A microsponge formulation of hydroquinone 4% and retinol 0.15% in the treatment of melasma and postinflammatory hyperpigmentation

Disorders of hyperpigmentation such as melasma and postinflammatory hyperpigmentation (PIH) are common, particularly among people with darker skin types. Hydroquinone (HQ) bleaching creams are considered the gold standard for treating hyperpigmentation. Recently, a new formulation of HQ 4% with retinol 0.15% entrapped in microsponge reservoirs was developed for the treatment of melasma and PIH. Microsponges were used to release HQ gradually to prolong exposure to treatment and to minimize skin irritation. The safety and efficacy of this product were evaluated in a 12-week open-label study. A total of 28 patients were enrolled, and 25 completed the study. Study end points included disease severity, pigmentation intensity, lesion area, and colorimetry assessments. Adverse events also were recorded. Patients applied the microentrapped HQ 4% formulation to the full face twice daily (morning and evening). A broad-spectrum sunscreen was applied once in the morning, 15 minutes after application of the test product. Patients were evaluated at baseline and at 4, 8, and 12 weeks. The microentrapped HQ 4%/retinol 0.15% formulation produced improvement at all study end points. Improvement in disease severity and pigmentation intensity was statistically significant at weeks 4, 8, and 12 compared with baseline (P<.001). Lesion area and colorimetry measurements also were significantly improved at each visit (P<.001). Microentrapped HQ 4% was well tolerated, with only one patient discontinuing because of an allergic reaction, which was not considered serious. In this open-label study, microentrapped HQ 4% with retinol 0.15% was safe and effective.     

An efficacy study of 3 commercially available hydroquinone 4% treatments for melasma

Melasma is a common disorder of hyperpigmentation typically characterized by relatively symmetric brown or gray-brown patches on sun-exposed facial areas. Treating melasma is challenging because of the prolonged time to response and the substantial relapse rate when therapy is discontinued. The objective of this 12-week study was to compare the clinical efficacy and tolerability of 3 hydroquinone 4%-containing creams in the treatment of melasma. The 3 creams were cream A (microencapsulated hydroquinone 4% and retinol 0.15% with antioxidants); cream B (hydroquinone 4% and retinol 0.3% with antioxidants); and cream C (fluocinolone acetonide 0.01%, hydroquinone 4%, and tretinoin 0.05%). This 2-arm, split-face, right-left bilateral, evaluator-blinded study compared cream A and cream B in treatment arm 1, and cream A and cream C in treatment arm 2. Evaluator-blinded study assessments were conducted at baseline and weeks 4, 8, and 12. Results from treatment arm 1 demonstrated that at weeks 8 and 12, treatment with cream A showed statistically significant improvements over cream B in the efficacy assessments of overall disease severity (week 8, P=.005; week 12, P=.028), lesion area (week 8, P=.005; week 12, P=.003), pigmentation intensity (week 8, P=.012; week 12, P=.012), and Melasma Area and Severity Index (MASI) score (week 8, P= .002; week 12, P= .012). Results from treatment arm 2 demonstrated that at weeks 4 and 8, treatment with cream A was similar to cream C in the efficacy assessments of overall disease severity, lesion area, pigmentation intensity, MASI score, and global evaluation of response to treatment. At week 12, cream A continued to demonstrate sustained improvements in each of the above efficacy assessments; however, cream C showed a decrease in improvement of these efficacy assessments because subjects were switched to placebo for the last 4 weeks of treatment. All 3 treatments were well-tolerated. These data confirm previous findings that the unique delivery system of microencapsulated hydroquinone 4% and retinol 0.15% with antioxidants is safe and effective for use in treating melasma, and the data show that this novel nonsteroidal product should be considered when weighing long-term treatment options.     

Safety and efficacy of 4% hydroquinone combined with 10% glycolic acid, antioxidants, and sunscreen in the treatment of melasma

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 randomized 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.     

