***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Melasma is difficult to clear . Many agents have been used , such as hydroquinone , and glycolic acid and glycolic acid peels , kojic acid , a tyrosinase inhibitor in the fungus Aspergilline oryzae . OBJECTIVE To see if the addition of 2 % kojic acid in a gel containing 10 % glycolic acid and 2 % hydroquinone will improve melasma further . METHODS Forty Chinese women with epidermal melasma were treated with 2 % kojic acid in a gel containing 10 % glycolic acid and 2 % hydroquinone on one half of the face . The other half was treated with the same application but without kojic acid . The side receiving the kojic acid was r and omized . Determination of efficacy was based on clinical evaluation , photographs and self- assessment question naires at 4 weekly intervals until the end of the study at 12 weeks . The non-parametric Wilcoxon 's rank sum test was used for statistical analysis . RESULTS All patients showed improvement in melasma on both sides of the face . The side receiving the kojic acid did better . More than half of the melasma cleared in 24/40 ( 60 % ) patients receiving kojic acid compared to 19/40 ( 47.5 % ) patients receiving the gel without kojic acid . In 2 patients , there was complete clearance of melasma , and this was on the side where kojic acid was used . Side effects include redness , stinging , and exfoliation . These were seen on both sides of the face , and they settled by the third week . CONCLUSION The addition of kojic acid to a gel containing 10 % glycolic acid and 2 % hydroquinone further improves melasma OBJECTIVE To compare the efficacy and safety of Jessner 's solution with 30 % salicylic acid as superficial chemical peeling agents in treating epidermal melasma in Asian skin . STUDY DESIGN Double blind , r and omized , interventional comparative study . PLACE AND DURATION OF STUDY Department of Dermatology , Combined Military Hospital , Malir Cantt , Karachi , from January to December 2004 . PATIENTS AND METHODS Sixty consenting patients with epidermal melasma were r and omly divided into two groups . Group A was treated with Jessner 's solution and Group B with 30 % salicylic acid . Baseline Melasma Area Severity Index ( MASI ) score was noted and peeling started at 2-weekly intervals . Sunscreen in morning and moisturizer at night were prescribed in all patients . MASI score and adverse effects were recorded biweekly . Treatment was stopped at 12 weeks and patients were followed-up at 4 weekly intervals for further 12 weeks . Final MASI score and adverse effects were noted at the end of follow-up period . Mean MASI scores were compared using paired sample t-test and one-way ANOVA . RESULTS Difference in baseline , treatment end and follow-up end MASI scores was not statistically significant between the two groups ( p 0.54 , 0.26 , and 0.55 respectively ) . On the other h and , within group analysis of difference between pre and posttreatment MASI score was highly significant in both groups ( p<0.0001 ) . Adverse effects were mild and comparable in both groups . CONCLUSION Jessner 's solution and 30 % salicylic acid are equally effective and safe peeling agents for use in epidermal melasma in Asian skin BACKGROUND AND DESIGN Melasma is an acquired , masklike , facial hyperpigmentation . The pathogenesis and treatment of melasma in black ( African-American ) patients is poorly understood . We investigated the efficacy of topical 0.1 % all-trans-retinoic acid ( tretinoin ) in the treatment of  melasma in black patients . Twenty-eight of 30 black patients with melasma completed a 10-month , r and omized , vehicle-controlled clinical trial in which they applied either 0.1 % tretinoin or vehicle cream daily to the entire face . They were evaluated clinical ly ( using our Melasma Area and Severity Index ) , colorimetrically , and histologically . RESULTS After 40 weeks , there was a 32 % improvement in the Melasma Area and Severity Index score in the tretinoin treatment group compared with a 10 % improvement in the vehicle group . Colorimetric measurements showed lightening of melasma after 40 weeks of tretinoin treatment vs vehicle . Lightening of melasma , as determined clinical ly , correlated well with colorimetric measurements . Histologic examination of involved skin revealed a significant decrease in epidermal pigmentation in the tretinoin group compared with the vehicle group . Side effects were limited to a mild " retinoid dermatitis " occurring in 67 % of