Clinical evaluation of a topical ethyl lactate treatment of acne vulgaris (author's transl)]

The efficacy of a lotion containing 10 p. 100 ethyl lactate was evaluated in a double-blind clinical trail during 8 weeks. Test subjects were 45 male and female patients with polymorphous juvenile acne. They were divided into three groups and received the following treatments: Group A: oral antibiotic + topical placebo lotion. Group B: oral antibiotic + topical ethyl lactate lotion. Group C: topical ethyl lactate lotion only. The lotions were applied twice daily with a swab of cotton-wool. The antibiotic doses (tetracycline hydrochloride) were decreased as the trial progressed. Patients were examined before the trial, then after 1, 2, 4, 6 and 8 weeks. At each visit, comedones, microcysts, pustules and nodules were counted on a skin surface of 9 cm2. Colour photographs were taken before and at the end of the trial and served for counting inflammatory lesions. Also, at each visit, skin lipids were sampled and analysed by I. R. spectrophotometry in order to asses the effect of the treatments on the free fatty acid/triglyceride ratio. The treatments showed similar effectiveness as regards comedones and microcysts, but only treatments A and B succeeded in reducing the number of inflamed lesions. With respect to the latter, the combined treatment B (oral antibiotic + topical ethyl lactate lotion) was more effective than treatment A (oral antibiotic + topical placebo); both treatments were more effective than treatment C (topical ethyl lactate lotion only). At the end of the trial, all three groups of patients showed significant overall improvement, but acne scores (total number of lesions) did not differ significantly between treatments. When comparing these results with literature data concerning the effects of vitamin A acid and benzoyl peroxide, it appears that ethyl lactate is slightly less effective for topical treatment of acne than vitamin A acid, but slightly more effective than benzoyl peroxide. It should be underlined that ethyl lactate is well tolerated by the skin. Analysis of sebum samples failed to yield evidence of a decrease in the free fatty acid/triglyceride ratio in skin lipids of the patients irrespective of the treatment applied.     

A comparison of the effectiveness of topical tetracycline, benzoyl-peroxide gel and oral oxytetracycline in the treatment of acne

A proprietary topical tetracycline preparation (Topicycline) was compared with an alcohol-based 5% benzoyl-peroxide gel and with oral oxytetracycline (250 mg twice daily) using a randomized group-comparative double-blind study in 69 patients with mild to moderate acne. Facial acne grades improved significantly in all three treatment groups over the 12-week study period but chest acne grades did not change significantly and only oxytetracycline produced a significant improvement in back grade. All three treatment groups produced a significant reduction in facial inflamed and non-inflamed lesions apart from oxytetracycline which failed to produce a significant reduction in inflamed lesions. However, there were no overall significant differences between the three treatment groups either in improvement of acne grade or in reduction of inflamed and non-inflamed lesions. We conclude that topical tetracycline is as effective as either 5% benzoyl-peroxide gel or 250 mg oxytetracycline twice daily in the treatment of mild to moderate acne.     

Clinical and microbiological comparisons of isotretinoin vs. tetracycline in acne vulgaris

The aim of this study was to compare the clinical and microbiological effect on Propionibacterium acnes of oral tetracycline plus topical adapalene vs. oral isotretinoin in moderate to severe acne vulgaris. Male and female acne patients with moderate or severe inflammatory disease were enrolled and assigned randomly to 6 months of treatment with oral tetracycline hydrochloride plus topical adapalene, or oral isotretinoin, in a controlled, open study. After cessation of oral treatment the antibiotic-treated group received topical adapalene for the 2-month follow-up period. Clinical and microbiological assessments were performed. Skin samples for microbial identification and quantification were taken at baseline, after 2, 4 and 6 months of treatment, and 2 months after cessation of treatment. Patients treated with isotretinoin showed prolonged significant remission compared with the other group. The density of resistant propionibacteria did not change significantly in any of the groups and there was no correlation between resistant P. acnes and the clinical response in any of the regions investigated. Antibiotic treatment was found to be a good alternative to isotretinoin, regardless of the presence of antibiotic-resistant P. acnes, although isotretinoin had a better effect, with prolonged remission after treatment.     

