Abstract
Background:
Concerns remain regarding whether oral antibiotic or isotretinoin use for acne are associated with increased risk of inflammatory bowel disease (IBD); little is known about whether acne itself is associated with IBD.
Objective:
To determine whether isotretinoin exposure, oral tetracycline-class antibiotic exposure, and/or acne itself are associated with IBD.
Methods:
A propensity score matched cohort study was performed using TriNetX between 2001 and 2022 to compare the 1-year incidence of IBD between those without acne compared to those with acne managed without systemic medications, acne managed with oral tetracycline-class antibiotics, and acne managed with isotretinoin.
Results:
There was a statistically significant association between acne and risk of incident IBD (Odds ratio 1.42; 95% CI 1.23–1.65). There was no statistically significant association between oral tetracycline-class antibiotic or isotretinoin exposure and IBD.
Limitations:
Use of electronic health data; potential for misclassification bias.
Conclusion:
This matched cohort study identifies an association between acne and IBD. These data provide further reassurance regarding the use of isotretinoin in the treatment of acne.
Keywords: acne, isotretinoin, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, tetracyclines, doxycycline, minocycline
Introduction
For patients with moderate-to-severe acne, oral antibiotics and isotretinoin are mainstays of treatment.1–3 However, there have been concerns about whether these treatments may be associated with increased risk of inflammatory bowel disease. These concerns have resulted in substantial litigation, including thousands of lawsuits filed against isotretinoin manufacturers.4
Although early case reports suggested a potential association between isotretinoin and inflammatory bowel disease, well-designed cohort studies and meta-analyses have not supported such an association.5 Notably, many studies that have identified a potential association between isotretinoin and inflammatory bowel disease have not adequately controlled for prior oral antibiotic exposure.6,7
While several meta-analyses have suggested an association between oral antibiotic exposure and inflammatory bowel disease (IBD),8,9 few have specifically explored this association in the setting of acne, where oral tetracycline-class antibiotics are the most commonly prescribed systemic treatment.2,10 In addition, although there is overlap in inflammatory pathways that are activated in acne and inflammatory bowel disease, there is a lack of research exploring whether acne itself may be associated with IBD.11–14
The purpose of this study was to examine whether isotretinoin exposure, oral tetracycline-class antibiotic exposure, and/or acne itself are independent risk factors for the subsequent development of inflammatory bowel disease using a new user, active comparator, propensity score matched design to minimize risk of unmeasured confounding that has limited prior studies.
Methods
Dataset
This study was conducted using the TriNetX (TriNetX LLC, Cambridge, MA 02140, USA) proprietary patient repository and analytic platform. The TriNetX Analytics Research Network includes over 106 million patients. The TriNetX Analytics Network provides access to pseudonymized deidentified patient-level data presented in aggregate format (i.e. dataset contains individual patient level data; analyses and results are presented at the group level when using the TriNetX query builder interface) from electronic healthcare records (EHRs, including diagnoses and dispensed prescription medicines) from 69 healthcare organizations mainly in the United States (~90%), with additional health systems in Europe, Latin America, and Asia-Pacific.
Data from the years 2001 to 2022 were accessed via the TriNetX platform and analyzed in October 2022 using the built-in TriNetX query builder, which use TriNetX’s built-in proprietary algorithms.
