Acne treatment and inflammatory bowel disease: What is the evidence?
2011; Elsevier BV; Volume: 65; Issue: 3 Linguagem: Inglês
10.1016/j.jaad.2011.04.016
ISSN1097-6787
AutoresAli Alikhan, Gregory P. Henderson, Lauren Becker, Gabriel F. Sciallis,
Tópico(s)Autoimmune and Inflammatory Disorders
ResumoTo the Editor: The association between inflammatory bowel disease (IBD) and acne treatment has gained much attention from the media and has led to legal concerns. We aim to inform dermatologists of studies examining the link between IBD and isotretinoin, and IBD and tetracyclines, as such studies have primarily been published in the gastroenterology literature. PubMed queries (“isotretinoin,” “antibiotic,” “tetracycline,” “minocycline,” or “doxycycline” followed by “inflammatory bowel disease,” “Crohn disease,” or “ulcerative colitis”) yielded 10 pertinent studies.An association between isotretinoin and IBD was first discussed in the mid-1980s1Schleicher S.M. Oral isotretinoin and inflammatory bowel disease.J Am Acad Dermatol. 1985; 13: 834-835Abstract Full Text PDF PubMed Scopus (38) Google Scholar, 2Brodin M.B. Inflammatory bowel disease and isotretinoin.J Am Acad Dermatol. 1986; 14: 843Abstract Full Text PDF PubMed Scopus (32) Google Scholar; several cases have since been described.3Crockett S.D. Gulati A. Sandler R.S. Kappelman M.D. A causal association between isotretinoin and inflammatory bowel disease has yet to be established.Am J Gastroenterol. 2009; 104: 2387-2393Crossref PubMed Scopus (47) Google Scholar IBD patients who did not experience worsening of their condition using isotretinoin have also been reported.4Rosen T. Unkefer R.P. Treatment of pyoderma faciale with isotretinoin in a patient with ulcerative colitis.Cutis. 1999; 64: 107-109PubMed Google Scholar Two case-controlled studies have recently been published (Table I).5Bernstein C.N. Nugent Z. Longobardi T. Blanchard J.F. Isotretinoin is not associated with inflammatory bowel disease: a population-based case-control study.Am J Gastroenterol. 2009; 104: 2774-2778Crossref PubMed Scopus (97) Google Scholar, 6Crockett S.D. Porter C.Q. Martin C.F. Sandler R.S. Kappelman M.D. Isotretinoin use and the risk of inflammatory bowel disease: a case-control study.Am J Gastroenterol. 2010; 105: 1986-1993Crossref PubMed Scopus (121) Google Scholar Bernstein et al5Bernstein C.N. Nugent Z. Longobardi T. Blanchard J.F. Isotretinoin is not associated with inflammatory bowel disease: a population-based case-control study.Am J Gastroenterol. 2009; 104: 2774-2778Crossref PubMed Scopus (97) Google Scholar did not demonstrate an association between IBD and isotretinoin, whereas Crockett et al6Crockett S.D. Porter C.Q. Martin C.F. Sandler R.S. Kappelman M.D. Isotretinoin use and the risk of inflammatory bowel disease: a case-control study.Am J Gastroenterol. 2010; 105: 1986-1993Crossref PubMed Scopus (121) Google Scholar demonstrated an association between ulcerative colitis and isotretinoin. The database in the study of Crockett et al included more IBD cases, but Bernstein et al’s study database was more comprehensive, being part of a universal health care system. Bernstein et al included all cases of isotretinoin use prior to IBD diagnosis, whereas Crockett et al examined cases in which isotretinoin was taken in the 12 months prior to IBD diagnosis; this temporal stringency may improve the case for causality. Furthermore, Crockett et al examined the effects of isotretinoin dose and exposure, whereas Bernstein et al. did not. Neither discussed recent or distant usage of antibiotics in their subjects. Finally, while Crockett et al state that acne was not independently associated with ulcerative colitis (UC) or IBD, they did not examine acne by severity/subtype, an important confounding factor.Table IStudies examining the link between isotretinoin and IBDStudy design (authors, year)OutcomeCommentsCase-control study of IBD patients using the University of Manitoba IBD Epidemiology Database (Bernstein et al,5Bernstein C.N. Nugent Z. Longobardi T. Blanchard J.F. Isotretinoin is not associated with inflammatory bowel disease: a population-based case-control study.Am J Gastroenterol. 