|CURRENT BEST EVIDENCE
|Year : 2014 | Volume
| Issue : 2 | Page : 108-113
Current best evidence from pigmentary dermatology
Gitesh U Sawatkar, Muthu Sendhil Kumaran
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||15-Dec-2014|
Muthu Sendhil Kumaran
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh - 160 012
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Sawatkar GU, Kumaran MS. Current best evidence from pigmentary dermatology. Pigment Int 2014;1:108-13
Jalaly NY, Valizadeh N, Barikbin B, Yousefi M. Low-power fractional CO 2 laser versus low-fluence Q-switch 1,064 nm Nd:YAG laser for treatment of melasma: A randomized, controlled, split-face study. Am J Clin Dermatol 2014;15:357-63.
Melasma is a very common cosmetic concern of facial skin discoloration, almost entirely seen in women in the reproductive years. It typically appears on the upper cheeks, upper lip, forehead, and chin of women 20-50 years of age. Topical depigmenting agents, sun protection, chemical peels, and dermabrasion, are some of the treatment modalities for this chronic disorder.
In this article, low-power fractional CO 2 laser was compared with low-fluence Q-switch 1064 nm neodymium-doped: Yttrium aluminum garnet (Nd:YAG) laser for treatment of melasma in a randomized, controlled, split-face pattern. Forty healthy female patients above the age of 18 years with symmetrical melasma and Fitzpatrick skin types II-IV were recruited for the study. Wood's lamp examination was done for determining the type of melasma. During the study period, patients were asked to avoid sun exposure and apply sunscreen (sun protection factor 30) every 2 hourly. With the aid of a computer randomization program, each side of the face was randomly allocated to either low-fluence Q-switch 1064 nm Nd:YAG or low-power fractional CO 2 laser. Low-fluence Q-switch 1064 nm Nd:YAG (Spectra; Lutronic Inc., Korea) was used to deliver 1.5-2 J/cm 2 with 7 mm spot sizes with five passes to one side of the face. Other side of the face received one pass of low-power fractional CO 2 laser (Mixel; Hironic Co., Ltd., Korea) with a power of 1 W and density of 0.7. This treatment was carried out at every 3 weeks for five consecutive sessions, and the patients were followed for 2 months after the last treatment session. The Melanin Index (MI), modified Melanin Area and Severity Index (mMASI), and patients' self-evaluation were done at baseline, 1 month, and 2 months after the last treatment session. At 1 month follow-up, after the first treatment and at the endpoint of the study (2 months), the mean mMASI score was reduced more on the side treated with fractional CO 2 laser than on the side treated with Q-switch 1064 nm Nd:YAG laser (P < 0.001), but no statistically significant differences were observed between the mean MI scores for each side (P = 0.1). The reductions in MI and mMASI scores at 2-month follow-up on the fractional CO 2 laser-treated side were significantly greater than on the Q-switch 1064 nm Nd:YAG laser-treated side (both P < 0.001). The efficacy of fractional CO 2 laser in reducing the MI score was statistically significant in the patients with epidermal and dermal melasma compared with the Q-switch 1064 nm Nd:YAG laser (P < 0.05). Side effects such as sunburn-like erythema and transient edema with low-fluence Q-switch 1064 nm Nd:YAG laser treatment and erythema, burning sensation, edema, and scaling, lasting for at least 3 days after low-power fractional CO 2 laser-treatment were seen.
Comments: Melasma is chronic resistant condition to most of the therapies. Search is still ensuing for a more effective therapy with long lasting results. Laser, including ablative and nonablative lasers and intense pulsed light (IPL) have been tried for the treatment of melasma. Studies demonstrated that ablative CO 2 laser resurfacing can result in improvement in melasma, but total epidermal ablation can result in hyperpigmentation or irregular pigmentation. To overcome this side effect, fractional CO 2 resurfacing lasers have been developed which have columns of coagulation in micro-thermal zones with no destructive effect on the epidermis. However, it also not completely devoid of any side-effects. Reports have complications such as scarring and postinflammatory hyperpigmentation (PIH) especially in darker skin type patients. In the current study, treatment with low-power fractional CO 2 showed promising results with few side effects.
