“Ampicillin rash,” a phenomenon unique to patients with Epstein-Barr virus acute infectious mononucleosis (AIM) treated with ampicillin, was first reported in the 1960s. The incidence was estimated as being between 80% and 100%, and the figures have not been reviewed since those first accounts. We sought to establish the current incidence of rash associated with antibiotic treatment among children with AIM.
A retrospective study of all hospitalized children diagnosed as having AIM based upon positive Epstein-Barr virus serology in 2 pediatric tertiary medical centers in Israel.
Of the 238 children who met the study entry criteria during the study period, 173 were treated with antibiotics. Fifty-seven (32.9%) of the subjects treated with antibiotics had a rash during their illness compared with 15 (23.1%) in untreated patients (P = .156; not significant). Amoxicillin was associated with the highest incidence of antibiotic-induced rash occurrence (29.5%, 95% confidence interval: 18.52–42.57), but significantly lower than the 90% rate reported for ampicillin in past studies. Age, gender, ethnicity, and atopic or allergic history were not associated with the development of rash after antibiotic exposure. Among the laboratory data, only increased white blood cell counts were more prevalent among subjects who did not develop an antibiotic-induced rash.
The incidence of rash in pediatric patients with AIM after treatment with the current oral aminopenicillin (amoxicillin) is much lower than originally reported.
Dear Editor,
we read with interest the article by Chovel-Sella et al. on the incidence of rash after amoxicillin treatment in children with acute infectious mononucleosis (AIM) Epstein-Barr virus (EBV)-associated (1). The main finding of this study is that the incidence of rash previously reported as 90% to 100% with ampicillin and quoted in the Nelson Textbook of Pediatrics up to 80% with both ampicillin or amoxicillin (2-4), was much lower (29.5%)(1). The authors suggest, as an explanation of this difference, the homogeneity of the population studied and encouraged others to carry out similar studies in other ethnic and racial populations to validate their findings.
We conducted a retrospective study of all children evaluated at the Emergency Department and/or admitted at Meyer Children's University Hospital of Florence, Italy with a diagnosis of AIM EBV-associated (positive immunoglobulin M to the viral capsid antigen, VCA IgM) from January 2010 to February 2013. In our study a rash was considered to be associated to antibiotic treatment if it developed after administration of the first dose of antibiotic. One hundred and eighty three children were diagnosed as having AIM associated to EBV and 75 children were treated with oral amoxicillin. Twenty-four (32%) out of 75 children treated with amoxicillin developed a rash. Our population was predominantly European and particularly 67 out of 75 children treated with amoxicillin were Italian, 1 was English, 2 were Peruvian and 5 were African. As a control group we considered 123 children with mononucleosis-like syndrome with negative VCA IgM and negative also for other bacterial or viral etiologies (Streptococcus pyogenes, enterovirus, adenovirus, cytomegalovirus). Sixty- one of these children were treated with oral amoxicillin and 3 of them (4.9%) developed rash after treatment (p<0.001; OR 9.09; 95% CI 2.4- 40.47 when compared to children with AIM EBV-associated). As a second finding, Chovel-Sella et al. found a slightly higher incidence of rash (23.1%) in untreated children with AIM EBV-associated as compared to the literature (1). As a possible explanation they speculated that all the children enrolled in their study were hospitalized and had a more severe and complicated disease. Our data confirm this finding (40/183, 21.8% children with rash unrelated to treatment), but we did not found any difference according to hospitalization status (6/40, 15% hospitalized vs 34/40, 85% not hospitalized).
In conclusion, our results confirm the main finding of the article by Chovel-Sella et al (1). The incidence of rash after amoxicillin treatment in children with AIM EBV-associated is lower than previously reported (2- 4). Our finding does not support Chovel-Sella's hypothesis that ethnic factors may influence rash onset, and we find more plausible that amoxicillin (or different preparations recently available) could favor rash onset less than ampicillin as hypothesized by the authors.
References 1.Chovel-Sella A, Ben Tov A, Lahav E, et al. Incidence of rash after amoxicillin treatment in children with infectious mononucleosis. Pediatrics. 2013;131:1424-1427. 2.Patel BM. Skin rash with infectious mononucleosis and ampicillin. Pediatrics. 1967;40:910-911. 3.Pullen H, Wright N, Murdoch JM. Hypersensitivity reactions to antibacterial drugs in infectious mononucleosis. Lancet. 1967;2:1176-1178. 4.Jenson HB. Epstein-Barr virus. In: Kliegman RM, Stanton BF, Schor NF, St. Gems JW, Behrman RE, eds. Nelson Textbook of Pediatrics, 19th ed. Philadelphia, PA: Elsevier Saunders; 2011:1105-1110
Conflict of Interest:
None declared