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D O I 1 0 . 1 1 1 1 / j . 1 3 6 5 - 2 1 3 3 . 2 0 0 7 . 0 8 2 8 6 . x Efficacy of tetracyclines in the treatment of acne vulgaris:a reviewT. Simonart, M. Dramaix* and V. De Maertelaer  Department of Dermatology, Erasme University Hospital, 808 Route de Lennik, B-1070 Brussels, Belgium*Department of Biostatistics, School of Public Health, Universite´ Libre de Bruxelles, Brussels, Belgium Department of Biostatistics and Medical Informatics, IRIBHM, Universite´ Libre de Bruxelles, Brussels, Belgium Background Oral tetracyclines are routinely used for the management of inflamma- tory acne. However, there is a lack of evidence-based data on their relative effec- tiveness and appropriate dosages.
Objectives To assess the relative effectiveness and the optimal dosage of tetracyclines for the treatment of inflammatory acne.
Methods We designed a systematic review of the clinical trials (1962–2006) inves- tigating oral tetracyclines for the treatment of inflammatory acne. We obtained data from MEDLINE, PubMed, Current Contents, reference lists and specialisttextbooks.
Results There was substantial heterogeneity in the design of the trials. We identi- fied only seven randomized trials which were set up to compare the efficacy oftetracyclines in reducing acne lesion counts. These showed no evidence of superi-ority of one tetracycline over another. Overall, there was also no significantdifference between the available tetracyclines in terms of improvement in inflam-matory (32 trials, P = 0Æ898) and noninflammatory (23 trials, P = 0Æ429)lesions. In the range of investigated dosages, the antibiotic dosage had no impacton efficacy in inflammatory (P = 0Æ609) and noninflammatory (P = 0Æ654)lesions. There was no decrease in efficacy during the study period.
Conclusions There is insufficient evidence to support one tetracycline rather thananother in terms of efficacy. In the range of investigated dosages, the antibioticdosage seems to have no impact on efficacy. Despite increased resistance to anti-biotics, oral tetracycline formulations displayed no change in efficacy duringthe study period. Further studies are, however, required to determine if the anti-inflammatory properties of tetracyclines are sufficient in managing acne.
Oral tetracyclines are indicated for the management of moder- by climate (for example doxycycline, known to have the ate and severe acne, acne that is resistant to topical treatment, potential to cause dose-dependent photosensitivity, is less and acne that covers large parts of the body surface.1–3 commonly prescribed in southern Europe), by various phar- Despite major concerns over antibiotic-resistant acne in Eur- macoeconomic considerations, and by the lack of evidence- ope and in the U.S.A.,4,5 tetracyclines continue to play an based data on efficacy.1 It has previously been suggested that integral role in the management of acne1–4 and are considered the beneficial effect of tetracycline is due to the inhibition of as the first-line oral antibiotic therapy in acne.4,6 The most Propionibacterium acnes accompanied by a reduction in sebum free commonly prescribed tetracyclines are first-generation cyclines fatty acids and extracellular lipases. However, the effect of tetra- (tetracycline HCl and oxytetracycline) and second-generation cyclines on acne may be due not only to an antimicrobial cyclines (doxycycline, minocycline and lymecycline).1 Sec- effect but also to their ability to reduce neutrophil chemo- ond-generation cyclines have a better pharmacokinetic profile, taxis as well as on their inhibitory effect on cytokines and which has been thought to be associated with increased anti- matrix metalloproteinase (MMP)-9.7 Based on this contention, acne efficacy, but are more expensive.1 The preferred choice recent studies have shown that subantimicrobial-dose doxy- of cyclines varies greatly from physician to physician and cycline (40 mg daily) reduced the number of both inflamma- from country to country, which may be partly accounted for tory and noninflammatory lesions in patients with moderate Journal Compilation Ó 2007 British Association of Dermatologists • British Journal of Dermatology 2008 158, pp208–216 Acne and tetracyclines, T. Simonart et al. 209 acne.8,9 No detectable antimicrobial effect on the skin flora quality indicators: year of publication or completion; and percentage of subjects not evaluated after treatment. Wher- Thus, although oral tetracyclines are one of the cornerstones ever possible, ‘intention-to-treat’ data were used in the analy- of acne management, several questions remain unanswered sis. Possible relationships between the duration of treatment (e.g. regarding the most efficient tetracycline, the optimal and the year of publication, and between the dosage and the dose of antibiotic, the optimal duration of treatment). Given year of publication, were investigated with Spearman’s cor- the high number of patients with acne treated with antibiotics, relation coefficients (rs) based on all (inflammatory and non- it is surprising that so little effort has been expended by clini- inflammatory) lesions. The efficacy of the treatment as cians, researchers, regulatory authorities and drug companies expressed by the proportion of reduction in inflammatory in determining guidelines for the use of tetracyclines in acne.
and noninflammatory lesion counts was compared between The aim of this study was to conduct a systematic review on the four groups of cyclines with Kruskal–Wallis tests. Possible the efficacy of first-generation cyclines, doxycycline, mino- relationships between the efficacy of the treatment and the cycline and lymecycline in the treatment of moderate to severe mean dose, treatment duration and year of publication were investigated with the use of a multiple regression (enter pro-cedure) for inflammatory lesions and for noninflammatory A systematic electronic search strategy was used to retrieve all clinical trials investigating therapy with oral tetracyclines forinflammatory acne published between 1962 and March 2006.
