Cutaneous mastocytosis

Cutaneous mastocytosis is a rare condition in which an abnormal number of mast cells accumulate in the skin. It usually causes persistent patches or small lesions that may itch, become red or swell, particularly when rubbed or in response to certain triggers.

What is cutaneous mastocytosis?

Mast cells are cells of the immune system that occur naturally in the skin and other tissues.

They play a part in inflammatory responses and the body’s defences. When activated, they release substances such as histamine, which can cause itching, redness, swelling and other symptoms.

In mastocytosis, a group of mast cells multiplies abnormally. When, following a proper assessment, it is confirmed that the accumulation is confined to the skin, the condition is referred to as cutaneous mastocytosis.

Although it is classified as a clonal disorder, most paediatric cutaneous forms have a favourable prognosis and do not behave like an aggressive cancer.

The condition can occur at any age, but its clinical significance is not exactly the same in children and adults.

In childhood, the condition is usually confined to the skin and often improves as the child grows. In adults, similar lesions may form part of systemic mastocytosis, which usually has an indolent course; consequently, the investigation is typically more extensive.

The lesions arise from the accumulation of mast cells in specific areas. Furthermore, these cells can become activated and release inflammatory mediators, causing the patches to become red, raised or more itchy.

Main cutaneous forms

The appearance of the lesions may vary depending on age and the type of mastocytosis.

Maculopapular cutaneous mastocytosis

This is the most common form. It produces persistent patches or small raised areas, usually brown, reddish or yellowish in colour.

In children, the lesions tend to vary in size and appearance. In adults, they are usually smaller, more numerous and similar in appearance.

This form was traditionally known as urticaria pigmentosa, a term that may still appear in medical reports or older literature.

Cutaneous mastocytoma

This is a single lesion or a small number of plaques or nodules containing a high concentration of mast cells. It mainly occurs in babies and young children. It may increase in size, become reddened or form a blister when rubbed.

The prognosis is usually favourable, and the condition often diminishes or disappears as the child grows.

Diffuse cutaneous mastocytosis

This is a rare form in which large areas of the skin show an accumulation of mast cells. The skin may be thickened, take on a yellowish or orange hue and form blisters, particularly during the first few months of life.

Due to its extensive nature and the potential for intense release of mediators, it requires specialist monitoring.

Why does it occur?

Mastocytosis is not caused by an infection, an allergy, stress or any specific behaviour.

In many cases, there is an acquired mutation in the KIT gene, which plays a role in the growth and survival of mast cells. This change causes the cells to multiply or remain in the tissues for longer than usual. Generally, these changes occur only in the affected cells and are not passed on from parents to children.

Stress, heat, friction or other stimuli may trigger symptoms in some people, but they are not the cause of the condition.

What symptoms can it cause?

Symptoms depend on the number of mast cells, the extent of the lesions and the ease with which these cells release their mediators.

Skin manifestations

The lesions usually remain visible for months or years. They may be flat or slightly raised and may be a different colour to the rest of the skin.

The most common symptoms are:

• Itching.

• Redness.

• Temporary thickening.

• A sensation of heat.

• Swelling.

In children with extensive forms of the condition, blisters may also appear, particularly during the early years of life. When a lesion is rubbed, it may become red, swollen and itchy. This reaction is known as Darier’s sign and can help the doctor recognise the condition.

It is not advisable to rub the lesions repeatedly to test for this. In young children or in cases of extensive disease, vigorous rubbing may cause a significant release of mediators.

Symptoms caused by mast cell activation

In some people, the release of histamine and other substances can cause more generalised symptoms.

Episodes of the following may occur:

• Generalised redness or flushing.

• Widespread itching.

• Abdominal pain, nausea or diarrhoea.

• Heart palpitations.

• Dizziness or a feeling of faintness.

• Difficulty breathing.

• A drop in blood pressure.

These symptoms are not unique to mastocytosis and must be interpreted within the clinical context.

The presence of general symptoms does not prove organ involvement

Mast cells can release substances that cause hot flushes, dizziness or digestive discomfort. These episodes do not in themselves confirm systemic mastocytosis, which requires specific diagnostic criteria.

