title: Toward an Objective Diagnostic Test for Bacterial Cellulitis.
abstract: BACKGROUND
  Prior studies repeatedly showed that cultures of skin lesions diagnosed as "cellulitis" are usually negative. However, lack of a gold standard for diagnosis (against which culture might be judged) and failure to assess the human immune response are important limitations of prior work. In this pilot study, we aimed to develop a criterion standard for research on bacterial cellulitis, to evaluate the sensitivity of procalcitonin for bacterial cellulitis, and to use gene expression analysis to find other candidate diagnostic markers.
  
  
  METHODS
  We classified lesions via biopsies, 16s rRNA gene detection, culture, and histopathology. We quantified procalcitonin expression in blood. We also used Nanostring technology to quantify transcription of immunomodulators that may distinguish cases from inflamed controls.
  
  
  RESULTS
  Of 28 participants, 15 had a clinical diagnosis of cellulitis, six had a diagnosis of non-infectious dermatitis, and seven were normal volunteers. Of the "cellulitis" patients, three (20%) had pathogens isolated, and were designated confirmed cases. Procalcitonin was undetectable in all three. HLA-DQA1 was expressed 34-fold more in confirmed cases vs. controls (fold change of geometric mean). Heat maps depicting multiplex gene expression analysis revealed a distinct profile of gene expression in confirmed cases relative to comparators.
  
  
  CONCLUSIONS
  Most "cellulitis" patients had microbiologically-negative biopsies. Procalcitonin was undetectable, and HLA-DQA1 elevated, in confirmed bacterial cases. Multivariable transcriptomic profiling results supported our algorithm's ability to identify patients with true bacterial cellulitis. A larger sample may allow discovery of an immunological signature capable of distinguishing bacterial cellulitis from its mimics in clinical practice.
authors.affiliation: Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, United States of America.
authors.forename: Daniel J
authors.identifier: http://orcid.org/0000-0002-8517-9702
authors.initials: DJ
authors.lastname: Pallin
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, United States of America.
authors.forename: Lynn
authors.initials: L
authors.lastname: Bry
authors.affiliation: Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, United States of America.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Dwyer
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, MA, United States of America.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Lipworth
authors.affiliation: Department of Pediatrics, National Jewish Medical Health, Denver, CO, United States of America.
authors.forename: Donald Y
authors.initials: DY
authors.lastname: Leung
authors.affiliation: Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, United States of America.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Camargo
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, MA, United States of America.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kupper
authors.affiliation: Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, United States of America.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Filbin
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, United States of America.
authors.forename: George F
authors.initials: GF
authors.lastname: Murphy