2009; 104: 2774-2778Crossref PubMed Scopus (97) Google Scholar 2009)2008 IBD cases1.2% of IBD cases used isotretinoin before diagnosis compared with 1.1% of control subjects using isotretinoin (statistically insignificant). This is similar to the percentage of IBD patients who used isotretinoin after diagnosis (1.1%).There was no difference when IBD was subdivided as CD and UC.Inclusion criteria required that persons residing in the province for at least 2 years were designated as having IBD only if they had at least 5 separate physician claims and/or hospitalizations; persons residing in the province for less than 2 years were included in the IBD cohort if they had at least 3 separate physician claims and/or records.Acne severity or its association with IBD was not addressed.Mean number of days between the first isotretinoin prescription and initial IBD diagnosis for IBD patients who used isotretinoin before IBD diagnosis was 1102.4 days.Case-control study of patients in the PharMetrics Patient-Centric Database (an American insurance claims database) (Crockett et al,6Crockett S.D. Porter C.Q. Martin C.F. Sandler R.S. Kappelman M.D. Isotretinoin use and the risk of inflammatory bowel disease: a case-control study.Am J Gastroenterol. 2010; 105: 1986-1993Crossref PubMed Scopus (121) Google Scholar 2010)8189 IBD casesUC strongly associated with isotretinoin exposure in the 12 months before diagnosis (OR: 4.36 [95% CI: 1.97-9.66]). UC was also associated with isotretinoin exposure in the 24 months before diagnosis (OR: 2.90 [95% CI: 1.17-7.20), but to a lesser extent.There was no association between isotretinoin exposure and subsequent CD development.Increasing dose of isotretinoin was associated with elevated UC risk (OR per 20-mg dose increase: 1.50 [95% CI: 1.08-2.09])Risk of UC was highest in those cases exposed to isotretinoin for at least 60 days compared with nonusers (OR: 5.63 [95% CI: 2.10-15.03])A diagnosis of acne was not independently associated with UC (OR: 1.25 [95% CI: 0.98-1.58]).Inclusion criteria required that all subjects meet primary IBD definition (≥3 IBD diagnoses on separate dates or ≥1 IBD diagnosis and 1 IBD-specific medication) with at least 12 months of continuous enrollment prior to first IBD claim.Although acne was not associated with UC, the authors never stratified/subtyped acne (eg, mild, moderate, or severe) to see if more severe acne was associated with UC.CD, Crohn disease; CI, confidence interval; IBD, inflammatory bowel disease; OR, odds ratio; UC, ulcerative colitis. Open table in a new tab Patient questionnaire studies have screened for associations between IBD and environmental factors (Table II), including those that could affect the gut microflora. Many,7Gilat T. Hacohen D. Lilos P. Langman M.J. Childhood factors in ulcerative colitis and Crohn’s disease. An international cooperative study.Scand J Gastroenterol. 1987; 22: 1009-1024Crossref PubMed Scopus (322) Google Scholar, 8Wurzelmann J.I. Lyles C.M. Sandler R.S. Childhood infections and the risk of inflammatory bowel disease.Dig Dis Sci. 1994; 39: 555-560Crossref PubMed Scopus (140) Google Scholar, 9Gearry R.B. Richardson A.K. Frampton C.M. Dodgshun A.J. Barclay M.L. Population-based cases control study of inflammatory bowel disease risk factors.J Gastroenterol Hepatol. 2010; 25: 325-333Crossref PubMed Scopus (175) Google Scholar but not all,10Van Kruiningen H.J. Joossens M. Vermeire S. Joossens S. Debeugny S. Gower-Rousseau C. et al.Environmental factors in familial Crohn’s disease in Belgium.Inflamm Bowel Dis. 2005; 11: 360-365Crossref PubMed Scopus (52) Google Scholar studies show an association between greater antibiotic use and subsequent Crohn disease (CD). These studies rely on patient recall and are best viewed as hypothesis generating. Four population-based retrospective studies have demonstrated an association between preceding antibiotic use and IBD development (Table III).11Card T. Logan R.F. Rodrigues L.C. Wheeler J.G. Antibiotic use and the development of Crohn’s disease.Gut. 2004; 53: 246-250Crossref PubMed Scopus (129) Google Scholar, 12Margolis D.J. Fanelli M. Hoffstad O. Lewis J.D. Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease.Am J Gastroenterol. 