Pigment International

: 2014  |  Volume : 1  |  Issue : 1  |  Page : 36--39

Current best evidence from pigmentary dermatology

Gitesh U Sawatkar, Savita Yadav 
 Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Correspondence Address:
Savita Yadav
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh 160 012

How to cite this article:
Sawatkar GU, Yadav S. Current best evidence from pigmentary dermatology.Pigment Int 2014;1:36-39

How to cite this URL:
Sawatkar GU, Yadav S. Current best evidence from pigmentary dermatology. Pigment Int [serial online] 2014 [cited 2022 May 23 ];1:36-39
Available from: https://www.pigmentinternational.com/text.asp?2014/1/1/36/135441

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Budamakuntla L, Loganathan E, Suresh DH, Shanmugam S, Suryanarayan S, Dongare A, et al. A randomised, open-label, comparative study of tranexamic acid microinjections and tranexamic acid with microneedling in patients with melasma. J Cutan Aesthet Surg 2013;6:139-43.

Melasma is a common cosmetic problem among patients of Asian ethnicity. Multiple factors have been implicated in its development, but none offers a precise explanation for this chronic disorder. Although an array of treatment modalities are available with varying success, none provides a satisfactory outcome.

This study was carried out to compare the therapeutic efficacy and safety of tranexamic acid (TA) microinjections versus TA with microneedling in melasma patients in a prospective, randomized, open label manner. A sample size of 60 patients was taken with 30 patients in each of the treatment arms. One group received multiple microinjections of TA (4 mg/mL) intradermally at 1 cm intervals into the melasma lesions, to a maximum of 8 mg to the entire affected area, using a 100 U/mL insulin syringe with a 4 mm mesoneedle. In the other group microneedling was carried out for about 4-5 times. Then TA, 0.5-1 ml (4 mg/mL), was applied over this area, and the procedure was repeated 4-5 times. The procedure was done 3 times at monthly intervals and then patient were followed-up for further 3 months at monthly intervals. The assessment was carried with the help of clinical photographs, melasma area severity index (MASI) scoring, physician global assessment, and patient global assessment and complications/adverse events if any were recorded. Among the 60 patients, all had Fitzpatrick skin Type of IV or V and most of them had centrofacial or malar pattern of melasma. The microinjection group showed an improvement of 35.7%, with a reduction of mean baseline MASI from 6.93 ± 2.16 to 4.45 ± 1.69 at the end of third follow-up. Whereas in the micro needling group, the mean MASI decreased from 9.11 ± 4.09 at baseline to 5.06 ± 2.14 at the end of third follow-up, showing an improvement of 44.41%. However, there was no significant difference in the improvement in MASI scores between the microinjection and the microneedling group. Apart from transient discomfort, burning sensation, and erythema no other major side-effects were observed.

Comments: Melasma is a relatively common, chronic acquired facial skin disorder of hyperpigmentation. Various depigmenting agents such as hydroquinone, tretinoin, kojic acid, chemical peels and a combination of these form the treatment armamentarium for it. Recently, studies have shown that trans-4-aminomethylcyclohexanecarboxylic acid (TA) can prevent ultraviolet (UV)-induced pigmentation. TA is mainly used for its antihemorrhagic and antifibrinolytic properties. It competitively inhibits the activation of plasminogen to plasmin, by binding to specific sites of both plasminogen and plasmin, a protein that forms the framework of blood clots.

Tranexamic acid prevents the binding of plasminogen to the keratinocytes thereby inhibiting the plasmin activity induced by UV radiations. This results in less free arachidonic acids and diminished ability to produce prostaglandins, which ultimately decreases melanocyte tyrosinase activity. Oral administration of TA has been shown to be a new potential treatment modality for the treatment of melasma. This study has utilized localized microinjections and microneedling to deliver TA. Patients receiving TA through microneedling showed a better response than those receiving through microinjections, though the difference was not statistically significant. Local administration of TA can obviate many of the serious side-effects associated with systemic administration of TA. The study has demonstrated good results with both techniques in terms of reduction in the MASI score and satisfactory patient outcome. However, the sample size was quite small, and the follow-up period was too short. Some of the patients were already using depigmenting agents. Hence, it would be difficult to assess the prime role of TA in such patients. This study demonstrates a new promising way for the treatment of melasma. A larger trial combining TA with other existing topical therapies can help to develop more assuring treatment for melasma.

