|Year : 1992 | Volume
| Issue : 5 | Page : 323-327
Evaluation of topical erythromycin and topical lactate with or without systemic ketoconazole in acne vulgaris
Lalthleng Liani, JS Pasricha
Source of Support: None, Conflict of Interest: None
Four groups of 16 patients each, having acne vulgaris, were treated with (1) 5% lactate lotion, applied all over the face twice a day, (2) 5% lactate lotion topically along with 200 mg ketoconazole orally per day, (3) 2% erythromycin lotion topically all over the face twice a day, and (4) 2% topical erythromycin lotion with oral ketoconazole, respectively. The efficacy of these regimes was evaluated by counting the number of comedones, inflammatory lesions, and cysts separately, before starting the treatment and at 4, 8, and 12 weeks of treatment. Percent reduction in the number of inflammatory and comedonic lesions respectively at the end of 3 months of treatment was 61 .1 % and 44.0% with lactate lotion, 62.6% and 32.8% with lactate lotion combined with oral ketoconazole, 66.4% and 62.2% with erythromycin lotion alone, and 78.1% and 48.8% with erythromycin lotion and oral ketoconazole.
The overall improvement was graded into 3 categories i.e.,. excellent response, moderate response, and poor response. Lactate lotion produced excellent, moderate, and poor responses in 3,10, and 3 patients respectively; lactate lotion with ketoconazole in 1,12, and 3 patients; erythromycin lotion alone in 4,8, and 4 patients; and erythromycin lotion with ketoconazole in 1, 15, and nil patients respectively with respect to the inflammatory lesions. The results with respect to the comedonic lesions were 3, 7, and 6 patients; 1, 6, and 9 patients; 4, 6, and 6 patients; and 1, 8, and 7 patients in the respective categories. All the agents were well tolerated.
Keywords: Acne, Lactate lotion, Erythromycin lotion, Ketoconazole
|How to cite this article:|
Liani L, Pasricha J S. Evaluation of topical erythromycin and topical lactate with or without systemic ketoconazole in acne vulgaris. Indian J Dermatol Venereol Leprol 1992;58:323-7
|How to cite this URL:|
Liani L, Pasricha J S. Evaluation of topical erythromycin and topical lactate with or without systemic ketoconazole in acne vulgaris. Indian J Dermatol Venereol Leprol [serial online] 1992 [cited 2020 Feb 19];58:323-7. Available from: http://www.ijdvl.com/text.asp?1992/58/5/323/3837
| Introduction|| |
A large variety of therapeutic agents have been proposed for the treatment of acne, each agent having its specific effect on one or more of the aetiopathogenic mechanisms. Since bacterial infection plays a significant role in the severer forms of acne, a large proportion of the anti-acne agents consists of antibacterial agents and almost all of them are fairly effective.,, The major problem in the treatment of acne however, is that acne tends to recur whenever the treatment is stopped. It is therefore necessary to design a treatment schedule which can be adopted as part of the daily routine and is safe even when continued for several years because the treatment for acne has to be continued till the patient attains the age when the acne regresses spontaneously. We are reporting our results of treatment with 2 topical agents namely lactate lotion and erythromycin lotion with and without oral ketoconazole.
| Material and Methods|| |
Sixty four patients having acne vulgaris were taken up for this study, but pregnant patients or those who were taking contraceptive pills or other drugs especially systemic antibiotics or those having other diseases requiring concomitant treatment were not included. These patients were randomly divided into 4 groups of 16 patients each. One group was treated with lactate lotion prepared by mixing 5 ml lactic acid with 25 ml glycerol and made to 100 ml with distilled water; the second group was treated with lactate lotion topically supplemented with oral ketoconazole 200 mg tablet a day; the third group was treated with 2% erythromycin lotion topically, and the fourth group with 2% erythromycin lotion topically along with ketoconazole orally. The lotions were applied all over the face twice a day and the patients in group I and III were given placebo capsules containing glucose to match the treatment for the other 2 groups given oral ketoconazole. All patients were asked to wash their face with an ordinary soap before applying the topical medicines, but not to wash the face in between the applications. They were also required to shampoo their hair as frequently as possible, and not to apply any oil, cream, or any other greasy cosmetic to their hair or skin. There were no dietary prohibitions.
