What Caught My Eye
By: CARRA | October 31, 2016 | What Caught Our Eye
By Kenneth N. Schikler, MD
Chief, Divisions of Pediatric Rheumatology & Adolescent Medicine
University of Louisville School of Medicine
Kosair Children’s Hospital
It is not unusual for pediatric rheumatologists to be asked to see a child with persistent fever, without arthritis, who may or may not have had rash. Usually by the time the rheumatologist is called, the child has often been treated with antibiotics, and bacterial cultures have been done and were negative, and serologic or PCR studies for tick related illnesses and other infectious etiologies are in process or negative. Viral studies are done, and how specific/ disease related is the finding of a positive recovery of a respiratory pathogen from a nasal swab?
In JAMA 2016 316 (8) 835, Herberg et al have published “Diagnostic Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children”. Their findings in a study that looked at the RNA expression signatures in febrile children who had:
- Bacterial syndromes with recovered/identified bacterial pathogens,
- Bacterial syndromes with no bacterial recovery,
- No classic syndrome nor recovery of infectious agent,
- Biral syndrome with virus identified,
- Biral syndrome without virus identified, and
- Henoch Schonlein Purpura or JIA.
The JIA patients were sampled at time of diagnosis or “early in disease”, but subtypes of JIA were not identified and median C-RP was 0.1. They also included in their analysis findings of the work of others in children with SLE.
Of interest to me, in their preliminary data they found two transcripts, IF144L and FAM89A showed reciprocal expression in viral and bacterial infection. In response to viral infection, mediated by type 1 interferon, IF144L was upregulated, while in children with septic shock FAM89A was upregulated.
In Arthritis and Rheumatology 2009, Barnes and colleagues reported on gene expression profiles in new onset JIA and in systemic JIA in addition to IL-6 and TLR/IL-1R pathways being activated, the Peroxisome Proliferative activated Receptor (PPAR) was identified.
FAM89A is reported to be one of the targets of PPAR gamma in an animal model reported by Tero-Pekka Alastalo et al in Journal of Clinical Investigation2011 Sep;121(9):3735-46. It would have been wonderful if the investigation could have included children with systemic JIA in active stages, to see if FAM89A expression discriminates septic children from innately toxic non-infected children. Still, the potential for being able to eliminate a viral etiology to rash and persistent fever would certainly be helpful.
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