Jun HJ, Cho SH, Lee JD, Kim HS. A split-face, evaluator-blind randomized study on the early effects of Q-switched Nd: YAG laser plus Er: YAG micropeel (combined therapy) versus Q-switched Nd: YAG alone in light solar lentigines in Asians. Lasers Med Sci 2013. [Epub ahead of print]

Solar lentigines are the major sign of photo-aging in people belonging to Asian ethnicity. They are the result of variable proliferation of melanocytes and accumulation of melanin in keratinocytes following chronic exposure to UV radiation and as such their incidence increases with increasing age.

In this study, while treating lentigines the combination of Q-switched neodymium-doped: Yttrium aluminum garnet (YAG) (QSNY) with superficial erbium: YAG (Er: YAG) micropeel was compared with QSNY laser alone in relation to pigment reduction and side-effects. The study was a randomized controlled split-face study with a sample size of 15 patients.

All the patients received combined QSNY and superficial Er: YAG micropeel or QSNY alone over either part of the face in a randomized fashion. This treatment procedure was conducted in a single session. Treatment assessment was based on the clinical photograph (baseline, 2 weeks and 4 weeks postprocedure), which was reviewed by two independent, blinded physicians and patient's subjective satisfaction at the 2 weeks and 4 weeks follow-up. At the 2 weeks follow-up, no difference was found in pigment improvement between the two treatment groups. However, the QSNY laser alone group showed significantly higher improvement than the combined treatment group at 1-month follow-up. At 2-weeks of follow-up, patients' satisfaction score was higher in the combined treatment group, but it lacked any difference with other treatment option at 4-weeks of follow-up.

Comments: Solar lentigines result from epidermal hyperplasia with variable proliferation of melanocytes and accumulation of melanin in keratinocytes in response to chronic UV radiation exposure. Though a benign condition, it is considered as an independent risk factor for the development of melanoma. Available treatments consist of bleaching agents (like hydroquinone), cryotherapy and laser surgery. Many new laser systems claim an advantage for treating pigmented lesions by selectively destroying melanin.

This study evaluates any advantage of combining superficial Er: YAG micropeel to QSNY for the treatment of solar lentigines in Asian population. The wavelength (300-1200 nm) of QSNY laser is strongly absorbed by the melanin. Furthermore, its pulse duration is shorter than the thermal relaxation time of a melanosome (50-280 ns).

Erbium: YAG laser, is an ablative laser, capable of removing a thin layer of skin with an ablation depth controlled by effective fluence. In this study, both combined therapy and QSNY alone were equally effective in reducing light solar lentigines. Patients' satisfaction score was more with combined treatment procedure, which could possibly be due to the enhancement of skin tone and texture accountable to the Er: YAG micropeel. However, at the end of 1 month, postinflammatory hyperpigmentation (PIH) and subtle emergence of melasma were more common in combined treatment group. The follow-up period of this study was short, so the long-term nature of PIH cannot be ascertained. This side-effects in the combined treatment group resulted in a significant difference in the physician's score, in support of QSNY monotherapy. The study infers that QSNY monotherapy has more favorable qualities than the combined treatment for the treatment of light solar lentigines in Asians. Based on this, further studies with a larger sample size, long-term follow-up, and use of lasers with modified parameters would enable to develop a more optimal treatment modality for light solar lentigines in Asian skin.

Kumar R, Parsad D, Singh C, Yadav S. Four compartment method: A simplified and cost-effective method of noncultured epidermal cell suspension for the treatment of vitiligo. Br J Dermatol 2014;170:581-5.

