title: Clonal mast cell proliferation in pruriginous skin in hypereosinophilic syndrome.
abstract: BACKGROUND
  Hypereosinophilic syndrome (HES) is defined as a high eosinophilic granulocyte count in peripheral blood and other tissues. It can be associated with clonal and non-clonal haematological neoplastic diseases.
  
  
  METHODS
  Here we present a patient with a 27-year history of pruritus, urticarial lesions, recurrent diarrhoea, depression and a monoclonal gammopathy in the setting of HES.
  
  
  RESULTS
  The patient presented with erythemas, disseminated plaques, papules and scaling. Eosinophils continuously increased from 14% in 2002 to 65% in 2011. Tryptase levels were >20 µg/l. Skin biopsies were unspecific. In the bone marrow biopsy 30% of eosinophilic differentiated precursors and 10% plasma cells were noticed. Skin and bone marrow initially not indicative for mast cell proliferation were investigated for clonal mast cell proliferation. By immunostaining, single tryptase-, CD117c- and CD25-positive mast cells were detected not only in bone marrow, but also in the skin. Molecular investigations revealed a D816V exon 17 mutation of the c-KIT gene in bone marrow and skin biopsies.
  
  
  CONCLUSIONS
  In this patient HES was associated with high tryptase levels with 2 underlying clonal cell populations - IgGκ-positive plasma cells and single clonal mast cells with a high percentage of eosinophils in the bone marrow with symptoms of a clonal mast cell activation syndrome. Because of 3 minor criteria the patient finally fulfilled the criteria for systemic mastocytosis (according to the WHO). Patients with high tryptase levels and symptoms of mast cell activation syndrome should be investigated for clonal mast cell disease even in the absence of increased mast cells in the skin and bone marrow.
authors.affiliation: Department of Dermatology, Medical University of Graz, Graz, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Wiednig
authors.forename: C
authors.initials: C
authors.lastname: Beham-Schmid
authors.forename: B
authors.initials: B
authors.lastname: Kranzelbinder
authors.forename: E
authors.initials: E
authors.lastname: Aberer
mesh_terms: D000368:Aged; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology*; D049109:Cell Proliferation; D003863:Depression / Q000209:etiology; D003967:Diarrhea / Q000209:etiology; D004890:Erythema / Q000209:etiology; D005260:Female; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000097:blood / Q000150:complications / Q000473:pathology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008407:Mast Cells / Q000737:chemistry / Q000473:pathology*; D034721:Mastocytosis, Systemic / Q000150:complications / Q000473:pathology*; D009154:Mutation; D010265:Paraproteinemias / Q000209:etiology; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics; D011536:Prurigo / Q000150:complications; D012867:Skin / Q000473:pathology*; D053802:Tryptases / Q000032:analysis / Q000097:blood
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit; D019009:Proto-Oncogene Proteins c-kit; D053802:Tryptases