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Mastocytoses
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
The mastocytoses are a group of disorders of clonal 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 (see figure), mastocytoma, diffuse and erythrodermic cutaneous mastocytosis, and telangiectasia macularis eruptiva perstans. An international task force has proposed a revised classification of cutaneous mastocytosis into maculopapular cutaneous mastocytosis with monomorphic and polymorphic variants, diffuse cutaneous mastocytosis, and cutaneous mastocytoma, with the elimination of telangiectasia macularis eruptiva perstans. The cutaneous forms of mastocytosis may be present with or without systemic manifestations. In pediatric patients, the cutaneous lesions usually are not associated with systemic involvement and often have spontaneous resolution around puberty. In adult patients, the cutaneous lesions usually are chronic and are associated with systemic mastocytosis. Adult patients should be classified because the type and stage of systemic mastocytosis has therapeutic and prognostic implications. 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 antiinflammatory agents (NSAIDs) 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 determine the type of specialty physician to whom a referral should be made for further evaluation.
Patients with systemic mastocytosis require long-term follow-up because associated non-mast–cell clonal hematologic disorders, such as myelodysplastic or myeloproliferative syndromes and lymphoproliferative disorders, may develop.
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.
In many cases cutaneous mastocytomas may involute spontaneously; they rarely are 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 during childhood. 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 H 1 antihistamines to alleviate pruritus and whealing. Oral disodium cromoglycate has been efficacious in some individuals. The role and efficacy of topical high potency glucocorticoid preparations with plastic-film occlusion, of narrowband ultraviolet B (NB-UVB) phototherapy, of psoralens and ultraviolet A (PUVA) photochemotherapy, and UVAl phototherapy have not been subjected to controlled clinical trials or remain anecdotal.
The use of tyrosine kinase inhibitors and 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 Investigation
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Skin biopsy
Cutaneous manifestations in patients with mastocytosis: consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology
Hartmann K, Escribano L, Grattan C, et al. J Allergy Clin Immunol 2016; 37: 35–45.
The major criterion for cutaneous involvement in patients with mastocytosis is typical skin lesions that are associated with Darier sign. Minor criteria include increased numbers of mast cells in biopsy specimens of lesional skin and an activating KIT mutation in lesional skin tissue. In lesional skin biopsy specimens, the number of mast cells is increased four to eightfold, which is about 40 mast cells/mm 2 . The use of an antibody against tryptase should be the standard histochemical marker to detect and quantitate mast cells. No specific, aberrantly expressed marker of clonal cutaneous mast cells has been identified.
Comparison of azelastine and chlorpheniramine in the treatment of mastocytosis
Friedman BS, Santiago ML, Berkebile C, et al. J Allergy Clin Immunol 1993; 92: 520–6.
In a double-blind, randomized, crossover trial in 13 subjects with urticaria pigmentosa and systemic mastocytosis, the administration of both azelastine and chlorpheniramine for 4 weeks was associated with a reduction in pruritus.
Rupatadine improves quality of life in mastocytosis: a randomized, double-blind, placebo controlled trial
Siebenhaar F, Förtsch A, Krause K, et al. Allergy 2013; 68: 949–52.
In a double-blind, randomized, placebo-controlled, crossover trial in seven patients with cutaneous mastocytosis and in 23 with indolent systemic mastocytosis, the administration of rupatadine for 28 days was associated with a 16.1% reduction (p = 0.004) in the mean ltchyQoL total score and 30.3% reduction (p = 0.001) in pruritus.
Comparison of the therapeutic efficacy of cromolyn sodium with that of combined chlorpheniramine and cimetidine in systemic mastocytosis: results of a double-blind clinical trial
Frieri M, Alling DW, Metcalfe DD. Am J Med 1985; 78: 9–14.
Five of six patients with systemic mastocytosis had less pruritus and four of six had less urticaria while receiving chlorpheniramine and cimetidine. There was no beneficial effect in those receiving disodium cromoglycate.
Oral disodium cromoglycate in the treatment of systemic mastocytosis
Soter NA, Austen KF, Wasserman SI. N Engl J Med 1979; 301: 465–9.
In a double-blind, crossover study in five patients with systemic mastocytosis and urticaria pigmentosa, in 15 of 18 trials oral disodium cromoglycate ameliorated pruritus and whealing.
Urticaria pigmentosa: clinical picture and response to oral disodium cromoglycate
Czarnetzki BM, Behrendt H. Br J Dermatol 1981; 105: 563–7.
In a blind, crossover trial, three children and 10 adults with urticaria pigmentosa were treated with oral disodium cromoglycate or placebo for 1 month, respectively. Relief of pruritus was observed in 67.7% of children and in 70% of adults.
Urticaria pigmentosa: systemic evaluation and successful treatment with topical steroids
Guzzo C, Lavker R, Roberts LJ II, et al. Arch Dermatol 1991; 127: 191–6.
In seven of nine adult patients with urticaria pigmentosa, the topical application of betamethasone dipropionate ointment 0.05% under occlusion overnight to half of the body for 6 weeks was associated with resolution of the lesions, with a maximum response within 3–12 weeks after the cessation of treatment. Lesions began to recur between 6 and 9 months after completing therapy. Retreatment for 6 months followed by once-weekly application of betamethasone dipropionate ointment under occlusion kept the patients clear of lesions, with the longest follow-up time being 2.5 years.
The appropriate method for using topical glucocorticoids in patients with urticaria pigmentosa needs to be determined in controlled trials.
Topical corticosteroids versus ‘wait and see’ in the management of solitary mastocytoma in pediatric patients: a long-term follow-up
Patrizi A, Tabanelli M, Neri I, et al. Dermatol Ther 2015; 28: 57–61.
In 130 patients with mastocytomas, 62 were treated with clobetasol cream, and 68 were untreated. A retrospective analysis showed no statistical differences between the two groups in the number of resolved or partially improved subjects. Complete remission occurred in an average of 16.4 months with treatment and 37.5 months without treatment. Average follow-up time was 56.3 months, with a range of 4 to 142 months.
Although the resolution of mastocytomas may occur with or without treatment, the time to resolution is faster with treatment using topical glucocorticoids, which are effective and safe considering the long time for resolution.
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