Design
Patients were eligible if they were age 9–49 years old. Patients with acne were identified using ICD10-CM codes (L70.0; L70.8; L70.9).15 To evaluate for potential associations between acne, oral tetracycline-class antibiotic use, and isotretinoin use with inflammatory bowel disease, we created four cohorts: 1) no acne: patients with no encounters for acne, no prior oral tetracycline-class antibiotic, spironolactone, or isotretinoin exposure as well as a primary care visit (ICD-10-CM code Z00.00: Encounter for general adult medical examination without abnormal findings or Z00.129: Encounter for routine child health examination without abnormal findings; this last criteria of a primary care visit was included to reduce potential for bias due to frequency of interaction with the healthcare system); 2) acne managed without systemic medications: patients with an encounter for acne, but no prior oral tetracycline-class antibiotic, spironolactone, or isotretinoin exposure; 3) acne managed with oral tetracycline-class antibiotic: patients with an encounter for acne and oral tetracycline-class antibiotic exposure, but no prior isotretinoin or spironolactone exposure; 4) acne managed with isotretinoin: patients with an encounter for acne and isotretinoin exposure, but no prior oral tetracycline-class antibiotic or spironolactone exposure. We focused on oral tetracycline-class antibiotics as these represent the vast majority of antibiotic prescriptions for acne.2 We also attempted to create a comparator cohort of those treated with spironolactone to reflect more moderate-to-severe acne, as there are no reports linking spironolactone to risk of inflammatory bowel disease, but this analysis was limited by insufficient sample size for accurate outcome estimation (fewer than 10 events per group).
New onset inflammatory bowel disease was identified using ICD10-CM codes and separated into Crohn’s disease (K50x) and ulcerative colitis (K51x). Patients with a prior diagnosis of inflammatory bowel disease (K50x, K51x) were excluded.
Statistical Analysis
Propensity score matching was used to improve comparability between groups. To minimize the potential risk of unmeasured confounding, cohorts were balanced at baseline for age, sex, race, ethnicity, and combined oral contraceptive use.16 This was done using the TriNetX built-in algorithm, which was based on 1:1 nearest neighbor matching with a caliper of 0.1 SDs.
The primary outcome was the incidence of inflammatory bowel disease within 1-year following the index date (defined as the first encounter with a diagnosis of acne for the acne cohort and the first prescription of interest for the oral tetracycline-class antibiotic and isotretinoin cohorts). Logistic regression was used to assess the odds for the outcome of interest between the cohorts. A follow-up period of 1-year was chosen to minimize the risk of surveillance bias, as patients getting monthly visits for isotretinoin may be more likely to be diagnosed with inflammatory bowel disease earlier than those being seen less frequently for other acne treatments.6
The primary comparisons are as follows: 1) Association between acne and risk of inflammatory bowel disease – comparison between those without acne and those with acne managed without systemic medications (to avoid potential confounding due to use of systemic medications for acne that may be independently associated with IBD); 2) Association between oral tetracycline-class antibiotic exposure and risk of inflammatory bowel disease – comparison between those with acne managed with of oral tetracycline-class antibiotics versus those with acne managed without systemic medications; 3) Association between isotretinoin exposure and risk of inflammatory bowel disease – comparison between those with acne managed with isotretinoin versus those with acne managed without systemic medications. Since acne itself may be associated with inflammatory bowel disease, we also compared patients managed with isotretinoin to those managed with of oral tetracycline-class antibiotics to adjust for the potential impact of acne severity on the risk of developing inflammatory bowel disease. This study was exempt for institutional board review as it only used de-identified data. This study was reported in accordance with the STROBE and RECORD-PE guidelines.
Results
Potential association between acne and inflammatory bowel disease
We identified 351,670 patients with acne managed without systemic medications who were matched with 353,381 controls without acne. After matching, the mean age was 22.0 (SD 10.2), 32.1% were male, 59.6% were White. The groups were all well matched on age, sex, race, ethnicity, and combined oral contraception exposure (Table 1).
