Clinical Reference / Therapeutic Strategies / Urticaria Pigmentosa / Mastocytosis

Urticaria Pigmentosa / Mastocytosis


Key Points

  • Mastocytosis can occur at any age, and may involve the skin, or affect internal organs including the bone marrow and liver/spleen/lymphatic tissues
  • Urticaria pigmentosa is a form of cutaneous mastocytosis most common in childhood, characterized by brown papules, plaques, or nodules, which may urticate when stroked.
  • Patients with cutaneous mastocytosis may have a single isolated mastocytoma, diffuse cutaneous mastocytosis, urticaria pigmentosa, or a rare form of mast cells in the skin seen in adults characterized by telangiectasias and faint lesions, called telangiectasia macularis eruptiva perstans.

Introduction

Mastocytosis includes a wide variety of cutaneous diseases with variable systemic involvement; this chapter will focus specifically on urticaria pigmentosa (UP), with a brief review of other forms of cutaneous mastocytosis. The three most common types of cutaneous mastocytosis are urticaria pigmentosa (UP), diffuse cutaneous mastocytosis, and the presence of a single mastocytoma. Urticaria pigmentosa is most common in childhood, and less likely to have systemic involvement than adult forms of mastocytosis. Most patients develop mastocytosis in childhood, before the age of 2, with 60-80% of patients having lesions during the first year of life; lesions can even be present at birth. UP is the most common form of cutaneous mastocytosis and represents up to 70-90% of cases. Mastocytosis occurs in patients of all ethnic backgrounds and in both men and women. Most cases are sporadic, but there are rare cohorts of familial cases, including disease reported in monozygotic twins. Cases of adult mastocytosis have been identified with alterations in the KIT tyrosine kinase (CD117), particularly point mutations in codon 816 of the c-kit proto-oncogene. This leads to activated KIT, and increased mast cell development. This genetic mutation is less common in children with mastocytosis.

The skin findings of childhood mastocytosis often include isolated tan or brown plaques or nodules (isolated mastocytomas) or variable numbers of brown macules, papules, and small plaques or dermal-based nodules (urticaria pigmentosa); some patients may have extensive, almost erythrodermic involvement with diffuse cutaneous mastocytomas. UP generally appears in childhood, and lesions often develop on the trunk and/or extremities; the face, palms, and soles are generally spared. Adult mastocytosis generally presents with small subcentimeter reddish-brown macules or flat-papules, generally on the trunk and extremities. Telangiectasia macularis eruptiva perstans (TMEP) is a less common presentation seen almost exclusively in adults, where patients have fainter, lighter, more subtle macules and small papules, intermixed with more prominent telangiectasias. While most forms of cutaneous mastocytosis will appear hyperpigmented or brown at times, TMEP is generally flesh colored and indistinct, with a very subtle clinical appearance. Adults may rarely develop diffuse cutaneous mastocytosis.

Mast cells in the skin represent a large concentration of inflammatory mediators, as mast cells often contain granules of histamine. Stroking or rubbing a lesion of cutaneous mastocytosis can elaborate these signaling molecules, and often results in a localized wheal response, where the lesion while form a hive; this is called “Darier’s sign.” Darier’s sign can be seen in isolated mastocytomas, childhood urticaria pigmentosa, and diffuse cutaneous mastocytosis; lesions of TMEP often harbor smaller collections of mast cells and are less apt to urticate when stroked.

In UP, systemic involvement is rare. Most childhood cases will experience a limited course and spontaneous resolution by adolescence. A subset of children whose disease persists may behave more like adult cases of cutaneous mastocytosis, and may warrant c-kit testing or other workup. Adults with cutaneous mastocytosis are at risk for variable amounts of bone marrow involvement. Patients may have hepatic or splenic involvement with mast cell infiltration, and lymph node enlargement may occur. Adults also may develop skeletal lesions due to mastocytosis with opacities or lucencies seen on radiographic imaging; patients may also develop osteosclerosis or osteoporosis. Due to the mast cell burden, patients may occasionally develop gastrointestinal symptoms, including pain, diarrhea, nausea, or vomiting. Patients with mastocytosis should have a thorough physical examination, serum tryptase, blood count with differential, and often a skin biopsy. Patients with an abnormal tryptase level, abnormal blood count, or systemic symptoms warrant further evaluation.

Treatment of mastocytosis is predominantly symptomatic. Indolent cases or cases with isolated, asymptomatic lesions often do not require therapy. As lesions may urticate in response to physical stimulus, patients should be advised to avoid heat and friction to lesions. Patients with mastocytomas, particularly those with high numbers of lesions and disease burden, should avoid mast cell degranulating agents. This list includes alcohol, anticholinergic agents, NSAIDs, aspirin, narcotics, and polymyxin B. Anesthetic agents may trigger anaphylactoid reactions in patients with mastocytosis, and if patients require surgery or general anesthesia, the surgical team and anesthesiologist should be aware of the diagnosis and consulted regarding the safest systemic agents. Histamine receptor antagonists (H1 or H2 blockers, alone or in combination) may help alleviate some of the symptoms of mastocytosis. Cromolyn sodium has been used for GI symptomatic control. Patients with extensive skin disease have been treated with light therapy, including psoralen plus UVA (PUVA) therapy; patients may degranulate during the initiation of such treatment and should be counseled and monitored closely, particularly in cases of high disease burden. Potent topical steroids may eliminate local symptoms and can in some cases resolve the cutaneous lesion entirely. Intralesional steroids may also help with isolated or limited cutaneous mastocytomas. Patients with systemic disease may be at risk for large degranulation episodes and can experience anaphylactoid reactions and life threatening hypotension; patients at risk for this should carry an EpiPen at all times.

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