Evaluation of a therapeutic strategy for the treatment of acne vulgaris with conventional therapy

Four hundred and twenty patients with moderate to severe acne vulgaris were treated with oral erythromycin and topical benzoyl peroxide to determine the optimum dose regimes. Our results show that the response was significantly less in patients with a greater severity of acne, with truncal acne and in those with a higher sebum excretion rate. There was a significantly better clinical result in patients given Ig erythromycin daily than in those given 0.5 g daily (plus topical therapy in both groups). The relapse rate on stopping antibiotics is also significantly less in patients given I g daily and this dosage did not produce any increase in side effects. We suggest that any patient requiring oral antibiotics should initially be given I g daily of erythromycin (or tetracycline) for up to six months, plus topical therapy.     

Acne treatment with topical erythromycin and zinc: effect of Propionibacterium acnes and free fatty acid composition

A double-blind investigation has been conducted to examine the effect of topical 4% erythromycin/1.2% zinc acetate solution and its vehicle on quantitative bacterial counts (skin surface washings) of propionibacterium acnes and the free fatty acids of the skin surface. The logarithmic counts for P. acnes in the erythromycin/zinc group showed a significant reduction (98%) following 10 weeks of therapy. This compared with a 43% change shown for the vehicle-control group. A significant reduction (69%) in the percentage of free fatty acids in the surface lipids was seen at week 4 in the erythromycin/zinc group as compared to the control group. Triglyceride levels were significantly increased at all time points for the erythromycin/zinc group as compared to the control group. There was also a significant decrease (69%) in inflammatory lesions shown for the erythromycin/zinc treatment group at week 8 as compared to a 9% reduction in the control group.     

Über den Einfluß der Tetracyclintherapie bei Acne vulgaris auf Menge und Zusammensetzung der Hautoberflächenlipide bei verschiedener Dosierung

Zusammenfassung Bei 25 Acnekranken wurden vor und nach einer 8 wöchigen Tetracyclintherapie die Menge der Hautoberflächenlipide und die nach Entfetten in 2 Std ersetzte Lipidmenge bestimmt. Außerdem wurden die Hautoberflächenlipide jeweils dünnschichtchromatographisch analysiert. 13 Patienten erhielten 8 Tage lang 1 g Oxytetracyclin täglich und dann 7 Wochen lang 100 mg Oxytetracyclin täglich; die restlichen 12 Patienten erhielten 8 Wochen lang täglich 1 g Oxytetracyclin. Während die Quantität der Hautoberflächenlipide unbeeinflußt blieb, kam es bei der höheren Dosierung zu einer signifikanten Verminderung des Anteils der freien Fettsäuren, der Wachsester und des Cholesterin an den Hautoberflächenlipiden zugunsten der Triglyceride. Bezüglich der freien Fettsäuren und der Triglyceride fanden sich bei der niedereren Dosierung die gleichen Verhältnisse.

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Skin surface lipids: qualitative and quantitative determination after tetracycline therapy in acne vulgaris. I

Summary Quantitative determination of the skin surface lipids was carried out in 25 patients with acne before and after treatment with tetracycline for 8 weeks. Determinations were performed immedeately and 2 h after defatting the skin surface. In addition, the lipids were analysed by thin-layer-chromatography. 13 patients received 1 g oxytetracycline per day for 8 days which was followed by a daily administration of 100 mg oxytetracycline for 7 weeks. In 12 patients 1 g oxytetracycline was administrated daily for 8 weeks.Quantitatively there was no change in the amount of skin surface lipids recovered. The group of patients treated with higher dosage tetracycline showed significant reduction of free fatty-acids, wax esters and cholesterol, while the amount of triglycerides was elevated. This free fatty acids-triglyceride relation was also observed in the group of patients treated with low dosage tetracycline.

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Wir danken Herrn Dipl. Chem. W. Wiegand für die Beratung bei der Durchführung der Versuche.     

A comparison of comedonal and skin surface lipids from hairless dogs showing clinical signs of acne

