Cutaneous mastocytosis is a form of mastocytosis that primarily affects the skin. There are three main forms of the condition: maculopapular cutaneous mastocytosis (also called urticaria pigmentosa), solitary cutaneous mastocytoma, and diffuse cutaneous mastocytosis. There is also an exteremely rare form called telangiectasia macularis eruptiva perstans. The signs, symptoms and severity of the condition vary by subtype. Cutaneous mastocytosis is usually caused by changes (mutations) in the KIT gene. Most cases are caused by somatic mutations which are not inherited or passed on to the next generation. However, it can rarely affect more than one family member and be inherited in an autosomal dominant manner. Treatment is usually symptomatic and may include oral antihistamines, topical steroids, and/or photochemotherapy.

Normal Function

The KIT gene provides instructions for making a member of a protein family called receptor tyrosine kinases. Receptor tyrosine kinases transmit signals from the cell surface into the cell through a process called signal transduction. The KIT protein is found in the cell membrane of certain cell types where a specific protein, called stem cell factor, attaches (binds) to it. This binding turns on (activates) the KIT protein, which then activates other proteins inside the cell by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions. This process, called phosphorylation, leads to the activation of a series of proteins in multiple signaling pathways.

The signaling pathways stimulated by the KIT protein control many important cellular processes such as cell growth and division (proliferation), survival, and movement (migration). KIT protein signaling is important for the development and function of certain cell types, including reproductive cells (germ cells), early blood cells (hematopoietic stem cells), white blood cells called mast cells, cells in the gastrointestinal tract called interstitial cells of Cajal (ICCs), and cells called melanocytes. Melanocytes produce the pigment melanin, which contributes to hair, eye, and skin color.

Health Conditions Related to Genetic Changes

Piebaldism

At least 69 KIT gene mutations have been identified in people with piebaldism. This condition is characterized by white patches of skin and hair caused by a lack of melanocytes in those areas. The mutations responsible for piebaldism lead to a nonfunctional KIT protein. The loss of KIT signaling is thought to disrupt melanocyte migration and proliferation during development, resulting in patches of skin that lack pigmentation.

Gastrointestinal stromal tumor

Mutations in the KIT gene are the most common genetic changes associated with gastrointestinal stromal tumors (GISTs). GISTs are a type of tumor that occurs in the gastrointestinal tract, most commonly in the stomach or small intestine. In most cases, these KIT gene mutations are acquired during a person's lifetime and are called somatic mutations. Somatic mutations, which lead to sporadic GISTs, are present only in the tumor cells and are not inherited. Less commonly, KIT gene mutations that increase the risk of developing GISTs are inherited from a parent, which can lead to familial GISTs.

KIT gene mutations associated with GISTs create a protein that no longer requires binding of the stem cell factor protein to be activated. As a result, the KIT protein and the signaling pathways are constantly turned on (constitutively activated), which increases the proliferation and survival of ICCs, leading to GIST formation.

Systemic mastocytosis

Somatic mutations in the KIT gene have been found to play a role in systemic mastocytosis. This condition is a blood disorder that typically appears after adolescence, varies in severity, and can affect many different body systems. Systemic mastocytosis occurs when mast cells abnormally accumulate in tissues. Mast cells normally trigger inflammation during an allergic reaction and signal an immune response when they are activated by an environmental trigger.

In most cases of systemic mastocytosis, the accumulated mast cells have a KIT gene mutation. More than 80 percent of individuals with systemic mastocytosis have a mutation in the KIT gene that replaces the protein building block (amino acid) aspartic acid with the amino acid valine at position 816 in the protein (Asp816Val or D816V). This and other KIT gene mutations result in production of altered proteins that are constitutively activated. As a result, signaling pathways that promote the proliferation of cells are overactive, which leads to increased production of mast cells and accumulation of the cells in various tissues. Cells with altered KIT proteins are more active than normal, leading to increased immune responses and signs and symptoms of systemic mastocytosis. In systemic mastocytosis, the excess mast cells lead to an increased immune response and signs and symptoms similar to an allergic reaction, such as skin redness and warmth (flushing), nausea, abdominal pain, nasal congestion, low blood pressure (hypotension), and headache.