tretinoin-treated patients . Among the patients in this study in comparison with comparably recruited white patients , melasma was reported to have begun at a later age and was more likely to be in a malar distribution . CONCLUSIONS This controlled study demonstrates that topical 0.1 % tretinoin lightens melasma in black patients , with only mild side effects Treatment of melasma , a hyperpigmentation disorder , remains a challenge . The primary objective of two 8-week , multicenter , r and omized , investigator-blind studies was to compare the efficacy and safety of a hydrophilic cream formulation containing tretinoin 0.05 % , hydroquinone 4.0 % , and fluocinolone acetonide 0.01 % ( RA+HQ+FA ) with the dual-combination agents tretinoin plus hydroquinone ( RA+HQ ) , tretinoin plus fluocinolone acetonide ( RA+FA ) , and hydroquinone plus fluocinolone acetonide ( HQ+FA ) . All agents had the same drug concentration and vehicle . A total of 641 adult patients , predominantly female , with moderate to severe melasma and Fitzpatrick skin types I through IV , were r and omized to the various treatment groups . Due to the similarity of the study design s , the results of the 2 studies were combined and are reported here . The primary efficacy analysis involved the proportion of intent-to-treat patients in each treatment group whose condition had completely cleared by week 8 . The results of the combined clinical trials demonstrated that significantly more of the patients treated with RA+HQ+FA ( 26.1 % ) experienced complete clearing compared with the other treatment groups ( 4.6 % ) at the end of week 8 ( P<.0001 ) . In addition , at week 8 , a 75 % reduction in melasma/pigmentation was observed in more than 70 % of patients treated with RA+HQ+FA compared with 30 % in patients treated with the dual-combination agents . The most common adverse reactions seen with all treatment groups were erythema , skin peeling , burning , and /or stinging sensation . The majority of treatment-related adverse events were of mild severity BACKGROUND Patients with dermal or mixed-type melasmas are often refractory to various treatments . Intense pulsed light has been used to treat melanocytic lesions with promising results . OBJECTIVE The purpose of this study was to clarify the effectiveness of intense pulsed light for refractory melasma in Asian persons . METHODS Seventeen patients were treated with intense pulsed light  , during four sessions at 4-week intervals . The patients were also given 4 % hydroquinone cream and broad-spectrum sunscreens to prevent and treat postinflammatory hyperpigmentation .  Sixteen patients in the control group were treated with hydroquinone cream and sunscreens . The treatment efficacy was evaluated using reflectance spectrophotometer and patient satisfaction question naire . RESULTS Patients in the intense pulsed light group achieved an average of 39.8 % improvement in relative melanin index , compared to 11.6 % improvement in the control group ( p<0.05 ) at Week 16 . Six ( 35 % ) patients in the intense pulsed light group had more than 50 % improvement , compared to two ( 14 % ) patients in the control group . Two patients in the intense pulsed light group , however , experienced transient postinflammatory hyperpigmentation , and partial repigmentation was noted 24 weeks after the last treatment session . CONCLUSION Intense pulsed light is a safe and effective treatment for  refractory melasma in Asian persons , with minimal side effects . Further treatment sessions are required for maintenance therapy Melasma is an endocrine‐mediated facial hypermelanosis with epidermal and occasionally dermal components . We tested in a r and omized double‐blind design the effect of a whitening formulation ( Thiospot intensive ® ) on this skin disorder . The product containing ethyl linoleate , thioctic acid , octadecenedioic acid , lactic acid and ethylhexyl methoxycinnamate was applied twice daily for 3 months by 20 young women . Another control group of seven women received a non‐skin lightening formulation . Clinical assessment s were made at 1‐month intervals . In addition , objective measurements of the hypermelanosis were performed using narrow‐b and reflectance spectrophotometry , image analysis of video‐recorded ultraviolet light reflection ( ULEV method ) and photodensitometry of the corneomelametry test . A significant lightening effect was evidence d beginning the second month of treatment with the whitening formulation . No significant effect