Certain animals in a colony of hairless dogs (Mexican Hairless x Beagle) display the clinical features of acne vulgaris, including both open and "closed" comedones, milia, pustules, and abscesses. In order to compare the canine disease with human acne, lipids from the various types of noninflamed lesions and from the skin surface were analyzed by thin-layer (TLC) and gas-liquid (GLC) chromatography. TLC of total nonhydrolyzed lipid from comedones and milia gave similar patterns, with free sterol, ceramides, and free fatty acids comprising the bulk of the material and sterol esters and wax diesters as minor components. Skin surface samples contained mainly sterol esters and wax diesters, with smaller amounts of free sterol and only trace amounts of ceramides. GLC analysis of total hydrolyzed fatty acids from comedones showed similar patterns for the various lesions types, with 22 to 26 carbon acids comprising 55-65% of the total; these acids comprised only 19% of the total hydrolyzed skin surface samples. Analyses by argentation TLC and GLC/mass spectrometry showed the lesional lipids contained significant amounts of alpha-hydroxy-16:0, 16:1, 18:1 and 18:2, but only trace amounts of these appeared in the surface lipid. Fatty acid analysis of individual lipid classes show that the long chain, saturated fatty acids occur predominantly in the free fatty acid and polar lipid fractions and not in the wax diester of sterol ester fractions. Since wax diesters and sterol esters are products of sebaceous gland lipid synthesis, whereas free sterols, fatty acids, and ceramides are characteristic epidermal lipids, the data indicate that the lipids obtained from the acne lesions of dogs are primarily epidermal in origin and that sebaceous gland contribution is minimal in plugged follicles.     

Über das Verhältnis der freien und veresterten Fettsäuren im Laufe der Behandlung der Akne vulgaris mit Tetracyclinen

Zusammenfassung Die Autoren zeigten, indem sie die infrarote Spektroskopie zur Darstellung der fettartigen Substanzen der Hautoberfläche verwendeten, daß die oral gegebene Tetracyclinbehandlung bei der Akne vulgaris nicht in jedem Fall die Quantität der freien Fettsäuren im Talg herabsetzt. Andererseits konnten sie zeigen, daß sich die Menge der freien Fettsäuren in den fettartigen Substanzen der Hautoberfläche bei wiederholter Darstellung der Spektren binnen einigen Tagen, auch ohne jegliche Behandlung, veränderte.

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Summary Examining the infra-red spectra of the skin surface lipids in cases of acne vulgaris treated with tetracyclines orally, the authors showed that the quantity of free aliphatic fatty acids did not decrease in every case after this treatment. Moreover, in some cases the quantity of the free fatty acids decrease in the same person without any treatment within a few days.

     

Optimizing use of oral antibiotics in acne vulgaris

Oral antibiotics are commonly used to treat acne vulgaris, primarily in patients presenting with moderate to severe facial or truncal disease severity. These agents are most appropriately used in combination with a topical regimen containing benzoyl peroxide and a topical retinoid. The most common oral antibiotics for treating acne vulgaris are the tetracycline derivatives, although macrolide agents such as erythromycin have also been used extensively. Over the past 4 decades, as the sensitivity of Propionibacterium acnes to several oral and topical antibiotics has decreased, the efficacy of oral tetracycline and erythromycin has markedly diminished, leading to increased use of doxycycline, minocycline, and other agents, such as trimethoprim/sulfamethoxazole.     

Topical clindamycin treatment of acne. Clinical, surface lipid composition, and quantitative surface microbiology response

A double-blind study has been conducted to examine the effect of topical 1% clindamycin hydrochloride hydrate in a hydroalcoholic vehicle as compared to the effect of the vehicle alone. Fourteen patients applied clindamycin or vehicle alone twice daily for eight weeks. Free fatty acid surface lipid percentages, quantitative bacterial counts, and clinical response were assessed every two weeks. A significant reduction (88%) in the percentage of free fatty acids in the surface lipids was seen in the clindamycin-treated group and not in the vehicle-treated group. There was no significant change in the surface microflora. Despite the short duration of treatment, objective clinical improvement was seen in three of nine treated patients, while none was observed in the placebo-treated patients.     

THE EFFECT OF CLINDAMYCIN IN ACNE-A CLINICAL AND LABORATORY INVESTIGATION

Summary.— Skin surface lipid composition and sebum excretion rate were determined before and after one and 2 months of therapy in patients taking clindamycin for severe acne vulgaris. All patients showed marked clinical improvement. Clindamycin produced a significant reduction in skin surface free fatty acids and a significant reciprocal increase in skin surface triglycerides after one and 2 months of therapy. There was no significant change in the sebum excretion rate. These results support the hypothesis that free fatty acids are important in the pathogenesis of acne vulgaris.     

