Clinical and histological evaluation of 1% nadifloxacin cream in the treatment of acne vulgaris in Korean patients

Objectives Nadifloxacin is a fluoroquinolone with broad‐spectrum antibacterial activity. Although it is used as an acne treatment in some European countries, it has not been used to treat Korean acne patients. We aimed to evaluate the clinical efficacy and safety of 1% nadifloxacin cream and the histological changes it incurs when used to treat mild to moderate facial acne in Korean patients. Methods An eight‐week, randomized, prospective, split‐face, double‐blind, vehicle‐controlled trial was performed. All participants were treated with 1% nadifloxacin cream on one‐half of the face and vehicle cream on the other, twice per day for eight weeks. Results At final visits, inflammatory acne lesions were reduced by 70% on nadifloxacin‐treated skin and increased by 13.5% on vehicle‐treated skin; non‐inflammatory acne lesions showed reductions of 48.1 and 10.1%, respectively. A significant difference was observed between the two treatments at four weeks. Histopathological examinations of the acne lesions showed decreased inflammation and interleukin‐8 expression but no change in transforming growth factor‐β expression in nadifloxacin‐treated skin compared with vehicle‐treated skin after eight weeks of treatment. Conclusions Nadifloxacin 1% cream is an effective, safe, and well‐tolerated topical treatment for Korean patients with mild to moderate acne vulgaris. Histopathological changes after nadifloxacin treatment were well correlated with clinical outcomes. Therefore, nadifloxacin can be used as an effective and safe treatment option in the management of mild to moderate acne in Asian subjects.     

An observational study of methionine‐bound zinc with antioxidants for mild to moderate acne vulgaris

APC is a novel methionine‐based zinc complex with antioxidants that has been used in acne as a nutritional supplement. This is based on the proven role of zinc and antioxidants in improving acne, specially the inflammatory lesions. The objectives of this study are to explore the efficacy, safety, and tolerability of APC in acne patients with mild to moderate facial acne vulgaris. In this exploratory trial, 48 patients were treated with oral APC thrice a day for 3 months followed by a 4‐week treatment‐free period. At the end of treatment (Week 12), there was a statistically significant improvement in the global acne count (p < 0.05), which began after 8 weeks (p < 0.05). Almost 79% (38/48) of the patients had 80–100% improvement. There was a significant reduction in pustules (8 weeks (p < 0.05) and 12 weeks (p < 0.001)), and papules and closed comedones (8 weeks (p < 0.05) and 12 weeks (p < 0.001)). Only two patients had side effects. The current data indicate that treatment with oral APC thrice daily for 12 weeks in patients with mild to moderate facial acne vulgaris is efficacious and well tolerated. As the onset of action is late, concomitant topical therapy can enhance the results.     

Comparison of micronized tretinoin gel 0.05% and tretinoin gel microsphere 0.1% in young adolescents with acne: a post hoc analysis of efficacy and tolerability data

Acne vulgaris is common in young adolescents. Retinoids are widely used but may be associated with poor tolerability. This post hoc analysis of 483 participants aged 10 to 14 years with mild to moderate acne compared efficacy and tolerability of once-daily treatment with micronized tretinoin gel 0.05%, tretinoin gel microsphere 0.1%, and vehicle over 12 weeks. In study 1, inflammatory and noninflammatory lesion reduction and treatment success was comparable between tretinoin gel 0.05% and tretinoin gel microsphere 0.1%. Inflammatory (46.3%) and noninflammatory (45.7%) lesion reductions with tretinoin gel 0.05% were significantly greater than vehicle (37.1% and 27.9%, respectively) (both P<.001). In study 2, inflammatory and noninflammatory lesion reductions and treatment success with tretinoin gel 0.05% (30.6%, 39.1%, and 19%, respectively) were significantly greater than vehicle (10.9%, 16.9% [both P<.001], and 4% [P=.008], respectively). Tretinoin gel 0.05% was significantly better tolerated than tretinoin gel microsphere 0.1% (P<.001); the majority of adverse events (AEs) were mild, occurring in the first 2 weeks. Fourteen percent of participants reported dry skin, 8% skin burning sensation, 5% erythema, and 5% dermatitis exfoliative with tretinoin gel 0.05% compared with 32%, 11%, 23%, and 23%, respectively, with tretinoin gel microsphere 0.1% (all P<.001, except skin burning sensation). In this secondary analysis of acne in young adolescents aged 10 to 14 years, micronized tretinoin gel 0.05% provided a comparable lesion reduction and treatment success versus tretinoin gel microsphere 0.1%, with a better cutaneous tolerability profile.     

