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. Author manuscript; available in PMC: 2013 Jun 5.
Published in final edited form as: Arch Dermatol. 2011 Nov 21;148(3):326–332. doi: 10.1001/archdermatol.2011.355

Association of pharyngitis with oral antibiotic use for the treatment of acne: A cross sectional and prospective cohort study

David J Margolis 1,2, Matthew Fanelli 1, Eli Kupperman 1, Maryte Papadopoulos 1, Joshua P Metlay 1,3, Sharon Xiangwen Xie 1, Joseph DiRienzo 1,4, Paul H Edelstein 5
PMCID: PMC3673016  NIHMSID: NIHMS474637  PMID: 22105812

Abstract

Objective

To prospectively evaluate the association between antibiotics used to treat acne and pharyngitis

Design

Cross sectional and 9-month prospective cohort

Setting

Urban University setting.

Patients or other participants

University students

Intervention

Participants were asked to fill out a survey form, swabbed for culture, and had a visual examination for acne.

Main outcome measure

Report of pharyngitis

Results

Cross-sectional: 10 of the 15 students on oral antibiotics for acne reported an episode of pharyngitis in the previous 30 days, whereas 47 of the 130 students not receiving oral antibiotics, but who had acne, reported an episode of pharyngitis in the prior month. The unadjusted odds ratio associating current oral antibiotic use in acne patients to a self-reported episode of pharyngitis was 3.53 (95% CI = 1.14–10.95)

Cohort study: There were 358 female and 218 male participants. 36 (6.2%) subjects were on oral antibiotics for acne during the study and 96 (16.6%) received topical antibiotics for acne. Using mixed model logistic regression, the odds ratio was 4.34, (CI=1.51–12.47) associating oral antibiotic use with pharyngitis. Less than 1% of subjects were colonized by Group A Streptococcus, which was not associated with pharyngitis.

Conclusions

Our studies show that that the odds of reporting pharyngitis is more than 3 times baseline in patients on oral antibiotics for acne, versus those that are not on oral antibiotics. The true clinical importance of these findings needs to be evaluated further by prospective studies but this finding is not associate with Group A Streptococcus.

Introduction

Many inconsistent concerns have been voiced about the safety of long-term use of antibiotics(1–4). Because of the high prevalence of acne and the frequent use of antibiotics to control acne, individuals undergoing therapy to treat their acne are an ideal group in which to study the effects of long-term antibiotic use. Both topical and oral antibiotics are used in the treatment of these patients- the most commonly are clindamycin and erythromycin as topical therapies and the tetracyclines (tetracycline, doxycycline, and minocycline) are used as oral therapy(5,6).

Previous studies have shown an association between the use of oral antibiotics in those with acne and the development of pharyngitis(7–10). For example, a recent retrospective cohort study using a general medical database in the UK showed an association between pharyngitis and individuals using antibiotics for acne versus those not using antibiotics(8). The hazard ratio for this association was 2.15 (CI=2.05–2.23)(8). The reason for this increased risk was not apparent. One study showed that for patients on oral antibiotics for acne, there was a higher colonization rate of Group A Streptococcus (GAS) than those who were not on oral antibiotics, 33% vs. 10%, respectively(11). As such, it could be possible that oral antibiotics used to treat acne result in an increase in the colonization rates of GAS, with a resulting increase in the frequency of symptomatic infection. One hypothesis surmised that the increased colonization could be due to a decreased prevalence in organisms known to prevent the colonization of GAS, such as Streptococcus salivarius(12,13). It is important, however, to realize that most URTI’s are not of bacterial origin and are likely due to viral illnesses(14); specifically only about 10% of pharyngitis is due to bacterial infections and of those 90% are caused by GAS(14,15). It is, however, possible that bacterial colonization could facilitate infection by viral organisms. Unfortunately these previous studies were not prospective and longitudinal, so establishing a direct relationship between URTI and GAS in those using antibiotics for acne was not possible.