A double-blind study of the effects of 13-cis-retinoic acid on acne, sebum excretion rate and microbial population

Forty-eight acne patients were treated orally with 13-cis-retinoic acid in a double-blind dose response study. There was a marked clinical improvement with a concomitant reduction in sebum excretion rate (SER) and production rate of free fatty acids (FFA). Microbial numbers decreased significantly; the decrease in propionibacteria was greater than that of aerobic bacteria. The decline in micro-organisms occurred after the reduction in sebum and FFA production. This suggests that the effect of the drug upon micro-organisms is secondary to the change in sebum excretion but it is nevertheless an important factor in the resolution of the acne.     

Antibiotic resistance patterns in coagulase-negative staphylococci after treatment with topical erythromycin, benzoyl peroxide, and combination therapy

Antibiotic resistance of the resident cutaneous bacterial flora is a well recognized consequence of systemic antibiotic therapy. In this study, we followed the development of antibiotic resistance of coagulase-negative staphylococci (CNS), the most numerous aerobic bacteria found on the skin surface, during treatment with three topical antimicrobial agents used to treat acne vulgaris. Groups of 20 subjects received either topical erythromycin, benzoyl peroxide or a combination of the two for 16 weeks. After 12 weeks of treatment with erythromycin, the aerobic flora was dominated by S. epidermidis which was completely resistant to erythromycin. In addition there was an increase in resistance to clindamycin and tetracycline. Treatment with benzoyl peroxide and the combination of erythromycin and benzoyl peroxide resulted in a significant reduction in the number of aerobic bacteria without any change in the resistance pattern to erythromycin or other antibiotics.     

Acne vulgaris: is the bacterial population size significant?

The levels of Propionibacterium acnes (P. acnes) and members of the Micrococcaceae were enumerated in two separate studies. The first investigation on the foreheads of thirty-five mild and thirty-five moderate acne patients showed no significant difference in the bacterial populations of the two groups. The second investigation of twelve patients on 250 mg tetracycline twice daily for 3 months showed no significant difference compared to pre-treatment data in the bacterial population during the successful treatment period. The data indicate that greater numbers of bacteria are not associated with increasing severity of acne and that the effectivenss of oral tetracycline in treating the disease can not be explained by a reduction in the number of viable bacteria.     

Azithromycin for the treatment of acne

BACKGROUND: Acne affects a large number of young adults, including women, who often present with facial as well as truncal involvement. Systemic antimicrobial agents currently used for the reduction of inflammatory papules and cysts require frequent administration and are sometimes associated with uncomfortable side-effects contributing to a decrease in compliance. METHODS: Ninety-nine episodes of inflammatory acne in 79 patients treated with oral antimicrobial agents were studied retrospectively over a period of 46 weeks. Patients were treated with tetracycline, erythromycin, minocycline, and doxycycline, the most commonly prescribed oral antimicrobials used to treat acne. Individuals that were unable to tolerate this therapy or had failed conventional therapy were treated with the azalide antibiotic azithromycin, given in a single oral 250-mg dose three times a week. The other agents were administered daily in divided doses as is current practice. Patients were also on topical care. RESULTS: The efficacy and reported side-effects were examined for all agents. Significant improvement was noted in 4 weeks. All agents were effective in reducing inflammatory lesions and improving acne. Azithromycin produced a slightly higher percentage of patients with a greater than 80% reduction in their inflammatory acne lesions (85.7%) vs. an average of 77.1% for all other agents. All differences observed were not statistically significant. CONCLUSIONS: The results show that azithromycin is a safe and effective alternative in the treatment of inflammatory acne with few side-effects and good compliance, and suggest the need for further investigation with a clinical trial that will compare the long-term efficacy and tolerability.     

Topical clindamycin versus systemic tetracycline in the treatment of acne: Results of a multiclinic trial

In a multiclinic double-blind trial, 305 patients with moderate to severe acne vulgaris were treated with oral tetracycline hydrochloride, 250 mg (N: 103), a 1% solution of clindamycin phosphate (N: 105), or placebo (N: 97) twice daily for 8 weeks. The response to treatment was evaluated by lesion counts and overall clinical improvement at 2, 4, 6, and 8 weeks. Both topical clindamycin and oral tetracycline significantly reduced papule and pustule counts compared to placebo; they were rated significantly higher than placebo on the physician's and the patient's overall evaluation at the end of the treatment period. No serious side effects were reported with any of the study medications.     

