{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:48:58Z","timestamp":1791845338323,"version":"4.3.4"},"reference-count":41,"publisher":"American Academy of Pediatrics (AAP)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,4,1]]},"abstract":"\n Objective.<\/jats:title>\n An increase in the incidence of necrotizing fasciitis (NF) occurring in previously healthy children with primary varicella was noted in the Washington State area between December 1993 and June 1995. Our objective was to investigate ibuprofen use and other risk factors for NF in the setting of primary varicella.<\/jats:p>\n <\/jats:sec>\n \n Methods.<\/jats:title>\n Case-control study. Demographic information, clinical parameters, and potential risk factors for NF were compared for cases and controls. Cases of NF were analyzed to identify potential determinants of NF complicated by renal insufficiency and\/or streptococcal toxic shock syndrome. Multivariate logistic regression was used to evaluate the association between ibuprofen use and NF. A case was defined as a child with NF hospitalized within 3 weeks of primary varicella (n = 19). Controls were children hospitalized with a soft tissue infection other than NF within 3 weeks of primary varicella (n = 29). Odds ratios (ORs) of ibuprofen, as well as other potential risk factors were evaluated. In addition, demographic and clinical data as well as other potential risk factors were compared between cases and controls.<\/jats:p>\n <\/jats:sec>\n \n Results.<\/jats:title>\n After controlling for gender, age, and group A streptococcus isolation, cases were more likely than controls to have used ibuprofen before hospitalization (OR, 11.5; 95% confidence interval, 1.4 to 96.9). In most children, ibuprofen was initiated after the onset of symptoms of secondary infection. Children with NF complicated by renal insufficiency and\/or streptococcal toxic shock syndrome were more likely than children with uncomplicated NF to have used ibuprofen (OR, 16.0; 95% confidence interval, 1.0 to 825.0). Children with complicated NF also had a higher mean maximum temperature (40.9\u00b0C vs 39.3\u00b0C), and a longer mean duration of secondary symptoms (1.7 days vs 0.6 days) before admission than children with uncomplicated NF.<\/jats:p>\n <\/jats:sec>\n \n Conclusion.<\/jats:title>\n Ibuprofen use was associated with NF in the setting of primary varicella. Additional studies are needed to establish whether ibuprofen use has a causal role in the development of NF and its complications during varicella.<\/jats:p>\n <\/jats:sec>","DOI":"10.1542\/peds.103.4.783","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T19:45:45Z","timestamp":1092426345000},"page":"783-790","source":"Crossref","is-referenced-by-count":156,"title":["A Case-Control Study of Necrotizing Fasciitis During Primary Varicella"],"prefix":"10.1542","volume":"103","author":[{"given":"Danielle M.","family":"Zerr","sequence":"first","affiliation":[{"name":"From the From the Division of Infectious Disease, Department of Pediatrics, Children's Hospital and Regional Medical Center\/University of Washington; the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Russell","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, University of Washington; the"},{"name":"Seattle-King County Public Health Department, Seattle Washington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Duchin","sequence":"additional","affiliation":[{"name":"Division of Allergy and Infectious Disease, Department of Medicine, University of Washington; and the"},{"name":"Seattle-King County Public Health Department, Seattle Washington."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Koutsky","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, University of Washington; the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig E.","family":"Rubens","sequence":"additional","affiliation":[{"name":"From the From the Division of Infectious Disease, Department of Pediatrics, Children's Hospital and Regional Medical Center\/University of Washington; the"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[1999,4,1]]},"reference":[{"key":"2021121009330469900_B1","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/S0196-0644(94)70320-5","article-title":"Serious group A \u03b2-hemolytic streptococcal infections complicating varicella.","volume":"23","author":"Cowan","year":"1994","journal-title":"Ann Emerg Med."},{"key":"2021121009330469900_B2","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1542\/peds.96.3.428","article-title":"Group A \u03b2-hemolytic streptococcal bacteremia: historical overview, changing incidence, and recent association with varicella.","volume":"96","author":"Doctor","year":"1995","journal-title":"Pediatrics."},{"key":"2021121009330469900_B3","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1097\/00006454-199206000-00004","article-title":"Complications of varicella requiring hospitalization in previously healthy children.","volume":"11","author":"Jackson","year":"1992","journal-title":"Pediatr Infect Dis J."},{"key":"2021121009330469900_B4","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1097\/00006454-199602000-00011","article-title":"Invasive group A streptococcal infections in children with varicella in Southern California.","volume":"15","author":"Vugia","year":"1996","journal-title":"Pediatr Infect Dis J."},{"key":"2021121009330469900_B5","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1097\/00006454-199101000-00017","article-title":"Streptococcal toxic shock-like syndrome as a complication of varicella.","volume":"10","author":"Bradley","year":"1991","journal-title":"Pediatr Infect Dis J."