|Year : 2014 | Volume
| Issue : 1 | Page : 1-4
Advances in photodermatology in 2013: part I (preclinical and laboratory research)
Medhat El-Mofty, Wedad Z Mostafa, Rehab A Hegazy
Department of Dermatology, Faculty of Medicine, Cairo University, Cairo, Egypt
|Date of Submission||26-Feb-2014|
|Date of Acceptance||03-Apr-2014|
|Date of Web Publication||24-Jul-2014|
Wedad Z Mostafa
MD, 10 Gameyet El Nesr St., Dokki 12311, Cairo
Source of Support: None, Conflict of Interest: None
Photodermatology is the study of the interaction between light, visible and ultraviolet, and the skin. It is one of the major areas of interest for research. The endless pursuit for profound understanding of its mechanisms of action, the real players involved in delivering its therapeutic effects, and those responsible for its deleterious implications deem 'photodermatology' a constantly developing territory. In the coming review, we will discuss some of the important preclinical and laboratory research studies in the domain of photodermatology published during the past year attempting to highlight the latest achievements and findings.
Keywords: 2013, laboratory, photodermatology, research
|How to cite this article:|
El-Mofty M, Mostafa WZ, Hegazy RA. Advances in photodermatology in 2013: part I (preclinical and laboratory research). Egypt J Dermatol Venerol 2014;34:1-4
|How to cite this URL:|
El-Mofty M, Mostafa WZ, Hegazy RA. Advances in photodermatology in 2013: part I (preclinical and laboratory research). Egypt J Dermatol Venerol [serial online] 2014 [cited 2019 May 26];34:1-4. Available from: http://www.ejdv.eg.net/text.asp?2014/34/1/1/136451
| Introduction|| |
The domain of research in photodermatology has always been put under the spotlight with great efforts being spent in trials to reach more profound understanding of this therapeutic tool in its different perspectives. In the coming part, we will throw light on the most important studies concerned with this realm carried out during the past year.
| Mechanisms of action|| |
Phototherapy, T-helper 17 cells, and T-regulatory cells
The study of the possible roles played by both T-helper (Th) 17 and T-regulatory cells (Tregs) in the development and progression of autoimmune diseases  has gained much ground over the past years. The imbalance that exists between both lineages in the form of overexpression of Th17 and downregulation of Tregs is now regarded by many as one of the major culprits in the pathogenesis of diseases such as psoriasis ,, and vitiligo ,,,,,.
Recently, both narrow band (NB)-ultraviolet-B (UVB) and psoralen (P)-UVA radiations have been found to induce a restoration of the Th17/Tregs imbalance in both psoriasis , and vitiligo . A study performed on psoriasis patients concluded that the efficacy of NB-UVB in resolving psoriatic plaques was directly related to reduction in a number of pathogenic cytokines, including interleukin-17 secreted by Th17 and interleukin-22, and that this reduction did not occur in nonresponsive psoriatic plaques . Furthermore, Furuhashi et al.  concluded that P-UVA therapy resolved the Tregs dysfunction present in psoriasis and restored the Th17/Tregs imbalance. Moftah et al.  demonstrated the ability of NB-UVB to significantly reduce both the CD4 + CD25 high Tregs% and FoxP3 + Tregs% populations in nonsegmental vitiligo patients.
It is therefore conceivable that a profound analysis of the mechanisms through which phototherapy exerts its effect on restitution of the balance between both lineages would pave the way for new therapeutic options.
Interference with gene expressions
Li et al.  studied the mRNA expression profiles and differentially expressed genes from peripheral blood T cells of psoriatic patients before and after NB-UVB treatment using RNA sequencing, and results were validated by real-time reverse-transcription PCR. They demonstrated that a total of 129 genes were differentially expressed in the peripheral blood T lymphocytes of psoriatic patients with 83 genes being downregulated and 46 upregulated when compared with healthy individuals. These genes are involved in the cell cycle, apoptosis, inflammation, and some other processes directly linked to the pathogenesis of psoriasis. These genetic changes were reversed in psoriatic patients with good clinical outcomes, highlighting the assumption that the treatment success might, at least partially, be attributed to the effect of NB-UVB on peripheral blood T-cell gene expression. The study draws attention to a different perspective by which phototherapy could act, not only in psoriasis, but also in the whole spectrum of diseases where this line of therapy has proven beneficial.