2010; 105: 2610-2616Crossref PubMed Scopus (129) Google Scholar, 13Hildebrand H. Malmborg P. Askling J. Ekbom A. Montgomery S.M. Early-life exposures associated with antibiotic use and risk of subsequent Crohn’s disease.Scand J Gastroenterol. 2008; 43: 961-966Crossref PubMed Scopus (88) Google Scholar, 14Shaw S.Y. Blanchard J.F. Bernstein C.N. Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease.Am J Gastroenterol. 2010; 105: 2687-2692Crossref PubMed Scopus (305) Google Scholar Of these, 3 examined IBD patients while one examined acne patients, and only two examined tetracycline usage. In a cohort of 94,487 young adults with acne, the adjusted odds ratio (OR) for developing IBD with the tetracycline family of antibiotics was 1.39 (95% confidence interval [CI]: 1.02-1.90).12Margolis D.J. Fanelli M. Hoffstad O. Lewis J.D. Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease.Am J Gastroenterol. 2010; 105: 2610-2616Crossref PubMed Scopus (129) Google Scholar CD, but not UC, maintained this association with tetracycline (OR: 1.61 [0.995-2.63]) and doxycycline (OR: 2.25 [1.27-4.00]), and non-significantly with minocycline (OR 1.28 [0.72-2.30]). In all 4 studies, no adjustments were made for acne severity, total amount of antibiotic administered, or patient adherence. The fact that tetracyclines do not specifically target the gut flora makes this association quite surprising.Table IISelf-reported questionnaire-based studies exploring the association between IBD and environmental factorsStudy design (authors, year)Environmental factor (subset of total results)OutcomeOR (95% CI)LimitationsCase-control multicenter self-administered questionnaire to IBD patients (Gilat et al,7Gilat T. Hacohen D. Lilos P. Langman M.J. Childhood factors in ulcerative colitis and Crohn’s disease. An international cooperative study.Scand J Gastroenterol. 1987; 22: 1009-1024Crossref PubMed Scopus (322) Google Scholar 1987)499 IBD casesAntibioticsRecurrent respiratory infectionsHospitalization for respiratory infectionsCDUC, CDIBDNot reported1.58 (0.98-2.58)∗, 1.25 (0.85-1.89)∗Not reported∗Authors claim statistical significance but reported that confidence interval crosses 1.No correction for making multiple comparisons. This increases the chance of a type 1 error where the null hypothesis is rejected when it is, in fact, true.Case-control study of IBD patients from North Carolina with neighbor controls (Wurzelmann et al,8Wurzelmann J.I. Lyles C.M. Sandler R.S. Childhood infections and the risk of inflammatory bowel disease.Dig Dis Sci. 1994; 39: 555-560Crossref PubMed Scopus (140) Google Scholar 1994)503 IBD casesPenicillin exposurePenicillin exposure after correction for frequency of infectionChildhood infectionsCDCD, UC1.18 (0.98-3.31)∗Not significant4.76 (2.65-8.23)2.37 (1.19-4.71)∗Crosses the confidence interval of 1.No correction for multiple comparisonsCase-control study of IBD patients recruited from public and private clinics and hospitals in Canterbury, New Zealand (Gearry et al,9Gearry R.B. Richardson A.K. Frampton C.M. Dodgshun A.J. Barclay M.L. Population-based cases control study of inflammatory bowel disease risk factors.J Gastroenterol Hepatol. 2010; 25: 325-333Crossref PubMed Scopus (175) Google Scholar 2010)1291 IBD casesAntibiotics given >4 times per year during adolescenceAppendectomyTonsillectomyInfectious mononucleosisSmokingCDCD, UCCDCDCD, UC1.89 (1.16-3.09)1.57 (1.11-2.22), 0.41 (0.27-0.63)1.37 (1.03-1.83)1.64 (1.11-2.43)1.99 (1.48-2.68), 0.67 (0.48-0.94)No correction for multiple comparisons (102-item questionnaire)Case-control study comparing 21 Belgian families having high prevalence of CD with 10 matched control families (Van Kruiningen et al,10Van Kruiningen H.J. Joossens M. Vermeire S. Joossens S. Debeugny S. Gower-Rousseau C. et al.Environmental factors in familial Crohn’s disease in Belgium.Inflamm Bowel Dis. 2005; 11: 360-365Crossref PubMed Scopus (52) Google Scholar 2005)74 CD casesAntibioticsAppendicitis during adolescenceSkin diseaseSmokingChildhood respiratory infectionsCDCDCDCDCDNo associationNot reported2.71 (1.05-7.0)Not reportedNo associationsOnly CD examined, not UCTertiary referral centerNo correction