Table 1 –
Patient Characteristics
| Acne cohort | Antibiotic cohort | Isotretinoin cohorts | ||||||
|---|---|---|---|---|---|---|---|---|
| Characteristic | No Acne (N = 354,954) | Acne (N = 354,954) | Acne (N = 146,438) | Oral Antibiotics (N = 146,438) | Acne (N = 11,316) | Isotretinoin† (N = 11,316) | Oral Antibiotics (N = 11,316) | Isotretinoin‡ (N = 11,316) |
| Age, y, mean (SD) | 22.0 (10.2) | 22.0 (10.2) | 24.1 (9.9) | 24.1 (9.9) | 21.1 (7.6) | 21.1 (7.6) | 21.1 (7.6) | 21.1 (7.6) |
| Female, % | 67.9 | 67.9 | 65.3 | 65.3 | 50.5 | 50.5 | 50.5 | 50.5 |
| Race | ||||||||
| White, % | 59.6 | 59.6 | 68.2 | 68.2 | 75.4 | 75.3 | 75.4 | 75.3 |
| Black, % | 19.8 | 19.8 | 15.0 | 15.1 | 5.7 | 5.7 | 5.7 | 5.7 |
| Asian, % | 3.6 | 3.6 | 3.1 | 3.1 | 4.0 | 4.1 | 4.1 | 4.1 |
| American Indian or Alaska Native, % | 0.4 | 0.4 | 0.4 | 0.4 | 0.5 | 0.5 | 0.4 | 0.5 |
| Native Hawaiian or Pacific Islander, % | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 |
| Unknown, % | 16.5 | 16.5 | 13.2 | 13.1 | 14.3 | 14.3 | 14.3 | 14.3 |
| Ethnicity | ||||||||
| Hispanic, % | 10.9 | 10.9 | 8.2 | 8.3 | 8.1 | 8.1 | 8.2 | 8.1 |
| Non-Hispanic, % | 63.6 | 63.6 | 71.6 | 71.5 | 71.9 | 71.9 | 71.8 | 71.9 |
| Unknown, % | 25.5 | 25.5 | 20.2 | 20.2 | 20.0 | 20.0 | 20.0 | 20.0 |
| Combined Oral Contraceptives, % | 15.0 | 15.0 | 26.5 | 26.8 | 30.3 | 30.5 | 30.5 | 30.5 |
comparison for isotretinoin versus those with acne managed without systemic medications.
comparison for isotretinoin versus oral tetracycline-class antibiotics
There was a statistically significant association between acne and risk of incident IBD (Odds ratio [OR] 1.42; 95% CI 1.23–1.65) with an absolute risk difference of 0.04% (95% CI 0.02%−0.05%). The OR was 1.56 (95% CI 1.30–1.87) for incident Crohn’s disease and 1.62 (95% CI 1.33–1.97) for ulcerative colitis (Table 2).
Table 2 –
One-year incidence of inflammatory bowel among patients with acne compared to patients without acne
| No Acne | Acne | Odds Ratio | 95% CI | |||||
|---|---|---|---|---|---|---|---|---|
| Patients, total, n | Patients with incident outcome, n | IR/1000 | Patients, total, n | Patients with incident outcome, n | IR/1000 | |||
| Outcomes | ||||||||
| Any inflammatory bowel disease | 353,381 | 293 | 0.83 | 351,670 | 415 | 1.18 | 1.42 | 1.23–1.65 |
| Crohn’s disease | 353,942 | 191 | 0.54 | 352,723 | 297 | 0.84 | 1.56 | 1.30–1.87 |
| Ulcerative colitis | 354,226 | 158 | 0.45 | 353,363 | 255 | 0.72 | 1.62 | 1.33–1.97 |
Potential association between oral tetracycline-class antibiotics and inflammatory bowel disease
We identified 144,986 patients with acne managed with oral tetracycline-class antibiotics who were matched with 144,711 patients with acne managed without systemic medications. The groups were well matched, with a mean age of 24.4 (SD 9.9), 34.7% were male, 68.2% were White (Table 1).
Compared to those with acne managed without systemic medications, there was not a statistically significant association between oral tetracycline-class antibiotic use for acne and risk of incident IBD (Odds ratio [OR] 1.00; 95% CI 0.82–1.22) with an absolute risk difference of 0.0% (95% CI −0.027%−0.026%). The OR was 1.09 (95% CI 0.86–1.38) for incident Crohn’s disease and 0.78 (95% CI 0.61–1.00) for ulcerative colitis (Table 3).