Vitiligo is chronic pigmentary disorder with worldwide incidence. Though a continuous research is still ongoing concerning its pathogenesis and treatment, a definitive solution is still awaited. Currently available treatment options for it are broadly divided into medical, surgical and phototherapy. Of these, surgical treatment and phototherapy are available only at specialized centers, making these treatment options unavailable for many patients belonging to remote places.

In this article, a simplified and easy way of noncultured epidermal cell suspension (NCECS) preparation, termed as: Four compartment (FC) method has been described. The conventional NCECS preparation requires a special laboratory setup and personnel specific expertise. The FC method, described here, is not only user friendly, but also cost-effective and has obviated the needs of all sophisticated laboratory requirements. In this study, six patients with stable vitiligo were treated with NCECS prepared by the FC method.

A split-thickness graft taken from the thigh was used to prepare cell suspension. This graft was transferred in the first compartment of FC petri dish and incubated with 0.25% trypsin and 0.02% ethylenediaminetetraacetic acid solution at 37°C for 1 h. The trypsin was washed off with phosphate buffered saline solution in compartment two and then sub subsequently in compartment three. Finally, in the fourth compartment, the epidermis was separated from the dermis and cells were dislodged from the basement membrane with the help of forceps. Thereafter, a homogenous cell suspension was prepared using a sterile syringe. The suspension thus created was uniformly spread using an 18-gauge needle attached to a tuberculin syringe over the dermabraded vitiliginous skin. It was then covered with tight occlusive dressings (consisting of collagen, sterile transparent occlusive dressing, surgical pad, and finally elastic plaster), so as to prevent any dislodgment of the applied suspension. The dressing was removed after a period of 7 days. Out of the six patients, four had excellent repigmentation (90-100%) and two had good repigmentation (>75%) after a follow-up period of 4 months. None of the patients developed any cutaneous or systemic adverse effects.

Comments: A variety of surgical procedures such as, NCECS, cultured autologous melanocytes, minigrafts, split thickness grafts, suction blister grafts are available for the treatment of vitiligo. Among all these techniques NCECS is safer, effective and can be used to treat large areas in one sitting. However, the availability of this treatment option is limited as it depends not only on dexterity of dermatologist but also needs a specific laboratory setup. The FC method for the preparation of NCECS described in this article is simple which can be easily mastered. Also, it doesn't require any sophisticated instruments or laboratory setup. The results observed were good to excellent after a long follow-up period of 4 months. However, the number of patients included in the study was quite small. Hence, this article describes a new modified NCECS technique which can be easily practiced and mastered in routine dermatology clinics, thereby making wider availability of this procedure for the patients.

Mehryan P, Zartab H, Rajabi A, Pazhoohi N, Firooz A. Assessment of efficacy of platelet-rich plasma (PRP) on infraorbital dark circles and crow's feet wrinkles. J Cosmet Dermatol 2014;13:72-8.

Infraorbital circles also called as periorbital hyperpigmentation (POH) is a common dermatological condition seen in day-to-day practice. In this study, platelet, rich plasma (PRP) was tried for the treatment of POH and crow's feet wrinkles. A single session of intradermal injection of PRP (1.5 ml) into tear trough area and crow's feet wrinkle on each side was performed in 10 patients (mean age: 41.2 years) having these symptoms for at-least a year. Assessment was done with respect to: melanin content, color homogeneity, epidermal stratum corneum hydration, and wrinkle volume and visibility index, at baseline and 3 months posttreatment. Along with this, physician's global assessment and participants' satisfaction were also evaluated for this treatment modality. Statistically significant improvement was seen only in the infra orbital color homogeneity. Other parameters such as, melanin content, stratum corneum hydration, wrinkle volume, and visibility index did not show any statistically significant changes. Apart from mild burning sensation (all patients), transient bruising/echymoses (60% of patients), no other major side-effect was observed.

Comments: Periorbital hyperpigmentation is a common distressing cosmetic concern, particularly in women. Many factors contribute to it like genetics, dermal melanin deposition, post inflammatory hyperpigmentation secondary to dermatitis (atopic or allergic contact dermatitis), stress, peri-orbital edema, and many more. Though many topical preparations are available in the market, a definitive treatment is still missing for this chronic pigmentary problem. This study attempted to find effects of PRP on POH and crow's feet wrinkles.