Postinflammatory hyperpigmentation is one of the major side effects of Q-switch 1064 nm Nd:YAG laser when used at high fluence. Q-switch 1064 nm Nd:YAG laser when used at sub-photothermolytic fluence reduces the epidermal and dermal pigment with a low rate of complications and recurrence. The reason proposed for this effect is the destruction of the melanin granules and its dispersion in the cytoplasm without any significant cellular destruction when the Q-switch 1064 nm Nd:YAG laser is used at low fluence. The current study demonstrated a significant decrease in mean MI and mMASI scores between the first and last visit with the use of this laser. However, in the current study, the follow-up duration is relatively small; thus, the long the long-term efficacy, relapse, and any other side effects cannot be determined. Furthermore, the sample size of the cohort was small. Although the low-power fractional CO 2 laser was superior to the low-fluence Q-switch 1064 nm Nd:YAG laser but further studies are needed with large sample size and long duration of follow-up.
Yang Y, Huang G, Yan X, Qing Z. Clinical analysis of thyroglobulin antibody and thyroid peroxidase antibody and their association with vitiligo. Indian J Dermatol 2014;59:357-60.
Vitiligo is a chronic depigmenting disorder characterized by various patterns of presentation. The etiopathogenesis of the disease is still an enigma. Many autoimmune disorders including thyroid dysfunction and autoimmunity have been associated with it. This study was conducted to determine whether vitiligo was associated with thyroid autoimmunity and figure out its relationship with age and gender. A total of 87 patients with vitiligo (77 vulgaris and 10 segmental) and 90 healthy individuals (with no family history of vitiligo and other autoimmune diseases) were enrolled in the study. The hormones assayed were serum antithyroid autoantibodies (thyroglobulin antibody [TG-Ab] and thyroid peroxidase antibody [TPO-Ab]), free thyroid hormones T3 (FT3), free T4 (FT4), and thyroid stimulating hormone (TSH). In addition, physical examination and thyroid ultrasonography were done. The assessed parameters, that is, TG-Ab, TPO-Ab, FT3, FT4, and TSH were higher in vitiligo patients than in control subjects. Among 13 vitiligo patients with elevated TSH, 12 (92.3%) were the patients with vitiligo vulgaris and 1 (7.6%) had segmental vitiligo. Both the study groups (vitligo patients and controls) were divided in five groups (<11 years, 11-20 years, 21-40 years, 41-60 years, and >60 years, respectively). In 11-20 years and 21-40 years, subgroups of vitiligo patients, the positive frequencies of TG-Ab and TPO-Ab were significantly higher than the corresponding subgroups of healthy controls. Vitligo patients in the young age group (11-20 years age) had comparatively high positivity for TG-Ab and TPO-Ab than other age groups. The positive frequencies of TG-Ab and TPO-Ab in female vitiligo patients were significantly higher than female healthy controls. During the 3-year follow-up, 14 cases of vitiligo patients and one control had been diagnosed with autoimmune thyroid disease among 20 vitiligo patients and six healthy subjects with positive TPO-Ab and TG-Ab.