for multiple comparisons (176-item questionnaire)CD, Crohn disease; CI, confidence interval; IBD, inflammatory bowel disease; OR, odds ratio; UC, ulcerative colitis. Open table in a new tab Table IIIPopulation-based case-control studies examining the link between tetracyclines and IBDStudy design (authors, year)DrugOutcomeOR (95% CI)CommentsRetrospective case-control study of CD patients from a UK general practitioner database (Card et al,11Card T. Logan R.F. Rodrigues L.C. Wheeler J.G. Antibiotic use and the development of Crohn’s disease.Gut. 2004; 53: 246-250Crossref PubMed Scopus (129) Google Scholar 2004)587 CD casesAntibiotic prescriptions during the preceding 2 to 5 yearsTetracycline∗Subgroup analysis.Metronidazole/tinidazole∗Subgroup analysis.Other antibiotics (penicillins, cephalosporins, macrolides, sulfonamides, quinolones)∗Subgroup analysis.Drugs other than antibioticsNicotineCDCDCDCDCDCD1.32 (1.05-1.65)1.33 (1.01-1.77)1.71 (1.05-2.76)No association1.54 (1.38-1.70)1.55 (1.22-1.98)Database representing 5% of UK’s population containing diagnosis, treatment, and prescriptions dataOnly CDAssociations existed not only for antibiotics but also for drugs in general (excluding antibiotics).Acne severity not assessedRetrospective population-based case-control study of CD in Sweden (Hildebrand et al,13Hildebrand H. Malmborg P. Askling J. Ekbom A. Montgomery S.M. Early-life exposures associated with antibiotic use and risk of subsequent Crohn’s disease.Scand J Gastroenterol. 2008; 43: 961-966Crossref PubMed Scopus (88) Google Scholar 2008)1098 CD casesFor inpatient setting only:Pneumonia 5 years oldOtitis media (inpatient) <5 years oldCDPediatric CDAdult CDCDCD3.54 (1.78-7.04)2.74 (1.04-7.21)4.94 (1.83-13.34)No associationNo associationPneumonia diagnosis used a surrogate marker for antibiotic use.Otitis media, often treated with antibiotics, was not associated with CD.The possibility exists of reverse causality where the infection is rather the risk factor for CD.Only CDRetrospective population-based case-control study of pediatric CD in a Canadian province (Shaw et al,14Shaw S.Y. Blanchard J.F. Bernstein C.N. Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease.Am J Gastroenterol. 2010; 105: 2687-2692Crossref PubMed Scopus (305) Google Scholar 2010)36 pediatric CD casesAntibiotics given at age 1 prescription given2-4 prescriptions>4 prescriptionsPediatric CDPediatric CDPediatric CD2.9 (1.2-7.0)2.9 (1.1-7.8)5.0 (1.3-18.9)Only looks at antibiotics given during first year of lifeFor early-onset (<13 years of age) IBD; mean age 8.4 yearsOnly pediatric CDSmaller sample sizeRetrospective population-based case-control study from a UK general practitioner database (Margolis et al,12Margolis D.J. Fanelli M. Hoffstad O. Lewis J.D. Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease.Am J Gastroenterol. 2010; 105: 2610-2616Crossref PubMed Scopus (129) Google Scholar 2010)94,487 young adults with acne followed up for more than 406,000 person-years (of whom 61.2% had previous exposure to tetracyclines)Tetracyclines as a classTetracycline/oxytetracycline∗Subgroup analysis.Doxycycline∗Subgroup analysis.Minocycline∗Subgroup analysis.Tetracyclines as a class∗Subgroup analysis.Tetracycline∗Subgroup analysis.Doxycycline∗Subgroup analysis.IBDIBDIBDIBDUCCDCD1.39 (1.20-1.90)1.46 (1.03-2.07)1.58 (1.02-2.46)NSNS1.61 (0.995-2.63)2.25 (1.27-4.00)UK-based database with size, structure, and content similar to database used in study of Card et alOnly looked at tetracyclines and not at other medicationsData spanned up to 7-year periodLow rate of isotretinoin in population studiedAcne severity not assessed.CD, Crohn’s disease; CI, confidence interval; IBD, inflammatory bowel disease; NS, not significant; OR, odds ratio; UC, ulcerative colitis; UK, United Kingdom.∗ Subgroup analysis. Open table in a new tab There may be an association between certain acne treatments and IBD, but there may simply be an association between severe acne and IBD,15McAuley D. Miller R.A. Acne fulminans associated with inflammatory bowel disease. Report of a case.Arch Dermatol. 