Abstract
Acne vulgaris is a universal skin disease with multifactorial pathogenesis. Although an extensive range of treatment options exist for acne, a substantial number of patients are still struggling for an optimal treatment option due to the side effects or contraindications to the conventional acne treatment. Negative air ions (NAIs) are electrically charged molecules that naturally exist in the atmosphere. Since they are natural component of air, there are no known side effects and contraindications to their application. Furthermore, among the identified benefits of NAIs, certain mechanisms are related to acne pathogenesis, allowing them to be attractive candidates for acne treatment. Here, we describe three patients with acne who showed considerable clinical improvement after NAI therapy. All of the patients had failed to tolerate traditional acne treatment options. In all three cases, considerable improvement was observed in acne severity and the number of total lesions. Based on the three cases and a review of literature underlying the effects of NAIs, we suggest that NAIs may be a safe and effective alternative therapeutic option for acne vulgaris.
Keywords: Acne vulgaris, Complementary therapies, Negative air ions
INTRODUCTION
Acne vulgaris is a common disease of pilosebaceous units, characterized by the release of inflammatory mediators, hyperkeratinization, increased sebum production, and colonization by Cutibacterium acnes1. It is a universal skin disease affecting more than 85% of adolescents, and accounts for more than 30% of patients visiting dermatology clinics2. The current treatment guideline suggests various treatment options, such as topical or oral antibiotics and retinoids, with qualified evidence3. However, these treatment options may be accompanied by various side effects such as antibiotic resistance or skin irritation and be contraindicated for a substantial number of patients who are young, preparing for pregnancy, or have underlying internal diseases. Owing to these limitations, the general public has been opting for more natural and safer treatment options such as complementary and alternative medicine but the evidence for these treatments is often lacking4.
Negative air ions (NAIs) are electrically charged molecules that naturally exist in the atmosphere5. Many experiments have been performed utilizing NAIs, due to their advantage of being natural components of air without any side effects. Dermio Care® (Weyergans High Care AG, Western Rhineland, Germany) is a novel facial treatment device that relies on highly concentrated NAIs, which enrich the surrounding oxygen. The device generates 5.5×106 negative ions/cm3 that encounter the facial skin under a protecting helmet (Fig. 1). The treatment procedure is highly tolerable, and it does not cause any pain or irritation.
We report of three patients with acne who showed considerable clinical improvement after NAI therapy. Patients who had failed to tolerate common treatment methods were selected as candidates for NAI therapy. All patients were instructed to use the same cosmetic products that they had been using before the treatment. NAI therapy was performed using Dermio Care®, which was applied twice a week for 20 minutes in each treatment session. Written informed consent was obtained from the patients and their guardians to publish the photographs and clinical results. To the best of our knowledge, this is the first clinical report regarding NAI therapy for the treatment of acne.
CASE REPORT
Case 1 is that of a 12-year-old girl (Fitzpatrick skin phototype [FST] IV) who presented to our clinic with facial acne. On presentation, she had moderate facial acne with Global Acne Assessment Score (GAAS) (Supplementary Table 1) of 2. Prior to her visit, she had undergone multiple sessions of chemical peeling and acne extraction but had voluntarily stopped the treatment owing to pain and irritation. The patient’s mother had refused administration of topical antibiotics and retinoids because of the young age of the patient. On presentation, the patient had multiple erythematous papules on her cheek and perioral area (Fig. 2A). As part of the protocol, she was treated with Dermio Care® twice a week for 4 weeks, resulting in a total of 8 treatment sessions. Significant improvement was observed on photographic follow-up after 8 sessions of treatment (Fig. 2B).
Case 2 is that of a 14-year-old girl (FST IV) who presented to our clinic with acne lesions that had repeatedly aggravated for 2 years. On presentation, she was graded as GAAS score of 2 with several inflammatory papules and closed comedones on her forehead (Fig. 3A). Prior to her visit, she had been prescribed with topical benzoyl peroxide/clindamycin but had been nonadherent to the treatment owing to skin irritation and inconvenience of daily application. She was treated using the same protocol as used for Case 1, and she tolerated the procedure very well. After 4 weeks of treatment (8 sessions in total), notable improvement of acne lesions was observed (Fig. 3B).
Case 3 is that of a 21-year-old Asian male (FST IV) who presented to our clinic with acne lesions on his mandibular area. On presentation, he was graded as GAAS of 2 with multiple inflammatory acne lesions and brown-colored macules, indicative of post-inflammatory hyperpigmentation (Fig. 4A). Prior to his visit, he had been treated with topical retinoids but had suffered from skin irritation and had voluntarily discontinued the treatment. After 3 weeks of NAI treatment (6 sessions in total), a visible reduction in acne lesions as well as post-inflammatory hyperpigmentation were noted (Fig. 4B).