The response to treatment was evaluated by counting the number of comedones (open and closed), inflammatory lesions (papules and papulopustules), and cysts separately, before starting the treatment and at 4, 8, and 12 weeks of treatment. The counting of lesions was limited to the face only. The improvement was judged by calculating the percent reduction in the number of each category of lesions for each patient at the end of 12 weeks of treatment. Patients with a reduction by 90-100% were considered to have an excellent response, those with a reduction by 5090% were considered to have good response, while those having a reduction by less than 50% were considered to have poor response. In addition, at each visit, the patient was asked about the cosmetic acceptability or any side effects of this treatment. Patients given oral ketoconazole were also evaluated for any possible hepatotoxicity by estimating the levels of transaminases before starting the treatment and also at 4 and 12 weeks of treatment.
| Results|| |
All 4 treatment regimes produced a progressive reduction in the number of lesions in a majority of the patients. This reduction was evident even after the first 4 weeks of treatment and continued further as the treatment was continued. The inflammatory lesions responded better as compared to the non inflammatory lesions. The average percent reduction in the number of inflammatory as well as the non inflammatory lesions, and the degree of improvement obtained with the 4 treatment regimes are shown in [Table - 1][Table - 2] respectively. There were however, 9, 8, 7, and 3 patients respectively in the 4 groups in whom the number of inflammatory lesions actually increased at one stage or the other during the treatment period. In most (7, 4, 2, and 2) of these patients, the increase in the number of lesions was only 1 or 2 lesions and therefore insignificant, though in 2 patients in group I the increase was by 5 and 14 lesions, in 4 cases in the group II the increase was by 3, 3, 6, and 7 lesions, in 5 cases in group III the increase was by 3, 3, 4, 8, and 8 lesions respectively and in 1 case in group IV the increase was by 4 lesions. With continued treatment, however, in all these cases except in 1 case in group I, the number of lesions eventually decreased and at the end of 12 weeks the final number of lesions was less than the number before starting the treatment.
The comedonic lesions present in all the cases and the cystic lesions present in only a few cases in each group also showed similar trends though the percent reduction in the number of comedonic lesions was relatively less, while the cystic lesions were slower to respond.
Statistically, the differences between the various groups were not significant.
With lactate lotion, 4 patients complained of a feeling of greasy ness on the skin, and another 4 patients complained of a burning or pricking sensation on the skin. Erythromycin lotion produced dryness of the skin, burning, and itching sensation in 4, 8, and 4 cases respectively. In none of these cases the side effects were severe enough to necessitate stoppage of the treatment No case showed evidence of contact hypersensitivity. Ketoconazole also was well tolerated by the patients; the levels of SGOT and SGPT remained within normal limits in all the patients given oral ketoconazole.
| Comments|| |
Since the tendency to develop acne is likely to continue for' several years, the mainstay of treatment should preferably be a safe topical treatment. It is for this reason that we decided to try topical lactate and topical erythromycin. Both the agents were found to be almost equally effective though erythromycin seemed to produce a slightly superior effect. Topical erythromycin has been tried in several previous studies and found to be useful., The main limitations of topical erythromycin would be, (1) that as a general rule antibiotics which are used systemically, are not applied topically, and (2) topical antibiotics have a variable chance of causing contact hypersensitivity.  Since its introduction in 1974, sub erythromycin has been used extensively in patients having acne but the instances of contact hypersensitivity are extremely rare. In the 16-centre survey on the causes of contact dermatitis conducted in India recently, erythromycin was not included for routine testing but none of the cases had been suspected to have contact hypersensitivity to erythromycin. sub Thus for practical purposes, erythromycin can be considered to be a safe and effective anti-acne agent.