Differential influence on serum 25-hydroxyvitamin D 3 level
It has been widely accepted that UVB radiation increases serum 25-hydroxyvitamin D 3 [25(OH)D]; however, the influence of UVA1 and UVA/NB-UVB phototherapy on serum vitamin D levels remained obscure. An open nonrandomized study  was carried out on 116 dermatological patients undergoing phototherapy, of whom 38 received UVA1, 30 received both UVA and NB-UVB, and 48 received NB-UVB alone. Treatment was provided two to three times a week and lasted 53-90 days. After completion of phototherapy, it appeared that both NB-UVB and UVA/NB-UVB increased 25(OH)D serum level significantly, whereas UVA1 therapy alone induced a reduction in serum 25(OH)D concentrations. Despite the fact that the influence of a precise skin disease could not be excluded because of the heterogeneous diagnoses included, it remains clear that not all phototherapeutic modalities have a favorable impact on vitamin D concentrations. Thus, it would seem logical to recommend providing supplementary vitamin D for such patients receiving phototherapeutic lines reported to impose a negative influence on vitamin D levels. This recommendation is in need for further studies to validate its beneficial effect on the response as well as on the protection of patients from such a downside.
| New topicals|| |
A novel topical cream that selectively delivers narrow band-ultraviolet-B on sunlight exposure (in-vitro study)
Although the treatment efficacy of NB-UVB artificial light sources is well documented, the long time and cost commitment of therapy remains a barrier to treatment adherence. Natural sunlight is without doubt an ideal source of accessible UVB radiation especially in sunny climates; however, exposure to natural sunlight generally results in erythema before the accumulation of sufficient dosage of therapeutic wavelengths of UVB, sometimes necessitating cessation of treatment. McCoy et al.  introduced a novel topical cream that when combined with natural sunlight permits the therapeutic wavelength of 311 nm to pass and prevents the other wavelengths. This cream contains two molecules that were found best for delivering NB-UVB from natural sunlight: a-glucosyl hesperidin, a glucosylated derivative of a natural plant flavonoid, and diethylamino hydroxybenzoyl hexyl benzoate. This newly designed topical formulation with a unique ability to selectively deliver NB-UVB when exposed to sunlight could offer photoresponsive patients a more convenient phototherapy option, potentially increasing their compliance.
Protective effect of mango extract against ultraviolet-B-induced skin aging (animal study, in vivo)
One of the most important extrinsic factors that enhance skin aging is chronic sun exposure, and therefore UV radiation, a problem that could be combated to some extent by antioxidants. Mangifera indica L. (Anacardiaceae) is a medicinal plant whose extracts have been described as antioxidants with anti-inflammatory and immunomodulatory activities, proposing it as an eligible protective candidate against UVB-induced skin aging. This proposal was confirmed in a recent study  conducted on 15 hairless mice. All mice received UVB radiation and five of them additionally received an oral administration of 0.1 ml of water containing 100 mg of mango extract/kg body weight/day. Through histopathological examination as well as analysis of their skin replica, the latter group showed significant reduction in the mean length of wrinkles and epidermal hypertrophy compared with the other group. Furthermore, a marked increase in their collagen bundles was observed. These encouraging results indicating the antiphotoaging activity of mango extract in UVB-irradiated hairless mice deserve to be taken to the next level, as they potentially offer a valuable adjuvant to the present phototherapeutic protocols.
| Assessment tools|| |
Vitiligo Potential Repigmentation Index
Several scoring systems have been proposed to assess the severity and response of vitiligo under treatment , such as the Vitiligo Area Scoring Index  and the Vitiligo European Task Force evaluation system . However, none of these methods provide information on the remaining melanocytes within a lesion, upon which existence in epidermis and hair follicle reservoirs, the ultimate magnitude of repigmentation, depends ,,. Benzekri et al.  recently conducted a prospective observational study aiming to develop and validate a simple Potential Repigmentation Index (PRI) intended for the evaluation of repigmentation potential in nonsegmental vitiligo through taking into account the postulated 'available' melanocytes in both locations (epidermis and hair follicles). This index depends on classifying the lesions into four categories (A, B, C, and D) and is then calculated by establishing the ratio between the number of lesions with an expected good response rate (type A+type B) and the number of anticipated refractory lesions (type C+type D). Simply, PRI is equal to (type A+type B)/(type C+type D); accordingly, the higher the PRI, the higher the probability of achieving good repigmentation. Furthermore, PRI takes into account both the total number of lesions and the individual capacity of each lesion to repigment on the basis of scoring of the various lesions (A, B, C, and D). Thus, PRI might be valuable for evaluating the global prognosis of repigmentation in vitiligo.
Besides, PRI offers several additional advantages: simplicity thus practicality and affordability in daily clinical practice as well as enabling the delivery of a more realistic picture to patients and directing toward the most appropriate therapeutic approach. In addition, using PRI can channel patient selection in clinical studies, thus patients with similar repigmentation potential can be subjected to the same study, thus creating nonbiased studies allowing for better assessment and comparison of different therapeutic modalities. Definitely, the PRI is an important prognostic addition to the assessment tools, leading to a more comprehensive patient evaluation to be used in combination with other scoring systems such as Vitiligo Area Scoring Index.
