Introduction

Mastocytosis is a rare condition characterised by the accumulation and proliferation of clonal mast cells in various organs, including the skin, bone marrow, spleen, lymph nodes, and gastrointestinal tract.¹ The disease could be classified into systemic mastocytosis and cutaneous mastocytosis.

What is cutaneous mastocytosis?

The term cutaneous refers to the skin. Therefore, Cutaneous mastocytosis (CM) specifically refers to cases where only the skin is affected.In children, mastocytosis typically develops exclusively in the skin, with minimal or no involvement of other organs.² Cutaneous mastocytosis commonly occurs in children.³ It affects both sexes equally and shows no predominance in any race. Cutaneous mastocytosis in children is typically a benign condition that may be present from birth.⁴ It can manifest during the neonatal period, in infancy (under 6 months), or during childhood (6 months to 16 years). During puberty, the skin lesions tend to fade and eventually disappear.⁵

Overview of the types of cutaneous mastocytosis

According to the WHO, cutaneous  mastocytosis could be classified into three (3), namely:⁵

Maculopapular cutaneous mastocytosis (MPCM)

Maculopapular cutaneous mastocytosis (MPCM), previously known as urticaria pigmentosa, is the most prevalent form of cutaneous mastocytosis constituting about 70% of cutaneous mastocytosis cases in pediatrics.^2,16

MPCM is further divided into two variants: a monomorphic variant and a polymorphic variant.  The monomorphic variant is characterised by small maculopapular lesions while the polymorphic variant has larger lesions of varying size and shape. The latter is commonly observed in paediatric patients. Based on clinical findings, the monomorphic variant commonly persists from childhood through adulthood if it occurs in children, whereas the polymorphic variant typically resolves by puberty.³

Diffuse cutaneous mastocytosis (DCM)

Diffuse cutaneous mastocytosis (DCM) occurs in roughly 5% of paediatric CM cases and is distinguished from other types by its unique characteristics.² DCM appears early, within the first few months of life, and occasionally even at birth.²

Mastocytoma of the Skin

In children, approximately 25% of CM cases are mastocytomas, typically presenting as either single or multiple lesions.²

Causes and pathophysiology.

The exact cause of cutaneous mastocytosis is still unknown. Genetic mutations and environmental factors have been linked to the condition. However, the exact interplay between these factors and how they lead to the development of cutaneous mastocytosis is still not fully understood.

Genetic Factors

Mutation of the KIT gene leads to over-activation of the receptor for mast cell growth factor, resulting in an overproduction of mast cells in the skin.⁶

Role of Mast Cells

Mast cells function as effector cells in allergic and hypersensitivity disorders, becoming activated through both immunoglobulin E and non-immunoglobulin E pathways.⁷ Mast cells are found in all vascularised tissues and serve as sources of inflammatory and regulatory mediators in various infections and diseases including cutaneous mastocytosis. Their cytoplasm contains numerous granules filled with chemical mediators, cytokines, proteoglycans, and proteases. Activation of mast cells occurs through several surface receptors, including FcεRI, toll-like receptors (TLR), Mas-related G-protein-coupled receptor X2 (MRGPRX2), and cytokine receptors. When activated by immunoglobulin E, mast cells release histamine eicosanoids, prostaglandins, leukotrienes, heparin, proteases, and cytokines into the extracellular environment, playing a role in body defence in response to triggers.^6,8 These chemicals have their specific effect on the body. For example, histamine causes the blood vessels to dilate. Leading to increased blood flow. This can make the skin itchy and swollen.

Triggers for mast cell activation 

A variety of factors can trigger mast cell activation. These triggers include:

• Venoms – bees, snakes
• IgG immune complexes
• Drugs – NSAIDs, antibiotics, opioids.
• Bacteria, viral and parasitic infections 
• Physical factors – Conditions such as heat, cold, vibration, stress, sunlight, and physical exertion. 
• Emotional factors – Stress, anxiety 
• Eating certain foods such as nuts, spicy food containing Monosodium glutamate (MSG)¹¹ 