Based on our prior studies studies, using better designs, our goal was to more directly establish the relationships between antibiotic use, bacterial colonization patterns, and URTI among patients with acne. To that end, we first attempted to replicate the finding that individuals receiving antibiotics for acne are more likely to report pharyngitis in a cross-sectional study of a group of college students. We then conducted a prospective cohort study of college students in order to validate this observation. We further hypothesized that these changes might include increased colonization of the throat by GAS and decreased colonization with S. salivarius, a natural inhibitor of GAS growth. Specifically, we followed a cohort of students over a school-year and queried them about the development of pharyngitis; their use of antibiotics for acne, both oral and topical; examined them for the presence of acne; and obtained oral and pharyngeal cultures. These cultures were used to assess whether they were colonized with GAS or S. salivarius. S. salivarius was selected because it is an organism that is known to produce a substance that is toxic to GAS and is found in the same microflora. S. salivarius is also thought to be sensitive to the tetracycline antibiotics, while GAS is not. Our hypothesis was that prolonged use of oral antibiotics for acne is responsible for changes in the microbial flora of the throat leading to an increased risk of developing pharyngitis.

Methods

Population and Data Collection

Subjects were recruited throughout the campus of the University of Pennsylvania, an urban campus of about 10,000 students. All subjects were fulltime undergraduate or graduate students with access to student health services. The University population offers many advantages for this research because, by age, these individuals have a high prevalence of acne, they are frequently prescribed antibiotics for the treatment of their acne, they are generally otherwise healthy, and they are geographically concentrated near the study team. Subjects with and without acne were eligible for this study. A subject was defined to have acne based on one of three criteria: 1) if they were determined by a trained expert on the day of the visit to have acne; 2) if they were currently using oral or topical treatments specifically for acne; or 3) if they had evidence of acne elsewhere on the body (e.g., chest) besides the face. Because of the effect that isotretinoin has on acne and epidermal differentiation, subjects using isotretinoin for acne were excluded from the study.

Informed consent approved by the University of Pennsylvania Institutional Review Board was obtained from all students. In addition the study was approved by the Office of Student Life of the University of Pennsylvania. We conducted two studies: one was cross-sectional and one was a longitudinal cohort study. The cross-sectional study consisted of a single study visit in January and February of 2007. Evaluations for this study were similar to those described below for the first visit of the longitudinal study (albeit the survey information was briefer). For the longitudinal study, subjects were followed for up to three visits (the beginning of Fall semester, the end of Fall semester, and near the end of Spring semester) over a single school year in 2007/8. On each visit, the subject completed a self-administered survey, underwent a visual examination for acne using the Allen and Smith grading scale, had their throat swabbed to culture for GAS, and had a distal tongue swab to culture for S. salivarius. None of the subjects enrolled in the cross-sectional study were enrolled in the longitudinal study and none were enrolled our previous studies. The survey consisted of questions asking about their acne history, their treatments for acne, whether they were currently or had recently (within the last 60 days for the first survey and then since the last survey) used antibiotics, and if they had been recently evaluated for pharyngitis (i.e. Have you seen a healthcare provider because you were sick with a sore throat or have you been evaluated for a sore throat within the last 30 days?). At each visit, each subject had their throat (GAS) and distal tongue (S. salivarius) swabbed in duplicate for culture using Copan rayon swabs in Amies transport medium (Copan Diagnostics, Corona, Calif). The biologic material was placed in the eSwab transport solution and hand-delivered to the laboratory within 4 hours of collection. The swab in the transport system was then vortexed to produce a homogenous suspension. Selective and differential media were used to grow GAS and S. salivarius (SXT blood agar and Mitis-Salivarius agar with 1% tellurite media, respectively, (BD BBL, Franklin Lakes, NJ). Two culture plates for GAS were set up for each patient specimen, one from each of the two oropharyngeal swabs. The bacteria of interest were identified using conventional microbiologic criteria(16). S. salivarius was identified using an immunodiagnostic method(16,17). A pilot study showed that 98.6% of 223 S.salivarius isolates identified by conventional methods were correctly identified using a PCR method(17). Bacteriocin-like inhibiting substance (BLIS) production of all S. salivarius isolates was determined as described previously, using both direct and indirect assays, using three different GAS indicator strains(18–20). Antimicrobial susceptibility of a selected sampling of S. salivarius isolates was by disk diffusion testing, as previously described(21).

