Mastocytoses

Published on 18/03/2015 by admin

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Last modified 18/03/2015

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Mastocytoses

Nicholas A. Soter

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

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The mastocytoses are a group of disorders of mast cell proliferation that may exhibit both cutaneous and systemic features. Clinical manifestations result from mast-cell activation and from infiltration of various organs. The World Health Organization has classified mastocytosis into disease categories: cutaneous mastocytosis, indolent systemic mastocytosis, systemic mastocytosis with a non-mast cell clonal hematologic disorder, aggressive systemic mastocytosis, mast cell leukemia, mast cell sarcoma, and extracutaneous mastocytoma. The most frequent site of organ involvement in individuals with mastocytosis is the skin. Cutaneous forms include urticaria pigmentosa (shown here), mastocytoma, diffuse and erythrodermic cutaneous mastocytosis, and telangiectasia macularis eruptiva perstans. The cutaneous forms of mastocytosis may be present with or without systemic manifestations. Only the treatment of the cutaneous features will be discussed.

Management strategy

An important aspect of therapy of the cutaneous lesions of mastocytosis is avoidance of triggering factors, which may include temperature changes, friction, physical exertion, ingestion of alcohol, the use of non-steroidal anti-inflammatory agents or opiate analgesics, and emotional stress. Of concern is the possibility of anaphylaxis after stings by Hymenoptera spp., which may occur even in patients receiving venom immunotherapy.

A history seeking systemic features should be undertaken, as well as a physical examination to determine the types of skin lesions and to assess for lymphadenopathy and hepatosplenomegaly. The presence of specific systemic manifestations will dictate the type of specialty physician to whom a referral should be made.

Patients with systemic mastocytosis require long-term follow-up, as 10–30% may develop associated non-mast-cell clonal hematologic disorders such as myelodysplastic or myeloproliferative syndromes, leukemias, or lymphomas.

A skin biopsy should be obtained in all individuals with cutaneous lesions. A complete blood count with differential analysis, a blood chemistry profile that includes liver function tests, and a blood tryptase level should be obtained in all patients with cutaneous lesions, except those with mastocytomas. If there are abnormalities of the complete blood count, a bone marrow examination should be obtained. Plasma histamine levels are not useful to screen patients. Twenty-four hour urine levels of mast cell mediators may be obtained in patients with systemic features. Abdominal imaging studies provide a non-invasive means to assess the lymph nodes, liver, and spleen. In patients with bone pain, a 99Tc bone scan is useful. Osteoporosis may be detected by bone density analysis.

In many cases cutaneous mastocytomas may involute spontaneously; it is rarely described in adults. Childhood urticaria pigmentosa regresses spontaneously in approximately 50% of cases and urticaria pigmentosa in adults in 10%. Diffuse and erythrodermic cutaneous mastocytosis usually resolves spontaneously between the ages of 15 months and 5 years. Telangiectasia macularis eruptiva perstans tends to be a chronic condition.

Most of the therapeutic reports have been in patients with urticaria pigmentosa and, to a lesser extent, in diffuse and erythrodermic cutaneous mastocytosis. The major therapeutic measure is the administration of oral H1 antihistamines to alleviate pruritus and whealing. The use of antihistamines that interfere with the HERG K+ channel and cause cardiac arrhythmias should be avoided. Oral disodium cromoglycate has been efficacious in some individuals. The role and efficacy of topical high-potency glucocorticoid preparations with plastic-film occlusion, of narrow-band ultraviolet B (NB-UVB) phototherapy, of psoralens and ultraviolet A (PUVA) photochemotherapy, and UVA1 phototherapy have not been subjected to controlled clinical trials or remain anecdotal. Cytoreductive therapy to reduce mast-cell proliferation is not recommended in patients with only cutaneous manifestations. There is no therapy that will eradicate the mast cells in the cutaneous lesions.

Specific investigations

Surrogate markers of disease in mastocytosis.

Akin C, Metcalfe DD. Int Arch Allergy Immunol 2002; 127: 133–6.

Measurement of the histamine metabolites N-methylhistamine and methylimidazole acetic acid in 24-hour urine specimens is the preferred method of assessing baseline levels in patients with systemic mastocytosis, and these levels correlate with the amount of the mast cell burden. The levels of the major urinary metabolite of prostaglandin D2 (9α,11β-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-ene-1,20-dioxic acid) and thromboxane B2 or its metabolites in plasma and urine are elevated in patients with systemic mastocytosis. Soluble forms of CD 25, the α-chain of the interleukin-2 receptor, and CD 117, the receptor for stem cell factor, may be elevated in the circulation in systemic mastocytosis. A c-kit mutation may be detected in lesional tissues, such as skin and bone marrow in systemic mastocytosis.

Although these surrogate disease markers of mastocytosis are valuable tools in diagnosing the extent of disease, they should not be obtained routinely.