Platelet rich plasma is a rich source of platelet-derived growth factors (PDGF)αα, PDGFαβ and PDGFββ, transforming growth factors (TGF) β1, TGFβ2, vascular endothelial growth factor and epidermal growth factor along with fibrin, fibronectin and vibronectin. It acts as a stimulant for fibroblast proliferation and collagen release in tissue cultures. PRP has been shown to decrease the melanin index following fractional carbon dioxide laser resurfacing. This is the first clinical trial of the effects of PRP on POH. This study showed a fair to good improvement in POH (80% of the patients) after a follow-up period of 3 months. The exact mechanism by which the improvement was achieved is lacking. The stability of this improvement is also not certain, as the follow-up period was short. Lack of the control group and small sample size are the other limitations of this study. Further studies using other treatment modalities in combination with PRP in a randomized control manner need to be carried before establishing any certain effective PRP based treatment for POH.

Zhang DM, Hong WS, Fu LF, Wei XD, Xu AE. A randomized controlled study of the effects of different modalities of narrow-band ultraviolet B therapy on the outcome of cultured autologous melanocytes transplantation in treating vitiligo. Dermatol Surg 2014;40:420-6.

Vitiligo is a common, chronic, acquired, pigmentary disorder carrying a lot of social stigma. A variety of surgical treatments are available and further research is still ongoing to improve their efficacy. This study tries to evaluate the advantage of combining phototherapy narrow band ultraviolet B (NB-UVB) with surgery (cultured autologous melanocyte transplantation) and also states the timing of phototherapy, which would have greatest added advantage. A total of 473 stable vitiligo patients were recruited and randomly divided in four groups. Group 1 (no of patients: 117) received 20 sessions of phototherapy before transplantation, Group 2 (no of patients: 118) 30 session after transplantations, while Group 3 (no of patients: 120) received 20 session before and 30 sessions after transplantation. In Group 4 (no of patients: 118) only surgery was performed. The schedule for phototherapy was twice a week on nonconsecutive days and in Groups 2 and 3 it was started 2 weeks after surgery. For cultured autologous melanocyte transplantation, the graft was taken from a normal pigmented area of the abdomen. The melanocyte suspension prepared from this graft was then applied over the vitiliginous area, which was denuded with a carbon dioxide laser. The patients were evaluated at day 10 and at months 1, 2, 3 and 6 posttransplantation. Extent of repigmentation was categorized as excellent (≥90%), good (50-89%), fair (20-49%), or poor (<20%), and the side-effects if any were recorded. More than 50% repigmentation were achieved in 92.6% of the patients in Group 1, 89.3% in Group 2, 94.8% in Group 3, and 72.7% in Group 4. Mean extent of repigmentation within the treated vitiliginous areas was highest in Group 3 (87.7%), whereas it was 83.5%, 79.9%, and 68.1%, in Group 1, Group 2 and Group 4 respectively.

Comments: Narrow band ultraviolet B (spectrum from 311 to 312 nm), is considered as one of the most effective phototherapy treatment option for vitiligo. It can be used either alone or in combination with other topical or systemic treatments. This study shows that combining NB UVB with cultured autologous melanocyte transplantation has an advantage by helping in expansion and spread of the transferred melanocytes. The effect is higher if NB UVB is administered prior to surgery and continuing it after transplantation. However, whether it's the total dose of NB UVB or the conducive microenvironment provided by the immunosuppressive effect of NB UVB needs to be ascertained. NB UVB has multimodality of action in vitiligo like enhancing the release of β fibroblast growth factor and endothelin-1 from keratinocytes, which induces melanocyte proliferation, helping in melanocyte migration (through induction of phosphorylated focal adhesion kinase on melanocytes) and immunosuppressive effect by inducing T lymphocytes apoptosis. This study shows that providing NB UVB prior to and after cultured autologous melanocyte transfer can accelerate the repigmentation. Hyperpigmentation can occur when NB UVB is given both prior and after surgery, but it is usually transient.