In all three cases, notable clinical improvement was observed in the severity of acne and the number of total lesions (GAAS score 0 or 1). None of the patients reported any adverse effects of the treatment.
DISCUSSION
The possible therapeutic mechanism of NAIs on acne may be summarized as follows: 1) resolution of the reactive oxygen species (ROS), 2) control of inflammation by activating natural killer (NK) cells, and 3) positive effects on emotions and behaviors.
First, several animal studies have revealed that ROS are significantly reduced upon exposure to NAIs6. Further, the activity of erythrocyte cytosolic superoxide dismutase (SOD) was considerably increased after pretreatment with NAIs7. These results suggest that the NAIs reduce ROS by stimulating SOD, which converts superoxide into hydrogen peroxide. Oxidative stress plays an important role in the pathogenesis of acne. Previous studies have shown that lipid peroxidation is the driving force behind comedogenesis, and neutrophil-derived ROS is involved in acne inflammation8. Thus NAIs may render therapeutic effects on acne lesions by targeting such ROS-related pathogenesis of acne.
Second, a previous animal study showed that NAIs significantly enhanced the cytotoxic activity of NK cells9. The role of NK cells in the pathogenesis of acne has rarely been studied. However, its role in synovitis-acne-pustulosis-hyperostosis-osteomyelitis (SAPHO) syndrome, a chronic inflammatory condition in which acne is the central cutaneous manifestation, has been recently recognized. The proportion and absolute counts of NK cells were considerably reduced in patients with SAPHO, resulting in an uninhibited upregulation of T helper type 17 and 1 (Th17/Th1) cell response10. Interestingly, the Th17/Th1 cell response is enhanced by C. acnes and is thought to be an important immunologic process in the development of acne11. Therefore, it can be speculated that NAIs, by enhancing the cytotoxic activity of NK cells, may reduce inflammation induced by C. acnes.
Last but not least, several studies have suggested that anxious or agitated individuals experience relief upon exposure to NAIs12. Others have shown that NAIs exert protective effects against acute and chronic stress13. The anti-stress effects of NAIs are explained by serotonin-mediated arousal mechanisms and their antihypoxic effects14. Stress is a well-known aggravating factor of acne, and is highly correlated with acne severity15. This association is explained by the stress-induced hormones inducing sebaceous hyperplasia or the stress-related neuroactive substances activating inflammation16. As a result, the positive effects of NAIs against stress may preserve acne against stress-induced aggravation and inflammation.
Based on the three clinical cases of acne patients successfully treated with NAIs, we have discussed the possible mechanisms underlying the effects of NAIs. However, the above-mentioned mechanisms should be further investigated in order to investigate the direct mechanism of action of NAIs on acne. Furthermore, all our patients were young Asians with FST IV, who presented with mild-to-moderate acne (GAAS score 2). Therefore, further studies on larger-scale populations and comparative studies evaluating NAI as a monotherapy vs. in combination with other therapeutic modalities are warranted.
In conclusion, based on these preliminary clinical results, we suggest that NAI therapy has the potential to be an easy, safe, and effective alternative adjuvant therapy for acne. Although NAI therapy may not be considered as a curative therapy, it can be regarded as a valuable adjuvant and complementary treatment for acne. As the general public has been showing an increasing interest in more natural and safer treatment options, it is necessary to further investigate alternative therapeutic options for the treatment of acne vulgaris4,17.
Footnotes
CONFLICTS OF INTEREST: The authors have nothing to disclose.
FUNDING SOURCE: None.
SUPPLEMENTARY MATERIALS
Supplementary data can be found via http://anndermatol.org/src/sm/ad-34-216-s001.pdf.