Comments: Among the various etiological factors, autoimmunity is considered to play a major role in the causation of vitiligo. Vitligo is considered to be an autoimmune disease, wherein there is loss of melanocytes from the epidermis. This study ascertained the fact that differences exist in terms of serum thyroid parameters between vitiligo patients and healthy controls, as they found significantly higher occurrence of TG-Ab and TPO-Ab in vitiligo patients compared to healthy subjects, and all of the patients positive for TG-Ab and TPO-Ab having vitiligo vulgaris. In addition, study revealed female vitiligo patients to be significantly more positive for TG-Ab and TPO-Ab compared to female controls. The highest positivity of TG-Ab and TPO-Ab was in 11-20 years age group of vitiligo patients, as has been reported in previous studies. However, the study failed to find any increase occurrence of these antibodies in the age group of <10 years of age. A slightly higher level of TSH was found in the vitiligo patients, indicating a mild damage. About 70% of vitiligo patients positive for TG-Ab and TPO-Ab were diagnosed as having autoimmune thyroid diseases at average 2.5 years. A number of autoimmune disorders are associated with vitiligo like, autoimmune thyroid diseases, rheumatoid arthritis, type 1 diabetes, psoriasis, pernicious anemia, and many more indicating the presence of genetically determined susceptibility. As T-cell mediated autoimmune diseases, Graves' disease and Hashimoto's thyroiditis have lymphocytic infiltration in the thyroid parenchyma. Similarly, skin biopsies from vitiligo skin lesion show dermal and epidermal lymphocytic infiltrate, consisting activated T-cells, which are thought to cause melanocyte destruction. Studies have also identified immunogenetic associations with vitiligo and autoimmune thyroid diseases. Vitiligo is associated with human leukocyte antigen (HLA)-DR4, whereas thyroid disease is associated with Class 1 and Class II HLA including HLA-DR. Graves' disease has been associated with HLA-DR3. This study finds young female patients with vitiligo to have higher positivity of TG-Ab and TPO-Ab, and trend toward to development of autoimmune thyroid disease, suggesting screening for TG-Ab and TPO-Ab for an early diagnosis and treatment of autoimmune thyroid diseases.
Sehrawat M, Arora TC, Chauhan A, Kar HK, Poonia A, Jairath V. Correlation of vitamin D levels with pigmentation in vitiligo patients treated with NBUVB therapy. ISRN Dermatol 2014;2014:493213.
Vitiligo is chronic pigmentary disorder with a worldwide distribution. Though a continuous research is still ongoing concerning its pathogenesis and treatment, a definitive solution is still awaited. Multiple theories have been proposed for the etiology of vitligo like, autoimmune diathesis, genetic factors, defective free radical defense, accumulation of neurochemical substances, chemicals (4-tertiary butyl phenol), psychological factors like stress, and an intrinsic defect of the function of melanocytes probably contribute in variable proportions to the destruction of pigment cells. This article suggests that at least a part of narrowband ultraviolet B (NBUVB) induced repigmentation in vitiligo may be explained by NBUVB induced vitamin D3 synthesis and hence sought to evaluate the vitamin D status in vitiligo patients before, during, and after NBUVB therapy and correlated it with repigmentation.
The study involved 30 patients of generalized vitiligo, and an equal number of age and sex matched consenting healthy controls. Serum 25-hydroxyvitamin D 25(OH) D levels were measured at baseline in both study group and subsequently in vitiligo patients on NBUVB therapy at 6 weeks and 12 weeks. NBUVB phototherapy was given thrice weekly on nonconsecutive days for 12 weeks. All patients were examined at 6 weeks interval, and Vitiligo Area Severity Index (VASI) was calculated on each occasions. In the study group, 24 (80%) patients had deficient (<25 nmol/L) and 6 (20%) had insufficient baseline levels (25-75 nmol/L) of 25(OH) D. Whereas, 90% ( =27) of the controls had insufficient (25-75 nmol/L) levels and 10% ( =3) had deficient (<25 nmol/L) 25(OH)D levels. None of the subjects in the study group or control group had normal (75-250 nmol/L) levels of 25(OH)D levels. The level of 25(OH) D was significantly low in the vitligo patients group. Baseline mean VASI score was 21.66 ± 17.21. Correlation between mean VASI and mean 25(OH)D levels was weak among vitiligo patients and was statistically insignificant before starting the phototherapy. Following phototherapy, mean improvement in VASI and 25(OH)D at 6 and 12 weeks showed weak and moderate correlation, respectively, but the results were statistically insignificant. The most common type of pigmentation observed was perifollicular. Majority of the patients did not have any side effects, while a few had erythema (16.66%), blistering (10%), and pruritus (13.33%), and acne form eruption.
