove ...

caused by excessive numbers of

mast cells A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...

in the skin that produce

hives Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...

or lesions on the skin when irritated.

Signs and symptoms

Urticaria pigmentosa is characterized by excessive amounts of

mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...

s in the skin. Red or brown spots are often seen on the skin, typically around the chest, forehead, and back. These mast cells, when irritated (e.g. by rubbing the skin, heat exposure), produce too much

histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered in ...

, triggering an allergic reaction that leads to hives localized to the area of irritation, sometimes referred to as

Darier's sign Darier's sign is a change observed after stroking lesions on 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 a ...

. Severe itching usually follows, and scratching the area only serves to further symptoms. Symptoms can be mild (flushing and hives that require no treatment), moderate (diarrhea,

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...

, nausea/vomiting, headache, and fainting), or life-threatening (vascular collapse requiring emergency treatment and hospitalization).

Cause

The majority of urticaria pigmentosa cases are caused by a

point mutation A point mutation is a genetic mutation where a single nucleotide base is changed, inserted or deleted from a DNA or RNA sequence of an organism's genome. Point mutations have a variety of effects on the downstream protein product—consequences ...

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

816 of the

proto-oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

c-kit Proto-oncogene c-KIT is the gene encoding the receptor tyrosine kinase protein known as tyrosine-protein kinase KIT, CD117 (cluster of differentiation 117) or mast/stem cell growth factor receptor (SCFR). Multiple transcript variants encoding diff ...

. 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 Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...

normally at position 816 in the c-kit protein has been replaced with

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...

valine Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deprotonat ...

respectively) have been associated with early manifestation of the disease (mean age of onset: 1.3 and 5.9 months respectively). The c-kit gene is encoded on the q12 locus of chromosome 4.

Irritants

Several factors can worsen the symptoms of urticaria pigmentosa: *

Emotional stress In psychology, stress is a feeling of emotional strain and pressure. Stress is a type of psychological pain. Small amounts of stress may be beneficial, as it can improve athletic performance, motivation and reaction to the environment. Excess ...

* Physical stimuli such as heat, friction, and excessive exercise * Bacterial toxins *

Venom Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a sti ...

* Eye drops containing

dextran Dextran is a complex branched glucan (polysaccharide derived from the condensation of glucose), originally derived from wine. IUPAC defines dextrans as "Branched poly-α-d-glucosides of microbial origin having glycosidic bonds predominantly C-1 ...

NSAID Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

s *

Alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

Morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...

The classification of NSAIDs can be disputed.

Aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...

, 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.

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

can be used to treat urticaria pigmentosa. Many common anti-allergy medications are useful because they reduce the mast cell's ability to react to histamine. At least one clinical study suggested that

nifedipine Nifedipine (3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate), sold under the brand name Adalat and Procardia, among others, is a calcium channel blocker medication used to manage angina, high blood pressure, Ra ...

, a

calcium channel A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels. Comparison tables The following tables e ...

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 stabilizers are medications used to prevent or control certain allergic disorders. They block mast cell degranulation, stabilizing the cell and thereby preventing the release of histamine and related mediators. One suspected pharmaco ...

Gastrocrom, a form of

cromoglicic acid Cromoglicic acid (INN)—also referred to as cromolyn (USAN), cromoglycate (former BAN), or cromoglicate—is traditionally described as a mast cell stabilizer, and is commonly marketed as the sodium salt sodium cromoglicate or cromolyn sodium. ...

has also been used to reduce mast cell degranulation.

Epidemiology

Urticaria pigmentosa is a

, affecting fewer than 200,000 people in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

References

External links

{{Congenital malformations and deformations of integument Rare diseases Dermal and subcutaneous growths