Clinical evidence of the endocrinological influence of a triphasic oral contraceptive containing norgestimate and ethinyl estradiol in treating women with acne vulgaris. A pilot study

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the efficacy of a triphasic combination oral contraceptive (OC) containing norgestimate and ethinyl estradiol in the treatment of women with acne vulgaris. METHODS: 12 female patients were included and 10 completed the trial. Over a period of 6 months, efficacy was assessed by means of facial acne lesion counts, by an investigator's global assessment, by patients' self-assessments and by measuring epidermal moisture and skin surface lipids. In addition, a photo documentation was compiled and hormone levels were measured. RESULTS: After 6 months of therapy, the number of acne counts improved. The success of treatment was rated positively both by the investigator and by all patients but one who did not report any changes. Skin surface lipids were significantly reduced while skin hydration showed no significant change. Testosterone and progesterone decreased, and sex-hormone-binding globulin increased, significantly. CONCLUSION: Our data show that an OC containing norgestimate and ethinyl estradiol is a good therapeutic option for women of fertile age suffering from mild to moderate acne vulgaris.     

Effect of systemic erythromycin stearate on the inflammatory lesions and skin surface fatty acids in acne vulgaris

In a 6-week and double-blind study the efficacy of systemic administered erythromycin stearate and doxycycline was compared in 56 patients with facial acne vulgaris. With both antibiotics a statistically significant improvement was demonstrated without any difference between the two groups. No patient had to withdraw therapy due to side-effects. Another part of this investigation correlates the degree of inflammation in acne vulgaris with the fatty acid level in human skin surface lipids before and after systemic erythromycin stearate therapy. This antibiotic reduced the amount of fatty acids 25--50% after a month of medication. The reduction was correlated with a definite clinical improvement in 14 of the 17 patients.     

Topical azelaic acid and the treatment of acne: a clinical and laboratory comparison with oral tetracycline

Topical azelaic acid and oral tetracycline were compared in a 6-month double-blind study for treatment of acne vulgaris in 45 male subjects with clinical acne. Their acne was graded, inflamed or non-inflamed, lesions were counted and the density of their skin microflora was measured. Both treatments were of benefit and produced only a few minor side-effects. Although oral tetracycline was more effective than azelaic acid, the differences were only just significant. The average reduction in numbers of cutaneous micrococcaceae and Propionibacterium sp. with azelaic acid treatment was 224 and 30-fold, respectively. In a separate group of 11 male subjects with physiological acne the effect of azelaic acid on sebum excretion rate was assessed, and little change was detected.     

Importance of intercellular lipids in water-retention properties of the stratum corneum: induction and recovery study of surfactant dry skin

Summary In order to further clarify the role of intercellular lipids in the water-retention properties of the stratum corneum, forearm skin of six healthy male volunteers was treated with 5% sodium dodecyl sulfate (SDS) for 1, 10, and 30 min. All treatment periods induced chapping and scaling of the stratum corneum without any inflammatory reaction, accompanied by a significant decrease in its water-retention function. Electron-microscopic analysis of SDS-treated stratum corneum revealed selective depletion of the lipids from the intercellular spaces, accompanied by marked disruption of multiple lamellae structures. Lipid analysis also showed a considerable and selective loss of intercellular lipids such as cholesterol, cholesterol ester, free fatty acid, and sphingolipids. To evaluate the recovery potential for intercellular lipids, lipids which were separated as sebaceous-rich lipids (SLs) and stratum corneum lipids (SCLs) wer applied daily on SDS-treated forearm skin. Two daily applications of the SCLs which were emulsified at 10% concentration in W/O (water in oil) cream caused a significant increase in conductance, accompanied by a definite improvement in the level of scaling over no application or W/O emulsion base only, whereas SLs in the W/O emulsion base led to no significant recovery in either conductance value or scaling. When two daily topical applications of four chromatographically separated lipid fractions (cholesterol ester, free fatty acid, cholesterol, and sphingolipid) from the SCL were carried out at 1% concentration in the same system, the cholesterol ester and sphingolipid fractions were found to induce a significant increase in the conductance value over no application. In contrast, the free fatty acid and cholesterol fractions showed no significant increase in conductance value. Similarly, the scaling which occurred after SDS treatment had a tendency to decrease after the two daily applications with the fractions of cholesterol ester, sphingolipids, and free fatty acid as compared with that of the base emulsion. These findings strongly suggest that sphingolipids, possibly in combination with other neutral lipids, play an essential role in the establishment or maintenance of water-retention capacity in the stratum corneum.