was observed with the control product The efficacy of 20 % azelaic acid cream and 4 % hydroquinone cream , both used in conjunction with a broad-spectrum sunscreen , against melasma was investigated in a 24-week , double-blind study with 329 women . Over the treatment period the azelaic acid cream yielded 65 % good or excellent results ; no significant treatment differences were observed with regard to overall rating , reduction in lesion size , and pigmentary intensity . Severe side effects such as allergic sensitization or exogenous ochronosis were not observed with azelaic acid Melasma is a common disorder of cutaneous hyperpigmentation predominantly affecting the faces of women . Little is known about the aetiology of melasma , and treatment is frequently disappointing . Topical tretinoin is of benefit in treating other forms of hyperpigmentation , for example liver spots , and we therefore investigated its effectiveness in melasma . Thirty‐eight women completed a r and omized , vehicle‐controlled study , in which they applied 0.1 % tretinoin ( n=19 ) or vehicle cream ( n=19 ) once daily to the face for 40 weeks BACKGROUND Melasma , also known as mask of pregnancy , is a common , acquired hypermelanosis seen in women with Fitzpatrick skin types II-V , and is often recalcitrant to treatment with depigmentation agents . Glycolic acid has been added to hydroquinone formulations in the past to enhance their depigmentation effects , but may cause irritation , leading to postinflammatory hyperpigmentation . AIM To assess the safety and efficacy of a cream containing 4 % hydroquinone , 10 % buffered glycolic acid , vitamins C and E , and sunscreen ( Glyquin , ICN Pharmaceuticals , Costa Mesa , USA ) vs. a cream containing sunscreen alone in the depigmentation of epidermal melasma of the face . METHODS Thirty-nine Hispanic women , Fitzpatrick skin types III-V , with bilateral epidermal melasma were enrolled in a r and omized controlled trial lasting 12 weeks . Patients underwent twice-daily full-face application with the study cream or with the cream containing sunscreen only .  Changes in pigmentation were measured using a mexameter , the melasma area and severity index ( MASI ) , and a global evaluation by the patient and blind investigator . Safety evaluations were performed at each follow-up visit . RESULTS Thirty-five patients completed the trial . Irritation was more common with the study cream , but resolved with temporary cessation of cream application and the addition of moisturizers . Mexameter results demonstrated a significant decrease in the degree of pigmentation using the study cream compared with the cream containing sunscreen alone ( P < 0.0001 ) . Fifteen of 20 patients ( 75 % ) using the study cream improved , whereas only two of 15 patients ( 13 % ) improved using sunscreen alone . CONCLUSIONS A cream containing 4 % hydroquinone , 10 % buffered glycolic acid , vitamins C and E , and sunscreen is safe and effective in the treatment of melasma BACKGROUND Melasma is a common disorder of facial hyper‐pigmentation among Asian women . Many modalities of treatment are available but none is satisfactory . OBJECTIVE This study was undertaken to see if glycolic acid peels are effective and safe in the treatment of melasma and fine facial wrinkling . METHODS Ten Asian women with moderate to severe melasma were recruited into the study . The women had twice daily applications of a cream containing 10 % glycolic acid and 2 % hydroquinone ( Neostrata AHA Age Spot and Skin Lightening Gel ) to both sides of the face , and glycolic acid peels every 3 weeks ( 20–70 % ) to one‐half of the face using Neostrata Skin Rejuvenation System . All patients had to use a sunblock ( SPF 15 % ) . At regular intervals and at the end of 26 weeks ( or after eight peels ) the degree of improvement of pigmentation and fine facial wrinkling on each side of the face were assessed . Any skin irritation or side effects were also noted . Assessment was by an independent dermatologist , the patients themselves , and the use of the Munsell color chart and photographs . The nonparametric Wilcoxon Rank‐Sum test was used for statistical analysis . RESULTS The melasma and fine facial wrinkling improved on both sides of the face . The side that received glycolic acid peels did better but the results were not statistically significant ( P > 0.059 ) . CONCLUSION A cream containing 20 % 
    Output:
    
The current limited evidence supports the efficacy of multiple interventions .