It has already been proven to correlate with the response to NB-UVB therapy , directing to the limitation of its utilization in potential responders.
Mitochondrial DNA damage as a biomarker for ultraviolet exposure
The accumulation of mitochondrial DNA (mtDNA) damage has been strongly connected to the general aging process in tissues as well as to the development of cancer in many tissues, including human skin. This scenario is linked to the key roles of mitochondrial function and mtDNA in terms of energy and oxidative stress production as well as a mediator of apoptosis. The measurement of mtDNA damage proved to be a highly sensitive biomarker of ultraviolet radiation (UVR) exposure and oxidative stress in human skin .
| External influences|| |
Energy saving lamps
A preliminary investigation showed that UVR emissions from compact fluorescent lamps (CFLs) can pose a risk to the skin of photosensitive individuals. To assess this risk, a larger-scale study  was carried out on 301 patients with a range of photodermatoses aiming to determine a safe alternative light source for photosensitive individuals. Twenty healthy controls were included to investigate if CFL emissions have the potential to induce skin responses in normal individuals. In all, 200 patients were directly exposed to a single-envelope CFL on the inner forearm with lamps positioned at 5 cm; 11 of these patients were further tested to a double-envelope CFL. A total of 101 patients were tested to emissions from a light-emitting diode (LED). The 20 healthy individuals were exposed to the single-envelope CFL. Skin assessments were made immediately and 24 h postirradiation. Skin erythema was induced by the single-envelope CFL in the following patients: 16 of 53 chronic actinic dermatitis, seven of 52 polymorphic light eruption, five of nine solar urticaria, one of two actinic prurigo, one of one erythropoietic protoporphyria, and two of 20 healthy individuals. The double-envelope CFL eliminated or reduced the skin response in all 11 patients tested. The LED did not induce any UVR-provoked skin responses. This study highlighted that UVR from CFLs can aggravate the skin of photosensitive and healthy individuals specially when situated in close proximity; however, double-envelope lamps reduce this risk. LEDs offer a safer alternative light source that eliminates the risk for UVR-induced skin erythema, and thus could be advised for photosensitive individuals.
Glass and photoprotection
UVR has known adverse effects on the skin and eyes. Practitioners are becoming more aware of the importance of outdoor photoprotection; however, little attention has been directed to the exposure of the skin and eyes to UVR through the window glass or sunglasses. The amount of UV transmission through glass depends mainly on the type of the glass [Table 1]. All types of commercial and automobile glass block the majority of UVB; however, the degree of UVA transmission depends on the type of glass. Laminated glass offers better UVA protection than tempered glass; new safety regulations for automobiles may result in increased use of laminated glass for side windows. Window films can be applied to glass to increase UVR protection. Sunglasses need to be compliant with one of the national standards; a wraparound style or side shields offer the best protection. Increased understanding by practitioners on the transmission of UVR through glass, window films, and sunglasses would allow them to better educate the public and to better manage photosensitive patients .
|Table 1: Amount of ultraviolet transmission through glass depends mainly on the type of the glass|
Click here to view
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
|1.||Weaver CT, Harrington LE, Mangan PR, Gavrieli M, Murphy KM. Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity 2006; 24 :677-688. |
|2.|| Furuhashi T, Saito C, Torii K, Nishida E, Yamazaki S, Morita A. Photo (chemo) therapy reduces circulating Th17 cells and restores circulating regulatory T cells in psoriasis. PLoS One 2013; 8 :e54895. |
|3.|| Johnson-Huang LM, Suárez-Fariñas M, Sullivan-Whalen M, Gilleaudeau P, Krueger JG, Lowes MA. Effective narrow-band ultraviolet B radiation therapy suppresses the IL-23/IL-17 axis in normalized psoriasis plaques. J Invest Dermatol 2010; 130 :2654-2663. |