Long-term efficacy and tolerability of tacrolimus 0.03% ointment in infants:* a two-year open-label study

Background Tacrolimus ointment is effective for treatment of moderate to severe atopic dermatitis (AD) in children aged ≥2 years (Br J Dermatol, 2004; 150: 554). Here, efficacy and tolerability of tacrolimus 0.03% ointment were evaluated in 50 infants aged <2 years at start of treatment. Methods Infants with AD previously enrolled in a tacrolimus ointment pharmacokinetics trial were eligible for a 24‐month open‐label phase II study. Tacrolimus 0.03% ointment was applied to affected areas until clearance. In cases of exacerbation or clinical worsening, patients restarted treatment. Results Mean ± SD Eczema Area and Severity Index (EASI) score improved, from 11.2 ± 10.5 baseline to 2.6 ± 4.1 at endpoint (24 months); mean affected body surface area decreased from 25.2 ± 21.1% to 5.1 ± 9.0%, with improvement on all items of the Physicians’ Assessment of Individual Signs. The Physicians’ Global Evaluation of Clinical Response showed a result of “cleared”/“excellent” for 63.3% of patients; 85.7% of parents/guardians assessed symptoms as “much better.” Treatment was well tolerated, with common, nonserious respiratory infections and gastroenteritis the most frequently reported adverse events. The most common application‐site events were infections and pruritus. Over 98% of blood samples showed tacrolimus concentrations <1.0 ng/ml; >40% showed concentrations below the lower limit of quantification (0.0250 ng/ml). Conclusions Over a period of two years, tacrolimus 0.03% ointment was associated with substantial clinical improvement of AD in infants aged <2 years. Treatment tolerability was similar to that seen in older children.     

Prospective, open-label, comparative study of clindamycin 1%/benzoyl peroxide 5% gel with adapalene 0.1% gel in Asian acne patients: efficacy and tolerability

Background  Used as individual agents, topical antibiotics and benzoyl peroxide are known to be effective in treatment of acne. Clindamycin phosphate 1% with benzoyl peroxide 5% (CDP/BPO) is a new combination gel, made by rationale, in that combination drug is more effective than either ingredients used alone. Adapalene 0.1% (ADA) is the third-generation retinoid, shown to be as effective as other topical retinoid with well tolerability.
Objectives  To compare the efficacy and tolerability in combination of CDP/BPO in comparison with ADA in Asian patients with mild to moderate acne vulgaris.
Methods  Total of 69 patients, including 31 patients for CDP/BPO group and 38 for ADA group, with mild to moderate acne vulgaris were enrolled for a 12-week prospective, randomized, open-label comparative study of topical agents. Efficacy was assessed by lesion counts, acne grading system, and global improvement. Adverse events were also evaluated in scale of 0 (none) to 3 (severe).
Results  Both CDP/BPO and ADA were effective in reducing lesion counts and acne severity scale and showed significant global improvement. However, CDP/BPO offered greater efficacy against inflammatory lesions than ADA. Both drugs were well tolerated with minimal adverse drug reactions.
Conclusion  Combination formulation of CDP/BPO and ADA were shown to be both effective in decreasing total, inflammatory, and non-inflammatory lesion counts along with well tolerability in Asian patients with mild to moderate acne vulgaris.

Conflicts of interest

None declared     

Comparative study of therapeutic effects of 20% azelaic acid and hydroquinone 4% cream in the treatment of melasma

Background Melasma is an irregular brown or grayish‐brown symmetric facial hypermelanosis, often affecting women, especially those living in areas with intense ultraviolet radiation. Objective Comparison of therapeutic effects of 20% azelaic acid and 4% hydroquinone cream in the treatment of melasma. Methods Twenty‐nine women with melasma were recruited. Fifteen patients were treated with 4% hydroquinone cream and 14 patients were treated with azelaic acid cream for 2 months. The cream was applied twice daily. A broad‐spectrum sunscreen was used concomitantly by both groups. The Melasma Area Severity Index (MASI) scores were determined prior to treatment and at each follow‐up. Results The mean MASI score before treatment was 7.2 ± 3.2 in the hydroquinone group and 7.6 ± 3.5 in the azelaic acid group, with no significant difference between them (t‐test, CI 95% = ?2.9 to 2.2). One month after treatment, the mean MASI score reached 6.7 ± 3.4 with hydroquinone and 6.3 ± 3.4 with azelaic acid with no significant difference between them (t‐test, CI 95% = ?2.2 to 3). After 2 months’ treatment, the MASI score was 6.2 ± 3.6 with hydroquinone and 3.8 ± 2.8 with azelaic acid, a significant statistical difference (t‐test, CI 95% = 0.03–4.9). Conclusions In conclusion, this study suggests that 20% azelaic acid cream applied twice daily may be more effective than hydroquinone 4% in reducing mild melasma. However, because this was an open trial, it is suggested that further studies involving large groups of patients be conducted to achieve a more conclusive result.     