},{"key":"2021121009330469900_B6","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S0022-3476(05)82144-4","article-title":"Apparent increase in the incidence of invasive group A \u03b2-hemolytic streptococcal disease in children.","volume":"118","author":"Givner","year":"1990","journal-title":"J Pediatr."},{"key":"2021121009330469900_B7","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1542\/peds.57.3.306","article-title":"Varicella gangrenosa due to group A \u03b2-hemolytic streptococcus.","volume":"57","author":"Smith","year":"1976","journal-title":"Pediatrics."},{"key":"2021121009330469900_B8","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1097\/00006454-198507000-00025","article-title":"Necrotizing fasciitis of the abdominal wall as a complication of chickenpox.","volume":"4","author":"Kyong","year":"1985","journal-title":"Pediatr Infect Dis J."},{"key":"2021121009330469900_B9","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1177\/000992288802700706","article-title":"Necrotizing fasciitis as a complication of chickenpox.","volume":"27","author":"Falcone","year":"1988","journal-title":"Clin Pediatr (Phila)."},{"key":"2021121009330469900_B10","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1097\/00006454-199507000-00007","article-title":"Group A streptococcal necrotizing fasciitis complicating primary varicella: a series of fourteen patients.","volume":"14","author":"Brogan","year":"1995","journal-title":"Pediatr Infect Dis J."},{"key":"2021121009330469900_B11","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1093\/clinids\/20.5.1333","article-title":"Group A streptococcal necrotizing fasciitis following varicella in children: case reports and review.","volume":"20","author":"Wilson","year":"1995","journal-title":"Clin Infect Dis."},{"key":"2021121009330469900_B12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1056\/NEJM198907063210101","article-title":"Severe group A streptococcal infections associated with a toxic shock-like syndrome and scarlet fever toxin A.","volume":"321","author":"Stevens","year":"1989","journal-title":"N Engl J Med."},{"key":"2021121009330469900_B13","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1097\/00006454-199602000-00012","article-title":"Risk factors for invasive group A streptococcal infections in children with varicella: a case-control study.","volume":"15","author":"Peterson","year":"1996","journal-title":"Pediatr Infect Dis J."},{"key":"2021121009330469900_B14","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1136\/bmj.290.6484.1786","article-title":"Haemolytic streptococcal gangrene and non-steroidal anti-inflammatory drugs.","volume":"290","author":"Brun-Buisson","year":"1985","journal-title":"Br Med J."},{"key":"2021121009330469900_B15","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1097\/00007611-199106000-00030","article-title":"Necrotizing fasciitis and nonsteroidal anti-inflammatory drugs.","volume":"84","author":"Smith","year":"1991","journal-title":"South Med J."},{"key":"2021121009330469900_B16","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1093\/infdis\/155.1.143","article-title":"Fulminant necrotizing fasciitis and nonsteroidal anti-inflammatory drugs.","volume":"155","author":"Rimailho","year":"1987","journal-title":"J Infect Dis."},{"key":"2021121009330469900_B17","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0002-9378(95)90205-8","article-title":"Necrotizing fasciitis in the puerperium.","volume":"173","author":"Rowan","year":"1995","journal-title":"Am J Obstet Gynecol."},{"key":"2021121009330469900_B18","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/S0140-6736(85)92604-2","article-title":"Necrotising fasciitis after diflunisal for minor injury.","volume":"2","author":"Krige","year":"1985","journal-title":"Lancet."},{"key":"2021121009330469900_B19","first-page":"165","article-title":"Influence of phenylbutazone on leukocyte chemiluminescence and function.","volume":"86","author":"Solberg","year":"1978","journal-title":"Acta Pathol Microbiol Scand."},{"key":"2021121009330469900_B20","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1056\/NEJM197409262911302","article-title":"Inhibition of granulocyte adherence by ethanol, prednisone, and aspirin, measured with an assay system.","volume":"291","author":"MacGregor","year":"1974","journal-title":"N Engl J Med."},{"key":"2021121009330469900_B21","first-page":"258","article-title":"Influence of phenylbutazone on the phagocytic and bactericidal activities of neutrophil granulocytes.","volume":"82","author":"Solberg","year":"1974","journal-title":"Acta Pathol Microbiol Scand B Microbiol Immunol."},{"key":"2021121009330469900_B22","first-page":"448","article-title":"Influence of phenylbutazone on leukocyte glucose metabolism and function.","volume":"20","author":"Kjosen","year":"1976","journal-title":"J Reticuloendothel Soc."},{"key":"2021121009330469900_B23","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1001\/jama.1993.03500030088038","article-title":"Defining the group A streptococcal toxic shock syndrome: rationale and consensus definition.","volume":"269","author":"The Working Group on Severe Streptococcal Infections","year":"1993","journal-title":"JAMA."},{"key":"2021121009330469900_B24","first-page":"1","article-title":"Ibuprofen as an over-the-counter drug: is there a risk for renal injury?","volume":"39","author":"Mann","year":"1993","journal-title":"Clin Nephrol."},{"key":"2021121009330469900_B25","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1056\/NEJM198403013100905","article-title":"Renal syndromes associated with nonsteroidal antiinflammatory drugs.","volume":"310","author":"Clive","year":"1984","journal-title":"N Engl J Med."