Table 3 –
One-year incidence of inflammatory bowel among patients with acne treated with oral tetracycline-class antibiotics
| Acne | Oral tetracycline-class antibiotic | Odds Ratio | 95% CI | |||||
|---|---|---|---|---|---|---|---|---|
| Patients, total, n | Patients with incident outcome, n | IR/1000 | Patients, total, n | Patients with incident outcome, n | IR/1000 | |||
| Outcomes | ||||||||
| Any inflammatory bowel disease | 144,711 | 191 | 1.32 | 144,986 | 191 | 1.32 | 1.00 | 0.82–1.22 |
| Crohn’s disease | 145,264 | 130 | 0.89 | 145,436 | 142 | 0.98 | 1.09 | 0.86–1.38 |
| Ulcerative colitis | 145,602 | 142 | 0.98 | 145,723 | 111 | 0.76 | 0.78 | 0.61–1.00 |
Potential association between isotretinoin and inflammatory bowel disease
We identified 11,199 patients with acne managed with isotretinoin who were matched with 11,199 patients with acne treated without systemic medications as well as 11,199 patients managed with isotretinoin who were matched with 11,210 patients with acne managed with oral tetracycline-class antibiotics. The groups were well matched, with a mean age of 21.1 (SD 7.6), 49.5% were male, 75.3% were White (Table 1).
Compared to those with acne treated without systemic medications, there was not a statistically significant association between isotretinoin use for acne and risk of incident IBD (OR 1.29; 95% CI 0.64–2.59) with an absolute risk difference of 0.036% (95% CI −0.063%−0.135%) (Table 4).
Table 4 –
One-year incidence of inflammatory bowel among patients with acne treated with isotretinoin in comparison to patients with acne treated without oral tetracycline class antibiotics, spironolactone, or isotretinoin
| Acne | Isotretinoin | Odds Ratio | 95% CI | |||||
|---|---|---|---|---|---|---|---|---|
| Patients, total, n | Patients with incident outcome, n | IR/1000 | Patients, total, n | Patients with incident outcome, n | IR/1000 | |||
| Outcomes | ||||||||
| Any inflammatory bowel disease | 11,194 | 14 | 1.25 | 11,199 | 18 | 1.61 | 1.29 | 0.64–2.59 |
| Crohn’s disease | 11,241 | 12 | 1.07 | 11,231 | 12 | 1.07 | 1.00 | 0.45–2.23 |
| Ulcerative colitis | 11,247 | 11 | 0.98 | 11,255 | 14 | 1.24 | 1.27 | 0.58–2.80 |
Compared to those with acne treated with oral tetracycline-class antibiotics, there was not a statistically significant association between isotretinoin use for acne and risk of incident IBD (OR 1.13; 95% CI 0.57–2.21) with an absolute risk difference of 0.018% (95% CI −0.084%−0.12%). The OR for incident Crohn’s disease was 1.00 (95% CI 0.45–2.23). Due to insufficient sample size for accurate outcome estimation (fewer than 10 events for the tetracycline group), it was not possible to conduct a subgroup analysis examining differences in ulcerative colitis (Table 5).
Table 5 –
One-year incidence of inflammatory bowel among patients with acne treated with isotretinoin in comparison to patients with acne treated with oral tetracycline-class antibiotics
| Oral tetracycline-class antibiotics | Isotretinoin | Odds Ratio | 95% CI | |||||
|---|---|---|---|---|---|---|---|---|
| Patients, total, n | Patients with incident outcome, n | IR/1000 | Patients, total, n | Patients with incident outcome, n | IR/1000 | |||
| Outcomes | ||||||||
| Any inflammatory bowel disease | 11,210 | 16 | 1.43 | 11,199 | 18 | 1.61 | 1.13 | 0.57–2.21 |
| Crohn’s disease | 11,231 | 12 | 1.07 | 11,231 | 12 | 1.07 | 1.00 | 0.45–2.23 |
| Ulcerative colitis 1 | - | - | - | - | - | - | - | - |
Could not accurately estimate since the number of outcomes in the tetracycline group was ≤ 10
Discussion
In this cohort study using the TriNetX dataset, we identify a statistically significant association between acne and incident inflammatory bowel disease. Our findings are aligned with prior work suggesting a potential association between acne and inflammatory bowel disease.14,17 This association may reflect shared pathogenic pathways involved in both acne and IBD. Aberrant Th17 immunity is thought to be involved in the pathogenesis of IBD.12 Similarly, Cutibacterium acnes has been shown to promote Th17 responses in acne patients.11,18 This mechanism is further supported by associations between other chronic inflammatory skin diseases that involve Th17 and TNF activation such as rosacea, psoriasis, and hidradenitis suppurativa with IBD.19,20 However, it is important to consider that the absolute risk difference for this association between acne and IBD is small. Therefore, it is unlikely that population level screening is warranted among patients with acne.
