What are other Names for this Condition? (Also known as/Synonyms)

• CM (Cutaneous Mastocytosis)
• Mastocytosis of the Skin
• Skin Mastocytosis

What is Cutaneous Mastocytosis? (Definition/Background Information)

• Mastocytosis is a rare disorder that results from often abnormal and excessive numbers of mast cells in the skin and, rarely, in the organs. It is generally caused by a mutation in a protein termed C-KIT receptor, which resides on the surface of cells and binds to a factor (stem cell factor) that helps certain types of cells to grow
• Mast cells, which reside in the connective tissue, store chemicals important to initializing the inflammatory and allergic responses. They also have important immune functions (ingesting disease-causing microbes). Once activated, mast cells release chemicals including heparin, histamine, and serotonin that stimulate the body’s inflammatory response
• Cutaneous Mastocytosis (CM) is the most common form of mastocytosis affecting the skin; in this type, there is an increase in mast cells in skin. Infants are generally susceptible to this form of mastocytosis. The condition causes skin redness, itching, and swelling in the affected area
• According to the updated World Health Organization (WHO) classification (2016), the following subtypes of Cutaneous Mastocytosis are noted:
  • Maculopapular cutaneous mastocytosis (previously termed urticaria pigmentosa)
  • Diffuse cutaneous mastocytosis (DCM)
  • Mastocytoma of skin (or solitary mastocytoma)
  • Telangiectasia macularis eruptiva perstans (TMEP)
• The tests to diagnose Cutaneous Mastocytosis include general physical examinations, blood tests, skin biopsies, and genetic testing to detect KIT gene mutations. An absence of systemic signs and symptoms is important in establishing a diagnosis of Mastocytosis of the Skin
• Presently, there are no standard treatment options available for mastocytosis. Generally, a management of the symptoms and controlling the inflammatory response is needed; this may involve anti-histamine treatment. Children with Cutaneous Mastocytosis are generally known to recover over time, and the outcomes are typically good

Who gets Cutaneous Mastocytosis? (Age and Sex Distribution)

• Cutaneous Mastocytosis constitute nearly 90% of all mastocytosis, and over 65% of them develop in children
• In children, those aged 6 months and below (infants) are mostly affected. Almost all cases are observed within the first 2 years following the birth of the child
• Adults are also affected but to a much lesser extent than children; only about 5% of all mastocytosis cases in adults are Skin Mastocytosis
• Both males and females are equally susceptible to the condition
• Worldwide, it can affect all racial and ethnic groups

What are the Risk Factors for Cutaneous Mastocytosis? (Predisposing Factors)

• A majority of Cutaneous Mastocytosis cases are observed during infancy and early childhood
• A positive family history is rarely observed in mastocytosis; and, no other specific risk factors have been identified

However, in general, the following are believed to increase one’s susceptibility to mastocytosis:

• Smoking
• Exposure to radiation and industrial chemicals
• Chemotherapy
• In rare cases, viral infections

These factors are presumably not in play with childhood-onset mastocytosis.

There are also a host of factors that may trigger histamine release further aggravating the skin signs and symptoms in mastocytosis. Some of these include:

• Medications such as opioid painkillers, non-steroidal anti-inflammatory drugs (NSAIDs), vitamin supplements, antibiotics, anticholinergics, etc.
• Venom injection from snake bites and bee stings
• Emotional stress
• Lack of sleep
• Hot or cold weather, and temperature changes
• Certain viral and bacterial infections
• Iatrogenic factors such as application of local anesthetic, vaccines, administration of contrast media, and even certain invasive procedures

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Cutaneous Mastocytosis? (Etiology)

The cause of formation of Cutaneous Mastocytosis is mostly due to mutations in the KIT gene. In some cases, it is caused by unknown factors.

• Specifically, it is a small change (mutation) in the region of DNA of a receptor called C-KIT. This receptor is responsible for stimulating mast cells to grow and divide (proliferate)
• Mast cells that have defective C-KIT receptors are unable to respond to signals from their environment. Thus, they proliferate independently of external signals
• The overabundance of abnormal mast cells in skin causes the inappropriate stimulation of the inflammatory response. This leads to the signs and symptoms of Cutaneous Mastocytosis

In a vast majority of cases, the condition occurs sporadically. Occasionally, when Cutaneous Mastocytosis is inherited, an autosomal dominant pattern of inheritance is noted.

What are the Signs and Symptoms of Cutaneous Mastocytosis?

The signs and symptoms of Cutaneous Mastocytosis may vary from one individual to another. It may be mild or severe, and also depend on the specific form of mastocytosis.