Symptoms and clinical presentation

The skin manifestations of mastocytosis can vary widely. They can appear as isolated mastocytomas (localised collections of mast cells presenting as a tumour), maculopapular lesions (flat, discoloured areas with raised bumps), or in a diffuse form where the skin is uniformly affected over larger areas.¹⁰ Maculopapular lesions are the most frequently observed form of presentation.⁴ DCM presents with extremely severe symptoms. Polymorphic lesions of maculopapular cutaneous mastocytosis commonly develop on the trunk, extremities, scalp, or neck. Although less common, lesions can also be found on the palms, face, soles and sun-exposed areas of the body.¹¹

The skin lesions present as plaques, small solid skin-coloured bumps (papules), and large fluid-filled blisters.¹²

Patients may also experience mast cell mediator symptoms, including: 

• Itching (pruritus) 
• Erythema (redness)
• Swelling 
• Anaphylaxis¹³ which is a severe, potentially life-threatening reaction.  

During episodes of acute mast cell activation, systemic symptoms may manifest, such as nausea, vomiting, whole-body flushing, and shortness of breath.

Diagnosis

The diagnosis in most cases is based on the characteristic appearance of the skin lesions. Firstly, a comprehensive medical history of the child must be obtained.¹⁴ The diagnosis of cutaneous mastocytosis in children involves the following diagnostic procedures.  

Dermatological examination

Dermatological evaluation involves a thorough examination of skin lesions on different parts of the body, assessing their morphology and distribution across the body.¹⁴ Physical examination showing a positive Darier's sign is indicative of cutaneous mastocytosis. Darier's sign indicates that when the skin lesions are rubbed, they become swollen, red, and itchy.¹⁵

Laboratory blood test 

• Peripheral blood count 
• Differential blood count – neutrophils, eosinophils, monocytes, Lymphocytes and basophils.
• Routine biochemistries as required
• Baseline serum tryptase – In children with extensive skin lesions, elevated serum tryptase levels can occur due to a high number of mast cells in the skin, even without systemic mastocytosis diffuse.¹⁴ 

Histopathology

It involves analysing skin tissue samples obtained through biopsy and histologically examining them.

Treatment and management

Medical treatments

There are currently no therapies available that can change the natural course of cutaneous mastocytosis (CM) or permanently regress skin lesions associated with the condition. Treatments primarily focus on symptom relief and enhancing quality of life.¹⁴

Antihistamines

H1 histamine receptor blockers, such as first and second-generation antihistamines, are used to alleviate mast cell-mediated symptoms such as itching. Examples of these drugs include piriton, cetirizine and loratadine.

Corticosteroids

Short term use of topical and/ or oral corticosteroids in cases of MPCM and DCM. These drugs are to be used with caution children because prolonged used can lead to significant side effects.

Mast Cell Stabilisers 

These agents can ameliorate symptoms of cutaneous mastocytosis. An example of mast cell stabiliser is disodium cromoglycate.

Topical therapy with pimecrolimus 

1% cream which helps reduce symptoms of redness, itching and swelling.^.17

Avoidance of triggers

• Environmental triggers such as animal bites, insect stings, and inhaled chemicals
• Dietary – these include but are not limited to Monosodium Glutamates (MSG), nuts
• Medications – NSAID

Emergency Management

Adrenaline for Anaphylaxis

Adrenaline auto-injectors is used to treat anaphylactic reactions, which can be complications of cutaneous mastocytosis.

Children may be given medical alert bracelets to wear. This would speak for them in cases of emergency. They provide critical details about a person’s medical condition enabling first responders to deliver prompt and appropriate care. 

Summary

Cutaneous mastocytosis in children is a condition characterised by an abnormal accumulation of mast cells in the skin. This condition manifests in various forms, primarily as maculopapular cutaneous mastocytosis, diffuse cutaneous mastocytosis, and mastocytoma of the skin. The symptoms include skin lesions, flushing, abdominal pain, and in severe cases, anaphylaxis.

Cutaneous mastocytosis is caused by various activating mutations in the KIT gene. Upon exposure to specific triggers, mast cells release mediators that lead to the symptoms of cutaneous mastocytosis.

Diagnosing cutaneous mastocytosis in children is straightforward and can be made based on clinical signs and symptoms alone. The diagnosis involves a combination of clinical evaluation, skin biopsy, and laboratory tests.

Management of paediatric cutaneous mastocytosis is mainly based on strict avoidance of triggers, treatment with antihistamines, short-term use of corticosteroids and adrenaline auto-injectors for use in severe anaphylactic reactions.