Exposure Definition

Exposure to an antibiotic was defined as a subject report of current oral or topical antibiotic use (e.g. tetracyclines, erythromycin, clindamycin) for acne treatment that had been ongoing for at least one month. For the longitudinal study, antibiotic exposure had to be documented on the survey prior to the report of pharyngitis. Other exposures were also evaluated, as listed below as confounding variables.

Outcome and Confounding Variables

As noted above, our outcome of interest initially was the subject’s report of pharyngitis. For the cross-sectional study, the subjects were asked if they currently had pharyngitis or had it within the past 30 days. For the longitudinal study, this definition was modified. First, since this was a prospective study, to count as an outcome for this study, the symptoms of pharyngitis must have occurred after the first survey (i.e., after enrollment) and in order to mimic a previous retrospective cohort study(8) and to provide for a more specific outcome, pharyngitis was considered to have occurred if the subject noted that they had pharyngitis and if they and their symptoms were evaluated by a healthcare provider. A priori confounding was evaluated with respect to age, gender, ethnicity, presence and severity of acne, topical antibiotic use for acne (when oral antibiotic use was the exposure of interest), tooth flossing habits, tooth brushing habits, face washing habits, number of cavities, presence of diabetes, reported alcohol use, and reported tobacco use.

Statistical Analyses

The initial analysis for every variable consisted of characterizing the distribution of that factor. Characterization depended on the data and consisted of estimating the means (and standard deviations) for each evaluation. Initial univariate assessments of association, when appropriate, were performed using 2 × 2 tables and the Mantel-Haenszel statistic. For variables with more than one category, R × C chi-squared statistics was performed.

For the cross sectional study, our primary question was to assess the effect of various risk factors, particularly the use of oral antibiotics for acne, on the development of pharyngitis. The selection of variables for the multivariable model was based on purposeful selection and that the confounder altered the effect estimate by more than 10%(22). To assess the magnitude of association of a given risk factor with the outcome of interest, single variable and multivariable logistic regression models were created. Both unadjusted and fully adjusted (from a multiple variable logistic model) prevalence odds ratios were reported with 95% confidence intervals.

For the longitudinal study, to account for repeated measures in our longitudinal design we used a mixed-effect logistic regression allowing the repeated measures from the study subjects to be expressed as random-effects(23). Both unadjusted (from a single variable logistic model) and fully adjusted (from a multiple variable logistic model) odds ratios were evaluated with 95% confidence intervals. The selection of variables for the multivariable model was based on purposeful selection (i.e., variables thought to be clinically important) and that the confounder altered the effect estimate by more than 10%(22). All statistical tests were two-sided. Values were considered to be significant if p<0.05. Statistical analyses were performed using Stata 11.0 (Stata Corporation, College Station, TX).

Results

For the cross sectional study

The average age was 21.0 years (standard deviation 2.13), with a range from 18 to 27 years of age. There were 205 male participants and 57 female participants who were sampled in the winter or early spring. 4 participants did not record their gender on the questionnaire. Out of 266 total participants, 15 (5.6%) reported that they were currently using oral antibiotics for acne treatment, and 251 (94.4%) were not. Based on our diagnostic criteria, 145 (53.5%) students were determined to have acne, while 121 (44.6%) were determined to not have acne. Of the 145 who had acne, 15 (10.3%) were receiving oral antibiotics and 130 (89.7%) were not (Table 1). 10 of the 15 students on oral antibiotics for acne self-reported an episode of pharyngitis in the previous 30 days (66.7%), whereas 47 of the 130 students not receiving oral antibiotics, but who had acne, self-reported an episode of pharyngitis in the prior month (36.2%). Of the students without acne (n=121), none reported current use of oral antibiotics and 35 (28.9%) reported a recent episode of pharyngitis. Combining all students not receiving oral antibiotics (n=251), 82 (32.7%) reported an episode of pharyngitis in the prior 30 days.