Similar to prior meta-analyses, we do not identify an increased risk of IBD among those with acne treated with isotretinoin.5 Although there is some imprecision to our estimate, even at the limits of our 95% confidence interval, the potential absolute risk of IBD remains small. As a result, these data should provide more reassurance to patients and prescribers that isotretinoin does not appear to result in a meaningfully increased risk of inflammatory bowel disease. In addition, a recent case series has suggested that isotretinoin can be safely used in patients with stable IBD.21 These are important findings as isotretinoin is a valuable treatment for acne that can result in a durable remission of disease activity, prevent acne scarring, and reduce our overreliance on oral antibiotics for acne.2,3,22,23
In contrast to what has been observed in other settings,8,9 we did not identify an association between oral tetracycline-class antibiotic use for acne and IBD. A prior study using The Health Improvement Network found an association between tetracycline-class antibiotic use for acne and Crohn’s disease.10 In addition, cohort studies in other settings and multiple meta-analyses have found an association between lifetime oral antibiotic exposure and IBD.8,9 As a result, while the results of this study are reassuring that oral tetracycline-class exposure for acne may not be associated with a significant absolute risk of inflammatory bowel disease, given the potential for antibiotic resistance and other antibiotic associated complications, it remains important to be judicious in our use to oral antibiotics in the management of acne.22,24,25 Further study is needed given these conflicting findings.
Limitations
This study should be interpreted in the context of its design using retrospective electronic health record data available in TriNetX. Given concerns about potential associations between isotretinoin and IBD as well as the frequent visits required for isotretinoin due to iPLEDGE requirements,26 there is the potential for surveillance bias which could bias the study toward identifying an association between isotretinoin exposure and IBD. As a result, a 1-year follow-up period was chosen to mitigate this risk.6 Use of validated approaches to identify patients with acne reduces the risk of selection bias.15 In addition, propensity score matching was employed to improve comparability of the cohorts. We also explored comparator groups such as oral tetracycline-class use for acne to address the potential for confounding by acne severity. However, as isotretinoin users may have more severe acne than oral tetracycline-class antibiotic users, there is still the potential for residual confounding due to acne severity and these results should be interpreted cautiously. While efforts were made to address potential confounders such as combined oral contraceptive use and oral antibiotic use, it is not possible to assess smoking use and other potential environmental confounders using the TriNetX dataset. Although the TriNetX dataset includes patients from a diverse set of healthcare organizations, these organizations may not generalize to other populations. In addition, if patients received treatment for IBD from a healthcare organization not participating in the TriNetX network, this would not be captured and could introduce misclassification bias, though this may not be common if patients tend to prefer to stay within the same health system.
Conclusion
In this cohort study of patients in the TriNetX dataset, acne appears to be associated with a small, but statistically significant risk of IBD. There is no evidence to support a meaningful association between isotretinoin use for acne and IBD. Although there is also no evidence to support an association between oral tetracycline-class use for acne and IBD, antibiotics should continue to be prescribed thoughtfully given other risks of antibiotic use and prior literature suggesting antibiotic use may be associated with IBD.
Capsule Summary.
There is uncertainty regarding whether oral tetracycline-class antibiotics, isotretinoin, or acne are associated with inflammatory bowel disease.
In this matched cohort study, acne was associated with an increased risk of incident inflammatory bowel disease. There was no statistically significant increased risk of inflammatory bowel disease with oral tetracycline-class antibiotic or isotretinoin exposure.