Erythromycin 2 percent gel in the treatment of acne vulgaris

A gel formulation of erythromycin 2 percent was compared with its vehicle in a double-blind multicenter study involving patients with mild to moderate acne vulgaris. In an analysis of 187 patients treated twice daily for 8 weeks, erythromycin 2 percent gel proved to be significantly more effective than vehicle in reducing the numbers of both inflammatory and noninflammatory lesions. After 8 weeks, 60 percent of erythromycin-treated patients had good or excellent responses compared with 36 percent of those using vehicle (p = 0.001); the lesions in two patients using erythromycin were completely cleared. The majority of patients had a favorable impression of the cosmetic characteristics of the gel formulation.     

Hydrocortisone butyrate 0.1% cream in the treatment of chronic dermatitis

This multicenter, randomized, double-blind clinical trial involving 89 subjects (86 with chronic hand dermatitis and 3 with atopic dermatitis) compared the safety, efficacy, and cosmetic acceptability of 4 medium-potency topical corticosteroid products: hydrocortisone butyrate (HB) 0.1% cream (Locoid Lipocream), fluticasone propionate (FP) 0.05% cream (Cutivate), prednicarbate (PC) 0.1% cream (Dermatop), and mometasone furoate (MF) 0.1% cream (Elocon). Subjects were randomly assigned to 1 of 3 treatment groups (HB vs FP, HB vs PC, or HB vs MF) and further randomized to HB on the right or the left side, and FP, PC, or MF on the contralateral side. Treatments were self-administered twice daily for 2 weeks. Assessments of efficacy were based on the investigator ratings of signs and the subject ratings of signs and symptoms. Cosmetic acceptability was assessed by direct comparisons between products using a subject questionnaire. The results indicated comparable efficacy of all 4 medium-potency corticosteroid products and suggested that, compared to other corticosteroid creams, the HB vehicle yielded somewhat greater subject preference with respect to cosmetic appeal.     

The pinhole method using an erbium: YAG laser for the treatment of papular acne scars

Papular acne scars are skin‐colored or hypopigmented, soft and elevated lesions of the chin and trunk. Papular scars are one of the most difficult acne scars to treat. Herein, we reported two patients with papular acne scars on the chin that were successfully treated by the pinhole method using an Erbium (ER):YAG laser. Good cosmetic results were achieved in both patients. The side effects included mild, intra‐, and post‐procedural pain and erythema that resolved spontaneously within 2 weeks. The pinhole method with an Er:YAG laser could potentially be used as a safe and effective treatment for papular acne scars.     

Topical retinoids in acne – an evidence‐based overview

Topical retinoids are important tools in the management of acne because they act against comedones and microcomedones and have direct anti‐inflammatory effects. The substances approved for acne treatment comprise tretinoin (all‐trans‐retinoic acid),isotretinoin (13‐cis retinoic acid) as well as the synthetic third‐generation polyaromatic retinoids adapalene and tazarotene,the latter being approved for acne treatment in the US only.Retinaldehyde is used in cosmetic preparations against acne. All topical retinoids are effective as single agents in mild to moderate acne but differ in efficacy and tolerability. Tazarotene 0.1% is more effective than tretinoin 0.025% or 0.1% microsphere gel or adapalene 0.1% gel or cream (EBM‐level 2c). Adapalene 0.1% is equally effective to tretinoin 0.025% or tretinoin microsphere 0.1% gel or tretinoin 0.05% cream or isotretinoin 0.05% gel (EBM‐level 2c). Adapalene 0.1% gel is significantly better tolerated than tazarotene 0.1% gel, tretinoin 0.025% and tretinoin 0.05% gel, tretinoin 0.05% cream,tretinoin microsphere 0.1% gel or isotretinoin 0.05% gel (EBM‐level 2c).The safety profile of topical retinoids differs from their systemic counterparts and is related mainly to local adverse effects, such as erythema, dry‐ness,itching and stinging.The currently available evidence justifies the use of topical retinoids in most types of acne and during maintenance treatment.     