Table 1.

Cross-sectional study: Basic demographic and exposure information for all participants, those with acne and those without.

All participants (n=266) Those with acne (n=145) Those without acne (n=121)
Oral antibiotics 15(5.6%) 15(10.3%) 0(0%)
Topical antibiotics 41 (15.4%) 41 (28.3%) 0(0%)
Oral and/or topical 49 (18.4%) 49 (33.8%) 0 (0%)
Male 205 (77.1%) 112 (78.9%) 93 (76.9%)
Mean age 21.0 (SD 2.13) 20.5(SD 1.96) 21.7(SD2.15)
Smoker (any daily cigarette use) 67 (25.2%) 45 (31.0%) 22 (18.2%)
Report of pharyngitis 92(34.0%) 61 (35.3%) 31 (31.6%)
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Several variables were evaluated for their potential to be associated with pharyngitis (Table 1). Of note, 3 out of 145 (2.1%) students with acne were found to be colonized with GAS. 3 out of 266 (1.1%) total students were colonized with GAS. Out of the three, none were on oral antibiotics. This did not allow for a prevalence odds ratio to be calculated relating oral antibiotic use and colonization of GAS, since there were no patients with GAS colonization who were on oral antibiotics.

The initial, unadjusted odds ratio associating current oral antibiotic use in acne patients to a self-reported episode of pharyngitis was 3.53 (95% CI = 1.14–10.95) and the adjusted odds ratio was 4.93 (95% CI = 1.41–17.23) (Table 2).

Table 2.

Cross-sectional study: Prevalence odds ratios for developing pharyngitis with respect to several exposure variables with 95% confidence intervals presented unadjusted and adjusted (age, gender, ethnicity).

Unadjusted prevalence odds ratio Adjusted prevalence odds ratio
Those with acne All patients Those with acne All patients
Oral antibiotics 3.53 (1.14,10.9)* 4.12(1.36,12.4)# 4.93(1.41,17.2)# 6.52(1.88,22.6)#
Topical antibiotics 0.74(0.35,1.56) 1.00(0.48,1.97) 0.44(0.17,1.27) 0.78(0.34,1.80)
Oral and/or topical 1.01(0.55,2.22) 1.39(0.74,2.62) 0.45(0.15,1.38) 0.75(0.30,1.85)
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*

p<0.05,

#

p<0.01

For the longitudinal study

The median age in our study population was 21 (mean: 21.7, SD: 3.0), with a range of 16 to 38. There were 358 female and 218 male participants. No subjects who had enrolled in the cross-sectional study enrolled in the longitudinal study. 579 subjects participated in the first survey, 359 (62.0%) participated in the second survey, and 312 (53.9%) took part in the third survey. 285 (49.2%) of the subjects participated in all three surveys periods and 193 (33.3%) only participated in the first visit. Basic demographic variables and important covariates are listed in Table 3 for the first survey period. Out of the 579 total subjects, 358 (61.8%) were determined to have acne at some point during the study. 36 (6.2%) subjects were on oral antibiotics for acne during the study and 96 (16.6%) received topical antibiotics for acne. At the time of the first survey, 148 individuals (25.5%) noted a history of pharyngitis in the previous 30 days. During the follow-up period, 210 (36.3%) noted a history of pharyngitis and 43 (7.4%) noted a history of pharyngitis associated with a healthcare provider visit (table 3). Only eight (0.6%) throat cultures were positive for GAS (6 unique subjects) and only three of those had a moderate or heavy concentration of the bacteria. S. salivarius was cultured from 1,211 out of 1,228 (98.6%) tongue swabs and 96.1% had moderate or heavy growth. 48.1% of isolates produced BLIS. Antibiotic sensitivity was analyzed in a convenience sample of 222 S. salivarius isolates. 63% of these isolates were resistant to erythromycin, clindamycin or tetracycline, and 24% of the isolates were resistant to all three drugs; 58%, 31%, and 32% were resistant to erythromycin, clindamycin or tetracycline, respectively. The ability for S. salivarius to produce BLIS did not prevent the new onset of pharyngitis with an odds ratio of 1.07 (0.58, 2.00).