Funding sources:
Dr. Barbieri is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number K23AR078930-01A1. Dr. Kwatra is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number K23AR077073-01A1.
Footnotes
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Conflicts of Interest: Dr. Kwatra is an advisory board member/consultant for Abbvie, Aslan Pharmaceuticals, Arcutis Biotherapeutics, Castle Biosciences, Celldex Therapeutics, Galderma, Genzada Pharmaceuticals, Incyte Corporation, Johnson & Johnson, Leo Pharma, Novartis Pharmaceuticals Corporation, Pfizer, Regeneron Pharmaceuticals, and Sanofi and has served as an investigator for Galderma, Incyte, Pfizer, and Sanofi.
References
- 1.Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945–973.e33. [DOI] [PubMed] [Google Scholar]
- 2.Barbieri JS, James WD, Margolis DJ. Trends in prescribing behavior of systemic agents used in the treatment of acne among dermatologists and nondermatologists: A retrospective analysis, 2004–2013. J Am Acad Dermatol. 2017;77(3):456–463.e4. [DOI] [PubMed] [Google Scholar]
- 3.Barbieri JS, Bhate K, Hartnett KP, Fleming-Dutra KE, Margolis DJ. Trends in Oral Antibiotic Prescription in Dermatology, 2008 to 2016. JAMA Dermatol. 2019;155(3):290–297. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Isotretinoin, Acne, and Crohn’s Disease: A Convergence of Bad Skin, Bad Science, and Bad Litigation Creates the Perfect Storm. Gastroenterol Hepatol. 2013;9(11):752–755. [PMC free article] [PubMed] [Google Scholar]
- 5.Lee SY, Jamal MM, Nguyen ET, Bechtold ML, Nguyen DL. Does exposure to isotretinoin increase the risk for the development of inflammatory bowel disease? A meta-analysis. Eur J Gastroenterol Hepatol. 2016;28(2):210–216. [DOI] [PubMed] [Google Scholar]
- 6.Barbieri JS. Isotretinoin and risk of inflammatory bowel disease: More data to support lack of meaningful risk. J Am Acad Dermatol. 2021;84(1):228–229. doi: 10.1016/j.jaad.2020.07.041 [DOI] [PubMed] [Google Scholar]
- 7.Wright S, Strunk A, Garg A. Risk of new-onset inflammatory bowel disease among patients with acne vulgaris exposed to isotretinoin. J Am Acad Dermatol. 2021;84(1):41–45. doi: 10.1016/j.jaad.2020.07.042 [DOI] [PubMed] [Google Scholar]
- 8.Piovani D, Danese S, Peyrin-Biroulet L, Nikolopoulos GK, Lytras T, Bonovas S. Environmental Risk Factors for Inflammatory Bowel Diseases: An Umbrella Review of Meta-analyses. Gastroenterology. 2019;157(3):647–659.e4. doi: 10.1053/j.gastro.2019.04.016 [DOI] [PubMed] [Google Scholar]
- 9.Agrawal M, Sabino J, Frias-Gomes C, et al. Early life exposures and the risk of inflammatory bowel disease: Systematic review and meta-analyses. EClinicalMedicine. 2021;36:100884. doi: 10.1016/j.eclinm.2021.100884 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Margolis DJ, Fanelli M, Hoffstad O, Lewis JD. Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease. Am J Gastroenterol. 2010;105(12):2610–2616. [DOI] [PubMed] [Google Scholar]
- 11.Kistowska M, Meier B, Proust T, et al. Propionibacterium acnes promotes Th17 and Th17/Th1 responses in acne patients. J Invest Dermatol. 2015;135(1):110–118. [DOI] [PubMed] [Google Scholar]
- 12.Zhao J, Lu Q, Liu Y, et al. Th17 Cells in Inflammatory Bowel Disease: Cytokines, Plasticity, and Therapies. J Immunol Res. 2021;2021:8816041. doi: 10.1155/2021/8816041 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Murphy CL, Gibson D, Meyers LS. Inflammatory Bowel Disease and Acne. Off J Am Coll Gastroenterol ACG. 2009;104(9):2370. [DOI] [PubMed] [Google Scholar]