Treatment‐seeking behavior,knowledge and beliefs about acne vulgaris among adolescents: A cross‐sectional study in high school students in Tirana,Albania

Acne vulgaris is a common adolescents' disorder. Nevertheless, there is lack of knowledge about acne among adolescents. To evaluate the adolescents' knowledge and beliefs about acne, to investigate help‐seeking behavior and treatment preferences. A cross‐sectional study conducted in 10 public high schools in Tirana. A total of 2036 students enrolled. All participants were asked about socio‐demographic data, knowledge and beliefs about acne, treatment‐seeking behaviors and clinical preferences. Of participants 45.3% thought acne is a medical problem, 23.1% thought it's a cosmetic problem, and less than 10% thought acne is a normal condition for their age. Of adolescents 30% did not know that acne is not contagious, 49.7% believed acne is curable with prescribed medication, 33.4% thought acne heals by itself, and only 0.9% believed acne is non‐curable. Male adolescents were more likely to have lower level of knowledge and misconceptions about acne compared to females. Only 18.5% had consulted a dermatologist. The majority (54.7%) were using anti‐acne products recommended by their friends or pharmacists. Only minority of Albanian adolescents with acne consults a dermatologist. Age, gender and acne severity play a significant role in determining help‐seeking behavior. Patient and parent education can significantly improve the treatment outcome.     

Control of microcomedone formation throughout a maintenance treatment with adapalene gel, 0.1%

BACKGROUND: Microcomedones representing the clinically non-visible central precursor lesions of acne are induced by sebaceous hyperplasia as well as altered follicular growth and differentiation, and evolve into both comedones and inflammatory lesions. Thus, targeting microcomedone formation is essential in the prevention and therapeutic control of acne. OBJECTIVE: The aim of this study was to assess the capacity of adapalene gel, 0.1%, to control the number of microcomedones after a combination treatment followed by a maintenance treatment. METHODS: This was a single-site exploratory study in subjects with a diagnosis of mild to moderate acne vulgaris and the presence of at least 250 microcomedones per cm(2) at screening visit, counted via cyanoacrylate strips (CyASt). During the first 8 weeks, a combination of adapalene gel (0.1%) and benzoyl peroxide gel (2.5%) was applied. During the randomized, investigator-blinded, and vehicle-controlled 12-week maintenance phase, adapalene once daily (QD), or adapalene alternately with its vehicle once daily every other day (QoD), or vehicle QD were applied to the face. CyASt sampling on the forehead was done at baseline, week 8, and week 20. Lesion counting allowing calculating a defined success rate was done at all visits. RESULTS: A total of 54 subjects entered the combination phase, and 49 subjects were randomized into the maintenance phase: 16 in both the adapalene QD and the QoD group and 17 subjects receiving the vehicle. The microcomedone median count decreased for all groups until week 8 (end of combination phase) from 319 to 157. Microcomedone counts at the end of the maintenance phase (week 20) showed a significant percent difference (P = 0.04) between adapalene QoD (-53.5) and the vehicle (-42.1) and between adapalene QD (-50.6) and the vehicle (P = 0.037) compared with baseline. CONCLUSION: The application of adapalene gel, 0.1% monotherapy daily, or alternately every other day, significantly helps to control the microcomedone count during a 12-week maintenance treatment after a previous combination therapy with benzoyl peroxide in patients with mild to moderate acne.     

The role of topical dermocosmetics in acne vulgaris

Acne is a common chronic inflammatory disease and treatment modalities based on acne severity are well established. The role of dermocosmetics in dermatology, and in particular acne, is becoming more important as more research elucidates the mechanisms of action of products in the pathogenesis of acne. Dermocosmetics have the potential to be used as monotherapy or in combination with medical treatment. Therefore, it has become important for dermatologists to understand dermocosmetics to effectively and appropriately advise patients on their use. The objective of this review was to provide new insights into the role of traditional and novel ingredients in dermocosmetics for the treatment of acne, based on the authors’ objective assessment of the published literature. The type of products discussed include: those which have a sebostatic effect, such as topical antioxidants and niacinamide; agents targeting abnormal keratinization, such as salicylic acid, lipo‐hydroxy acid, alpha‐hydroxy acids, retinol‐based products and linoleic acid; agents targeting Propionibacterium acnes, such as lauric acid; and anti‐inflammatory agents such as nicotinamide, alpha‐linolenic acid and zinc salts. Despite the scientific advances in understanding these cosmetic ingredients, there still remains a lack of rigorous controlled studies in this area.     