Table 3.

Longitudinal cohort study: Basic demographic and exposure information for all participants, those with acne and those without acne.

All participants (n=579) Those with acne (n=306) Those without acne (n=273)
Oral antibiotics 21 (3.6%) 21(6.9%) 0(0)
Topical antibiotics 74 (12.8%) 74 (24.2%) 0 (0)
Oral and/or topical 86 (14.8%) 86(28.1%) 0(0)
Male 218 (37.8%) 111 (36.4%) 107(39.5%)
White 371(66.1) 191 (64.1%) 180(68.4%)
Mean age 21.6(SD3.2) 21.5 (SD 2.9) 21.8 (SD 3.6)
Smoker (any daily cigarette use) 107(18.6%) 55 (18.0%) 52 (19.2%)
Brush teeth at least twice daily 538 (93.7) 258 (84.9%) 230 (85.2%)
Floss teeth daily 439 (75.8%) 80 (26.1%) 60 (22.0%)
Any cavities 524(90.5%) 279 (91.2%) 245 (89.7%)
Wash face daily 138 (23.8%) 59(21.6%) 79(25.8%)
Drink alcohol at least weekly 257(44.5%) 132 (43.3%) 125(46.0%)
History of diabetes 2(0.4%) 1(0.3%) 1 (0.4%)
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We found that the use of oral antibiotics for the treatment of acne was strongly associated with a healthcare evaluation for pharyngitis in that 11.3% of those on oral antibiotic treatment reported pharyngitis but it was only reported by 3.3% of subjects who were not on oral antibiotics. Using mixed model logistic regression, the odds ratio was 4.34, (CI=1.51–12.47) associating oral antibiotic use with pharyngitis (Table 4). This is an estimated relative risk of 3.91(24). In order to provide for a comparison with the cross-sectional study, using any report of pharyngitis as the outcome, an OR of 2.68 (0.98, 6.16) was calculated. No association with pharyngitis was noted for those that used a topical antibiotic for acne (0.63; 0.22, 1.81). We evaluated and selected a priori several variables that might be associated with the onset of pharyngitis and these included: age, gender, ethnicity, presence and severity of acne, tooth flossing habits, tooth brushing habits, face washing habits, number of cavities, presence of diabetes, alcohol use, and tobacco use (Tables 3 and 4). These covariates did not confound our results and as a result only the unadjusted analyses are reported (Table 4).

Table 4.

Longitudinal cohort study: Adjusted (age, gender, ethnicity) odds ratios for developing pharyngitis with respect to several exposure variables with 95% confidence intervals

Variable Odds Ratio (95% Confidence Interval)
Oral antibiotics 4.34 (1.51,12.47)
Topical antibiotics 0.62 (0.22,1.81)
Acne severe 1.62 (1.10,2.40 )
Age 0.99 (0.90,1.08)
White 2.06 (0.85,5.03)
Female 0.60 (0.30,1.21)
Wash face regularly 1.02 (0.50,2.10)
Chews tobacco 2.23 (0.25,19.65)
Flosses regularly 0.70 (0.33,1.51)
More than 5 cavities 0.64 (0.33,1.51)
Smoker (any daily cigarette use) 1.21 (0.98,1.49)
Alcohol use daily 1.17 (0.91,1.50)
Has acne on chest 1.05 (0.47,2.35)
Has body piercings 3.61 (0.72,17.95)
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Comment