Core binding factor acute myeloid leukemia

MedlinePlus Genetics provides information about Core binding factor acute myeloid leukemia

Other cancers

Somatic mutations in the KIT gene have been identified in several cancers. KIT gene mutations are involved in some cases of acute myeloid leukemia, which is a cancer of a type of blood cell known as myeloid cells, and sinonasal natural killer/T-cell lymphoma (NKTCL), another blood cell cancer that occurs in the nasal passages. In addition, some people with seminoma, a type of testicular cancer, have a somatic KIT gene mutation. The genetic changes involved in acute myeloid leukemia and seminomas lead to a KIT protein that is constitutively activated. The constant signaling causes overproliferation of the cells that make up these tumors. It is unclear how the KIT mutations in NKTCL are involved in the condition.

Other Names for This Gene

• C-Kit
• CD117
• KIT_HUMAN
• mast/stem cell growth factor receptor Kit
• p145 c-kit
• PBT
• piebald trait protein
• proto-oncogene c-Kit
• proto-oncogene tyrosine-protein kinase Kit
• SCFR
• tyrosine-protein kinase Kit
• v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
• v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene-like protein

Genomic Location

Most cases of cutaneous mastocytosis are not inherited. They occur spontaneously in families with no history of the condition and are due to somatic changes (mutations) in the KIT gene. Somatic mutations occur after conception and are only present in certain cells. Because they are not present in the germ cells (egg and sperm), they are not passed on to the next generation.

Cutaneous mastocytosis can rarely affect more than one family member. In these cases, the condition is typically inherited in an autosomal dominant manner. This means that to be affected, a person only needs a change (mutation) in one copy of the responsible gene in each cell. A person with familial cutaneous mastocytosis has a 50% chance with each pregnancy of passing along the altered gene to his or her child.

Cutaneous mastocytosis is a form of mastocytosis that primarily affects the skin. There are three main forms that vary in severity: maculopapular cutaneous mastocytosis (also called urticaria pigmentosa), solitary cutaneous mastocytoma, and diffuse cutaneous mastocytosis. There is also an exteremely rare form called telangiectasia macularis eruptiva perstans.

Maculopapular cutaneous mastocytosis, the most common form of cutaneous mastocytosis, is characterized by itchy, brown patches on the skin. Although these patches may be mistaken for freckles or bug bites initially, they typically persist and gradually increase in number over several months to years. In young children, the patches may form a blister if itched or rubbed. Itching may worsen with changes in temperature, strenuous activity, emotional stress, and/or certain medications. Maculopapular cutaneous mastocytosis is most commonly seen in infants and young children and often fades by the teenaged years. In some cases, this condition may not develop until adulthood. These later onset cases generally last long-term and are more likely to progress to systemic mastocytosis.

Solitary cutaneous mastocytoma is a localized form of cutaneous mastocytosis. Like maculopapular cutaneous mastocytosis, this form is typically diagnosed in young children. However, it is characterized by an itchy area of reddish or brown skin that is often thickened. When itched, these patches of skin may swell, redden, and/or blister. This form typically resolves spontaneously with age.

Diffuse cutaneous mastocytosis, the most severe form of cutaneous mastocytosis, usually develops in infancy. Unlike the other forms of cutaneous mastocytosis, it affects most or all of the skin rather than appearing as distinct patches. In people affected by this condition, the skin is leathery and thickened. It may appear normal, yellowish-brown, or red in color. In some cases, there may also be widespread blistering. Additional symptoms may include hypotension, diarrhea, gastrointestinal bleeding, reddening of the skin (flushing), and anaphylactic shock.

The rarest form of cutaneous mastocytosis is called telangiectasia macularis eruptiva perstans. Unlike the other forms of cutaneous mastocytosis, this form is primarily diagnosed in adults and is generally not associated with pruritus and blistering. People affected by this condition have persistent brown patches of skin and extensive telegiactasia. Rarely, this form may progress to systemic mastocytosis.

Although there is currently no cure for cutaneous mastocytosis, treatments are available to manage the symptoms of the condition. In general, it is recommended that affected people avoid things that trigger or worsen their symptoms when possible. Certain medications such as oral antihistamines and topical steroids are often prescribed to relieve symptoms.

Affected adults may also undergo photochemotherapy which can help alleviate itching and improve the appearance of the patches; however, the condition is likely to recur within six to twelve months of the last treatment. People at risk for anaphylactic shock and/or their caregivers should be trained in how to recognize and treat this life-threatening reaction and should carry an epinephrine autoinjector at all times.