Tazarotene gel is safe and effective in the treatment of acne vulgaris: a multicenter, double-blind, vehicle-controlled study.

Retinoids reverse the abnormal pattern of keratinization seen in acne vulgaris. Tazarotene is the first of a novel family of topical receptor-selective acetylenic retinoids. This study evaluates the safety and efficacy of topical tazarotene 0.1% and 0.05% gels, in comparison to vehicle gel, applied once daily for 12 weeks, in the treatment of mild-to-moderate facial acne vulgaris. A total of 446 patients with facial acne vulgaris were enrolled, and 375 patients, ranging in age from 14 to 44 years, were evaluable in this multicenter, double-blind, randomized study. In comparison to vehicle gel, treatment with tazarotene 0.1% gel resulted in significantly greater reductions in noninflammatory and total lesion counts at all follow-up visits, and inflammatory lesion counts at Week 12. Tazarotene 0.05% gel resulted in significantly greater reductions in noninflammatory and total lesion counts than vehicle gel at Weeks 8 and 12. At Week 12, treatment success rates were 68% and 51% for tazarotene 0.1% and 0.05%, respectively (40% for vehicle gel). Tazarotene gel was an effective, safe, and generally well-tolerated therapy for the treatment of acne vulgaris.     

A Novel Gel Formulation of 0.25% Tretinoin and 1.2% Clindamycin Phosphate: Efficacy in Acne Vulgaris Patients Aged 12 to 18 Years

Abstract:  Treatments for mild to moderately severe acne usually combine retinoid and antimicrobial therapy. Recently, the US FDA approved the combination of 1.2% clindamycin (CLIN) and 0.025% tretinoin (RA) in a novel gel formulation for the treatment of mild to moderate acne, based on results from two 12-week, multicenter, double-blind Phase 3 trials in which patients were randomized to four treatment arms: CLIN/RA, CLIN, RA, and vehicle. The trials studied more than 4500 patients 12 years of age or older. In both trials, CLIN/RA gel produced significantly greater clinical improvements than vehicle or either monotherapy. CLIN/RA was safe and well tolerated in both trials and in a 52-week safety follow-up evaluation. The current study is a subgroup analysis that evaluates CLIN/RA's effects on acne lesion prevalence in 12- to 18-year-old patients with mild to severe baseline acne severity. CLIN/RA significantly reduced the number of inflammatory, noninflammatory, and total acne lesions after 12 weeks of treatment (p ≤ 0.004) in 1,710 patients aged 12 to 18 years. Relatively greater improvements were seen following CLIN/RA treatment compared to CLIN or RA monotherapy, or the vehicle gel beginning as early as 2 weeks following treatment initiation. This novel CLIN/RA gel for treating acne is tolerable and safe and offers clinicians and teen aged patients a new and efficacious intervention for acne vulgaris.
[Abstract amended after online publication date June 8, 2009]     

A novel gel formulation of clindamycin phosphate-tretinoin is not associated with acne flaring