The following bibliographic databases were searched: MED- tetracycline treatment efficacy in inflammatory acne,11–58 LINE (National Library of Medecine), PubMed (National Library of Medicine) and Current Contents. Selected key words efficacy,28,37,39,45,46,54,58–80 10 trials investigating doxycycline were: acne (vulgaris), antibiotic, treatment, tetracycline, oxy- systemic treatment efficacy8,9,20,62,68,69,81–84 and seven trials tetracycline, minocycline, lymecycline, doxycycline and clini- investigating lymecycline systemic treatment efficacy,77,80,85–89 cal trial. Other sources were textbooks and the reference list 57 of which were included.8,9,12,14,16,17,19–21,23,25–38,41,42,44– 52,54,56–58,62,66,69,71,72,75–81,83–88 Trials were excluded for thefollowing reasons: combination with other topical or systemicdrug with antiacne efficacy,18,53,55,64,68,73,74,82,89 use of obso- Study selection: inclusion and exclusion criteria lete drugs,11,15,22 antibiotic treatment < 1 month prior to We considered all clinical trials investigating the clinical effi- the study or selection of cases unresponsive to other anti- cacy of oral tetracyclines (oxytetracycline, lymecycline, doxy- biotics,24,53,59,61,63,67,74 duplicate reports,70 specific forms cycline and minocycline) in patients with mild to moderate of acne (nodulocystic acne,43,65 oil acne40), cross-over inflammatory acne. Excluded were duplicate trials, trials on severe nodulocystic acne or on other specific forms of acne,studies that reported on fewer than six patients, studies on obsolete drugs (demeclocycline), studies investigating theeffect of antibiotics in combination with other therapies (topi- A huge profusion of outcome measures has been reported, cal retinoids, topical antibiotics, benzoyl peroxide, azelaic including various acne grade ⁄ severity scores, as well as doc- acid, salicylic acid, isotretinoin, hormones) or after failure of tor’s and patient’s global assessments (Table 1), reflecting the another antibiotic therapy, split-face design studies and studies difficulties in defining which objective features best reflect with insufficient data on effectiveness or with no quantitative treatment efficacy. The most commonly reported objective methods of measurement. Studies published in non-English outcome measures were decrease in inflammatory lesions and languages for which a published English translation was not decrease in noninflammatory lesions (Table 1). Lesion count available were excluded. In case of double publications, the was also the only objective outcome measure reported in most elaborate publication was selected.
older81 and more recent studies,83,84 making comparisonacross clinical trials possible. Of the 57 eligible controlled tri-als identified in this study, 35 (61%) incorporated a lesion count. Thirty-two trials incorporated an inflammatory lesion We extracted information on factors that we hypothesized a (papules + pustules) count and 23 trials incorporated a priori to be potential sources of treatment effect variation.
noninflammatory lesion count. There were 22 double-blind Those included the dosage and the duration of treatment.
studies,28–30,34–36,41,42,44,47,48,50,52,56,58,69,72, Instead of using quality scoring, which has well-described three placebo-controlled trials,8,9,81 six single- methodological shortcomings,10 we examined the following blind trials38,66,75,83,84,86 and three open trials.45,76,78 Studies Journal Compilation Ó 2007 British Association of Dermatologists • British Journal of Dermatology 2008 158, pp208–216 210 Acne and tetracyclines, T. Simonart et al.
Table 1 Outcome measures used in clinical trials investigating systemic tetracyclines for acne Journal Compilation Ó 2007 British Association of Dermatologists • British Journal of Dermatology 2008 158, pp208–216 Acne and tetracyclines, T. Simonart et al. 211 evaluating the effect of tetracycline, minocycline, doxycycline for doxycycline (between 40 and 200 mg), for which some and lymecycline are summarized in Tables 2–5, respectively.