Warning signs

Most skin manifestations are not a medical emergency. A reaction involving difficulty breathing, swelling of the tongue or throat, fainting, sudden weakness or rapid deterioration requires immediate attention.

These symptoms may indicate anaphylaxis, a severe reaction caused by the widespread release of mediators.

Adrenaline is the first-line treatment. Some people should carry an auto-injector, but this is not automatically indicated: it depends on the patient’s medical history, the type of condition and individual risk.

Possible triggers

Mast cells can be activated by certain physical, emotional, environmental or pharmacological stimuli.

Triggers that have been described include:

• Friction.

• Sudden changes in temperature.

• Certain insect bites.

• Infections.

• Exercise.

• Stress.

• Alcohol.

• Certain medicines.

Not everyone reacts to the same triggers. It is not advisable to follow universal lists of prohibited foods, activities or medicines. Restrictions should be based on reactions that have occurred consistently or on individual medical advice.

A person who tolerates a food, a medicine or an activity does not need to avoid it simply because it appears on a generic list relating to mastocytosis.

How it is diagnosed

Diagnosis begins with a skin examination and a review of the patient’s medical history. The specialist assesses the appearance of the lesions, when they first appeared, how they have developed, and whether they become red or swollen in response to certain stimuli.

They will also ask about episodes of hot flushes, dizziness, breathing difficulties, digestive problems, reactions to insect bites or medicines, and a history of anaphylaxis.

Skin biopsy

When the appearance of the lesions does not allow for a definitive diagnosis, a biopsy may be carried out. The procedure involves taking a small skin sample under local anaesthetic. The sample is examined using techniques that enable the identification and assessment of the distribution of mast cells.

The result is interpreted in conjunction with the patient’s age, the appearance of the lesions and the other clinical findings.

Basal tryptase

Tryptase is a protein produced mainly by mast cells. Its concentration in the blood can provide information on the mast cell burden and help determine whether further tests are necessary. To establish the normal level, it must be measured at baseline, away from an acute reaction.

A normal tryptase level does not completely rule out systemic mastocytosis. Similarly, an elevated level does not confirm the diagnosis on its own, as other conditions can also cause it to rise.

KIT gene testing

In certain cases, a specific KIT mutation, known as KIT D816V, may be sought in blood, skin or bone marrow. A positive result may reinforce the suspicion of systemic involvement. A negative result does not completely rule it out.

This test helps to guide further investigation, but it does not replace clinical assessment nor does it allow the disease to be classified on its own.

How to assess possible systemic involvement

The aim is to determine whether the abnormal mast cells are confined to the skin or are also present in other tissues, particularly the bone marrow. The assessment is tailored to the patient’s age, symptoms, the extent of the lesions, tryptase levels and the results of initial tests.

In children

In a child with typical lesions, a good general condition and no warning signs, a bone marrow biopsy is not usually necessary. Blood tests and baseline tryptase levels may be requested depending on the extent of the disease and the symptoms.

Further tests are reserved for situations such as persistent abnormalities in blood tests, a progressive rise in tryptase levels, enlargement of the liver or spleen, or significant symptoms suggesting internal involvement.

In adults

In adults, characteristic skin lesions are more frequently associated with systemic mastocytosis, even when symptoms are mild. For this reason, assessment usually includes blood tests, baseline tryptase levels, testing for the KIT D816V mutation, and a search for possible signs of internal involvement.

Depending on the results and the specialist’s judgement, a bone marrow investigation may be necessary. A bone marrow biopsy does not necessarily imply that an aggressive disease is suspected. Its purpose is to correctly classify the mastocytosis and determine the most appropriate follow-up.

Cutaneous mastocytosis and systemic mastocytosis

Cutaneous mastocytosis is confined to the skin following appropriate assessment. Systemic mastocytosis involves the presence of clonal mast cells in one or more organs other than the skin, frequently in the bone marrow.

There are different systemic forms. The most common is indolent systemic mastocytosis, which may remain stable for many years and should not be confused with the advanced variants, which are much less common.

In many adults, there is no subsequent progression from the skin to other organs. Systemic involvement may have been present from the outset, even if it had not yet been identified.

Mastocytosis is also not synonymous with mast cell activation syndrome. The latter requires recurrent compatible episodes, changes in laboratory parameters during episodes, and a response to treatment according to specific criteria.

