Acne vulgaris future or investigational therapies

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Future or Investigational Therapies

Blue and Red Light

It has long been known that short term improvement can be achieved with sunlight. However, studies have shown that sunlight worsens acne long-term. More recently, visible light has been successfully employed to treat acne (Phototherapy) - in particular intense violet light (405-420nm) generated by purpose-built fluorescent lighting, dichroic bulbs, LEDs or lasers. Used twice weekly, this has been shown to reduce the number of acne lesions by about 64%;[1] and is even more effective when applied daily. The mechanism appears to be that a porphyrin (Coproporphyrin III) produced within P. acnes generates free radicals when irradiated by 420nm and shorter wavelengths of light.[2] Particularly when applied over several days, these free radicals ultimately kill the bacteria.[3] Since porphyrins are not otherwise present in skin, and no UV light is employed, it appears to be safe, and has been licensed by the U.S. FDA.[4] The treatment apparently works even better if used with red visible light (660 nanometer) resulting in a 76% reduction of lesions after 3 months of daily treatment for 80% of the patients;[5] and overall clearance was similar or better than benzoyl peroxide. Unlike most of the other treatments few if any negative side effects are typically experienced, and the development of bacterial resistance to the treatment seems very unlikely. After treatment, clearance can be longer lived than is typical with topical or oral antibiotic treatments; several months is not uncommon. The equipment or treatment, however, is relatively new and reasonably expensive to buy initially, although the total cost of ownership can be similar to many other treatment methods (such as the total cost of benzoyl peroxide, moisturizer, washes) over a couple of years of use.

Photodynamic Therapy

In addition, basic science and clinical work by dermatologists Yoram Harth and Alan Shalita and others has produced evidence that intense blue/violet light (405-425 nanometer) can decrease the number of inflammatory acne lesion by 60-70% in 4 weeks of therapy, particularly when the P.acnes is pretreated with delta-aminolevulinic acid (ALA), which increases the production of porphyrins. However this photodynamic therapy is controversial and apparently not published in a peer reviewed journal.

Less Widely Used Treatments

  • Azelaic acid (brand names Azelex, Finevin, Skinoren) is suitable for mild, comedonal acne.[6]
  • Zinc: Orally administered zinc gluconate has been shown to be effective in the treatment of inflammatory acne, although less so than tetracyclines.[7][8]
  • Tea Tree Oil (Melaleuca Oil) has been used with some success, comparable to benzoyl peroxide but without excessive drying, and has been shown to be an effective anti-inflammatory in skin infections. [9][10][11]
  • Nicotinamide, (Vitamin B3) used topically in the form of a gel, has been shown in a 1995 study to be more effective than a topical antibiotic used for comparison, as well as having fewer side effects.[12] Topical nicotinamide is available both on prescription and over-the-counter. The property of topical nicotinamide's benefit in treating acne seems to be its anti-inflammatory nature. It is also purported to result in increased synthesis of collagen, keratin, involucrin and flaggrin.
  • There are also certain treatments for acne mentioned in Ayurveda using herbs such as Aloe vera,[13] Aruna, Haldi (Turmeric),and Papaya.[14] There is limited evidence from conventional medical studies on these products.[9] Products from Rubia cordifolia, Curcuma longa (commonly known as Turmeric), Hemidesmus indicus (known as ananthamoola or anantmula), and Azadirachta indica (Neem) have been shown to have anti-inflammatory effects, but not aloe vera.[15]
  • Rofecoxib was shown to improve premenstrual acne vulgaris in a placebo controlled study.[16]
  • Naproxen or ibuprofen are used for some moderate acne for their anti-inflammatory effect.[17]

Future Treatments

A 2007 microbiology article reporting the first genome sequencing of a Propionibacterium acnes bacteriophage (PA6) said this "should greatly enhance the development of a potential bacteriophage therapy to treat acne and therefore overcome the significant problems associated with long-term antibiotic therapy and bacterial resistance."[18]