trials investigated the effect of subantimicrobial doses of anti- Several studies were not considered because they included no biotics.8,9 The most commonly used dosages were 500 mg for reproducible assessment of efficacy or no quantitative data on first-generation tetracyclines (eight of 18 trials), 100 mg for lesion count.12,14,16,17,19–21,23,25–27,32,33,37,46,49,51,54,57,62,71,76,85 minocycline (10 of 13 trials) and 300 mg for lymecycline(three of five trials). An increase in antibiotic dosage overtime was observed for the first-generation tetracyclines (n = 17, rs = 0Æ733, P = 0Æ001), but not for doxycycline The duration of treatment varied between 829,34,36,38,42 and (n = 6, rs = )0Æ334, P = 0Æ518), minocycline (n = 14, rs = 2444 weeks for first-generation tetracylines, between 481 and )0Æ246, P = 0Æ397) or lymecycline (n = 7, rs = )0Æ100, 248 weeks for doxycycline, between 678 and 2466 weeks for minocycline and was 12 weeks in all trials on lyme- Relatively few studies investigated the effect of antibiotic cycline77,80,86–88 (Tables 2–5). The most common trial dura- dosage on efficacy. One double-blind, placebo-controlled tion was 12 weeks (39% of the studies for tetracycline, 50% study showed that subantimicrobial-dose doxycycline (20 mg of the studies for doxycycline, 69% of the studies for mino- taken twice daily) significantly reduced the number of inflam- cycline and 100% of the studies for lymecycline). The median matory and noninflammatory lesions in patients with inflam- study duration was the same (12 weeks) for all investigated matory acne.8 One double-blind study found that minocycline antibiotics. There was no significant change in study duration 100 ⁄ 50 mg was superior for the treatment of inflammatory over time (n = 45, rs = 0Æ273, P = 0Æ070).
acne than minocycline 50 mg.80 A dose–response analysis ofpooled data showed no significant effect of drug dosage onefficacy either for inflammatory lesions (n = 32, r P = 0Æ609) or for noninflammatory lesions (n = 23, rs = Because the drug dosage varied over the study period in some trials (i.e. higher doses during the first weeks and then lowerdoses), we considered the mean drug dosage over the study period. The mean drug dosage varied from 375 to 1000 mgdaily for first-generation tetracyclines, between 50 and There are very few randomized trials that were set up to com- 100 mg daily for minocycline, and between 150 and 300 mg pare one tetracycline against another. We identified three ran- daily for lymecycline. Higher dosage variations were observed domized trials that compared tetracycline with minocycline Table 2 Summary of trials evaluating the effect of tetracycline aData extrapolated from graphs. NR, not reported.
Journal Compilation Ó 2007 British Association of Dermatologists • British Journal of Dermatology 2008 158, pp208–216 212 Acne and tetracyclines, T. Simonart et al.
Table 3 Summary of trials evaluating the effect of minocycline aData extrapolated from graphs. NR, not reported.
Table 4 Summary of trials evaluating the effect of doxycycline aData extrapolated from graphs. NR, not reported.
Table 5 Summary of trials evaluating the effect of lymecycline and that included lesion counts.28,45,58 The minocycline dos- twice daily,28 with tetracycline at a dose of 500 mg twice age was the same in those three trials (50 mg twice daily) daily58 or with tetracycline at an unspecified dose.45 Two tri- and was compared with tetracycline at a dose of 250 mg als found no statistically significant differences between the Journal Compilation Ó 2007 British Association of Dermatologists • British Journal of Dermatology 2008 158, pp208–216 Acne and tetracyclines, T. Simonart et al. 213 two therapies,28,58 while the other found minocycline to be superior.45 This study was, however, conducted under openconditions and several methodological flaws can be identified The aim of this study was systematically to review the results (tetracycline dosage not specified, absence of information on of clinical trials investigating oral tetracyclines for the treat- dropouts, absence of measure of statistical dispersion, variable ment of inflammatory acne and to determine the relative assessment intervals). Three other trials, including no lesion effectiveness and the optimal dosage of these antibiotics. To counts but grade ⁄ severity scores,37,46,57 also failed to demon- evaluate the efficacy of a therapy is difficult because the inter- strate the superiority of minocycline over tetracyline. Mino- pretation of the results is dependent on comparison of data cycline was compared with lymecycline in three trials.
from many different sources, and is hindered by wide varia- Minocycline at a mean dosage of 50 mg,80 58 mg,77 66 mg80 tions in trial methodology. Several methods of efficacy assess- or 100 mg86 over 12 weeks was compared with lymecycline ment, including various grades ⁄ scoring systems, have been at a dose of 175 (mean)77 or 300 mg80,86 over 12 weeks.
reported for the past 30 years. Of the reproducible outcome One large multicentre, randomized, double-blind trial77 and measures identified in this review, lesion count has been most one randomized, single-blind86 trial found that the efficacy widely employed and tested over the past 30 years. Of the 57 of minocycline (mean dosage over 12 weeks: 58 mg77 or eligible studies investigating oral tetracyclines in acne patients, 100 mg86) and lymecycline (mean dosage over 12 weeks: 61% included a lesion count. The advantage of this outcome measure is that it has been used almost consistently across old Another randomized, double-blind study80 found that mino- and recent studies, making comparison across trials possible.