Acne is a very common disease. In our cross-sectional and longitudinal studies of college students, respectively, 54.5% and 52.8% of our participants had acne and 33.8% and 28.1% of those with acne were using some type of antibiotic for treatment. An oral antibiotic was being used by 10.6% and 6.2%, respectively. As a treatment for acne, antibiotics have been considered extremely safe and effective(6,25,26). We have previously shown, in retrospective cohort and cross-sectional studies, an association between pharyngitis and the long-term use of antibiotics for acne(8,9,11,27,28). Our present studies confirm our original hypothesis that antibiotic use in acne patients is associated with an increase in the risk of self-reported pharyngitis. In our cross-sectional study, a student on oral antibiotics had an almost three and a half fold (3.53 (1.14–10.95)) increase in odds of reporting an episode of pharyngitis compared to students not on antibiotics at the time of the survey. Students on topical antibiotics showed no such association. In our longitudinal study, we now prospectively demonstrated that there is an association between antibiotic use for acne and, the more conservative outcome definition, having an episode of pharyngitis requiring a healthcare provider visit (4.34; 1.51,12.47). An additional feature of the current study was the assessment for GAS and S. salivarius colonization. However, contrary to our initial hypothesis and a preliminary report, our results did not demonstrate any association between colonization with either of these organisms and the risk of self-reported episodes of pharyngitis(11).

In our study, pharyngeal colonization with GAS was uncommon. In the cross-sectional study, 3 out of 266 (1.1%) participants were colonized by GAS. In the longitudinal study, in total, we noted only eight cultures out of more than 1,200 (0.6%) that revealed GAS from six separate subjects. Over 98% of cultures revealed S. salivarius, an organism that can potentially prevent the growth and colonization of GAS. Recovery of this organism was often heavy. The rates of colonization by these two organisms did not appear to be associated with antibiotic use.

The association between antibiotic use to treat acne and pharyngitis has been previously reported(8–11,28). Margolis et al. showed by a retrospective cohort study using an electronic health record, that a person on antibiotics for acne had more than 2 times increased likelihood of developing an upper respiratory tract infection compared to a person with acne not on an oral antibiotic(8). Our current study showed an even higher strength of association, albeit our rate was within the previously reported confidence interval. The study of Levy et al. also showed an increased colonization of GAS in antibiotic users versus non users (33% to 10%)(10). Our current study did not support this result. Our reported rates of GAS pharyngeal colonization is similar to historic reports in asymptomatic people aged 15 to 45 years, ranging from 0.8% to 3.2%, while the Levy et al was more of an outlier(29–31).

A possible mechanism for this effect of antibiotic use could be based on a decrease in normal resident flora in the oropharynx due to antibiotic exposure; thus causing the overgrowth of more virulent organisms. As an example, S. salivarius is part of the in resident flora of the mouth and throat, it can be sensitive to tetracyclines, and it has been shown to inhibit the overgrowth of GAS via an antibiotic-like substance called Bacteriocin-like Inhibitory Substance (BLIS) (32). This mechanism may still be correct but in our study we did not find alterations in colonization of S. salivarius or GAS diminution. However, the timing of our swabbing with respect to the onset of pharyngitis may not have been sufficient to reflect colonization status present during the period of pharyngitis.

Like all cohort studies there are several limitations to this study. We were only able to evaluate our study subjects at pre-determined time points during their school year. Furthermore, the study team was not permitted to treat the students and, due to privacy concerns, student health would not confirm the subject’s medical history. We therefore solely relied on the students’ reports. We do not know for sure if they had pharyngitis, but it is a self-limited condition that usually does not require medical intervention. Finally, unmeasured or not full measured risk factors could be associated with pharyngitis and antibiotic use for acne (i.e., measure or unmeasured confounders). One example could be cigarette use, which we did measure but may not have measured well. Our measurement was based on a survey question querying use based on no use, use up to one pack per day, and use over one pack per day. There was a disparity in use in our cross-sectional study between those who had acne and those who did not. This disparity was not noted in our cohort study. While cigarette smoking was associated with pharyngitis in our cross-sectional study (data not shown) it was not in our longitudinal study and based on our modeling criteria was not part of either final adjusted model. Better measurement might have yielded more consistent results.