References

  1. Kawada A, Aragane Y, Kameyama H, Sangen Y, Tezuka T (2002). "Acne phototherapy with a high-intensity, enhanced, narrow-band, blue light source: an open study and in vitro investigation". J Dermatol Sci. 30 (2): 129–35. PMID 12413768.
  2. Kjeldstad B (1984). "Photoinactivation of Propionibacterium acnes by near-ultraviolet light". Z Naturforsch [C]. 39 (3–4): 300–2. PMID 6730638.
  3. Ashkenazi H, Malik Z, Harth Y, Nitzan Y (2003). "Eradication of Propionibacterium acnes by its endogenic porphyrins after illumination with high intensity blue light". FEMS Immunol Med Microbiol. 35 (1): 17–24. PMID 12589953.
  4. "New Light Therapy for Acne" U.S. Food and Drug Administration, FDA Consumer magazine, November-December 2002 Notice
  5. Papageorgiou P, Katsambas A, Chu A (2000). "Phototherapy with blue (415 nm) and red (660 nm) light in the treatment of acne vulgaris" (PDF). Br J Dermatol. 142 (5): 973–8. PMID 10809858.
  6. MedlinePlus (2001-07-24). "Azelaic Acid (Topical)".
  7. Dreno B, Amblard P, Agache P, Sirot S, Litoux P (1989). "Low doses of zinc gluconate for inflammatory acne". Acta Derm Venereol. 69 (6): 541–3. PMID 2575335.
  8. Dreno B, Moyse D, Alirezai M, Amblard P, Auffret N, Beylot C, Bodokh I, Chivot M, Daniel F, Humbert P, Meynadier J, Poli F (2001). "Multicenter randomized comparative double-blind controlled clinical trial of the safety and efficacy of zinc gluconate versus minocycline hydrochloride in the treatment of inflammatory acne vulgaris". Dermatology. 203 (2): 135–40. PMID 11586012.
  9. 9.0 9.1 Mantle D, Gok MA, Lennard TW (2001). "Adverse and beneficial effects of plant extracts on skin and skin disorders". Adverse drug reactions and toxicological reviews. 20 (2): 89–103. PMID 11482001.
  10. Koh KJ, Pearce AL, Marshman G, Finlay-Jones JJ, Hart PH (2002). "Tea tree oil reduces histamine-induced skin inflammation". Br. J. Dermatol. 147 (6): 1212–7. PMID 12452873.
  11. Khalil Z, Pearce AL, Satkunanathan N, Storer E, Finlay-Jones JJ, Hart PH (2004). "Regulation of wheal and flare by tea tree oil: complementary human and rodent studies". J. Invest. Dermatol. 123 (4): 683–90. doi:10.1111/j.0022-202X.2004.23407.x. PMID 15373773.
  12. Shalita A, Smith J, Parish L, Sofman M, Chalker D (1995). "Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris". Int J Dermatol. 34 (6): 434–7. PMID 7657446.
  13. "Greenleaf Aloe Vera Gel". Brihans.
  14. Ayurveda Encyclopedia, "Acne Treatment"
  15. Jain A, Basal E (2003). "Inhibition of Propionibacterium acnes-induced mediators of inflammation by Indian herbs". Phytomedicine. 10 (1): 34–8. PMID 12622461.
  16. Tehrani R, Dharmalingam M (2004). "Management of premenstrual acne with Cox-2 inhibitors: A placebo controlled study". Indian J Dermatol Venereol Leprol [serial online]. 70: 345–348. Retrieved 2007-06-23.
  17. Dermnet NZ-Acne management
  18. Farrar MD, Howson KM, Bojar RA, West D, Towler JC, Parry J, Pelton K, Holland KT (2007). "Genome sequence and analysis of a Propionibacterium acnes bacteriophage" (PDF). J Bacteriol. 189 (11): 4161–7. PMID 17400737.

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