cycline 100 mg for 4 weeks followed by 50 mg for 8 weeks Variation in duration of the trials and assessment of the effi- was superior to minocycline 50 mg for 12 weeks or lyme- cacy by physicians at different time points may be another cycline 300 mg for 12 weeks in reducing the number of pap- factor hindering evidence-based practice. Most studies used ules, while no other clinically relevant between-treatment end points ranging from 8 to 12 weeks, which appears con- differences in lesion counts were present. Minocycline was sequent with the observation that the clinical effect of oral compared with comparable doses of doxycycline in one antibiotics typically requires 4–8 weeks.91 Although longer double-blind, double-dummy, randomized study [66 mg administration periods do not seem to be associated with (mean) for 12 weeks].69 Both drugs were found to be equally higher clinical efficacy, our results were adjusted for this effective in the treatment of acne vulgaris.69 The effect of cyclines on lesion count decrease has been Analogously, variation in antibiotic dosage across trials is analysed in a number of clinical trials that were not set up to another source of bias and inaccuracy. There is no consensus compare one tetracycline against another, making further on the optimal dosing of oral antibiotics in acne.91 The mean comparisons across trials possible (Tables 2–5). Overall, there drug dosage varied from 375 to 1000 mg daily for first-gen- was no significant difference between the available tetra- eration tetracyclines, between 50 and 100 mg daily for mino- cyclines in terms of efficacy in inflammatory (P = 0Æ898) and cycline, and between 150 and 300 mg daily for lymecycline.
noninflammatory lesion count (P = 0Æ429).
This study demonstrates that, within the range of the studied Neither the duration of the assessment, nor the drug dos- antibiotic dosages, low doses of cyclines were as efficient as age nor the year of publication had an impact on inflam- higher doses. This is in line with previous studies sugges- matory lesions (n = 32, multiple R = 0Æ139, P = 0Æ907) or ting that the beneficial effect of tetracyclines in patients with acne may be partly due to nonantimicrobial properties of P = 0Æ279). For inflammatory lesions, the partial correlation coefficients were: r = )0Æ006 (P = 0Æ976) for the duration showed that subantimicrobial-dose doxycycline resulted in a > 50% reduction in the number of acne lesions. Treat- r = 0Æ106 (P = 0Æ575) for the year of publication. For non- ment with subantimicrobial-dose doxycycline had no effect on inflammatory lesions, the partial correlation coefficients were: P. acnes or other microflora of the skin. It has been suggested r = )0Æ398 (P = 0Æ074) for the duration of treatment, that this antiacne effect of subantimicrobial-dose doxycycline r = 0Æ209 (P = 0Æ363) for the dosage, r = )0Æ042 (P = may be due its ability to reduce neutrophil chemotaxis as well 0Æ843) for the year of publication.
as on its inhibitory effect on cytokines and MMP-9.7 We also found that, despite dissemination of cross-resistant strains of propionibacteria,4 oral tetracycline formulations dis- played no change in efficacy during the study period. These A possible bias in the interpretation of the results could have results are in opposition with those found for topical ery- been a change in efficacy over time, as described for topical thromycin formulations,90 and may be explained by lower erythromycin.90 By contrast to topical erythromycin,90 oral resistance rates to orally administered tetracyclines or by non- tetracycline formulations displayed no change in efficacy dur- antimicrobial properties of cyclines.
There is a lack of evidence in the literature over the relative rs = )0Æ076, P = 0Æ674; noninflammatory lesions (n = 24), effectiveness of tetracyclines. Second-generation tetracyclines are known to have a better pharmacokinetic profile than Journal Compilation Ó 2007 British Association of Dermatologists • British Journal of Dermatology 2008 158, pp208–216 214 Acne and tetracyclines, T. Simonart et al.
first-generation tetracyclines.93,94 Minocycline has also greater For this reason, it is difficult to extrapolate data from one antimicrobial effects on P. acnes than first-generation tetracy- country to another. From this perspective, only first-genera- clines and doxycycline, and higher lipid solubility,94 favouring tion tetracyclines appear to be unequivocally cheaper than the its bioavailability in pilosebaceous units. However, very few randomized trials have been set up to compare the efficacy of Overall, there is insufficient evidence to support one tetra- tetracyclines in lesion count reduction. Those trials focused on cycline rather than another in terms of efficacy. Thus, the the comparison of minocycline with tetracycline or with other choice of tetracycline for acne should be based on criteria second-generation tetracyclines. Of the seven comparative ran- other than efficacy, such as cost and safety profile. In the domized trials included, six found no difference in lesion range of investigated dosages, the antibiotic dosage seems to count reduction. We then analysed the effect of tetracyclines have no impact on efficacy. Despite dissemination of cross- on lesion count reduction in trials that were not set up to resistant strains of propionibacteria, oral tetracycline formula- compare one tetracycline against another. Overall, this con- tions also displayed no change in efficacy during the study firms that, on the basis of reduction in lesion counts, all tetra- period. Further studies are, however, required to determine if cyclines appear to be similarly effective. In particular, second- the anti-inflammatory properties of tetracyclines are sufficient generation cyclines, which are the most expensive regimens and have replaced tetracycline as first-line antiacne antibioticsin many countries,2 were not found to be superior to first- generation tetracyclines. When comparing trials both withinand across tetracycline class, the summary estimates often 1 Dreno B, Bettoli V, Ochsendorf F et al. European recommendations demonstrate substantial heterogeneity. It would be tempting on the use of oral antibiotics for acne. Eur J Dermatol 2004; 14:391–9.
