Tazarotene versus tazarotene plus hydroquinone in the treatment of photodamaged facial skin: A multicenter,double‐blind,randomized study

Objectives: To compare the efficacy and tolerability of tazarotene plus hydroquinone versus tazarotene alone in the treatment of facial photodamage. Methods: Patients with facial mottled hyperpigmentation of at least moderate severity and an overall integrated assessment of photodamage score of at least moderate applied tazarotene 0.1% cream each evening and either hydroquinone 4% cream or placebo cream each morning for up to 24 weeks. Results: Among 131 patients enrolled, 114/124 (92%) with exit data completed. Both regimens were highly effective in reducing photodamage, with tazarotene plus hydroquinone showing superiority over tazarotene alone for some efficacy measures. The incidence of ?1‐grade improvement from baseline (on a scale of none, minimal, mild, moderate, or severe) was significantly greater with tazarotene plus hydroquinone than with tazarotene alone for lentigines (weeks 12–24, p?0.01) and mottled hyperpigmentation (week 16, p?0.05). The incidence of ?50% global improvement was also significantly superior with the combination regimen as early as week 8 (p?0.01). Both regimens were associated with good tolerability and high patient satisfaction (no significant between‐group differences). Conclusions: The adjunctive use of hydroquinone can enhance the efficacy of tazarotene in reducing dyspigmentation associated with photodamage.     

Cortexolone 17α-propionate 1% cream, a new potent antiandrogen for topical treatment of acne vulgaris. A pilot randomized, double-blind comparative study vs. placebo and tretinoin 0·05% cream

Background Acne vulgaris is a disorder of the pilosebaceous unit in which the androgens contribute to its onset and persistence. The use of antiandrogens is therefore potentially effective; however, antiandrogens for topical use are not available on the market. Cortexolone 17α‐propionate (CB‐03‐01; Cosmo S.p.A, Lainate, Italy) is a new potent topical antiandrogen potentially useful in acne vulgaris. Objectives To evaluate the safety and the topical efficacy of CB‐03‐01 1% cream in acne vulgaris as compared with placebo and with tretinoin 0·05% cream (Retin‐A^®; Janssen‐Cilag). Methods Seventy‐seven men with facial acne scored 2–3 according to Investigator’s Global Assessment (IGA) were randomized to receive placebo cream (n = 15), or CB‐03‐01 1% cream (n = 30), or tretinoin 0·05% cream (n = 32) once a day at bedtime for 8 weeks. Clinical efficacy was evaluated every 2 weeks including total lesion count (TLC), inflammatory lesion count (ILC), acne severity index (ASI) and IGA. Safety assessment included local irritancy score, laboratory tests, physical examination, vital signs and recording of adverse events. Results CB‐03‐01 1% cream was very well tolerated, and was significantly better than placebo regarding TLC (P = 0·0017), ILC (P = 0·0134) and ASI (P = 0·0090), and also clinically more effective than comparator. The product also induced a faster attainment of 50% improvement in all the above parameters. Conclusions This pilot study supports the rationale for the use of topical antiandrogens in the treatment of acne vulgaris. CB‐03‐01 1% cream seems to fit with the profile of an ideal antiandrogen for topical use.     

Daylight photodynamic therapy versus cryosurgery for the treatment and prophylaxis of actinic keratoses of the face − protocol of a multicenter,prospective, randomized,controlled, two-armed study

Background

Photodynamic therapy with daylight (DL-PDT) is efficacious in treating actinic keratosis (AK), but the efficacy of field-directed, repetitive DL-PDT for the treatment and prophylaxis of AK in photodamaged facial skin has not yet been investigated.