Comments: Vitamin D at cellular level modulates melanogenesis as studies have shown that vitamin D increases the tyrosinase content of melanocytes. NBUVB enhances the synthesis of interleukin-1, tumor necrosis factor-α, and leucotriene C-4 which induces melanocyte mitogenesis, melanogenesis, and melanocyte migration. Furthermore, there is an increase in the levels of 25(OH)D following NBUVB phototherapy. UVB portion of the sunlight (290-320 nm) brings about the photochemical conversion of 7-dehydrocholesterol to previtamin D3 in the stratum spinosum and stratum basale, a key step toward vitamin D3 synthesis. The current study compared the levels of 25(OH)D in patients of vitiligo before and after NBUVB phototherapy and correlated it with the extent of repigmentation. The study found comparatively low levels of vitamin D in vitiligo patients than control subjects and the level of 25(OH)D increased significantly with an increase in the cumulative dose of NBUVB. Comparison and correlation between mean improvement in VASI and 25(OH)D levels at 6 weeks was minimal, but it became moderate at 12 weeks with cumulative dose increase of NBUVB. This finding partly supports the role of Vitamin D3 in induction of melanogenesis, following the use of NBUVB. The most common pattern of repigmentation was perifollicular suggesting that melanin is produced by the melanocytes in hair follicles. Vitamin D may act to induce immature melanocytes in hair follicles. A shortcoming of the study is the small sample size and short duration. The study suggests that vitamin D might play a role in repigmentation with the use of NBUVB therapy. Future studies needed with large sample size to ascertain the role of vitamin D.
Kovacs D, Abdel-Raouf H, Al-Khayyat M, Abdel-Azeem E, Hanna MR, Cota C, et al. Vitiligo: Characterization of melanocytes in repigmented skin after punch grafting. J Eur Acad Dermatol Venereol 2014. doi: 10.1111/jdv. 12647. [Epub ahead of print].
Multiple treatment options are currently available for the treatment of vitiligo, and many more are currently under development process. For therapy-resistant, stable and localized vitiligo, dermato-surgical techniques are considered. These consist of procedures like suction blister grafting, punch grafting, follicular grafting, and cultured and noncultured melanocyte transplantation. Punch grafting is a simple and easy to learn surgical procedure, wherein biopsy punches are transferred from the normal donor site to the depigmented site. In the present study, the authors evaluated whether the repigmentation process clinically observed in areas among the grafts was caused by: Elongation of the dendrites of melanocytes located in the donor punches and the subsequent transfer of the pigment to the surrounding keratinocytes; the horizontal migration of activated melanocytes from the donor sites to the depigmented areas. Nine patients with vitiligo (8: Segmental vitiligo, 1: Nonsegmental vitligo) were enrolled in the study. The presence, distribution, and traits of melanocytes were analyzed over the biopsies collected from the repigmented skin between the punch grafts and biopsies from two donor areas. No stained cells for the premelanosome marker HMB45 were detected in any of the biopsies taken in the repigmented areas among the punch grafts. However, positive reactivity for MITF, c-kit, MART-1, and TRP1 was observed in all specimens, indicating the presence of melanocytes along the entire length of the section. Differently from the repigmented skin, the two donor samples displayed positive reactivity not only for MITF, c-kit, and MART1 but also for HMB45. Differently from the repigmented skin, the two donor samples displayed positive reactivity not only for MITF, c-kit and MART1 but also for HMB45. An intense positive reactivity for E-cadherin was detected in all epidermal layers of the two donor samples, whereas an overall decrease of its expression was observed in the repigmented skin specimens. Clinical outcome showed an excellent response in eight and fair result in one patient. Smaller punch grafts gave the best outcome, whereas bigger punch grafts on the knee exhibited a longer repigmentation time. Total number of labeled melanocytes was lower in biopsies collected from patients subjected to bigger size punch grafts in comparison to biopsies from patients who underwent smaller size punch grafts, showing a negative correlation between the immunohistochemical results and the size of the punch grafts.