Lactic acid, secreted by the eccrine sweat glands and a component of the normal lipid surface film of skin sub is a strong antibacterial agent against the common pathogens sub and also P. acnes, , and it is believed to contribute to the first line of defense against invading organisms.  Under a hypothesis that persons who develop severe acne could be secreting less lactic acid in their skin, lactic acid/sodium lactate  and ethyl lactate  were proposed as a remedy for acne and found to be effective. Lactic acid being a natural secretion of the skin, the chances of bacterial resistance to the agent or contact hypersensitivity are practically nil. The authors have not come across any case of contact dermatitis due to lactic acid/sodium lactate during the last 20 years of its clinical use. Nevertheless, by virtue of its ability to lower the pH of the skin, lactic acid often produces a stinging sensation over raw areas of the skin especially in freshly shaved areas, open wounds, or excoriated lesions. This sensation is transitory and lasts only a few seconds. Applications of large quantities of lactic acid/lactate on the skin may occasionally lead to a superficial cauterization of the skin which is followed by peeling of the skin. This reaction leads to a quicker clearance of the lesions, but if often scares the patient. Lactate lotion is, therefore, better applied with finger tips and the quantity of lactate required to produce optimum therapeutic effect is just the amount which disappears into the skin after a gentle massage.
The main effect of antibacterial agents is to control the bacterial flora of the skin and thus prevent the appearance of acne lesions. It is therefore necessary to apply the antibacterial agent (like a cosmetic) all over the acne-prone areas rather than limit the application to the acne lesions only.  Generally 2 applications a day provide adequate concentration of the agent for the major part of the day and night, but it is essential to instruct the patient not to wash off the agent after its application and in case the face is washed or the agent gets removed because of excessive sweating or wiping; the agent must be applied again.
Topical applications of antibacterial agents are essentially a preventive measure and thus the applications have got to be continued till the patient reaches the stage when he/she is no more prone to develop acne. sub If the treatment is discontinued earlier, the acne lesions are likely to reappear.
In a majority of the patients, acne can be kept under appropriate control with a regular use of the topical applications, though an occasional lesion may keep appearing once in a while. Under certain conditions however, as during summer and rainy season, in the premenstrual phase or during periods of emotional tension,  several acne patients are known to have aggravations in spite of topical therapy. During these phases, therefore, it would be appropriate to reinforce the topical treatment with systemic drugs. Most of the systemic antibiotics/antibacterial agents can be useful  unless the bacteria are resistant to the antibiotic used. Two factors however need careful consideration (1) the systemic antibiotic must be continued for 4-12 weeks for an optimum effect, and (2) smaller . doses of antibiotics as recommended in some previous studies run the risk of inducing bacterial resistance fo the antibiotic when used for prolonged periods as required for acne patients. We therefore recommend systemic antibiotics in full therapeutic doses and once the optimum therapeutic result is achieved, withdraw the same completely and revert the patient to the topical regime again. 
sub Ketoconazole can have a dual effect on acne vulgaris because it can act as an antibacterial agent for the cutaneous flora  and also has an antiandrogenic effect.  Whereas the cutaneous flora are adequately suppressed with a dose of 200 mg a day, it is necessary to use upto 600 mg a day for the antiandrogenic effect.  In our study therefore, the main effect of ketoconazole was presumably only antibacterial and not antiandrogenic. We did not use a higher dose of ketoconazole to produce an antiandrogenic effect because with higher doses there is an added risk of gynaecomastia and impotence in the males and disturbance of the menstrual cycle in the females. 
In the present study, we did not get spectacular results by adding oral ketoconazole, but since there was a general tendency to use ketoconazole for more severe cases of acne, and the results with ketoconazole were better than without it, it can be used as one of the systemic agents in case topical therapy alone is not adequate to control acne effectively.
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[Table - 1], [Table - 2]
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