Methods/design

In this multicenter, prospective, randomized, controlled, two-armed, observer-blinded trial, patients with a minimum of 5 mild-to-moderate AK lesions on photodamaged facial skin are randomly allocated to two treatment groups: DL-PDT with methyl aminolevulinate (MAL) and cryosurgery. In the DL-PDT group (experimental group), 5 treatments of the entire face are conducted over the course of 18 months. After preparation of the lesion and within 30 min after MAL application, patients expose themselves to daylight for 2 h. In the control group, lesion-directed cryosurgery is conducted at the first visit and, in the case of uncleared or new AK lesions, also at visits 2 to 5. The efficacy of the treatment is evaluated at visits 2 to 6 by documenting all existing and new AK lesions in the face. Cosmetic results and improvement of photoaging parameters are evaluated by means of a modified Dover scale.Primary outcome parameter is the cumulative number of AK lesions observed between visits 2 and 6.Secondary outcome parameters are complete clearance of AK, new AK lesions since the previous visit, cosmetic results independently evaluated by both patient and physician, patient-reported pain (visual analogue scale), patient and physician satisfaction scores with cosmetic results, and patient-reported quality of life (Dermatology Life Quality Index). Safety parameters are also documented (adverse events and serious adverse events).

Discussion

This clinical trial will assess the efficacy of repetitive DL-PDT in preventing AK and investigate possible rejuvenating effects of this treatment. (Trial registration: ClinicalTrials.gov Identifier: NCT02736760).

Trial registration

ClinicalTrials.gov Identifier: NCT02736760. Study Code Daylight_01. EudraCT 2014–005121-13.

     

Is benzoyl peroxide 3% topical gel effective and safe in the treatment of acne vulgaris in Japanese patients? A multicenter,randomized, double‐blind,vehicle‐controlled,parallel‐group study

Benzoyl peroxide (BPO) as an anti‐acne medication is not yet approved in Japan. This study evaluated the efficacy and safety of a once‐daily topical application of BPO 3% gel versus an inert vehicle gel in Japanese acne patients. Three hundred and sixty patients were randomized to receive BPO 3% or vehicle for 12 weeks. The primary efficacy end‐point was absolute change in number of total lesions (TL) from baseline to week 12 to demonstrate the superiority of BPO 3% versus vehicle. Secondary efficacy end‐points were absolute and percent change in TL, inflammatory lesions (IL), non‐inflammatory lesions (non‐IL) and Investigator's Static Global Assessment (ISGA). Change in TL counts from baseline to week 12 for BPO 3% was superior to vehicle (difference, ?21.0; P < 0.001). Absolute and percent reductions in TL, IL and non‐IL counts were greater for BPO 3% at all study visits. The proportion of patients with improvement in ISGA scores was significantly higher with BPO 3% than with vehicle from week 2. All adverse events were mild or moderate. Adverse drug‐related reactions were higher for BPO 3% (30%) than with vehicle (5%). Local tolerability scores of grade 1 or more (slight to moderate) were more frequent with BPO 3% than vehicle with the most significant differences observed in dryness (56% vs 27% at week 1–4), peeling (19% vs 9% at week 1–2) and burning/stinging (58% vs 15% at week 1–12). These results indicate that BPO 3% is effective while maintaining a favorable safety and tolerability profile in Japanese acne patients.     

A split‐face comparison of a new hyaluronic acid facial filler containing pre‐incorporated lidocaine versus a standard hyaluronic acid facial filler in the treatment of naso‐labial folds

This split‐face, single‐blind study compared the comfort and ease of injection of a new hyaluronic acid facial filler containing pre‐incorporated lidocaine (Juvéderm^® ULTRA 3) versus the established hyaluronic acid facial filler Restylane‐Perlane^®. A total of 126 individuals were treated with both products, randomly assigned to the right or left naso‐labial fold. Injector assessment‐indicated mean injection pain, pain of massaging the injected area and post‐injection discomfort (based on a scale of 0=no pain to 10=extreme pain) were 2.1, 0.9 and 0.4 for Juvéderm ULTRA 3, and 4.1, 3.3 and 1.7 for Restylane‐Perlane, respectively (p<0.0001). Patient assessment of the same parameters were 2.8, 1.3 and 0.4 for Juvéderm ULTRA 3, and 4.9, 3.6 and 1.8 for Restylane‐Perlane (p<0.0001). Injectors indicated that 92% of Juvéderm ULTRA 3 injections were ‘very easy’, compared with 21% for Restylane‐Perlane. Post‐treatment smoothness was comparable, but 95% of individuals preferred Juvéderm ULTRA 3 for overall injection comfort. A total of 95% of individuals indicated that Juvéderm ULTRA 3 was a more comfortable and gentle experience.     