Supplementary Table 1
Global Acne Assessment Score (GAAS)
ad-34-216-s001.pdf (41.8KB, pdf)
References
- 1.Scholz CF, Kilian M. The natural history of cutaneous propionibacteria, and reclassification of selected species within the genus Propionibacterium to the proposed novel genera Acidipropionibacterium gen. nov., Cutibacterium gen. nov. and Pseudopropionibacterium gen. nov. Int J Syst Evol Microbiol. 2016;66:4422–4432. doi: 10.1099/ijsem.0.001367. [DOI] [PubMed] [Google Scholar]
- 2.Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet. 2012;379:361–372. doi: 10.1016/S0140-6736(11)60321-8. Erratum in: Lancet 2012;379:314. [DOI] [PubMed] [Google Scholar]
- 3.Thiboutot DM, Dréno B, Abanmi A, Alexis AF, Araviiskaia E, Barona Cabal MI, et al. Practical management of acne for clinicians: an international consensus from the Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2018;78(2 Suppl 1):S1–S23.e1. doi: 10.1016/j.jaad.2017.09.078. [DOI] [PubMed] [Google Scholar]
- 4.Fox L, Csongradi C, Aucamp M, du Plessis J, Gerber M. Treatment modalities for acne. Molecules. 2016;21:1063. doi: 10.3390/molecules21081063. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Kosenko EA, Kaminsky YuG, Stavrovskaya IG, Sirota TV, Kondrashova MN. The stimulatory effect of negative air ions and hydrogen peroxide on the activity of superoxide dismutase. FEBS Lett. 1997;410:309–312. doi: 10.1016/s0014-5793(97)00651-0. [DOI] [PubMed] [Google Scholar]
- 6.Livanova LM, Levshina IP, Nozdracheva LV, Elbakidze MG, Airapetyants MG. The protective effects of negative air ions in acute stress in rats with different typological behavioral characteristics. Neurosci Behav Physiol. 1999;29:393–395. doi: 10.1007/BF02461074. [DOI] [PubMed] [Google Scholar]
- 7.Jiang SY, Ma A, Ramachandran S. Negative air ions and their effects on human health and air quality improvement. Int J Mol Sci. 2018;19:2966. doi: 10.3390/ijms19102966. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Akamatsu H, Horio T. The possible role of reactive oxygen species generated by neutrophils in mediating acne inflammation. Dermatology. 1998;196:82–85. doi: 10.1159/000017876. [DOI] [PubMed] [Google Scholar]
- 9.Yamada R, Yanoma S, Akaike M, Tsuburaya A, Sugimasa Y, Takemiya S, et al. Water-generated negative air ions activate NK cell and inhibit carcinogenesis in mice. Cancer Lett. 2006;239:190–197. doi: 10.1016/j.canlet.2005.08.002. [DOI] [PubMed] [Google Scholar]
- 10.Chong WP, van Panhuys N, Chen J, Silver PB, Jittayasothorn Y, Mattapallil MJ, et al. NK-DC crosstalk controls the autopathogenic Th17 response through an innate IFN-γ-IL-27 axis. J Exp Med. 2015;212:1739–1752. doi: 10.1084/jem.20141678. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Kistowska M, Meier B, Proust T, Feldmeyer L, Cozzio A, Kuendig T, et al. Propionibacterium acnes promotes Th17 and Th17/Th1 responses in acne patients. J Invest Dermatol. 2015;135:110–118. doi: 10.1038/jid.2014.290. [DOI] [PubMed] [Google Scholar]
- 12.Sulman FG, Levy D, Levy A, Pfeifer Y, Superstine E, Tal E. Air-ionometry of hot, dry dessert winds(Sharaw) and treatment with air ions of weather-sensitive subjects. Int J Biometeorol. 1974;18:313–318. doi: 10.1007/BF01463721. [DOI] [PubMed] [Google Scholar]
- 13.Baron RA. Effects of negative ions on cognitive performance. J Appl Psychol. 1987;72:131–137. [PubMed] [Google Scholar]
- 14.Livanova LM, Levshina IP, Nozdracheva LV, Kurochkina EV, Elbakidze MG, Aĭrapetiants MG. [The prophylactic effect of negatively charged air ions in acute stress in rats with different typological behavioral characteristics] Zh Vyssh Nerv Deiat Im I P Pavlova. 1996;46:564–570. Russian. [PubMed] [Google Scholar]
- 15.Chiu A, Chon SY, Kimball AB. The response of skin disease to stress: changes in the severity of acne vulgaris as affected by examination stress. Arch Dermatol. 2003;139:897–900. doi: 10.1001/archderm.139.7.897. [DOI] [PubMed] [Google Scholar]
- 16.O’Sullivan RL, Lipper G, Lerner EA. The neuro-immuno-cutaneous-endocrine network: relationship of mind and skin. Arch Dermatol. 1998;134:1431–1435. doi: 10.1001/archderm.134.11.1431. [DOI] [PubMed] [Google Scholar]
- 17.Magin PJ, Adams J, Pond CD, Smith W. Topical and oral CAM in acne: a review of the empirical evidence and a consideration of its context. Complement Ther Med. 2006;14:62–76. doi: 10.1016/j.ctim.2005.10.007. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplementary Table 1
Global Acne Assessment Score (GAAS)
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