2 Harper JC. An update on the pathogenesis and management of to try to find some reasons for individual differences, but acne vulgaris. J Am Acad Dermatol 2004; 51:S36–8.
there are too many possible explanations and too few trials to 3 Katsambas A, Papakonstantinou A. Acne: systemic treatment.
do this: reasons might include differences in trial design, length of follow-up, patient selection, adequacy of conceal- 4 Ross JI, Snelling AM, Carnegie E et al. Antibiotic-resistant acne: ment of allocation, adequacy of blinding, and source of fund- lessons from Europe. Br J Dermatol 2003; 148:467–78.
ing. Low adherence to therapy may be another source of bias 5 Eady EA, Gloor M, Leyden JJ. Propionibacterium acnes resistance: in the interpretation of these results.95 In the controlled situa- a worldwide problem. Dermatology 2003; 206:54–6.
6 Tsankov N, Broshtilova V, Kazandjieva J. Tetracyclines in derma- tions of clinical trials, medication adherence is likely to be tology. Clin Dermatol 2003; 21:33–9.
much better than outside the trial arena, so that the effective- 7 Sapadin AN, Fleischmajer R. Tetracyclines: nonantibiotic properties ness of first-generation tetracyclines (which need to be taken and their clinical implications. J Am Acad Dermatol 2006; 54:258–65.
on an empty stomach, without milk, and at least twice 8 Skidmore R, Kovach R, Walker C et al. Low-dose doxycycline mod- daily93) may be diminished by noncompliance in the context erately effective for acne. Arch Dermatol 2003; 139:459–64.
9 Parish LC, Parish JL, Routh HB, Witkowski JA. The treatment of This study has limitations regarding the choice of the ‘best acne vulgaris with low dosage doxycycline. Acta Dermatovenerol Croat2005; 13:156–9.
cycline’. This is an efficacy-based study. Our outcome mea- 10 Juni P, Witschi A, Bloch R, Egger M. The hazards of scoring the sures were the decrease in the number of inflammatory and quality of clinical trials for meta-analysis. JAMA 1999; 282:1054– noninflammatory lesions. Data on safety, tolerability and cost were not evaluated in this analysis but have been investigated 11 Hicks JH. Demethylchlortetracycline: a double-blind study in the in other studies.58 All tetracyclines are generally well tolerated, treatment of acne with attention to side-effects noted. Southern Med J but can produce transient mild gastrointestinal disturbances.1 However, two of the commonly prescribed tetracyclines may 12 Cornbleet T. Comparison of demethylchlortetracycline and tetra- cycline in acne. Arch Dermatol 1964; 89:144–6.
be associated with more specific adverse events. Doxycycline 13 Crounse RG. The response of acne to placebos and antibiotics.
is more likely than other cyclines to cause photosensitivity.
This effect is dependent on doxycycline dose, ultraviolet A 14 Fry L, Ramsay CA. Tetracycline in acne vulgaris. Clinical evaluation intensity and skin phototype.1 This drug should thus be used and the effect of sebum production. Br J Dermatol 1966; 78:653–60.
with caution in hot climates during the summer. Minocycline 15 Witkowski JA, Simons HM. Objective evaluation of demethylchlor- causes a number of rare but severe side-effects, including tetracycline hydrochloride in the treatment of acne. JAMA 1966; hypersensitivity reactions and autoimmune disorders (lupus- 16 Smith EL, Mortimer PR. Tetracycline in acne vulgaris. Br J Dermatol like syndrome, autoimmune hepatitis, arthritis, thyroiditis, polyarteritis nodosa).96 Thus, because of a lack of advantages 17 Ganpule M. Clomocycline and oxytetracycline in acne vulgaris.
over other tetracyclines, and an uncertain safety profile, there could be no justification in continuing to use minocycline as a 18 Ashurst PJ. Tetracycline in acne vulgaris. Practioner 1968; 200:539– One of the problems in attempting to include a cost com- 19 Lane P, Williamson DM. Treatment of acne vulgaris with tetra- ponent in developing international recommendations on anti- cycline hydrochloride: a double-blind trial with 51 patients. Br MedJ 1969; ii:76–9.
biotic use is the very large variation in drug prices worldwide.
