Keratolytics like SA are commonly used as first-line therapy in mild cases of acne because of their widespread availability OTC. SA is widely used as a topical thera- peutic agent for a variety of skin diseases, including acne, psoriasis, dandruff, and ichthyosis. Concentrations of SA ranging from 0.5% to 10% have been rec- ommended for acne, but the maximum strength allowed in nonprescription acne products in the United States is up to 2% by the FDA Final Acne Monograph. At higher concentrations up to 40%, SA is also used for wart and corn removal.
Why Does Salicylic Acid Have Such a Good Reputation in Acne?
As the microcomedone is believed to be the precursor to all acne lesions, it is logical to treat it with a comedolytic agent that will counteract the plugging of the follicles. SA is an effective drug for this due to its keratolytic activity. Although SA has long been used as a keratolytic agent, the mechanism of action remains unsolved. The action may occur due to the reduced cohesion between corneocytes, resulting in the shedding of epidermal cells, rather than “lysing” of keratin. This was investi- gated in numerous studies. In 1943, it was first claimed that SA acts by producing epidermal irritation, but there has been no substantiation of this finding (67). Further studies suggested that the keratolytic effect of SA consists of a reduction of intercellular stickiness, thereby reducing corneocyte adhesion. The so-called cementing substances are the site of action and not the stratum corneum itself (68 – 70). No damage of the living epidermis is caused by SA and it has been shown to cause no epidermal change beneath the stratum corneum (68). Further- more, there is no evidence that it works by lysing keratin. Keratin is a tough fibrous protein that remains in the intracellular region and it is regarded as unlikely that agents that promote desquamation do so by attacking this material (71). SA has no effect on the mitotic activity of the normal epidermis (69) and therefore does not influence the disordered cornification itself.
While the mechanism of action of SA’s main property remains uncertain, an additional action is well-established. Besides the keratolytic action of SA within the pilosebaceous unit, the value of the antibacterial action is often neglected. Since antibacterial colonization in the pore is deemed to be a main cause for spot
formation, the use of antibacterials in acne treatment or prevention plays a major role, as discussed earlier.
The antibacterial action of SA against P. acnes has been demonstrated in both in vitro and in vivo studies. MIC was determined at 0.25% (w/w) using the plate method. In vivo measurement also reveals the efficacy of SA within the pore, expected as penetration occurs through the transfollicular root to the follicle (72 – 75). Having penetrated into the pore, SA can start to work and inhibit bacteria growth.
SA also offers anti-inflammatory benefits in acne therapy, which have been reported in the literature (73,74,76). Anti-inflammatory activity was investi- gated using the UV model (76). Upon topical application to the skin of guinea pigs with UV dermatitis, SA exerted a distinct anti-inflammatory effect, which was most pronounced at concentrations between 0.5% and 5%. Its integrated activity over the range of concentrations tested, that is, from 0.05% to 5% and over a period from 4 to 26 hours after irradiation, equals that of the contact antiphlo- gistic agent bufexamac, which is a well-established active in clinical use (76).
The anti-inflammatory effect of SA might be adjuvant in acting not only against non-inflammatory but also against inflammatory lesions. Many clinical studies have proven the anti-acne efficacy of SA-containing products (77,78).
For instance, one study demonstrated that twice daily application of 2% SA alcohol-detergent lotion impregnated into pads was significantly better than the placebo in the treatment of mild-to-moderate acne. Significant benefit from the active therapy was evident at four, eight, and 12 weeks when total lesion counts were assessed. Regarding noninflamed lesions superiority over placebo could be demonstrated after eight and 12 weeks and for inflamed lesions after 12 weeks. These results strengthen the suggestion that SA has a primary effect on comedogen- esis. The observation that inflamed lesions were reduced at a later date could be explained by the fact that inflamed lesions arise from noninflamed lesions. There- fore, the efficacy against comedones will prevent the development of inflamed lesions, though this a lagged efficacy (77).
Another double-blind, controlled study evaluated the efficacy of 0.5% SA in an alcohol-detergent solution and placebo (pads soaked in buffered water). SA was shown to be more effective in reducing open and inflamed lesions than placebo (78).