An open-label tolerability and efficacy study of an aluminum sesquichlorhydrate topical foam in axillary and palmar primary hyperhidrosis

ABSTRACT:  Primary hyperidrosis (PH) is a disorder characterized by excessive eccrine sweat gland production that primarily involves the axillae as well as palms and soles. Common first-line topical treatment for PH consists of aluminum salts (AS) that act by physically blocking eccrine sweat gland ducts. However, primary irritant contact dermatitis is a common side effect of AS treatment. Recently, a new low-residue, thermophobic foam formulation containing 20% aluminum sesquichlorhydrate has been developed (Nidrox^®, Mipharm S.p.A.). To evaluate the local tolerability and efficacy of 20% aluminum sesquichlorhydrate foam in the treatment of axillary and palmar PH. Twenty subjects affected by PH were enrolled in a multicenter, open-label study. Local tolerability was evaluated by physicians assessing itching, burning, and skin irritation using a four-point score (from 0: no symptoms to 3: severe symptoms). Skin irritation was quantified with a visual score. Efficacy was assessed by means of Minor test score using a four-point score (range 0–3). The foam was applied to clean dry skin, every night during the first 2 weeks and three times a week during the following 2 weeks. Clinical evaluations were performed at baseline, at day 14 and at day 28. Patients were monitored throughout the study for adverse events. All 20 subjects completed the study. The foam induced a significant reduction of the Minor score in comparison with baseline values ( p =  0.0002) both at day 14 and at day 28. At the end of the 4-week treatment period, the foam reduced eccrine sweating by 61% (Minor score: 3.3 vs. 8.5). No skin irritation was observed during the trial except for one subject who experienced a mild and transient itching sensation. No other side effects were reported during the study. This new foam appears to be an effective and well-tolerated topical treatment in reducing sweating in patients with axillary and palmar PH.     

An open-label tolerability and efficacy study of an aluminum sesquichlorohydrate topical foam in axillary and palmar primary hyperhidrosis

Primary hyperidrosis (PH) is a disorder characterized by excessive eccrine sweat gland production that primarily involves the axillae as well as palms and soles. Common first-line topical treatment for PH consists of aluminum salts (AS) that act by physically blocking eccrine sweat gland ducts. However, primary irritant contact dermatitis is a common side effect of AS treatment. Recently, a new low-residue, thermophobic foam formulation containing 20% aluminum sesquichlorohydrate has been developed (Nidrox, Mipharm S.p.A.). To evaluate the local tolerability and efficacy of 20% aluminum sesquichlorohydrate foam in the treatment of axillary and palmar PH. Twenty subjects affected by PH were enrolled in a multicenter, open-label study. Local tolerability was evaluated by physicians assessing itching, burning, and skin irritation using a four-point score (from 0: no symptoms to 3: severe symptoms). Skin irritation was quantified with a visual score. Efficacy was assessed by means of Minor test score using a four-point score (range 0-3). The foam was applied to clean dry skin, every night during the first 2 weeks and three times a week during the following 2 weeks. Clinical evaluations were performed at baseline, at day 14 and at day 28. Patients were monitored throughout the study for adverse events. All 20 subjects completed the study. The foam induced a significant reduction of the Minor score in comparison with baseline values (p = 0.0002) both at day 14 and at day 28. At the end of the 4-week treatment period, the foam reduced eccrine sweating by 61% (Minor score: 3.3 vs. 8.5). No skin irritation was observed during the trial except for one subject who experienced a mild and transient itching sensation. No other side effects were reported during the study. This new foam appears to be an effective and well-tolerated topical treatment in reducing sweating in patients with axillary and palmar PH.     

An open-label pilot study to evaluate the efficacy and tolerability of a silicone gel in the treatment of hypertrophic scars using clinical and ultrasound assessments

Silicone gel sheets and intralesional corticosteroids are effective treatments for hypertrophic scars according to evidence studies. The aim of this study was to evaluate, both clinically and by ultrasound, the efficacy and tolerability of a topical self-drying silicone gel containing polysiloxane and silicone dioxide applied twice daily in eight hypertrophic scars. After 6 months all lesions showed evident clinical and/or ultrasound improvement, with a mean scar thickness reduction of 37% (range 20-54%). Although controlled trials in larger series of patients are necessary, our results suggest that the self-drying silicone gel may represent a safe and effective treatment for hypertrophic scars.     