Journal Compilation Ó 2007 British Association of Dermatologists • British Journal of Dermatology 2008 158, pp208–216 Acne and tetracyclines, T. Simonart et al. 215 20 Juhlin L, Liden S. A quantitative evaluation of the effect of oxy- 44 Greenwood R, Brummit L, Burke B, Cunliffe WJ. Acne: double tetracycline and doxycycline in acne vulgaris. Br J Dermatol 1969; blind clinical and laboratory trial of tetracycline, oestrogen–cypro- terone acetate, and combined treatment. Br Med J 1985; 291:1231– 21 Cotterill JA, Cunliffe WJ, Forster RA et al. A comparison of trimeth- oprim–sulphamethoxazole with oxytetracycline in acne vulgaris.
45 Ruping KW, Tronnier H. Acne therapy: results of a clinical multi- centre study with minocycline. Royal Soc Med Serv Int Congress Symp 22 Mills OH, Marples RR, Kligman AM. Acne vulgaris. Oral therapy with tetracycline and topical therapy with vitamin A. Arch Dermatol 46 Samuelson JS. An accurate photographic method for grading acne: initial use in a double-blind clinical comparison of minocycline 23 Cunliffe WJ, Forster RA, Greenwood ND et al. Tetracycline and and tetracycline. J Am Acad Dermatol 1985; 12:461–7.
acne vulgaris: a clinical and laboratory investigation. Br Med J 1973; 47 Gammon WR, Meyer C, Lantis S et al. Comparative efficacy of oral erythromycin versus oral tetracycline in the treatment of acne 24 Baer RL, Leshaw SM, Shalita AR. High-dose tetracyline therapy in vulgaris. J Am Acad Dermatol 1986; 14:183–6.
severe acne. Arch Dermatol 1976; 112:479–81.
48 Bladon PT, Burke BM, Cunliffe WJ et al. Topical azelaic acid and 25 Smith JG, Chalker DK, Wehr RF. The effectiveness of topical and the treatment of acne: a clinical and laboratory comparison with oral tetracycline for acne. Southern Med J 1976; 69:695–7.
oral tetracycline. Br J Dermatol 1986; 114:493–9.
26 Poulos ET, Tedesco FJ. Acne vulgaris: double-blind trial comparing 49 Al-Mishari MA. Clinical and bacteriological evaluation of tetra- tetracycline and clindamycin. Arch Dermatol 1976; 112:974–6.
cycline and erythromycin in acne vulgaris. Clin Ther 1987; 27 Blaney DJ, Cook CH. Topical use of tetracycline in the treatment of acne. Arch Dermatol 1976; 112:971–3.
50 Katsambas A, Towarky AA, Stratigos J. Topical clindamycin phos- 28 Cullen SI, Cohan RH. Minocycline therapy in acne vulgaris. Cutis phate compared with tetracycline in the treatment of acne vulgaris.
29 Panzer JD, Poche W, Meek TJ et al. Acne treatment: a comparative 51 Budden MG. Topical and oral tetracycline in the treatment of acne efficacy trial of clindamycin and tetracycline. Cutis 1977; 19:109–11.
vulgaris. Practitioner 1988; 8:669–74.
30 Michaelsson G, Juhlin L, Ljunghall K. A double-blind study of the 52 Hjorth N, Graupe K. Azelaic acid for the treatment of acne. A clini- effect of zinc and oxytetracycline in acne vulgaris. Br J Dermatol cal comparison with oral tetracycline. Acta Derm Venereol (Stockh) 31 Cunliffe WJ, Burke B, Dodman B, Gould DJ. A double-blind trial 53 Hughes BR, Murphy CE, Barnett J, Cunliffe WJ. Strategy of acne of zinc sulphate ⁄ citrate complex and tetracycline in the treatment therapy with long-term antibiotics. Br J Dermatol 1989; 121:623– of acne vulgaris. Br J Dermatol 1979; 101:321–5.
32 Harcup JW, Cooper J. The treatment of acne vulgaris in general 54 Eady EA, Cove JH, Holland KT, Cunliffe WJ. Superior antibacterial practice. A double-blind assessment of co-trimoxazole and tetra- action and reduced incidence of bacterial resistance in minocycline cycline. Practitioner 1980; 224:747–50.
compared to tetracycline-treated acne patients. Br J Dermatol 1990; 33 Jen I. A comparison of low dosage trimethoprim ⁄ sulfamethoxazole with oxytetracycline in acne vulgaris. Cutis 1980; 26:106–8.
55 Burton J. A placebo-controlled study to evaluate the efficacy of top- 34 Stoughton RB, Cornell RC, Gange RW, Walter JF. Double-blind ical tetracycline and oral tetracycline in the treatment of mild to comparison of topical 1 percent clindamycin phosphate (Cleocin moderate acne. J Int Med Res 1990; 18:94–103.
