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Best Bets

Best Bets. 12th july 2016. NsaiD use in Chicken Pox. James Harper Chris Phillips Tom Hutchinson. Clinical Scenario --------------------------------. Paediatric placement week Nine year old with chicken pox, some infected lesions. Patient was admitted for intravenous antibiotics.

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Best Bets

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  1. Best Bets 12th july 2016

  2. NsaiD use in Chicken Pox James Harper Chris Phillips Tom Hutchinson

  3. Clinical Scenario-------------------------------- • Paediatric placement week • Nine year old with chicken pox, some infected lesions. • Patient was admitted for intravenous antibiotics. • Paediatric consultant asked me if I would advise giving ibuprofen to a child with chicken pox in the community? Leading Question No?

  4. Why?-------------------------- • There are approximately 700,000 cases of chicken pox a year in England and Wales1 • Over 90% of people in the UK will contract chicken pox before adolescence2 • In children younger than 5 years of age, bacterial skin infection is the most common complication5 • But it is rare: 2.8 per 10004 • Anecdotally Ibuprofen is very commonly used in paediatric patients for fever both as an over the counter and as a prescribed medication. • Ibuprofen is better at bringing down a temperature than paracetamol6

  5. Possible Underlying Mechanism---------------------------------------------- •  In vitro studies • Decreases in neutrophil function after exposure to NSAIDs • Specifically aggregation, adherence and degranulation of neutrophils10 • Inhibition of prostaglandin synthesis9 • In vivo • Neutrophils from subjects taking therapeutic doses of ibuprofen, indomethacin, or piroxicam showed profiles of inhibited responses to an infective stimulant8 • Ibuprofen study in rats showed decreased survival from surgical wounds and in a cecal ligation and punction model11 • Suggestion that NSAIDs may play a role, not only in the cause of varicella-associated skin infections, but also in the general worsening of infections.

  6. PICO---------------------------------------------- • Population: • Intervention: • Comparator: • Outcome: • Paediatric Patients with Varicella Zoster • The use of NSAIDs • The use of a placebo/avoidance of NSAIDs • Development of secondary streptococcal skin infections

  7. Search Strategy---------------------------------------------- • PubMed/Cochrane Library • [varicella] AND [ibuprofen OR NSAID] • 140 results of which 14 were relevant and related to skin infections • Removed one in French, one in Spanish, one in Portuguese • 2 BMJ letters • 3 duplicates • 1 retrospective cohort study • 3 case control studies • 1 prospective cohort study • 1 commentary

  8. Critical ApPraisal---------------------------------------------- • Ann Epidemiol. 1997 Oct;7(7):440-5. Ibuprofen and skin and soft tissue superinfections in children with varicella. Choo PW, Donahue JG, Platt R. • Pediatrics. 2001 May;107(5):1108-15. Invasive group A streptococcal infection and nonsteroidalantiinflammatory drug use among children with primary varicella. Lesko SM, O'Brien KL, Schwartz B, Vezina R, Mitchell AA. • Pediatrics. 1999 Apr;103(4 Pt 1):783-90. A case-control study of necrotizing fasciitis during primary varicella. Zerr DM, Alexander ER, Duchin JS, Koutsky LA, Rubens CE. • Br J ClinPharmacol.2008 Feb;65(2):203-9. Nonsteroidal anti-inflammatory drug use and the risk of severe skin and soft tissue complications in patients with varicella or zoster disease. YannMikaeloff,AbbasKezouh, and SamySuissa. • Acta Derm Venereol. 2008;88(1):26-30. doi: 10.2340/00015555-0333. Bacterial skin infections in children hospitalized with varicella: a possible negative impact of non-steroidalanti-inflammatory drugs? Dubos F1, Hue V, Grandbastien B, Catteau B, Martinot A. • Int J Clin Pharm. 2015 Dec;37(6):975-7. doi: 10.1007/s11096-015-0184-2. NSAIDs in paediatrics: caution with varicella! Durand Let al

  9. Ann Epidemiol. 1997 Oct;7(7):440-5. Ibuprofen and skin and soft tissue superinfections in children with varicella. Choo PW, Donahue JG, Platt R.

  10. Pediatrics. 2001 May;107(5):1108-15. Invasive group A streptococcal infection and nonsteroidal antiinflammatory drug use among children with primary varicella. Lesko SM, O'Brien KL, Schwartz B, Vezina R, Mitchell AA.