The typical signs and symptoms of Cutaneous Mastocytosis include:

• Numerous discolored spots, especially in clusters
• Darier sign: It is the activation of mast cells by rubbing an area of the affected skin, which results in reddish skin that is itchy and swollen. This is usually seen in young children, within a few minutes of rubbing/scratching the skin. This is an important identifying sign of Cutaneous Mastocytosis
• Blisters and hives (urticaria); the skin rashes tend to increase in numbers over many months and years
• Some individuals may present widespread blistering
• Thickened spots with an orange-peel texture
• Severe itching (pruritus), which may worsen with factors such as temperature changes, physical activity, or certain medication
• Some individuals with Cutaneous Mastocytosis may present fatigue, fever, and night sweats

The presence of triggers, such as certain medications, sunlight, or medical procedures, may cause a flare up (inflammatory response) of the signs and symptoms.

How is Cutaneous Mastocytosis Diagnosed?

The following are some tests and exams that may be used in the diagnosis of Cutaneous Mastocytosis:

• Physical exam to detect skin abnormalities and comprehensive medical history evaluation
• The healthcare provider may attempt to elicit the Darier’s sign by rubbing or stroking one or more of the skin lesions. This may be often the only noninvasive test needed to establish a diagnosis. If systemic disease is considered based on medical history or a general physical exam, further tests may be undertaken
• Blood smear to detect:
  • Increased numbers of mast cells
  • Abnormally-shaped mast cells
  • Reduced numbers of red blood cells (anemia)
  • Reduced numbers of platelets (thrombocytopenia)
• Blood tests to detect:
  • Elevated total tryptase levels indicating mast cell increase to evaluate possible systemic disease
  • Elevated lactate dehydrogenase levels
  • Elevated alkaline phosphatase levels indicating possible bone involvement in systemic disease
• Skin biopsy to detect:
  • Clusters of mast cells
  • Abnormally-shaped mast cells
• Genetic tests to detect a KIT mutation, if necessary

Note:

• In almost all cases, the only needed tests would be trying to provoke Darier’s sign, or a skin biopsy.
• An absence of systemic signs and symptoms is important in establishing a diagnosis of Cutaneous Mastocytosis.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Cutaneous Mastocytosis?

Following are some of the complications that may arise from Cutaneous Mastocytosis:

• Emotional stress
• Uncontrollable inflammatory and allergic reactions; severe reactions may result in anaphylaxis that can be life-threatening
• Permanent tissue scarring
• Severe discomfort from itching
• Treatment-related complications
• Progression of Cutaneous Mastocytosis to systemic mastocytosis, particularly seen in cases where the onset of skin symptoms is after the child is 2 years old

How is Cutaneous Mastocytosis Treated?

Cutaneous Mastocytosis treatment depends on the severity and type of the skin condition, and on the age and health status of the individual. However, there is no cure for the condition.

• Cutaneous Mastocytosis that is confined/localized to a region and is “symptomless” may not require any treatment
• Avoiding and/or controlling the triggers that worsen the condition is important
• Antihistamine therapy may be recommended in some individuals
• Symptomatic Cutaneous Mastocytosis may be treated with phototherapy (PUVA or UVB)
• In case of anaphylaxis, subcutaneous epinephrine or adrenaline may be administered

Periodic monitoring or follow-up of the condition with the healthcare provider is recommended.

Note: Caution should be exercised while using non-steroidal anti-inflammatory medications (NSAIDs) such as Ibuprofen or naproxen. These medicines could cause upset stomach, as well as release of histamines, which could cause severe and adverse reactions.

How can Cutaneous Mastocytosis be Prevented?

Presently, it may be difficult to avoid Cutaneous Mastocytosis. However, some of the following factors may be considered:

• If there is a family history of the condition, then genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• Identify, avoid, or control the triggers for Cutaneous Mastocytosis

Other home care tips include:

• Always keeping skin clean and healthy
• Wearing gloves while applying ointment on the blisters is advised
• Children’s nails should be cut short so that infection from scratching the blisters can be avoided
• Frequent washing of hands is recommended
• The affected child or adult is best advised to stay indoors in case of any “flare ups”
• Patients may be advised to carry injectable epinephrine to overcome serious allergic reactions

Some narcotics used in general anesthesia can cause mast cells to release their chemicals, including histamine, leading to shock. Patients must be told to inform all physicians of their mast cell disease to protect them from this. A ‘permanent’ passive reminder such as a MedicAlert device is strongly recommended.

What is the Prognosis of Cutaneous Mastocytosis? (Outcomes/Resolutions)

Cutaneous Mastocytosis in children is usually not life-threatening and the condition generally resolves before puberty or during adolescence, in nearly 80% of the cases.

Additional and Relevant Useful Information for Cutaneous Mastocytosis:

Recently, it has been shown that the chemicals released by mast cells also affect the activities of the bone cells. These include bone-building osteoblasts and bone-digesting osteoclasts. Mast cells have been linked to stimulation of osteoclasts and inhibition of osteoblasts, resulting in bone deficiencies.