|4.|| Singh TP, Schön MP, Wallbrecht K, Michaelis K, Rinner B, Mayer G, et al. 8-methoxypsoralen plus ultraviolet A therapy acts via inhibition of the IL-23/Th17 axis and induction of Foxp3+ regulatory T cells involving CTLA4 signaling in a psoriasis-like skin disorder. J Immunol 2010; 184 :7257-7267. |
|5.|| Bassiouny DA, Shaker O. Role of interleukin-17 in the pathogenesis of vitiligo. Clin Exp Dermatol 2010; 36 :292-297. |
|6.|| Kotobuki Y, Tanemura A, Yang L, Itoi S, Wataya-Kaneda M, Murota H, et al. Dysregulation of melanocyte function by Th17 related cytokines: significance of Th17cell infiltration in autoimmune vitiligo vulgaris. Pigment Cell Melanoma Res 2012; 25 :219-230. |
|7.|| Wang CQ, Cruz-Inigo AE, Fuentes-Duculan J, Moussai D, Gulati N, Sullivan-Whalen M, et al. Th17 cells and activated dendritic cells are increased in vitiligo lesions. PLoS One 2011; 6 :e18907. |
|8.|| Dwivedi M, Laddha NC, Arora P, Marfatia YS, Begum R. Decreased regulatory T-cells and CD4+/CD8+ ratio correlate with disease onset and progression in patients with generalized vitiligo. Pigment Cell Melanoma Res 2013; 26 :586-591. |
|9.|| Lili Y, Yi W, Ji Y, Yue S, Weimin S, Ming L. Global activation of CD8+ cytotoxic T lymphocytes correlates with an impairment in regulatory T cells in patients with generalized vitiligo. PLoS One 2012; 7 :e37513. |
|10.||1Elela MA, Hegazy RA, Fawzy MM, Rashed LA, Rasheed H. Interleukin 17, interleukin 22 and FoxP3 expression in tissue and serum of non-segmental vitiligo: a case-controlled study on eighty-four patients. Eur J Dermatol 2013; 24 : [Epub ahead of print] |
|11.||1Moftah NH, El-Barbary RA, Ismail MA, Ali NA. Effect of narrow band-ultraviolet B on CD4+ CD25high FoxP3+ T-lymphocytes in the peripheral blood of vitiligo patients. Photodermatol Photoimmunol Photomed 2013; [Epub ahead of print]. |
|12.||1Li J, Hou R, Yang Y, Liu R, Zhao X, Li X, et al. Narrowband ultraviolet B interferes with gene expression in peripheral blood T cells of patients with psoriasis. Dermatology 2013; 226 :128-137. |
|13.||1Feldmeyer L, Shojaati G, Spanaus KS, Navarini A, Theler B, Donghi D, et al. Phototherapy with UVB narrowband, UVA/UVBnb, and UVA1 differentially impacts serum 25-hydroxyvitamin-D3. J Am Acad Dermatol 2013; 69 :530-536. |
|14.||1McCoy J, Goren A, Lotti T. In vitro evaluation of a novel topical cream for vitiligo and psoriasis that selectively delivers NB-UVB therapy when exposed to sunlight. Dermatol Ther 2013; [Epub ahead of print]. |
|15.||1Alghamdi KM, Kumar A, Taïeb A, Ezzedine K. Assessment methods for the evaluation of vitiligo. J Eur Acad Dermatol Venereol 2012; 26 :1463-1471. |
|16.||1Hamzavi I, Jain H, McLean D, Shapiro J, Zeng H, Lui H, et al. Parametric modeling of narrowband UV-B phototherapy for vitiligo using a novel quantitative tool: the Vitiligo Area Scoring Index. Arch Dermatol 2004; 140 :677-683. |
|17.||1Taïeb A, Picardo M. The definition and assessment of vitiligo: a consensus report of the Vitiligo European Task Force. Pigment Cell Res 2007; 20 :27-35. |
|18.||1Gauthier Y, Cario-Andre M, Taïeb A. A critical appraisal of vitiligo etiologic theories. Is melanocyte loss a melanocytorrhagy? Pigment Cell Res 2003; 16 :322-327. |
|19.||1Ardigo M, Muzio F, Picardo M, Brazelli V. Non invasive methods for vitiligo evaluation. In: Picardo M, Taïeb A, editors. Vitiligo. Berlin, Heidelberg: Springer-Verlag; 2010. 183-195. |
|20.||2Benzekri L, Ezzedine K, Gauthier Y. Vitiligo Potential Repigmentation Index: a simple clinical score that might predict the ability of vitiligo lesions to repigment under therapy. Br J Dermatol 2013; 168 :1143-1146. |
|21.||2Birch-Machin MA, Russell EV, Latimer JA. Mitochondrial DNA damage as a biomarker for ultraviolet radiation exposure and oxidative stress. Br J Dermatol 2013; 169 :9-14. |
|22.||2Fenton L, Ferguson J, Ibbotson S, Moseley H. Energy-saving lamps and their impact on photosensitive and normal individuals. Br J Dermatol 2013; 169 :910-915. |
|23.||2Almutawa F, Vandal R, Wang SQ, Lim HW. Current status of photoprotection by window glass, automobile glass, window films, and sunglasses. Photodermatol Photoimmunol Photomed 2013; 29 :65-72. |