Interferon alfa-2a in the treatment of Behçet disease: a randomized placebo-controlled and double-blind study

OBJECTIVE: To determine the therapeutic efficacy of interferon alfa-2a in the treatment of Beh?et disease. DESIGN: A randomized placebo-controlled and double-blind study. SETTING: University referral center. PATIENTS: Fifty patients with Beh?et disease were involved in the study. INTERVENTION: The patients were given interferon alfa-2a, 6 x 10(6) IU, subcutaneously 3 times per week or placebo for 3 months, and examined clinically at weekly intervals. MAIN OUTCOME MEASURES: For each mucocutaneous lesion and articular symptom, the mean frequency and duration were evaluated during the 3-month pretreatment, treatment, and follow-up periods. Pain for oral and genital ulcers was scored on a scale of 0 to 3. The ocular inflammatory score, the frequency of attacks, and changes in visual acuities for patients with ocular involvement were assessed before the study, at the end of treatment, and during the follow-up periods. In addition, overall responses at the end of the treatment period were graded as follows: complete remission, disappearance of all clinical signs and symptoms during treatment; partial remission, greater than a 50% decrease in the frequency, duration, and severity of pain for oral and genital ulcers and/or a decrease in the severity and frequency of ocular attacks; stable disease, less than a 50% change in the clinical signs and symptoms; and no effect or deterioration, ineffectiveness or worsening of clinical signs and symptoms. RESULTS: Twenty-three interferon alfa-2a- and 21 placebo-treated patients, ranging in age from 16 to 55 years (mean +/- SD age, 32.38 +/- 7.94 years), were evaluable for efficacy. Interferon alfa-2a treatment significantly decreased the duration (P=.02) and pain (P=.01) of oral ulcers and the frequency of genital ulcers (P=.03) and papulopustular lesions (P=.01). The mean frequency and duration of erythema nodosum-like lesions (P=.77 and.27, respectively), thrombophlebitis (P=.29 and.61, respectively), and articular symptoms (P=.92 and.74, respectively) also decreased. But there were no statistically significant differences. An improvement in the severity and the frequency of ocular attacks occurred in 5 of 6 patients in the interferon alfa-2a-treated group and in 1 of 3 patients in the placebo-treated group. Of the 23 patients in the interferon alfa-2a-treated group, 15 responded to treatment (2 complete and 13 partial responses); and of the 21 patients in the placebo group, 3 responded to treatment (3 partial responses) (P<.005). CONCLUSION: Interferon alfa-2a is an effective alternative treatment for Beh?et disease, particularly for the management of the mucocutaneous lesions of the disease.     

Comparison study of a Q‐switched alexandrite laser delivered with versus without compression in the treatment of dermal pigmented lesions

Background: The Q‐switched laser is the treatment of choice when attempting to improve dermal pigmented lesions. However, purpura and dyspigmentation are frequently observed after treatment. Objective: To compare the efficacy and complications of the Q‐switched alexandrite laser when delivered with versus without compression in the treatment of dermal pigmented lesions. Methods: Ten patients with dermal lesions were enrolled in the study. Each patient had a lesion treated with the Q‐switched alexandrite laser delivered with compression. Each patient also had a lesion treated with the Q‐switched alexandrite laser delivered without compression with the same fluence and spot size. The patients were evaluated for efficacy and treatment‐related side effects. Results: There was no significant difference in efficacy, but purpura and dyspigmentation were more likely when pigmented lesions were treated without compression. Conclusion: Purpura from Q‐switched laser treatment in darkly pigmented skin is due to mechanical injury of blood vessels. It is well known that pressure ‘diascopy’ eliminates blood from cutaneous vessels by coapting the vessel lumen. In this study, we used pressure applied by a glass window on the Q‐switched laser handpiece to remove cutaneous blood during laser exposure, making it possible to reduce purpura and dyspigmentation.     

The use of sucralfate suspension in the treatment of oral and genital ulceration of Beh?et disease: a randomized, placebo-controlled, double-blind study.

