Efficacy and Use of Salicylic Acid

15 May

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).

CONCLUSIONS

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.

ACKNOWLEDGMENTS

The  author would like  to  thank Nadine Selle, Carmen Matthies, Ed  Owen,  and

Friedrich Wolf for their  help  in preparing this manuscript.

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