Comments: The current study tries to elaborate biological and molecular mechanisms underlying the activation of melanocytes after punch grafting. Under physiological conditions, dissociation of melanocytes from the basal membrane and adjacent keratinocytes; proliferation; migration; and ultimately repositioning with dendrites extension and reconnection with the surrounding cells and basal membrane has been the sequence of events for maintaining the normal melanocyte homeostasis. The injury and the healing process due to the grafts may create a favorable environment for melanocyte stimulation by promoting all the steps occurring for the preservation of the normal melanocyte homeostasis. It has been hypothesized that after surgical procedures involving the dermal compartment, the activation of the melanocyte stem cell population in the dermis may contribute to the repigmentation process. Another process further promoting the repigmentation speculated was alterations at the dermal-epidermal junction and the heparanase increase following the graft. Additional medical treatments following the grafting, such as phototherapy, also promote the secretion of messengers, including matrix metalloproteinases and pro-melanogenic factors, further modulating melanocyte functions and melanin production. In the current study, melanocytes detected in the repigmented skin at the time of the biopsy appeared well-differentiated (positive expression of the melanosomal protein MART-1, co-expression of TRP1 and c-kit). Cell divisions are mostly observed in scarcely pigmented melanocytes at the limit between the pigmented and the nonpigmented portions of the follicle, suggesting that mitoses take place more during the amelanotic phase of melanocyte activation. It can be speculated that at the time of the biopsy, melanocytes, which migrated from the graft and were re-located in the depigmented area, have been stimulated to produce melanin to such an extent of being exhausted and therefore not showing any immature melanosomes. There is an enlargement of the epidermal intercellular spaces is observed during melanocyte migration, supporting of reduction of adhesion molecule E-cadherin in the repigmented skin. The study also demonstrated appropriate correlation between the number of melanocytes detected by the immunohistochemical analysis and the overall clinical outcome. The study infers activation of the microenvironment can be better promoted by a higher number of smaller punch grafts compared to a minor number of bigger punches, leading to stimulation of melanocytes induced by growth factors and mediators resulting in a more effective clinical outcome. Following punch grafting, melanocytes start migrating horizontally and repopulate the depigmented areas helped by down-modulation of adhesion molecules and the induction of mitogenic mediators. They produce and transfer the melanin to the surrounding keratinocytes until exhaustion and then persist in the newly pigmented site as functional and mature cells.
Prabha N, Mahajan VK, Mehta KS, Chauhan PS, Gupta M. Cosmetic contact sensitivity in patients with melasma: Results of a pilot study. Dermatol Res Pract 2014;2014:316219.
Melasma is chronic pigmentary disorder found commonly in patients of Asian ethnicity. To overcome it and for the overall enhancement of aesthetic look, a tremendous rise in the use of cosmetic and grooming products has been seen. However, cosmetics have been rarely implicated to cause melasma. Pigmented cosmetic dermatitis, a variant of pigmented contact dermatitis where cosmetic ingredients are the primary allergens. The current study tries to elaborate this aspect of cosmetic contact sensitivity in patients with melasma. A total of 67 patients (F:M = 55:12) with melasma and 10 volunteers without melasma were recruited for the study. Demographic data consisting age, sex, occupation, onset, duration, progress, clinical patterns of melasma, aggravating factor, use of cosmetics, and medications were recorded. Indian Cosmetic and Fragrance Series, Indian Sunscreen Series, personal cosmetic products of patients, and p-phenylenediamine (PPD) (1.0% pet), were used for patch testing with the help of Finn chamber method. Common cosmetics/skin care products used were cold creams and skin moisturizers (50 patients), medicated soaps (58 patients), fairness creams (39 patients), hair colors (17 patients), facial bleach (13 patients), and sunscreens (7 patients). A total of 29 patients was found to be positive with Indian Cosmetics and Fragrance Series while none showed a positive result from Indian Sunscreen Series. Cetrimide was the most common contact sensitizers (52%), followed by gallate mix (31%). Thiomersal elicited positive results in 7 (24%) patients among 39 patients using fairness creams. Polysenstivity, that is, positive patch test reactions to ≥2 allergens, was observed in 11 (38%) patients; 5 patients had sensitivity to 2 allergens, 5 patients to 3 allergens, and 1 patient to 5 allergens, respectively. Among the 42 patients, patch tested with their own cosmetics/skin care products "as is," one male patient showed positive reaction to fairness creams and one female patient showed positive reaction to her foundation lotion. Only two healthy volunteers were found to be positive.