We did use two different diagnostic algorithms for pharyngitis and we obtained similar results from similar populations using two different study designs. It is also possible, though unlikely that patients were mistaking pharyngitis for the more severe esophagitis as tetracyclines have been associated with pill-induced esophagitis. It is important to acknowledge, however, that if this was true and pharyngitis is being mistaken for esophagitis, our study would be reporting a serious disease at an unusually high frequency. One other possible shortcoming of this study is due to the nature of it being a prevalence study. This type of study, which is based on an assessment at a single point in time, can not be used to assess causation because the timing of the exposure (e.g. oral antibiotics) with respect to the outcome (e.g., pharyngitis) is not known.

Finally, with respect to our longitudinal study we did not have 100% follow up. It is possible that the loss of these subjects influenced our results. It is, however, likely that these individuals were missing at random. The study subjects did not know the hypotheses that we were testing. There were no statistical differences between those who only participated in the first survey and those who participated in more than one survey with respect to age, gender, presence of acne, the use of antibiotics to treat acne, a past history of pharyngitis, etc.

With respect to our microbial analysis, our goal was to evaluate oropharyngeal colonization. Based on our hypothesis we only cultured subjects for GAS and S. salivarius. Recently, we published a study evaluating the carriage rate of Staphylococcus aureus, which conversely appears to be decrease in those using oral antibiotics to treat their acne(7). Several studies have now shown that there are hundreds of species of bacteria that are part of our normal flora of our skin as well as our oropharynx that are not routinely cultured, and any one of these bacteria could be sensitive to the antibiotics used to treat acne and could have caused the self-reported pharyngitis, not just GAS, which we evaluated(33). It is also possible that the pharyngitis was caused by viruses. In any event, without further studies, it is impossible to ascertain any relationship between alteration in pharyngeal colonization and pharyngitis.

Conclusion

In conclusion, acne is a very prevalent condition that affects young adults and adolescents. About 2 million US individuals require treatment for acne every year, and 5 to 6 million doctor visits occur every year for acne(5,25,26). Upper respiratory tract infections are also very common, and are a major cause of decreased productivity in the United States(14,15). Pharyngitis is thought to cause over 200 million health care episodes every year, which causes our economy a loss of more than 25 billion dollars in economic revenue per year(34,35). Our studies show that that the odds of developing self-reported pharyngitis is more than 3 times baseline in patients on oral antibiotics for acne, versus those that are not on oral antibiotics. The true clinical importance of these findings needs to be evaluated further by prospective studies. However, this observation has now been noted in three cross-sectional studies, two retrospective cohort studies, and now a prospective longitudinal cohort study(7–10). While the cause of this phenomenon is not known and it should be considered with respect to the risks versus the benefits of using long-term oral antibiotics in acne patients, it is not due to group A Streptococcus.

Acknowledgments

Funding/Support: This study was supported by NIH, grant R01AR051185.

Role of sponsors: The sponsors had not role in the design and conduct of the study, in the collection, analysis and interpretation of data, or in the preparation, review, or approval of the manuscript.

We are indebted to Martha A.C. Edelstein and Andrew Baltus for their excellent technical assistance

Footnotes

Financial Disclosure of Authors: None reported

Author Contributions All authors had full access to all of the data from the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: DJM, MP, JPM, SXX, JD, PHE were involved in the study design and concept. Acquisition of data: DJM, MP, JPM, SXX, JD, and PHE. Analysis and interpretation: All authors. Drafting of manuscript: DJM, MF, EK, and MP. Critical revision of manuscript for important intellectual content: All authors. Statistical analysis: DJM, MF, EK, and JXX. Obtained funding: DJM. Administrative, technical or material support: DJM, MF, EK, MP, PHE. Study supervision: DJM, JPM, JD, PHE.

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