Whitney A. High, MD

Disclosures

June 10, 2010

Laboratory Studies

Measurement of the patient's serum tryptase revealed a level of 5.7 ng/mL (normal range is 1-15 ng/mL).

Discussion

Urticaria pigmentosa (UP) results from increased mast cells in the skin, with or without systemic involvement. The disorder is most common in children, but it can certainly present in adults. In adults, UP usually presents with dozens, if not hundreds, of hyperpigmented macules and papules, typically less than 1 cm in diameter.[1] These lesions have a red-brown color and may be associated with telangiectasias. The lesions often urticate with stroking (Darier's sign), a mechanical degranulation of the increased mast cells in the skin with release of histamine.

Telangiectasia macularis eruptive perstans (TMEP) is a related form of cutaneous mastocytosis. TMEP is rarer but is decidedly more common in adults. Although similarities exist and some features overlap between UP and TMEP,[2] UP usually presents with a higher number of lesions and more hyperpigmentation, and TMEP usually presents with fewer lesions and more telangiectasias.

The etiology of UP is not fully understood, but somatic mutations in the 816 codon of the c-kit proto-oncogene have often been associated with adult cases that are not familial.[3,4] This mutation leads to overactivation of the KIT pathway, leading to increased mast cell development in the skin and possibly elsewhere.

Cutaneous mastocytosis is often diagnosed by skin biopsy. The number of mast cells in the skin is increased and is generally proportional to the "thickness" of the lesions. In normal skin, mast cells comprise about 0.4% of the total cells, but in the macular, papular, and nodular lesions of cutaneous mastocytosis, mast cells may comprise about 3.5%, 16.1%, and 63.2% of the cells, respectively.[5] Special and immunohistochemical stains to accentuate mast cells and facilitate examination include: Giemsa, chloroacetate esterase, tryptase, or CD117.

When a dermatologist is confronted with a patient with cutaneous mastocytosis, it is important to evaluate for possible systemic involvement. Release of histamine from mast cells in the skin may result in pruritus, but the systemic release of increased amounts of histamine may have other effects as well. Patients should be queried with respect to headache or other neural or psychiatric symptoms, heart palpitations, syncope, or gastrointestinal issues. In fact, gastrointestinal involvement is a common extracutaneous issue, and it may present as diarrhea, abdominal pain, or gastritis and peptic ulcer disease.

A useful screening test for adults with cutaneous mastocytosis is serum total tryptase. The normal range for most individuals (except after anaphylactoid events) is 1-15 ng/mL. It has been observed that 50% of patients with serum total tryptase levels of 20-75 ng/mL have evidence of systemic disease, and all patients with levels in excess of 75 ng/mL have systemic disease.[6] Therefore, a tryptase level of > 20 ng/mL indicates a need for additional studies to exclude systemic disease, even in the absence of symptoms, hepatosplenomegaly, or blood count abnormalities.

Treatment

UP, like all cutaneous mastocytosis, is difficult to treat. In cutaneously limited disease, if the patient is not particularly troubled, treatment is not required.

Symptomatic care usually involves H1 receptor antagonists (diphenhydramine, hydroxyzine, cetirizine, loratidine, fexofenadine), sometimes with the addition of a H2 receptor antagonist (ranitidine, famotidine, nizatidine).[1] Doxepin, a tricyclic antidepressant with powerful anti-H1 receptor effects, may also be useful. Ketotifen fumarate is a drug with both antihistamine properties and mast cell stabilization properties, and it has been used successfully in cooperation with H2 antagonists.[7] Oral chromolyn sodium is particularly useful in controlling gastrointestinal complaints. Psoralen and ultraviolet A (PUVA) may also be effective.[8] Potent topical steroids may be employed, but involvement of a large area may practically limit the use of such modalities. Oral steroids, and even cyclosporine, may be effective in select cases with aggressive behavior, but these agents are not without risk for side effects, and other less toxic agents are typically sought.[9]

Other preventative steps should be employed to avoid excessive mast cell degranulation, with resultant release of histamine and symptoms. Heat and friction often cause mast cells to release histamine. Alcohol, aspirin and other nonsteroidal anti-inflammatory drugs, many narcotics, and polymyxin B should be avoided for the same reason. Occasionally, low-dose aspirin may be used to reduce symptoms of flushing, tachycardia, and syncope, but only by experts under certain circumstances.[10]

Because of a mechanism that includes inhibition of the KIT pathway, the tyrosine kinase inhibitor imatinib mesylate has been tried in patients with cutaneous and systemic mastocytosis, but it was proven rather ineffective in adults with disease caused by the codon 816 c-kit mutation.[11]

Adults with UP sometimes progress slowly to systemic disease, even when the initial presentation is confined to the skin, but degeneration to involve the bone marrow or otherwise aggressive and life-threatening disease is uncommon.[12]

Follow Up

Our patient was not particularly troubled by his condition and was interested only in conservative care. For his pruritus, he was placed on an H1 antagonist and H2 antagonist. Considering his report that sunlight reduced the number of lesions and his symptoms, something that has been reported by other patients as well, phototherapy may be employed in the future if his condition changes. His serum total tryptase will be measure annually or with changes in this health. Finally, he was warned that some anesthetics are dangerous for persons with mastocytosis and that he should always mention his condition to providers before any elective medical procedure is performed.

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