OBJECTIVE: To determine the efficacy of topically applied sucralfate suspension in the treatment of oral and genital ulceration of Beh?et disease. DESIGN AND SETTING: A randomized, placebo-controlled, double-blind study at a university referral center. PATIENTS: Forty patients with Behcet disease were included in the study. INTERVENTION: Patients were given topical sucralfate or placebo 4 times a day for 3 months and examined clinically at biweekly intervals. MAIN OUTCOMES MEASURES: For each lesion, the mean frequency, healing time, and pain were evaluated during the pretreatment, treatment, and follow-up periods. No patients were given any concurrent disease-specific or immunosuppressive topical and systemic drugs during the 9-month study period. RESULTS: Of the 40 patients included in the study, the results in 30 patients (16 patients treated with sucralfate and 14 patients treated with placebo, ranging in age from 16 to 52 years [mean+/-SD age, 34.3+/-8.1 years]) were evaluable for efficacy. Treatment with sucralfate decreased significantly the mean frequency, healing time, and pain of oral ulceration and healing time and pain of genital ulceration compared with the pretreatment period. The effectiveness of sucralfate on the frequency and healing time of oral ulceration continued during the post-treatment period. In the placebo group, no significant difference was found in measured parameters of oral and genital ulceration except the pain of the oral ulceration between the pretreatment and treatment periods. CONCLUSION: Our results showed that topical sucralfate suspension is an easy, safe, inexpensive, and effective treatment for oral and genital ulceration in patients with Beh?et disease.     

Comparison study of a long‐pulse pulsed dye laser and a long‐pulse pulsed alexandrite laser in the treatment of port wine stains

Background: Port wine stains (PWSs) are commonly treated by the pulsed dye laser. Recently, a long‐pulse pulsed alexandrite laser was used to treat bulky vascular malformations. Objective: In the present study, we compare the efficacy and complications of the long‐pulse pulsed dye laser (LPPDL) and the long‐pulse pulsed alexandrite laser (LPPAL) in the treatment of PWSs. Methods: Eleven patients with Fitzpatrick skin types III–IV were enrolled in this study. One section of each patient's PWS was treated with LPPDL and another section was treated with LPPAL. The patients' PWSs were evaluated for efficacy of elimination of erythema and for treatment‐related side effects. Results: Both LPPDL and LPPAL treatment are effective in the treatment of PWSs. Hyperpigmentation was seen in two areas treated with LPPDL and in three areas treated with LPPAL. Hypopigmentation was seen in one area treated with LPPAL, but not in any of the areas treated with LPPDL. There was no scarring. Conclusion: LPPAL works best with hypertrophic, purple PWSs, while LPPDL yields better clinical improvements with the flat, pink PWSs. Targeting of deoxyhemoglobin, deeper penetration, and higher fluence may explain the effectiveness of LPPAL in purple, hypertrophic PWSs. However, there is a risk of dyspigmentation when using the LPPAL.     

A randomized, investigator-blinded, time-ranging study of the comparative efficacy of 0.5% malathion gel versus Ovide Lotion (0.5% malathion) or Nix Crème Rinse (1% permethrin) used as labeled, for the treatment of head lice

Abstract:  One hundred seventy-two subjects with head lice participated in a five-way, investigator-blinded, parallel-group, active-controlled study comparing 0.5% malathion gel (30, 60, and 90 minutes applications), Ovide^® Lotion (0.5% malathion), and Nix^® Crème Rinse (1% permethrin). All subjects were treated on day 1. Participants were reevaluated at day 8 ± 1 and those with live lice were retreated with the same product, for the same duration as day 1. Cure, defined as the absence of live lice, was evaluated 14 ± 2 days after the last treatment and 161 subjects completed the study according to the protocol. Compared to Nix, treatment success rates were statistically superior for all malathion gel and Ovide^® groups. Retreatment rate for Nix was 70%, which was statistically more than the malathion groups. The highest treatment success rates were observed for the 30-minute malathion gel (98% intent-to-treat and 100% per-protocol [PP]) and the 8 to 12 hour Ovide^® application (97% intent-to-treat and 100% PP). In conclusion, the 30-minute malathion gel, which contains the same ingredients and concentrations as Ovide^®, provides comparable efficacy, offers increased safety and is more cosmetically acceptable than Ovide^®.     