Comments: Melasma is common pigmentary disorder with a long list of contributing factors in its etiology. Drugs containing phototoxic agents, phenothiazines, and anticonvulsants have been particularly linked to melasma. However, cosmetics have been rarely considered in the list of causes of melasma. Cosmetics have become a product of daily use which is continually increasing. A variety of cosmetics products is available in the market containing complex mixtures of perfumes, preservatives, emulsifiers and stabilizers, various lipids, and higher alcohols. Various chemicals in cosmetics (colophony, PPD, balsam peru, cetostearyl alcohol, lanolin, beeswax, formaldehyde, fragrances, musk mix, vanillin, rose oil, triclosan, or other antiseptics) have been implicated to cause multiple skin problems like primary irritant reactions, allergic contact dermatitis, photoallergic contact dermatitis, contact urticaria, pigment alteration, photosensitivity, brittle hair and nails, and so on. Hyperpigmentation, as in Berloque dermatitis, Riehl's melanosis, poikiloderma of Civatte, and erythrosis pigmentata faciei of Brocq, has been attributed to bergamot oil in eau-de-Cologne or from tars in cosmetics. Cetrimide was the most frequent allergen accounting for 52% of the positive results. Cetrimide is an antiseptic and major formulation excipient chemical in cosmetics, accounting for 52% of the positive results in the current study. The formulation excipients are inert substances that serve to solubilize, emulsify, sequester, thicken, foam, lubricate, or color the active component in the product. At times, particularly in sensitive skin people, it can lead to allergic contact dermatitis. Cosmetics, topical pharmaceutical preparations, foods, contain preservatives such as dodecyl gallate, octyl gallate, and propyl gallate (gallate mix). Over the previous decade, propyl gallate allergy has been seen to an increase due to the increasing use liposome containing creams. Thiomersal, a preservative in cosmetics, eye drops, contact lens solutions, vaccines, and antiseptics, is considered uncommon allergen and the reported thiomersal contact sensitivity in patients of cosmetic dermatoses or pigmented cosmetic dermatitis varies from 8% to 77%. Chronic use of topical mercury, a common ingredient of skin lightening soaps and fairness creams, may itself cause increased pigmentation due to the accumulation of mercury granules in the dermis via absorption through hair follicles and sebaceous glands. Phenyl salicylate is a preservative, denaturant for alcohol and fragrance ingredient in cosmetics, face and hand creams, mouthwashes, and sunscreen preparations, commonly used for the pleasant odor. There are reports of cheilitis from lip salve containing phenyl salicylate wherein both lip salve and phenyl salicylate elicited positive patch test reactions. In the current study, two patients with melasma and one control had a positive reaction to PPD but never had clinical contact dermatitis despite using hair colors in the past or perhaps being subtle clinically it remained unnoticed. PPD is a strong sensitizer commonly found in products like in textile or fur dyes, black rubber, temporary tattoos, photocopying, and printing inks. Chloroacetamide, a common preservative, is a well-known cause of cosmetic allergy. None of the patient elicited a positive reaction to it in the current study. Bronopol has shown a large number of positive reactions in various previous studies. In the current study, only one patient had a positive reaction to bronopol. Sunscreens are common causes of photo allergic contact dermatitis and are frequently present in cosmetics such as moisturizers, lip and hair preparations, and foundations. None was found to be positive in the current study. As photo patch testing was not performed, whether melasma among them is from photo allergic contact dermatitis remains unknown. Overall, it was observed that there was dissociation between the patch test results from individual cosmetics ingredients and the cosmetic products. The current study suggests to consider pigmented cosmetic dermatitis and cosmetics contact sensitivity in the etiologic factors when melasma is not associated with pregnancy, lactation, or hormone therapy.
Shaikh ZI, Mashood AA. Treatment of refractory melasma with combination of topical 5% magnesium ascorbyl phosphate and fluorescent pulsed light in Asian patients. Int J Dermatol 2014;53:93-9.