Furthermore, efficacy has been proven in a comparative study with BPO, which will be discussed separately.
Is There Another Use for Salicylic Acid Other than in Anti-acne Cosmetics?
SA can also be used as a peeling agent in high concentrations. However, at these high levels of SA, irritation or other adverse events are very likely and therefore such peelings must be done under the supervision and strict control of a physician.
SA peels are available in 20% and 30% concentrations. In general, superficial chemical peels are an invaluable accoutrement for dermatologists when treating fine wrinkles, photoageing, keratoses, acne, and dyspigmentation. It could be shown that SA peels facilitated the clearing of pustules, papules, and comedones. Moderate-to-significant clearing of acne vulgaris was also demonstrated (79). A further study using 20% to 30% SA in a hydroethanolic vehicle demonstrated that SA is useful as a single or multiple peeling agent for acne as well as for photo- damage and hyperpigmentation. SA as a peeling agent was useful for both come- donal and papular acne. Areas of intense inflammation showed decreased erythema, and pustules were rapidly dried at one or two days postpeel. Many
closed and open comedones were extruded by several days postpeel (80). When applied under strict control and indication, the SA peels can be regarded as safe and efficacious, and offer adjunctive benefit when treating acne vulgaris.
Comparison of Benzoyl Peroxide and Salicylic Acid
BPO and SA are both indicated for use in mild-to-moderate acne, but their main action of mechanism is different. While BPO has a strong antibacterial action, SA acts through a keratolytic action. Does this different action have any impact on the efficacy of the products? Is BPO more effective against inflamed lesions while SA predominantly acts against noninflamed lesions? Comparative studies demon- strated similar efficacy of both products or even slight superior efficacy of SA.
In a four-week crossover study, the efficacy of a 2% SA acne cleanser was compared with that of 10% BPO wash in the treatment of 30 patients with mild- to-moderate acne. The results demonstrated that only patients treated with the SA cleanser had a significant reduction in the number of comedones. However, when patients crossed over to BPO, acne worsened over the following two weeks and the number of comedones slightly increased. In contrast, the number of come- dones decreased in patients who first used BPO and then crossed over to SA. These results suggest that SA is more effective than BPO for the treatment of comedonal acne (81).
In another, 12-week double-blind study with 180 subjects, 2% SA, the vehicle solution, and a 5% BPO cream were compared. Surprisingly, SA was not only found to produce a substantially greater reduction from baseline in the number of comedones but also a reduction in inflammatory lesions when compared with
5% BPO (Fig. 4) (82).
The observed superiority of SA might be due to its mode of action. Since the primary lesion of acne is the microcomedo, a treatment that is effective in prevent- ing its formation will be effective in preventing inflammatory lesions into which the microcomedo can progress. As the action of SA is mainly keratolytic, it interferes in an earlier stage than BPO, and in consequence it seems to be superior in acting against later steps, the inflamed lesions. When evaluating the results of these
studies, it is also important to consider the different bases of the formulations. In order to obtain comparable data, identical formulation bases would have needed to be used to avoid any impact or efficacy of the base itself. Taken as a whole, BPO and SA are expected to have a similar efficacy in the treatment of mild-to-moderate acne with slight superiority of SA against comedones (Table 6).
The mainstay of acne treatment, particularly for mild-to-moderate acne, is topical medication. Most cases of comedonal or papular acne can be controlled without systemic therapy. Several actives exist for acne therapy, some of them can be used in cosmetic products and some are only available by prescription.
Although there are numerous newer antiacne actives available with different mechanisms of action, the old-timers BPO and SA are still the gold standard in mild-to-moderate acne treatment, particularly for cosmetics or OTC drugs. They can be used as mono-therapy or combined with other acne products, in order to achieve better efficacy or better tolerability.
A comprehensive range of data shows that both actives have been well- established in dermatology. They are effective and safe for use in mild-to-moderate acne.
The author would like to thank Nadine Selle, Carmen Matthies, Ed Owen, and
Friedrich Wolf for their help in preparing this manuscript.