  11. Pediatrics. 1999 Apr;103(4 Pt 1):783-90. A case-control study of necrotizing fasciitis during primary varicella. Zerr DM, Alexander ER, Duchin JS, Koutsky LA, Rubens CE.

  12. Br J ClinPharmacol.2008 Feb;65(2):203-9. Nonsteroidal anti-inflammatory drug use and the risk of severe skin and soft tissue complications in patients with varicella or zoster disease. YannMikaeloff,AbbasKezouh, and SamySuissa. • Nested case control study • 1994-2005 – 11 years of data collection • 140 111 had chickenpox • Of which 386 developed secondary bacterial skin infections • The rate of skin infections associated with NSAID use was increased (rate ratio of 4.9) • + = No recall bias, nested • - = Observational

  13. Acta Derm Venereol. 2008;88(1):26-30. doi: 10.2340/00015555-0333. Bacterial skin infections in children hospitalized with varicella: a possible negative impact of non-steroidalanti-inflammatory drugs? Dubos F1, Hue V, Grandbastien B, Catteau B, Martinot A. • Multi centre prospective study • 159 children admitted with varicella. 43 of whom developed superadded infections. • NSAIDs were associated with onset of superadded infection (p 0.005)

  14. Int J Clin Pharm. 2015 Dec;37(6):975-7. doi: 10.1007/s11096-015-0184-2. NSAIDs in paediatrics: caution with varicella! Durand Let al • International Journal of Clinical Pharmacy • Article summarises that whilst no causal relationship has been definitively demonstrated, an association between NSAID use in varicella and superadded infection, has been found. • Advocates that paracetamol remains the safest antipyretic to use in varicella

  15. The Bottom line---------------------------------------------- • There is evidence of ibuprofen being an independent risk factor for skin infections. • There is evidence of a possible underlying mechanism to support that. • However a persistent high fever after varicella infection may lead to ibuprofen use which itself is probably a sign of incipient soft tissue infection.  • Excess fear of ibuprofen can lead to excess use of paracetamol, which in overdose and especially in children can be hepatotoxic7 • Should prescription of NSAIDs be limited in VZV infections?

  16. References---------------------------------------------- • 1 DTB (2005a) Chickenpox, pregnancy and the newborn.Drug & Therapeutics Bulletin43(9), 69-72. • DH (2012) Immunisation against infectious disease- "The Green Book". Chapter 34 - Varicella.Department of Health. www.dh.gov.uk • Lichenstein, R. (2006) Pediatrics, chicken pox or varicella.emedicineWebMD. • YannMikaeloff,AbbasKezouh, and SamySuissa. Nonsteroidal anti-inflammatory drug use and the risk of severe skin and soft tissue complications in patients with varicella or zoster disease. Br J ClinPharmacol. 2008 Feb;65(2):203-9. • Guess, H.A., Broughton, D.D., Melton, L.J. and Kurland, L.T. (1986) Population-based studies of varicella complications.Pediatrics78(4 Pt 2), 723-727. • Purssell E. Treating fever in children: paracetamol or ibuprofen? Br J Community Nurs. 2002 Jun;7(6):316-20. • Ranganathan SS, Sathiadas MG, Sumanasena S, Fernandopulle M, Lamabadusuriya SP, Fernandopulle BM. Fulminant hepatic failure and paracetamol overuse with therapeutic intent in febrile children. Ind J Pediatr2006;73:871-5 • Kaplan HB, Edelson HS, Korchak HM, Given WP, Abramson S, Weissman G. Effects of non-steroidal anti-inflammatory agents on human neutrophil functions in vitro and in vivo. BiochemPharmacol. 1984;33:371–8 • Giagoudakis G, Markantonis SL. Relationships between the concentrations of prostaglandins and the nonsteroidalantiinflammatory drugs indomethacin, diclofenac, and ibuprofen. Pharmacotherapy. 2005;25:18–25 • Venezio FR, DiVincenzo C, Pearlman C, Phair JP. Effects of the newer nonsteroidal anti-inflammatory agents, ibuprofen, fenoprofen, and sulindac, on neutrophil adherence. J Infect Dis. 1985;152:690–4.  • Dong YL, Fleming RY, Yan TZ, Herndon DN, Waymack JP. Effect of ibuprofen on the inflammatory response to surgical wounds. J Trauma.1993;35:340–3

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