- 14.Alhusayen RO, Juurlink DN, Mamdani MM, et al. Isotretinoin use and the risk of inflammatory bowel disease: a population-based cohort study. J Invest Dermatol. 2013;133(4):907–912. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Barbieri JS, Weiner DM, Kakpovbia E, Nagler AR. Validating the optimal classification approach using ICD-10 codes to identify dermatology patients with acne. J Am Acad Dermatol. Published online July 22, 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Ortizo R, Lee SY, Nguyen ET, Jamal MM, Bechtold MM, Nguyen DL. Exposure to oral contraceptives increases the risk for development of inflammatory bowel disease: a meta-analysis of case-controlled and cohort studies. Eur J Gastroenterol Hepatol. 2017;29(9):1064–1070. doi: 10.1097/MEG.0000000000000915 [DOI] [PubMed] [Google Scholar]
- 17.Zhu J, Zhou D, Wei J, Li Y. Genetic liability to acne is associated with increased risk of inflammatory bowel disease: A Mendelian randomization study. J Am Acad Dermatol. 2022;87(3):702–703. doi: 10.1016/j.jaad.2022.04.050 [DOI] [PubMed] [Google Scholar]
- 18.Agak GW, Kao S, Ouyang K, et al. Phenotype and Antimicrobial Activity of Th17 Cells Induced by Propionibacterium acnes Strains Associated with Healthy and Acne Skin. J Invest Dermatol. 2018;138(2):316–324. doi: 10.1016/j.jid.2017.07.842 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Schneeweiss MC, Kirchgesner J, Wyss R, et al. Occurrence of inflammatory bowel disease in patients with chronic inflammatory skin diseases: a cohort study. Br J Dermatol. Published online June 19, 2022. doi: 10.1111/bjd.21704 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Li WQ, Cho E, Khalili H, Wu S, Chan AT, Qureshi AA. Rosacea, Use of Tetracycline, and Risk of Incident Inflammatory Bowel Disease in Women. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2016;14(2):220–225.e1–3. doi: 10.1016/j.cgh.2015.09.013 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Lopez CG, Kwak R, McCormack L, Zhou G, Charrow A. Impact of Isotretinoin on IBD Flare in Patients with Pre-Existing IBD Diagnosis: A Cross-Sectional Study. J Am Acad Dermatol. Published online May 18, 2022:S0190–9622(22)00818–0. doi: 10.1016/j.jaad.2022.05.024 [DOI] [PubMed] [Google Scholar]
- 22.Barbieri JS, Spaccarelli N, Margolis DJ, James WD. Approaches to limit systemic antibiotic use in acne: Systemic alternatives, emerging topical therapies, dietary modification, and laser and light-based treatments. J Am Acad Dermatol. 2019;80(2):538–549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Nagler AR, Milam EC, Orlow SJ. The use of oral antibiotics before isotretinoin therapy in patients with acne. J Am Acad Dermatol. 2016;74(2):273–279. [DOI] [PubMed] [Google Scholar]
- 24.Barbieri JS, Choi JK, Mitra N, Margolis DJ. Frequency of Treatment Switching for Spironolactone Compared to Oral Tetracycline-Class Antibiotics for Women With Acne: A Retrospective Cohort Study 2010–2016. J Drugs Dermatol JDD. 2018;17(6):632–638. [PubMed] [Google Scholar]
- 25.Barbieri JS, Choi JK, James WD, Margolis DJ. Real-world drug usage survival of spironolactone versus oral antibiotics for the management of female patients with acne. J Am Acad Dermatol. 2019;81(3):848–851. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Barbieri JS, Frieden IJ, Nagler AR. Isotretinoin, Patient Safety, and Patient-Centered Care-Time to Reform iPLEDGE. JAMA Dermatol. Published online October 30, 2019. doi: 10.1001/jamadermatol.2019.3270 [DOI] [PubMed] [Google Scholar]