Melasma is a common hyperpigmentary disorder seen, following the onset of the second decade of life. This disorder with ambiguous pathogenesis has several contributing factors such as genetic predisposition, exposure to ultraviolet light, pregnancy, oral contraceptives, endocrine dysfunction, hormonal treatments, drugs containing phototoxic agents, and stress. Armamentarium for the treatment of melasma is wide consisting numerous topical agents, systemic drugs, chemical peels, dermabrasion, and a variety of lasers and light-based devices. Combination of this different treatment modalities has also been used like, combinations of IPL therapy with hydroquinone (HQ)-based topical preparations, IPL and Q-switched (QS) ruby laser, and combined use of ultrapulse CO 2 laser and QS alexandrite laser. Treatment with lasers and light-based devices carries the risk of PIH. In this study, we evaluated the combination of 5% magnesium ascorbyl phosphate (MAP) and fluorescent pulsed light (FPL) for treatment of melasma with an intention to minimize the risk of PIH.
The study was carried on 70 patients not responding to one or more previously prescribed treatment modalities for a minimum period of 6 months. After the wash-off period of 3 months, patients were treated for 12 weeks (treatment phase) with daily topical application of 5% MAP at night and three sessions of FPL (570-950 nm) with an advanced fluorescent technology device at 3 rd , 6 th , and 9 th weeks (fluence 12-14 J/cm 2 ), pulse width 15 ms, pulse repetition rate 2/3 Hz, and spot size 3 cm 2 ). The follow-up period consisted of 12 weeks during which the patients were assessed with subjective and self-assessment and MASI. A total of 65 patients completed the study, which showed a decrease in the MASI score of 4.53 ± 1.5 at the 12 th week (end of treatment) and 6.35 ± 2.4 at the 24 th week (end of follow-up) from the baseline of value of 14.80 ± 3.4. Assessments done by an independent observer was good to excellent responses to treatment (scores 3 and 4) in 52.3% and 44.6% cases, respectively. Transient erythema in 5 (7.6%) patients and mild skin peeling in 4 (6.1%) after FPL were the only observed side effects.
Comments: Treatment for melasma has endless options. However, none of the treatment options provides a long lasting satisfactory outcome. HQ alone or incorporated in modified Kligman's formula is the most widely prescribed agent for treating melasma. Despite its efficacy, desquamation, burning, dryness, and pruritus are its frequently reported side effects. MAP is a stable ester of ascorbic acid that has antioxidant properties and inhibits melanogenesis in vitro and in vivo. It prevents free-radical production and has a protective effect against UVB radiation. Ascorbic acid decreases melanogenesis by interacting with copper at the active site of tyrosinase and by reducing dopaquinone by blocking dihydrochinindol-2-carboxyl acid oxidation. A randomized clinical trial comparing 4% HQ with 5% ascorbic acid in melasma concluded that although HQ showed better subjective response, there was no statistical difference in calorimetric measures, and ascorbic acid was almost devoid of side effects.
Many different types of lasers and IPL devices such as, QS Nd:YAG, QS ruby, and QS alexandrite have been used to treat melasma with variable results. In a pilot study done to treat melasma with fractional photothermolysis (FPT) (1550 nm) in 10 patients, it was found that six patients had 75-100% clearing of melasma based on clinical evaluation. Another split face study on 14 female patients with melasma treated with nonablative FPT (1540 nm) showed good results in skin types I and II but emphasized its critical evaluation in patients with darker skin complexions. PIH is the most frequent complication of lasers and light-based treatments, which can be reduced a bit by preoperative and postoperative use of topical bleaching agents, along with sun protection. Based on these recommendations, the study used 5% MAP cream as a bleaching agent in the preprocedure and postprocedure period. FPL is a noncoherent light that differs from light emitted by other IPL systems by its lower peak power, longer pulse width, and equally distributed fluence. The combination of these two different treatment modalities showed promising results with overall regression in mean MASI scores as these two endpoints were 69.3% and 57%, which were statistically significant. This clinical response might be due to selective photo thermolysis targeting the melanosomes, causing thermal denaturation and possibly mechanical injury by rapid thermal expansion by the FPL (570-950 nm). However, future work at cellular level would be needed to elucidate the exact mechanism. This suggests that the lower fluence should be selected for light-based treatments in patients with a darker skin color. The modest increase in mean MASI score at the end of 3 months posttreatment follow-up indicates a gradual recurrence of melasma. This implies that for persistent improvement, maintenance treatments are required. This necessitates for a study with longer follow-up (possibly up to 12 months) with some other topical therapies or laser therapies for sustaining the results.