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Fewer Symptoms Occur in Same-Serotype Recurrent Streptococcal Tonsillopharyngitis

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Fewer Symptoms Occur in Same-Serotype Recurrent Streptococcal Tonsillopharyngitis ORIGINAL ARTICLE Fewer Symptoms Occur in Same-Serotype Recurrent Streptococcal Tonsillopharyngitis Lucia H. Lee, MD; Elia Ayoub, MD; Michael E. Pichichero, MD Background: Most patients with acute rheumatic tial GABHS infection and was associated with a 0.2- or fever report no antecedent pharyngitis. greater log rise in either antistreptolysin O or anti– deoxyribonuclease B titer, indicating bona fide recur- Objective: To determine the clinical and microbio- rent infection; these recurrences all occurred within 55 logical characteristics of recurrent group A b-hemolytic days. Fewer patients with recurrent GABHS pharyngitis streptococcal (GABHS) tonsillopharyngitis. of the same serotype had headache (P=.02), sore throat (P=.006), fever (P=.008), pharyngeal erythema (P,.001), Design: Prospective randomized trial. pharyngeal edema (P,.001), pharyngeal exudate (P=.04), and adenitis (P=.03) compared with the initial episode. Subjects: Symptoms were recorded and throat cul- Chills, stomachache, scarlatina, tonsillar enlargement, and tures were obtained at 4 to 6, 18 to 21, and 32 to 35 days palatal petechiae were similar for both episodes. following the start of treatment. A subset of 60 patients with subsequent GABHS episodes occurring were evalu- Conclusions: Fewer symptoms occur during recurrent ated for a 0.2-or greater log rise in either antistreptoly- GABHS pharyngitis of the same serotype compared with sin O or anti–deoxyribonuclease B titer to confirm a bona the initial infection. These patients may be less likely to fide recurrence. seek physician attention, yet their infections put them at risk for sequelae. Results: Sixteen (27%) of 60 patients had recurrent GABHS tonsillopharyngitis of the same serotype that occurred 21 days or longer following the onset of the ini- Arch Otolaryngol Head Neck Surg. 2000;126:1359-1362 ROUP A b-hemolyticstrep- study period; 19 patients (6%) had the tococcal (GABHS) phar- same streptococcal serotype isolated yngitis accounts for sig- during the recurrences (Table 1). nificant childhood mor- These recurrences were detected at 21 bidity, but little is known to 34 days and 35 days or longer follow- aboutG the morbidity associated with recur- ing the initial infection in 74% and 26% rent GABHS pharyngitis. An increase in the of cases, respectively (mean, 30 days; cases of acute rheumatic fever (ARF) in chil- range, 21-55 days). Children with same- drenwasnotedinthelate1980sintheUnited serotype recurrences had significantly States.1-10 During this resurgence, many pa- fewer symptoms (headache, sore throat, tients with documented ARF had no recol- or fever) and signs (pharyngeal ery- lection of an episode of pharyngitis in the thema, pharyngeal edema, pharyngeal preceding months.3-5,7,11 During routine exudate, or adenitis) compared with the follow-up of patients in a comparative an- initial infections (Table 2). The fre- tibiotic study protocol, we serendipitously quency of chills, stomachache, scarla- notedthatsomepatientsreturnedwithfewer tina, tonsillar enlargement, and palatal and/or milder symptoms and signs of ton- petechiae were similar on both occa- From the Food and Drug sillopharyngitis, and had GABHS-positive sions; however, our statistical power to Administration, Rockville, Md throat cultures. We sought to determine the detect differences was limited by sample (Dr Lee); the Department of clinical characteristics and significance of size. Pediatrics, University of these recurrences. Ten patients (3%) had new acquisi- Florida, Gainesville (Dr Ayoub); and the tions of GABHS infection, which oc- Department of Microbiology RESULTS curred at a mean of 20 days (range, 11-33 and Immunology, University days) following the initial infection. These of Rochester Medical Center, Sixty (20%) of 295 children had a sub- patients did not show statistically signifi- Rochester, NY (Dr Pichichero). sequent GABHS pharyngitis during the cant differences for any sign or symptom (REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 126, NOV 2000 WWW.ARCHOTO.COM 1359 ©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 SUBJECTS AND METHODS hours, and then examined for b-hemolysis and colony mor- phology. All available strains of GABHS were typed by the STUDY DESIGN capillary precipitation method for M protein and the ag- glutination technique for T protein according to standard methods.13,14 Antistreptolysin O (ASO) and anti– Of the studies undertaken at the Elmwood Pediatric Group deoxyribonuclease B (anti–DNase B) titers were deter- in Rochester, NY, one comparative antibiotic trial provided the mined simultaneously on acute and on convalescent se- necessary