Urticaria Pigmentosa

Urticaria pigmentosa is the commonest form of cutaneous mastocytosis, with brown macules and papules containing clusters of mast cells. It usually starts in infancy and often settles by adolescence, while adult onset disease tends to persist and often reflects systemic mastocytosis.

Pathophysiology. Activating KIT variants cause mast cell accumulation in the dermis. Mediator release (histamine, tryptase, prostaglandin D2) produces itching, flushing and, when a lesion is rubbed, a wheal (Darier sign).

In children, disease is usually limited to skin and many have KIT variants other than D816V. In adults, KIT D816V is usual and bone marrow involvement is common.

Pattern differs by age: plaque or nodular lesions in infants, and small monomorphic lesions on the trunk and limbs in adults.

• Brown, red brown or yellow tan macules, papules or plaques on the trunk and limbs (palms, soles, face and scalp are usually spared in adults)
• Darier sign: wheal and surrounding erythema after stroking a lesion
• Itching, flushing, and blistering in infants
• Dermographism
• Episodes of systemic symptoms in some: abdominal pain, diarrhoea, palpitations, hypotension, anaphylaxis
• Triggers: friction, heat, fever, infection, vaccination, drugs (NSAIDs, opioids), anxiety

• Clinical examination: lesion pattern and Darier sign, with photographs and body surface involvement.
• Skin biopsy: increased mast cells in the dermis (toluidine blue, tryptase, CD117 staining), with KIT testing in adults.
• Serum baseline tryptase: in children, under 20 microgram/L suggests disease limited to skin; over 20 microgram/L needs further review.
• Adults: KIT D816V in peripheral blood, and bone marrow biopsy when baseline tryptase is raised, with full blood count, liver enzymes, calcium, bone density scan and abdominal imaging for organomegaly.
• Children with hepatosplenomegaly, cytopenia or very high tryptase: systemic workup.

Differential diagnosis.

• Systemic mastocytosis with skin involvement
• Solitary mastocytoma and diffuse cutaneous mastocytosis
• Langerhans cell histiocytosis and juvenile xanthogranuloma
• Congenital melanocytic naevus, café-au-lait macules and post-inflammatory pigmentation
• Papular urticaria and insect bites
• Mast cell activation syndrome

• Education and trigger avoidance: gentle handling, avoid friction over lesions, avoid hot baths and trigger drugs (NSAIDs, opioids, aspirin) unless needed.
• Antihistamine for itching and flushing: cetirizine 10 mg orally once daily in adults (children 1 to 5 years 2.5 mg twice daily; 6 to 11 years 5 mg twice daily), increased as needed.
• Topical corticosteroid for symptomatic lesions: mometasone 0.1% cream once daily for 2 to 4 weeks.
• Sodium cromoglicate 200 mg orally four times daily (children aged 2 to 12 years 100 mg four times daily) for gastrointestinal symptoms.
• Phototherapy: narrowband UVB or PUVA in adults with severe itching and widespread lesions, with attention to skin cancer risk.
• Anaphylaxis plan when tryptase is high or reactions have occurred: adrenaline auto injector 150 microgram for 7.5 to 25 kg, 300 microgram for 25 to 50 kg, 500 microgram for over 50 kg, with a written plan and training of carers.
• Vaccination and surgery: vaccination can proceed with antihistamine cover and observation for 30 minutes. Plan anaesthesia with premedication and careful choice of opioid.
• Resolution: most paediatric disease improves by adolescence, so avoid unnecessary long term medication.

Special groups.

• Adults: assume possible systemic mastocytosis, with adrenaline auto injector for venom reactions and bone health review.

Monitoring. Review children every 6 to 12 months with photographs. Review adults every 6 to 12 months with tryptase, full blood count, liver enzymes and bone density.

Referral and escalation. Refer to paediatric dermatology or allergy for children, and to haematology or an adult mastocytosis service for adults. Emergency for anaphylaxis or collapse with flushing.