What is the treatment?

Treatment depends on the extent of the lesions, the severity of the symptoms and the risk of systemic reactions.

In many people, it is not necessary to try to reduce the number of mast cells. The main aim is to control symptoms, protect the skin and prevent serious reactions.

Managing symptoms

Gentle skin care is recommended, along with maintaining adequate hydration and avoiding scratching or vigorous rubbing. H1 antihistamines are the standard treatment for itching, redness and other symptoms caused by histamine.

In some people, treatments for digestive discomfort or specific symptoms may be added. Topical corticosteroids may be used for limited periods on specific lesions, always under medical supervision.

These treatments help to control symptoms, but do not eliminate the accumulation of mast cells.

Preventing reactions

It is helpful to identify personal triggers and have a clear action plan in place. Where there is a significant risk of anaphylaxis, the medical team may prescribe an adrenaline auto-injector and teach you how to use it.

Antihistamines can complement the treatment of a reaction, but they are no substitute for adrenaline in the event of anaphylaxis.

Specialised treatments

Phototherapy may be used in some adults with extensive lesions and persistent symptoms. It can temporarily improve itching and the appearance of the skin, but does not usually lead to a permanent resolution. Omalizumab may be considered in specialist units for severe recurrent reactions or symptoms resistant to other treatments.

KIT inhibitors and treatments aimed at reducing mast cell numbers are not part of the standard management of cutaneous-only mastocytosis. They are primarily reserved for certain systemic forms.

Course and prognosis

The course of the condition depends primarily on the age at onset and the type of lesions.

In children

The prognosis is usually favourable. In many cases, the lesions shrink in size, become lighter in colour or disappear before or during adolescence. Paediatric mastocytomas also tend to regress as the child grows.

Some forms may persist, so the course of the condition is monitored according to the extent of the lesions, the symptoms and the results of the initial investigation. Diffuse forms require closer monitoring during the early years, although they may also improve gradually.

In adults

The lesions usually persist. The prognosis depends on whether the investigation confirms a disease confined to the skin or identifies systemic mastocytosis.

Where there is an indolent systemic form, the disease may remain stable for long periods. Advanced variants are much less common and do not represent the expected course of the disease for all individuals with cutaneous lesions.

Which specialists treat it

Cutaneous mastocytosis may require the involvement of several specialists, depending on the patient’s age, symptoms and the need to rule out involvement beyond the skin.

Dermatologists assess skin lesions, guide the diagnosis and may perform a biopsy where necessary. Allergists investigate symptoms related to the release of mediators, assess the risk of severe reactions and determine whether an adrenaline auto-injector is advisable.

At our hospital, we have a specialist unit for mastocytosis and mast cell disorders, which enables us to manage these conditions in a coordinated manner and to tailor the investigation, monitoring and treatment to each individual’s specific circumstances.

Haematology specialists are involved when systemic mastocytosis is suspected or confirmed, and when further investigation is required, for example, through a bone marrow biopsy.

In children, paediatric specialists coordinate follow-up and the involvement of other specialist departments where necessary.

Where the condition presents complex features, assessment at a unit with specific expertise in mastocytosis may be particularly useful.

Living with cutaneous mastocytosis

Most people can lead an active life and carry on with their usual activities.

It is not necessary to avoid all medicines, foods, sports or changes in temperature as a preventative measure. It is more useful to identify which triggers have actually caused symptoms and to put in place measures proportionate to the risk. It is advisable to inform healthcare professionals of the diagnosis before any surgical procedure, anaesthesia or the administration of a new medicine, particularly if there is a history of reactions.

In children, it may be helpful to explain the condition to the school or nursery if there is a risk of blisters, widespread reactions or the need for rescue medication.

Visible lesions can also have an emotional impact, particularly during adolescence or when they affect exposed areas. Aesthetic distress, self-consciousness or concern about reactions are all part of the experience of the condition and deserve attention.

Having a well-classified diagnosis helps to avoid both unnecessary alarm and an underestimation of the risk.

In many children, the condition improves as they grow older. In adults, although the lesions usually persist, appropriate monitoring and effective symptom management enable them to maintain a satisfactory quality of life.