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The clinical manifestations result from <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>\u2010derived mediators and, less frequently, from destructive infiltration of <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>s. Patients suffer from a variety of symptoms including pruritus, flushing and life\u2010threatening anaphylaxis. Whilst mastocytosis is likely to be suspected in a patient with typical skin lesions [i.e. urticaria pigmentosa (UP)], the absence of cutaneous signs does not rule out the diagnosis of this disease. Mastocytosis should be suspected in cases of recurrent, unexplained or severe insect\u2010induced anaphylaxis or symptoms of <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> degranulation without true allergy. In rare cases, unexplained osteoporosis or unexplained haematological abnormalities can be underlying feature of mastocytosis, particularly when these conditions are associated with elevated baseline serum tryptase levels. The diagnosis is based on the World Health Organization criteria, in which the tryptase level, histopathological and immunophenotypic evaluation of <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>s and molecular analysis are crucial. A somatic <jats:italic><jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content><\/jats:italic> mutation, the most common of which is D816V, is usually detectable in <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>s and their progenitors. Once a diagnosis of systemic mastocytosis (<jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>) is made, it is mandatory to assess the burden of the disease, its activity, subtype and prognosis, and the appropriate therapy. Mastocytosis comprises seven different categories that range from indolent forms, such as cutaneous and indolent <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>, to progressive forms, such as aggressive <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> leukaemia. Although prognosis is good in patients with indolent forms of the disease, patients with advanced categories have a poor prognosis.<\/jats:p>","DOI":"10.1111\/joim.12410","type":"journal-article","created":{"date-parts":[[2015,9,8]],"date-time":"2015-09-08T11:55:29Z","timestamp":1441713329000},"page":"211-228","source":"Crossref","is-referenced-by-count":61,"title":["Mastocytosis: the puzzling clinical spectrum and challenging diagnostic aspects of an enigmatic disease"],"prefix":"10.1111","volume":"279","author":[{"given":"T.","family":"G\u00fclen","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine and Allergy Karolinska University Hospital Huddinge Stockholm Sweden"},{"name":"Department of Medicine Clinical Immunology and Allergy Research Unit Karolinska Institutet Karolinska University Hospital Solna Stockholm Sweden"},{"name":"Mastocytosis Centre Karolinska Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"},{"name":"Centre for 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