},{"key":"2021121009330469900_B26","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1093\/infdis\/166.2.374","article-title":"Epidemiologic analysis of group A streptococcal serotypes associated with severe systemic infection, rheumatic fever, or uncomplicated pharyngitis.","volume":"166","author":"Johnson","year":"1992","journal-title":"J Infect Dis."},{"key":"2021121009330469900_B27","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/0140-6736(92)90339-5","article-title":"Clonal basis for resurgence of serious Streptococcus pyogenes disease in the 1980s.","volume":"339","author":"Cleary","year":"1992","journal-title":"Lancet."},{"key":"2021121009330469900_B28","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1097\/00006454-199105000-00001","article-title":"Association of exotoxin-producing group A streptococci and severe disease in children.","volume":"10","author":"Belani","year":"1991","journal-title":"Pediatr Infect Dis J."},{"key":"2021121009330469900_B29","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/0140-6736(90)92777-F","article-title":"Changing epidemiology of group A streptococcal infection in the USA.","volume":"336","author":"Schwartz","year":"1990","journal-title":"Lancet."},{"key":"2021121009330469900_B30","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1128\/iai.61.8.3369-3374.1993","article-title":"Association of phenotypic and genotypic characteristics of invasive Streptococcus pyogenes isolates with clinical components of streptococcal toxic shock syndrome.","volume":"61","author":"Talkington","year":"1993","journal-title":"Infect Immunol."},{"key":"2021121009330469900_B31","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1093\/infdis\/173.4.901","article-title":"Genetic and phenotypic diversity among isolates of Streptococcus pyogenes from invasive infections.","volume":"173","author":"Chaussee","year":"1996","journal-title":"J Infect Dis."},{"key":"2021121009330469900_B32","first-page":"342","article-title":"Necrotizing fasciitis\u2014the hazards of delay.","volume":"88","author":"Burge","year":"1995","journal-title":"J R Soc Med."},{"key":"2021121009330469900_B33","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1542\/peds.101.1.136","article-title":"Severe invasive group A streptococcal infections: a subject review.","volume":"101","author":"American Academy of Pediatrics","year":"1998","journal-title":"Pediatrics."},{"key":"2021121009330469900_B34","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1046\/j.1365-2567.1996.472535.x","article-title":"Oral aspirin and ibuprofen increase cytokine-induced synthesis of IL-1beta and of tumour necrosis factor-alpha ex vivo.","volume":"87","author":"Endres","year":"1996","journal-title":"Immunology."},{"key":"2021121009330469900_B35","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/1043-4666(94)90077-9","article-title":"Cyclooxygenase inhibitors enhance tumour necrosis factor production and mortality in murine endotoxic shock.","volume":"6","author":"Pettipher","year":"1994","journal-title":"Cytokine."},{"key":"2021121009330469900_B36","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1093\/infdis\/163.1.89","article-title":"Pretreatment with ibuprofen augments circulating tumor necrosis factor-alpha, interleukin-6 and elastase during acute endotoxinemia.","volume":"163","author":"Spinas","year":"1991","journal-title":"J Infect Dis."},{"key":"2021121009330469900_B37","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1056\/NEJM198808183190703","article-title":"Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura.","volume":"319","author":"Girardin","year":"1988","journal-title":"N Engl J Med."},{"key":"2021121009330469900_B38","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1182\/blood.V74.5.1704.1704","article-title":"Increased plasma levels of interleukin-6 in sepsis.","volume":"74","author":"Hack","year":"1989","journal-title":"Blood."},{"key":"2021121009330469900_B39","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0140-6736(87)91728-4","article-title":"Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease.","volume":"1","author":"Waage","year":"1987","journal-title":"Lancet."},{"key":"2021121009330469900_B40","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1086\/516110","article-title":"Nonsteroidal antiinflammatory drugs: concurrent or causative drugs in serious infection? (letter).","volume":"25","author":"Barnham","year":"1997","journal-title":"Clin Infect Dis."},{"key":"2021121009330469900_B41","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/S1047-2797(97)00040-9","article-title":"Ibuprofen and skin and soft tissue superinfections in children with varicella.","volume":"7","author":"Choo","year":"1997","journal-title":"Ann Epidemiol."}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/103\/4\/783\/841570\/783.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/103\/4\/783\/841570\/783.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T01:32:57Z","timestamp":1682731977000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/103\/4\/783\/65926\/A-Case-Control-Study-of-Necrotizing-Fasciitis"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,4,1]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[1999,4,1]]},"published-print":{"date-parts":[[1999,4,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.103.4.783","relation":{},"ISSN":["1098-4275","0031-4005"],"issn-type":[{"value":"1098-4275","type":"electronic"},{"value":"0031-4005","type":"print"}],"subject":[],"published":{"date-parts":[[1999,4,1]]}}}