title: Tryptase and histamine metabolites as diagnostic indicators of indolent systemic mastocytosis without skin lesions.
abstract: BACKGROUND
  Risk indicators of indolent systemic mastocytosis (ISM) in adults with clinical suspicion of ISM without accompanying skin lesions [urticaria pigmentosa (UP)] are lacking. This study aimed at creating a decision tree using clinical characteristics, serum tryptase, and the urinary histamine metabolites methylimidazole acetic acid (MIMA) and methylhistamine (MH) to select patients for bone marrow investigations to diagnose ISM.
  
  
  METHODS
  Retrospective data analysis of all adults, in whom bone marrow investigations were performed to diagnose ISM, was carried out.
  
  
  RESULTS
  In total, 142 patients were included. SM was absent in all 44 patients with tryptase <10 μg/l, in 45 of 98 (46%) patients with tryptase ≥10 μg/l and in 18 of 52 patients (35%) with tryptase >20 μg/l. Above 43 μg/l, all patients had ISM (n = 11). Male gender, insect venom anaphylaxis as presenting symptom, tryptase, MIMA, and MH were independent ISM predictors. If tryptase was ≥10 μg/l, the diagnostic accuracy of MIMA and MH was high (areas under the ROC curve 0.92).
  
  
  CONCLUSIONS
  In suspected patients without UP, the ISM risk is very low (if present at all) if tryptase is <10 μg/l. If tryptase is ≥10 μg/l, this risk depends on MIMA and MH, being low if these are normal, but high if these are elevated. Male gender and insect venom anaphylaxis are additional risk indicators. We recommend refraining from bone marrow examinations in suspected patients without UP if tryptase is <10 μg/l. Our results question the reliability of the minor diagnostic World Health Organization criterion of tryptase >20 μg/l.
authors.affiliation: Department of Allergology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. j.j.van.doormaal@.umcg.nl
authors.forename: J J
authors.initials: JJ
authors.lastname: van Doormaal
authors.forename: E
authors.initials: E
authors.lastname: van der Veer
authors.forename: P C
authors.initials: PC
authors.lastname: van Voorst Vader
authors.forename: P M
authors.initials: PM
authors.lastname: Kluin
authors.forename: A B
authors.initials: AB
authors.lastname: Mulder
authors.forename: S
authors.initials: S
authors.lastname: van der Heide
authors.forename: S
authors.initials: S
authors.lastname: Arends
authors.forename: J C
authors.initials: JC
authors.lastname: Kluin-Nelemans
authors.forename: J N G
authors.initials: JN
authors.lastname: Oude Elberink
authors.forename: J G R
authors.initials: JG
authors.lastname: de Monchy
mesh_terms: D000328:Adult; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D005260:Female; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000652:urine*; D008297:Male; D034721:Mastocytosis, Systemic / Q000150:complications* / Q000175:diagnosis*; D008761:Methylhistamines / Q000652:urine*; D008875:Middle Aged; D012372:ROC Curve; D012189:Retrospective Studies; D012306:Risk; D053802:Tryptases / Q000097:blood*; D014582:Urticaria Pigmentosa / Q000150:complications*
chemical_list: D007093:Imidazoles; D008761:Methylhistamines; C002667:methylimidazoleacetic acid; D006632:Histamine; D053802:Tryptases