1985; 121: 91-93Crossref PubMed Scopus (28) Google Scholar two inflammatory entities occurring in the same age group. Furthermore, those persons taking isotretinoin and tetracyclines see physicians more frequently (and perhaps have a greater chance of receiving other medical diagnoses). In our practice, we discuss these possible associations with our patients when prescribing tetracyclines and isotretinoin, but mention that not all studies have demonstrated a link, that the absolute risk is low, that no study has demonstrated a causal association, and that acne may be associated with other inflammatory disorders. To the Editor: The association between inflammatory bowel disease (IBD) and acne treatment has gained much attention from the media and has led to legal concerns. We aim to inform dermatologists of studies examining the link between IBD and isotretinoin, and IBD and tetracyclines, as such studies have primarily been published in the gastroenterology literature. PubMed queries (“isotretinoin,” “antibiotic,” “tetracycline,” “minocycline,” or “doxycycline” followed by “inflammatory bowel disease,” “Crohn disease,” or “ulcerative colitis”) yielded 10 pertinent studies. An association between isotretinoin and IBD was first discussed in the mid-1980s1Schleicher S.M. Oral isotretinoin and inflammatory bowel disease.J Am Acad Dermatol. 1985; 13: 834-835Abstract Full Text PDF PubMed Scopus (38) Google Scholar, 2Brodin M.B. Inflammatory bowel disease and isotretinoin.J Am Acad Dermatol. 1986; 14: 843Abstract Full Text PDF PubMed Scopus (32) Google Scholar; several cases have since been described.3Crockett S.D. Gulati A. Sandler R.S. Kappelman M.D. A causal association between isotretinoin and inflammatory bowel disease has yet to be established.Am J Gastroenterol. 2009; 104: 2387-2393Crossref PubMed Scopus (47) Google Scholar IBD patients who did not experience worsening of their condition using isotretinoin have also been reported.4Rosen T. Unkefer R.P. Treatment of pyoderma faciale with isotretinoin in a patient with ulcerative colitis.Cutis. 1999; 64: 107-109PubMed Google Scholar Two case-controlled studies have recently been published (Table I).5Bernstein C.N. Nugent Z. Longobardi T. Blanchard J.F. Isotretinoin is not associated with inflammatory bowel disease: a population-based case-control study.Am J Gastroenterol. 2009; 104: 2774-2778Crossref PubMed Scopus (97) Google Scholar, 6Crockett S.D. Porter C.Q. Martin C.F. Sandler R.S. Kappelman M.D. Isotretinoin use and the risk of inflammatory bowel disease: a case-control study.Am J Gastroenterol. 2010; 105: 1986-1993Crossref PubMed Scopus (121) Google Scholar Bernstein et al5Bernstein C.N. Nugent Z. Longobardi T. Blanchard J.F. Isotretinoin is not associated with inflammatory bowel disease: a population-based case-control study.Am J Gastroenterol. 2009; 104: 2774-2778Crossref PubMed Scopus (97) Google Scholar did not demonstrate an association between IBD and isotretinoin, whereas Crockett et al6Crockett S.D. Porter C.Q. Martin C.F. Sandler R.S. Kappelman M.D. Isotretinoin use and the risk of inflammatory bowel disease: a case-control study.Am J Gastroenterol. 2010; 105: 1986-1993Crossref PubMed Scopus (121) Google Scholar demonstrated an association between ulcerative colitis and isotretinoin. The database in the study of Crockett et al included more IBD cases, but Bernstein et al’s study database was more comprehensive, being part of a universal health care system. Bernstein et al included all cases of isotretinoin use prior to IBD diagnosis, whereas Crockett et al examined cases in which isotretinoin was taken in the 12 months prior to IBD diagnosis; this temporal stringency may improve the case for causality. Furthermore, Crockett et al examined the effects of isotretinoin dose and exposure, whereas Bernstein et al. did not. Neither discussed recent or distant usage of antibiotics in their subjects. Finally, while Crockett et al state that acne was not independently associated with ulcerative colitis (UC) or IBD, they did not examine acne by severity/subtype, an important confounding factor. CD, Crohn disease; CI, confidence interval; IBD, inflammatory bowel disease; OR, odds ratio; UC, ulcerative colitis. Patient questionnaire studies have screened for associations between IBD and environmental factors (Table II), including those that could affect the gut microflora. Many,7Gilat T. Hacohen D. Lilos P. Langman M.J. Childhood factors in ulcerative colitis and Crohn’s disease. An international cooperative study.Scand J Gastroenterol. 