Defocused diode laser therapy (830 nm) in the treatment of unresponsive skin ulcers: a preliminary trial

BACKGROUND: Skin ulcers with compromised healing remain a major problem for plastic and dermatological surgeons. Low incident levels of laser energy have been shown to increase the blood flow rate and volume and to accelerate the wound healing process, thus raising the possibility in augmenting treatment for skin ulcers.

METHODS: Preliminary controlled experiments with a 830?nm GaAlAs diode laser in axial pattern flap survival in the rat model showed statistically significant improvement in survival for the irradiated versus unirradiated control animals. In the present study, a newly developed defocused GaAlAs diode laser (830?nm, continuous wave, 669?mW/cm²) was applied once or twice per week in an uncontrolled study of five patients (aged between 5 and 81 years old, average 46.6 years old, doses from 6.3?J/cm² to 21?J/cm²) with previously unresponsive ulcers of various aetiologies.

RESULTS: In all five patients, the ulcers healed completely between 3 weeks and 7 months (22.8±19.3 weeks), without recurrence during a minimum 12‐month follow‐up.

CONCLUSIONS: Defocused 830?nm diode laser therapy was well tolerated, and was very effective in the treatment of this small number of compromised skin ulcers of different aetiologies and in a large range of patient ages. Further controlled studies in larger populations are required. Defocused diode laser therapy nonetheless appears to be a very useful adjunctive method in the treatment of slow‐to‐heal and non‐healing skin ulcers.     

Standardized diaper care regimen: a prospective, randomized pilot study on skin barrier function and epidermal IL-1α in newborns

Adaptation of skin barrier function and interleukin-1α (IL-1α) content in diapered and nondiapered skin are poorly characterized in newborns receiving standard skin care. In a monocentric, prospective pilot study 44 healthy, full-term neonates were randomly assigned to skin care with baby wipes (n = 21) or water-moistened washcloth (n = 23) at each diaper change. Transepidermal water loss (TEWL), skin hydration, skin-pH, IL-1α, and epidermal desquamation were measured on days 2, 14, and 28 postpartum. Microbiological colonization was evaluated at baseline and on day 28. Significantly lower TEWL was found on the buttock in the group using baby wipes compared to water. IL-1α and skin hydration significantly increased and pH decreased independent of skin care regimen. IL-1α was significantly higher in diapered skin compared to nondiapered skin. Although skin care with wipes seems to stabilize TEWL better than using water, the skin condition and microbiological colonization were comparable using both cleansing procedures. Increase of epidermal IL-1α may reflect postnatal skin barrier maturation. These data suggest that neither of the two cleansing procedures harms skin barrier maturation within the first four weeks postpartum. Longer observations on larger populations could provide more insight into postnatal skin barrier maturation.     

Colchicine and benzathine penicillin in the treatment of Behçet disease: a case comparative study

Beh?et disease is a chronic relapsing disease characterized by multiple signs and symptoms such as recurrent orogenital ulceration, eye involvement, skin manifestations, and other systemic involvement. Multiple therapeutic modalities have been used to treat Beh?et disease. These agents act through different mechanisms and are associated with a variety of side effects. We performed a case-comparative study to evaluate efficacy of combined colchicine and benzathine penicillin in the treatment and prophylaxis of Beh?et disease. Sixty-six patients who fulfilled the international study group criteria for diagnosis of Beh?et disease were included. The patients were divided into three groups: group 1 (20 patients) received 1.2 Mu benzathine penicillin injection monthly; group 2 (21 patients) received two tablets of colchicine daily (each tablet contained 0.5 mg); and group 3 (25 patients) received both 1.2 Mu benzathine penicillin injection monthly and two tablets of colchicine daily. Each patient was followed up monthly for 5 months, 4 months on treatment and 1 additional month followup. The clinical manifestation index (CMI), the numerical sum of the clinical features, was calculated for each patient initially and then monthly. Pathergy test was performed for each patient monthly. The CMI was reduced by colchicine and benzathine penicillin treatment, and the reduction was highly significant. The reduction in the CMI remains satisfactory and good for 1 month after stopping the treatment. When each colchicine and benzathine Penicillin are used alone the index is also reduced significantly, but this reduction is much less than when both drugs are used together and there is also rapid and earlier relapse. Based on our findings, the combination of colchicine and benzathine penicillin appears to be of greater efficacy in the treatment of Beh?et disease than the use of either drug alone.     