An open-label efficacy pilot study with pimecrolimus cream 1% in adults with facial seborrhoeic dermatitis infected with HIV

BACKGROUND: Seborrhoeic dermatitis (SD) is a common dermatosis in human immunodeficiency virus (HIV)-positive patients, many of whom do not respond satisfactorily to conventional topical treatments such as corticosteroids and antifungals. OBJECTIVE: A pilot study to investigate the efficacy and tolerability of pimecrolimus cream 1% in HIV-positive patients with facial SD. METHODS: In a single-centre study, 21 HIV-infected patients with mild to severe SD were treated twice daily with pimecrolimus cream 1% for 14 days. Thereafter, treatment was discontinued and patients followed up for 5 weeks. Skin involvement at baseline and on days 7, 14, 21, 35 and 49 was assessed using a four-point clinical score and digital photography. MAIN OUTCOME MEASURES: Efficacy and safety of pimecrolimus cream 1% treatment and incidence of relapse in the follow-up phase. Results Marked improvement was seen in clinical parameters at day 7, with >or= 90% patients clear of symptoms at day 14. Relapse was observed at day 35 but signs were milder than at baseline. All patients responded to therapy, despite their immunological status. Pimecrolimus did not alter CD4(+) and CD8(+) T-cell counts or viral load during the treatment period. CONCLUSION: Pimecrolimus cream represents a new, effective therapeutic option for facial SD in HIV patients.     

An open-label, pilot study examining the efficacy of curettage followed by imiquimod 5% cream for the treatment of primary nodular basal cell carcinoma

SUMMARY The short-term efficacy of imiquimod 5% cream for the treatment of primary superficial basal cell carcinoma has been established. This study investigated its efficacy following curettage (without electrodesiccation) for the treatment of primary nodular basal cell carcinoma on the trunk and limbs. Seventeen patients with a total of 34 lesions were enrolled. Curettage was used to de-bulk the lesion and confirm suitable histology. Lesions displaying more aggressive subtypes (such as micronodular or morpheoic components) were excluded. Lesions were treated daily for 6 to 10 weeks with imiquimod 5% cream. Three months post treatment all lesions were excised, and 32 of 34 treated lesions (94%) were histologically clear of basal cell carcinoma. Fourteen of 17 patients rated the cosmetic outcome of treatment as excellent or good. Curettage followed by imiquimod 5% cream is effective for the treatment of primary nodular basal cell carcinoma on the trunk and limbs, and most patients are pleased with the cosmetic outcome.     

A randomized controlled trial of the efficacy and safety of a fixed triple combination (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) compared with hydroquinone 4% cream in Asian patients with moderate to severe melasma

Background  Melasma is an acquired, chronic hypermelanosis for which therapy remains a challenge.
Objectives  To compare the efficacy and safety of a triple combination [TC: fluocinolone acetonide 0·01%, hydroquinone (HQ) 4%, tretinoin 0·05%] vs. HQ 4% after 8 weeks of treatment of moderate to severe facial melasma in Asian patients.
Methods  This was a multicentre, randomized, controlled, investigator-blinded, parallel comparison study. East and South-East Asian patients aged 18 years or older, with a clinical diagnosis of moderate to severe melasma, were enrolled in this study. Patients were enrolled at baseline and treated daily for 8 weeks with TC cream (one application at bedtime) or HQ cream (twice daily). There were four study visits: at baseline and weeks 2, 4 and 8. The primary efficacy variable was the melasma global severity score (GSS). Other outcome measures included Melasma Area and Severity Index, global improvement and patient satisfaction. Safety was assessed through the reporting of adverse events.
Results  TC had superior efficacy to HQ for the primary variable: 77/120 patients (64·2%) on TC had GSS 'none' or 'mild' at week 8 vs. 48/122 patients (39·4%) on HQ ( P  < 0·001). The secondary efficacy variables confirmed these results. Patient satisfaction was in favour of TC (90/127, 70·8%, vs. 64/129, 49·6%; P  = 0·005). More patients had related adverse events on TC (63/129, 48·8%) than on HQ (18/131, 13·7%) but most were mild and none was severe.
Conclusions  Efficacy in Asians and patient satisfaction were superior with the fixed TC than with HQ 4%.