Concern exists about using topical retinoids on patients with inflammatory acne lesions, fearing that a flare in inflammation will occur. In 3 multicenter, double-blind, randomized, phase 3 trials of a clindamycin phosphate 1.2%-tretinoin 0.025% gel (CLIN/RA), clinical evaluations after 2 weeks of treatment determined if flaring occurred in participants treated with tretinoin gel 0.025% (RA) monotherapy, and the difference in inflammation when treated with the combination formulation. Flaring was assessed as an increase in inflammatory lesions of 10% or greater or 20% or greater versus baseline. Most participants experienced improvement in lesions across treatment groups. Participants with mild acne at baseline treated with RA monotherapy had significantly higher rates of flaring compared with participants treated with vehicle gel (VEH) (P < .001). Treatment with CLIN/RA or clindamycin phosphate gel 1.2% (CLIN) monotherapy resulted in significantly lower rates of flaring than RA or VEH (P < .001 for all). Participants with moderate to severe acne showed no signs of RA-induced flaring. In each comparison, the CLIN/RA combination showed the lowest percentage of increased inflammatory lesions. These results indicate that RA-induced flaring may occur with mild inflammation; combining RA with CLIN prevents this flaring. Participants with moderate to severe inflammatory acne did not show an increase in inflammatory lesions compared with participants treated with VEH. Lack of flaring may result from either the novel vehicle formulation or the antiinflammatory effects of CLIN.     

Daylight photodynamic therapy with 1.5% 3‐butenyl 5‐aminolevulinate gel as a convenient,effective and safe therapy in acne treatment: A double‐blind randomized controlled trial

While daylight photodynamic therapy (PDT) is a simpler and more tolerable treatment procedure for both clinicians and patients, it has never been applied for acne treatment. In this study, we evaluated efficacy, safety and histological changes of facial acne after application of the novel variant of 5‐aminolevulinate (ALA)‐ester, 1.5% 3‐butenyl ALA‐bu gel, using daylight only as the potential visible light source. Forty‐six acne patients were randomly assigned to either ALA‐bu or vehicle application group in a double‐blind fashion. Both groups applied the allocated gel to facial acne lesions every other day for 12 weeks. At the final 12 week, both inflammatory and non‐inflammatory acne lesions had decreased significantly by 58.0% and 34.1% in the ALA‐bu group, respectively. Only a few patients expressed mild adverse effects. In the histopathological analysis, attenuated inflammatory cell infiltrations were observed and immunostaining intensities for interleukin‐8, interleukin‐1β, matrix metalloproteinase‐9 and phosphorylated nuclear factor‐κB were reduced concomitantly. Changes of their mRNA expression demonstrated comparable patterns. In conclusion, this ambulatory PDT was effective, very well tolerated and convenient for treating inflammatory acne lesions. Experimental results correlated well with clinical results. This novel regimen would provide a viable option for acne therapy.     

Topical Zinc Therapy for Acne Vulgaris

Abstract: A double-blind study of 30 patients with mild to moderate acne vulgaris was conducted to evaluate the efficacy of a topically applied 2% zinc sulfate solution for acne therapy. Over a 12-week period, no difference was noted between placebo- and zinc-treated participants in regard to either the number or type of acne lesions. The irritancy due to topically applied zinc was significantly greater (p 0.05) than that due to the placebo. Zinc serum levels were not significantly elevated between the two regimens before, during, or after treatment. This study suggests that topical zinc therapy alone is not of significant benefit in the treatment of acne vulgaris.     

Topical Zinc Therapy for Acne Vulgaris

A double-blind study of 30 patients with mild to moderate acne vulgaris was conducted to evaluate the efficacy of a topically applied 2% zinc sulfate solution for acne therapy. Over a 12-week period, no difference was noted between placebo- and zinc-treated participants in regard to either the number or type of acne lesions. The irritancy due to topically applied zinc was significantly greater (p less than or equal to 0.05) than that due to the placebo. Zinc serum levels were not significantly elevated between the two regimens before, during, or after treatment. This study suggests that topical zinc therapy alone is not of significant benefit in the treatment of acne vulgaris.     

Light‐emitting diode 415 nm in the treatment of inflammatory acne: An open‐label,multicentric, pilot investigation

Background. The management of acne remains a challenge, with current therapies linked to significant side effects and patient non‐compliance. Phototherapy using blue light has been proven in the treatment of acne vulgaris and offers the clinician an effective alternative.

Objective. To determine the effect of narrowband light‐emitting diode (LED) blue light in the reduction of inflammatory and non‐inflammatory lesions in patients with mild to moderate acne and to evaluate patient tolerance of the therapy.

Methods. Forty‐five patients were treated with high‐intensity pure blue light, 415?nm and 48?J/cm², receiving two treatments of 20?minutes per week for a period of 4–8 weeks. Clinical assessment was performed at baseline, and 2, 4 and 8 weeks after treatment. A patient's therapeutic response was measured using a global improvement scoring system.