design to assess same-serotype GABHS recurrences rum samples, collected at a mean of 19 days later (range, occurring shortly after documented GABHS tonsillopharyn- 9-29 days) for the initial and repeated episodes. Antibody gitis. This study prospectively compared the efficacy of cepha- titer assays were performed using previously described meth- lexin with penicillin treatment and was conducted between ods.15 A rise in either an ASO titer or an anti–DNase B titer June 1, 1981, and June 1, 1984.12 The protocol was approved of 0.2 log or greater was considered significant.16-18 Previ- by the local institutional review boards and informed consent ous studies showed that the peak of the antibody response wasobtained.Twohundredninety-fivepreviouslyhealthychil- to these streptococcal antigens occurs 2 to 4 weeks after dren aged 4 to 17 years were enrolled based on clinical symp- the acute pharyngitis and is followed by persistence of the toms of acute pharyngitis and a GABHS-positive throat cul- peak titer at the same level.19-21 Because an elevated anti- ture. Patients were excluded if they had 2 or more sore throats body level from serum obtained within this period could in the preceding 6 months, if they were treated with antibi- represent persistence of an elevated antibody from the pre- otics in the previous 2 weeks, or if they had a sibling concur- vious episode, titers obtained on serum samples during sub- rently enrolled in the study. The aspects of the original study sequent episodes of pharyngitis were considered signifi- design relevant to the purpose of this study included a record cantly increased if their value exceeded the peak titer of of all signs and symptoms on case report forms, serotyping the initial serum by 0.2 log or greater. of all available GABHS isolates, and confirmation of bona fide Drug compliance during the initial episode was con- initial and recurrent infection by analysis of acute and conva- firmed if a throat culture yielded no growth of GABHS dur- lescent serum samples for streptococcal antibodies. ing treatment. If adequate compliance was demonstrated and a 10-day antibiotic regimen was completed as deter- DATA COLLECTION mined by a dosing diary and return of empty antibiotic bottles, patients with a throat culture yielding GABHS dur- Patients were evaluated by their regular pediatrician at 4 to 6, ing a subsequent episode were evaluated for a bona fide 18 to 21, and 32 to 35 days following the start of treatment. GABHS recurrence using additional criteria. A bona fide Fever was defined by a temperature of 38°C rectally, 37.5°C recurrence included GABHS tonsillopharyngitis of the same orally, or 37°C axillary. Symptoms of sore throat, headache, serotype that occurred 20 days or longer following the on- chills,andstomachacheandsignsofpharyngealerythema,pha- set of the initial GABHS infection and was associated with ryngeal edema, pharyngeal exudate, scarlatina, and palatal pe- a 0.2-log or greater rise in either an ASO titer or an anti– techiae were recorded as present or absent. Cervical adenitis DNase B titer.20,22 Carriers were defined as patients with the and tonsillar size were recorded on a semiquantitative basis same serotype isolated during the initial visit and subse- usinga0to4+scale with 0 indicating absent; 1+, mild; 2+, mod- quent follow-up evaluation, but with less than a 0.2-log rise erate; 3+, severe; and 4+, extremely severe adenitis. Absent ton- in either an ASO titer or an anti–DNase B titer. Although sils, small, average, moderately enlarged, and severely enlarged antibiotics may suppress a rise in antibody titer,20 the 0.2- tonsillar size were assigned a score of 0, 1+, 2+, 3+, or 4+, re- log or greater rise in either an ASO titer or an anti–DNase spectively. For our analysis, tonsillar size was classified as pres- B titer was deemed a necessary criterion to distinguish same- ent if greater than 2+, and absent if 2+ or less. A throat culture serotype recurrences from carriers. Cases in which the iso- and blood sample for antibody determination were obtained late from the recurrent GABHS infection differed from the at each evaluation and sent to the laboratory of the late Hugh initial infection were considered new acquisitions. Since a Dillon, MD, in Birmingham, Ala, for analysis. Data on signs shift to a different serotype within a few weeks was highly and symptoms of GABHS were collected from multiple cen- unlikely to occur in carriers, serotype alone was believed ters on a standardized case report form. The dichotomous rat- to be sufficient to distinguish new acquisitions of GABHS ing scale we used to evaluate signs and symptoms reduced the from carriers. influence of subjective assessments by different observers. STATISTICAL ANALYSIS LABORATORY ANALYSIS The McNemar test was used for analysis of significant dif- All throat cultures obtained
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