Abstract
BackgroundPrior 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.MethodsWe 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.ResultsOf 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.ConclusionsMost “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.
Highlights
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
An editorial in Clinical Infectious Diseases compared cellulitis to pornography,[1] because both are recognized subjectively, based on the standard enunciated by U.S Supreme Court Justice Potter Stewart: "I know it when I see it." The subjectivity of the diagnosis of cellulitis has been the topic of several investigations, but these studies relied on expert opinion, which is subjective, as the reference standard
Skin infection diagnoses account for 6.3 million office visits and 3.8 million emergency department visits per year in the US alone.[5,6,7]
Summary
An editorial in Clinical Infectious Diseases compared cellulitis to pornography,[1] because both are recognized subjectively, based on the standard enunciated by U.S Supreme Court Justice Potter Stewart: "I know it when I see it." The subjectivity of the diagnosis of cellulitis has been the topic of several investigations, but these studies relied on expert opinion, which is subjective, as the reference standard These studies found that specialists deem generalists' diagnosis of cellulitis to be wrong in up to 74% of cases.[2,3,4] Prior studies have been limited by the lack of a control group, and lack of assessment of the human immune response. 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
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