Results. The mean improvement score was 3.14 at 4 weeks and 2.90 at 8 weeks. Nine patients experienced complete clearing at 8 weeks. The treatment was well tolerated, with 50% of patients highly satisfied with the treatment.

Conclusion. This open‐label study suggests the therapeutic efficacy of high‐intensity LED pure blue light in the treatment of acne vulgaris with no reported side effects.     

Randomized,controlled trial split‐faced study of 595‐nm pulsed dye laser in the treatment of acne vulgaris and acne erythema in adolescents and early adulthood

The high prevalence of acne vulgaris in teenagers has increased comorbidities. Lasers offer alternative options for acne treatment because they have rapid action, low systemic adverse effects, and do not require everyday treatment. To study the efficacy and patients’ satisfaction of 595‐nm pulse dye laser (PDL) treatment of acne vulgaris and acne erythema in adolescents and early adulthood, we designed a blocked‐randomized, split‐faced 595‐nm PDL (fluence 8 J/cm³ pulse duration 10 ms, spot size 7 mm, 2 session every 2 weeks) study in patients with mild to moderate acne by comparing the laser‐treated and non‐treated side. The acne lesion counts, acne erythema grading, and acne severity grading were evaluated at baseline and 2, 4, and 8 weeks. Thirty patients were recruited. The results showed no statistically significant difference except the papule count at week 4 which was ?1.828 on the treated side and 0.103 on the non‐treated side of the face, P‐value 0.0018. There was no statistically significant difference of acne severity grading and acne erythema grading between both sides of the face. The mean scores of patients’ satisfaction on the laser‐treated side were 75, 81, and 81%, respectively. The PDL treatment in this study reveals no significant improvement in acne therapy; however, the patients were satisfied with this laser treatment.     

Tazarotene cream for postinflammatory hyperpigmentation and acne vulgaris in darker skin: a double-blind, randomized, vehicle-controlled study

Previous investigations have reported the efficacy of tazarotene 0.1% cream for the treatment of dyschromia associated with photoaging and for acne vulgaris. The present investigation assessed tazarotene 0.1% cream for the treatment of postinflammatory hyperpigmentation (PIH) in a double-blind, randomized, vehicle-controlled study of 74 patients from darker racial ethnic groups who had acne. Once-daily application of tazarotene cream was shown to be effective against PIH, achieving significantly greater reductions compared with vehicle in overall disease severity and in the intensity and area of hyperpigmentation within 18 weeks (P< or =.05). Mean levels of erythema, burning, and peeling were no more than trace in both groups throughout the study, and mean levels of dryness were no more than mild in both groups. In our study, tazarotene cream was effective and well tolerated in the treatment of PIH in patients with darker skin.     

A randomized,double‐blind,placebo‐controlled trial to determine the efficacy and safety of lactoferrin with vitamin E and zinc as an oral therapy for mild to moderate acne vulgaris

Lactoferrin is an iron‐binding milk‐derived protein that has shown antibacterial and anti‐inflammatory effects in vitro and in vivo. The objective of this study was to determine the efficacy and safety of lactoferrin, combined with vitamin E and zinc, for mild to moderate acne vulgaris. In this randomized, double‐blind, placebo‐controlled trial, 168 subjects aged 13–40 years old were randomly assigned to take either a capsule formulation containing lactoferrin with vitamin E and zinc or placebo twice a day for 3 months. The primary outcome measure was a reduction in the number of acne lesions compared to placebo. A total of 164 subjects completed the study per protocol. The lactoferrin group (n = 82) showed a significant median percent reduction in total lesions as early as 2 weeks (14.5%, P = 0.0120), with the maximum reduction occurring at week 10 (28.5%, P < 0.0001) compared to placebo group (n = 82). Maximum reduction in comedones (32.5%, P < 0.0001) and inflammatory lesions (44%, P < 0.0001) was also seen at week 10 compared to placebo. Sebum scores were improved by week 12. No adverse events were observed during the trial. A twice daily regimen of lactoferrin with vitamin E and zinc significantly reduced acne lesions in people with mild to moderate acne vulgaris.