T) and oral tetracycline 500 mg ⁄ day in the treatment of acne 56 Norris JFB, Hughes BR, Basey AJ, Cunliffe WJ. A comparison of the effectiveness of topical tetracycline, benzoyl-peroxide gel and 35 Feucht CL, Allen BS, Chalker DK, Smith JG Jr. Topical erythromycin oral oxytetracycline in the treatment of acne. Clin Exp Dermatol 1991; with zinc in acne. A double-blind controlled study. J Am Acad 57 Khanna N. Treatment of acne vulgaris with oral tetracyclines. Int J 36 Gratton D, Raymond GP, Guertin-Larochelle S et al. Topical clinda- mycin versus systemic tetracycline in the treatment of acne. Results 58 Ozolins M, Eady EA, Avery AJ et al. Comparison of five antimicro- of a multiclinic trial. J Am Acad Dermatol 1982; 7:50–3.
bial regimens for treatment of mild to moderate inflammatory 37 Hubbell CC, Hobbs ER, Rist MT, White JW. Efficacy of mino- facial acne vulgaris in the community: randomised controlled trial.
cycline compared with tetracycline in treatment of acne vulgaris.
59 Coskey RJ. Acne: treatment with minocycline. Cutis 1976; 17:799– 38 Gibson JR, Darley CR, Harvey SG, Barth J. Oral trimethoprim ver- sus oxytetracycline in the treatment of inflammatory acne vulgaris.
60 Hersle K, Gisslen H. Minocycline in acne vulgaris: a double-blind study. Curr Ther Res Clin Exp 1976; 19:339–42.
39 Leyden JJ, McGinley KJ, Kligman AM. Tetracycline and minocycline 61 Cullen SI. Low-dose minocycline therapy in tetracycline-recalcitrant treatment. Effects on skin-surface lipid levels and Propionibacterium acne vulgaris. Cutis 1978; 21:101–5.
acnes. Arch Dermatol 1982; 188:19–22.
62 Smit F. Minocycline versus doxycycline in the treatment of acne 40 Czernielewski A, Swarczynska-Banys E. Oral treatment of acne vul- vulgaris. Dermatologica 1978; 157:186–90.
garis and oil acne with tetracycline. Dermatologica 1982; 165:62–5.
63 Rossman RE. Minocycline treatment of tetracycline-resistant and 41 Rapaport M, Puhvel SM, Reinser MR. Evaluation of topical erythro- tetracycline-responsive acne vulgaris. Cutis 1981; 27:196–207.
mycin and oral tetracycline in acne vulgaris. Cutis 1982; 30:122–35.
64 Revuz JE, Guillaume JC, Poli F et al. Controlled trial of minocycline 42 Braathen LE. Topical clindamycin versus oral tetracycline and pla- in acne patients. Royal Soc Med Serv Int Congress Symp Series 1985; cebo in acne vulgaris. Scand J Infect Dis 1984; 43:71–5.
43 Lester RS, Schachter GD, Light MJ. Isotretinoin and tetracycline in 65 Pigatto PD, Finzi AF, Altomare GF et al. Isotretinoin versus mino- the management of severe nodulocystic acne. Int J Dermatol 1985; cycline in cystic acne: a study of lipid metabolism. Dermatologica Journal Compilation Ó 2007 British Association of Dermatologists • British Journal of Dermatology 2008 158, pp208–216 216 Acne and tetracyclines, T. Simonart et al.
66 Monk BE, Almeyda JA, Caldwell IW et al. Efficacy of low-dose 81 Plewig G, Petrozzi JW, Berendes U. Double-blind study of doxy- cyproterone acetate compared with minocycline in the treatment cycline in acne vulgaris. Arch Dermatol 1970; 101:435–8.
of acne vulgaris. Clin Exp Dermatol 1987; 12:319–22.
82 Parsad D, Pandhi R, Nagpal R, Negi KS. Azithromycin monthly 67 Millar ED, Jolliffe DS, Leigh AP. A general practice study investigat- pulse vs daily doxycyclin in the treatment of acne vulgaris. J Dermatol ing the effect of minocycline (Minocin) 50 mg bd for 12 weeks in the treatment of acne vulgaris. Br J Clin Pract 1987; 41:882–6.
83 Kus S, Yucelten D, Aytug A. Comparison of efficacy of azithro- 68 Harrison PV. A comparison of doxycycline and minocycline in the mycin vs. doxycycline in the treatment of acne vulgaris. Clin Exp treatment of acne vulgaris. Clin Exp Dermatol 1988; 13:242–4.
69 Olafsson JH, Gudgierson J, Eggertsdottir GE, Kristjansson F. Doxy- 84 Thiboutot DM, Shalita AR, Yamauchi PS et al., on behalf of the Dif- cycline versus minocycline in the treatment of acne vulgaris: a ferin Study Group. Combination therapy with adapalene gel 0Æ1% double-blind study. J Dermatolog Treat 1989; 1:15–17.
and doxycycline for severe acne vulgaris: a multicenter, investiga- 70 Sheehan-Dare RA, Papworth-Smith J, Cunliffe WJ. A comparative tor-blind, randomized, controlled study. Skinmed 2005; 4:138–46.
study between topical clindamycin and oral minocycline in the 85 Blair C. Treatment of acne vulgaris with lymecycline. Practitioner treatment of acne vulgaris. Round Tables Series 1989; 19:24–30.