Once-daily topical brimonidine tartrate gel 0·5% is a novel treatment for moderate to severe facial erythema of rosacea: results of two multicentre, randomized and vehicle-controlled studies

Background Erythema of rosacea is thought to result from abnormal cutaneous vasomotor activity. Brimonidine tartrate (BT) is a highly selective α₂‐adrenergic receptor agonist with vasoconstrictive activity. Objective To determine the optimal concentration and dose regimen of topical BT gel for the treatment of erythema of rosacea and to evaluate its efficacy and safety. Methods In study A, 122 subjects were randomized to receive a single application of BT 0·07%, 0·18%, 0·5% or vehicle. In study B (4‐week treatment and 4‐week follow‐up), 269 subjects were randomized to receive BT 0·5% once daily, BT 0·18% once daily, vehicle once daily, BT 0·18% twice daily or vehicle twice daily. Evaluations included Clinician’s Erythema Assessment (CEA), Patient’s Self‐Assessment (PSA), Chroma Meter measurements and adverse events. Results In study A, a single application of topical BT gel reduced facial erythema in a dose‐dependent fashion. A significant difference between BT 0·5% and vehicle in Chroma Meter redness value was observed from 30 min to 12 h after application. In study B, BT 0·5% once daily had a statistically superior success profile (defined as a two‐grade improvement on both CEA and PSA over 12 h) compared with vehicle once daily on days 1, 15 and 29 (all P < 0·001). No tachyphylaxis, rebound of erythema or aggravation of other disease signs (telangiectasia, inflammatory lesions) was observed. All regimens were safe and well tolerated with similarly low incidence of adverse events. Conclusions Once‐daily BT gel 0·5% is well tolerated and provides significantly greater efficacy than vehicle gel for the treatment of moderate to severe erythema of rosacea.     

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.     

Is metronidazole 0.75% gel effective in the treatment of seborrhoeic dermatitis? A double-blind, placebo controlled study

The study aimed to evaluate the effectiveness of metronidazole 0.75% gel in patients with mild and moderate seborrhoeic dermatitis. Sixty-seven patients with seborrhoeic dermatitis were enrolled. Cases were randomly treated with metronidazole 0.75% gel or placebo for four weeks and were additionally followed up for another four weeks. Patients were evaluated by scoring before the treatment, once a week during the treatment and twice after the cessation of the treatment within a 15-day interval. Furthermore, patient satisfaction and doctor global evaluation were done at the end of the treatment and of the study as well. In the metronidazole group 33 patients (median age: 26, total severity score: 15.0 +/- 11.0 (median +/- interquartile range) and in the placebo group 34 patients (median age: 26, total severity score: 13.0 +/- 7.5) were enrolled in the study. Three patients from the metronidazole group and four patients from the placebo group did not attend to follow-up visits. Erythema, scales, papule, pruritus and the total severity scores in both group decreased significantly during the treatment when compared with the basal levels (p < 0.05). There was no difference between the two groups in terms of efficacy (p > 0.05). Total severity scores were found as 7.33 +/- 1.08 and 6.43 +/- 0.93 in the metronidazole and placebo groups at the end of the treatment, respectively. After the cessation of the treatment, all scores had increased rapidly. Total severity scores were 10.40 +/- 1.54 and 11.20 +/- 1.53 in the metronidazole and placebo groups one month after the cessation of the treatment, respectively. Both metronidazole 0.75% gel and the placebo were well tolerated by the patients. In conclusion, in the treatment of seborrhoeic dermatitis, administration of metronidazole 0.75% gel is well tolerated but it is only as effective as placebo and the disease severity quickly returns to the basal levels after the cessation of treatment.