1987; 22: 1009-1024Crossref PubMed Scopus (322) Google Scholar, 8Wurzelmann J.I. Lyles C.M. Sandler R.S. Childhood infections and the risk of inflammatory bowel disease.Dig Dis Sci. 1994; 39: 555-560Crossref PubMed Scopus (140) Google Scholar, 9Gearry R.B. Richardson A.K. Frampton C.M. Dodgshun A.J. Barclay M.L. Population-based cases control study of inflammatory bowel disease risk factors.J Gastroenterol Hepatol. 2010; 25: 325-333Crossref PubMed Scopus (175) Google Scholar but not all,10Van Kruiningen H.J. Joossens M. Vermeire S. Joossens S. Debeugny S. Gower-Rousseau C. et al.Environmental factors in familial Crohn’s disease in Belgium.Inflamm Bowel Dis. 2005; 11: 360-365Crossref PubMed Scopus (52) Google Scholar studies show an association between greater antibiotic use and subsequent Crohn disease (CD). These studies rely on patient recall and are best viewed as hypothesis generating. Four population-based retrospective studies have demonstrated an association between preceding antibiotic use and IBD development (Table III).11Card T. Logan R.F. Rodrigues L.C. Wheeler J.G. Antibiotic use and the development of Crohn’s disease.Gut. 2004; 53: 246-250Crossref PubMed Scopus (129) Google Scholar, 12Margolis D.J. Fanelli M. Hoffstad O. Lewis J.D. Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease.Am J Gastroenterol. 2010; 105: 2610-2616Crossref PubMed Scopus (129) Google Scholar, 13Hildebrand H. Malmborg P. Askling J. Ekbom A. Montgomery S.M. Early-life exposures associated with antibiotic use and risk of subsequent Crohn’s disease.Scand J Gastroenterol. 2008; 43: 961-966Crossref PubMed Scopus (88) Google Scholar, 14Shaw S.Y. Blanchard J.F. Bernstein C.N. Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease.Am J Gastroenterol. 2010; 105: 2687-2692Crossref PubMed Scopus (305) Google Scholar Of these, 3 examined IBD patients while one examined acne patients, and only two examined tetracycline usage. In a cohort of 94,487 young adults with acne, the adjusted odds ratio (OR) for developing IBD with the tetracycline family of antibiotics was 1.39 (95% confidence interval [CI]: 1.02-1.90).12Margolis D.J. Fanelli M. Hoffstad O. Lewis J.D. Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease.Am J Gastroenterol. 2010; 105: 2610-2616Crossref PubMed Scopus (129) Google Scholar CD, but not UC, maintained this association with tetracycline (OR: 1.61 [0.995-2.63]) and doxycycline (OR: 2.25 [1.27-4.00]), and non-significantly with minocycline (OR 1.28 [0.72-2.30]). In all 4 studies, no adjustments were made for acne severity, total amount of antibiotic administered, or patient adherence. The fact that tetracyclines do not specifically target the gut flora makes this association quite surprising. CD, Crohn disease; CI, confidence interval; IBD, inflammatory bowel disease; OR, odds ratio; UC, ulcerative colitis. CD, Crohn’s disease; CI, confidence interval; IBD, inflammatory bowel disease; NS, not significant; OR, odds ratio; UC, ulcerative colitis; UK, United Kingdom. There may be an association between certain acne treatments and IBD, but there may simply be an association between severe acne and IBD,15McAuley D. Miller R.A. Acne fulminans associated with inflammatory bowel disease. Report of a case.Arch Dermatol. 1985; 121: 91-93Crossref PubMed Scopus (28) Google Scholar two inflammatory entities occurring in the same age group. Furthermore, those persons taking isotretinoin and tetracyclines see physicians more frequently (and perhaps have a greater chance of receiving other medical diagnoses). In our practice, we discuss these possible associations with our patients when prescribing tetracyclines and isotretinoin, but mention that not all studies have demonstrated a link, that the absolute risk is low, that no study has demonstrated a causal association, and that acne may be associated with other inflammatory disorders.
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