71 Peacock CE, Price C, Ryan BE, Mitchell AD. Topical clindamycin 86 Bossuyt L, Bosschaert J, Richert B et al. Lymecycline in the treat- (Dalacin TTM) compared to oral minocyclineTM in treatment of ment of acne: an efficacious, safe and cost-effective alternative to acne vulgaris. A randomised observer-blind controlled trial in three minocycline. Eur J Dermatol 2003; 13:130–5.
university student health centres. Clin Trials J 1990; 27:219–28.
87 Cunliffe WJ, Meynadier J, Alirezai M et al. Is combined oral and 72 Sheehan-Dare RA, Papworth-Smith J, Cunliffe WJ. A double-blind topical therapy better than oral therapy alone in patients with comparison of topical clindamycin and oral minocycline in the moderate to moderately severe acne vulgaris? A comparison of the treatment of acne vulgaris. Acta Derm Venereol (Stockh) 1990; 70:534– efficacy and safety of lymecycline plus adapalene gel 0Æ1%, versus lymecycline plus gel vehicle. J Am Acad Dermatol 2003; 49:S218–26.
73 Gollnick HP, Graupe K, Zaumseil RP. Comparison of combined 88 Dubertret L, Alirezai M, Rostain G et al. The use of lymecycline in azelaic acid cream plus oral minocycline with oral isotretinoin in the treatment of moderate to severe acne vulgaris: a comparison of severe acne. Eur J Dermatol 2001; 11:538–44.
the efficacy and safety of two dosing regimens. Eur J Dermatol 2003; 74 Knaggs HE, Layton AM, Cunliffe WJ. The role of oral minocycline and erythromycin in tetracycline therapy-resistant acne – a retro- 89 Cassano N, Amoruso A, Alessandrini G et al. Treatment of inflam- spective study and a review. J Dermatolog Treat 1993; 4:53–6.
matory acne with a combination therapy with lymecycline and 75 Stainforth J, MacDonald-Hull SP, Papworth-Smith JW et al. A single- adapalene followed by maintenance treatment with adapalene. Eur J blind comparison of topical erythromycin ⁄ zinc lotion and oral mi- nocycline in the treatment of acne vulgaris. J Dermatolog Treat 1993; 90 Simonart T, Dramaix M. Treatment of acne with topical antibiotics: lessons from clinical studies. Br J Dermatol 2005; 153:395–403.
76 Darrah AJ, Gray PL. An open multicentre study to compare fusidic 91 Gollnick H, Cunliffe W, Berson D et al.; Global Alliance to Improve acid lotion and oral minocycline in the treatment of mild to mod- Outcomes in Acne. Management of acne: a report from a Global erate acne vulgaris of the face. Eur J Clin Res 1996; 8:97–107.
Alliance to Improve Outcomes in Acne. J Am Acad Dermatol 2003; 77 Grosshans E, Belaı¨ch S, Meynadier J et al. A comparison of the effi- cacy and safety of lymecycline and minocycline in patients with 92 Webster G, del Rosso GQ. Anti-inflammatory activity of tetra- moderately severe acne vulgaris. Eur J Dermatol 1998; 8:161–6.
cyclines. Dermatol Clin 2007; 25:133–5.
78 Gruber F, Grubisic-Greblo H, Kastelan M et al. Azithromycin com- 93 Zouboulis CC, Piquero-Martin J. Update and future of systemic pared with minocycline in the treatment of acne comedonica and acne treatment. Dermatology 2003; 206:37–53.
papulo-pustulosa. J Chemother 1998; 10:469–73.
94 Leyden JJ, Kaidbey K, Gans EH. The antimicrobial effects in vivo of 79 Dreno B, Moyse D, Alirezai M et al. Multicenter randomized compar- minocycline, doxycycline and tetracycline in humans. J Dermatolog ative double-blind controlled clinical trial of the safety and efficacy of zinc gluconate versus minocycline hydrochloride in the treatment 95 Gordis L. Conceptual and methodological problems in measuring of inflammatory acne vulgaris. Dermatology 2001; 203:135–40.
compliance. In: Compliance in Health Care (Haynes RB, Taylor DW, 80 Pie´rard-Franchimont C, Goffin V, Arrese JE et al. Lymecycline and Sackett DL, eds), Baltimore, MD: John Hopkins University Press, minocycline in inflammatory acne. A randomized, double-blind intent-to-treat study on clinical and in vivo antibacterial efficacy.
96 Haider A, Shaw JC. Treatment of acne vulgaris. JAMA 2004; Skin Pharmacol Appl Skin Physiol 2002; 15:112–19.
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