Successful treatment of bullous pemphigoid with dupilumab: a case and brief review of the literature.

Bullous pemphigoid is an autoimmune skin disease that results in formation of pruritic blisters. Most cases are treated with a combination of systemic and topical corticosteroids as well as other immunomodulatory drugs. Dupilumab is a fully human monoclonal antibody that acts as an antagonist against IL4Ra traditionally used in the treatment of atopic dermatitis. We present an 80-year-old man with moderate to severe bullous pemphigoid successfully treated with dupilumab.

An Unusual Presentation of Pyemotes ventricosus Dermatitis Presenting With Umbilicated Papules Mimicking Poxvirus Infection.

Pyemotes ventricosus mites are an uncommon cause of pruritic dermatitis seen most commonly in occupational exposure, prominently found in professionals such as farmers, landscapers, and factory workers who work with grains, wheat, dried beans, or grasses. The clinical description of the rash has typically been described as papular, erythematous, with a central vesicular lesion. We describe a case of Pyemotes dermatitis with an atypical clinical presentation. A 30-year-old man presented with pruritic, umbilicated papules, which involved his right lateral trunk and upper thigh leading to the submitted clinical impression of molloscum contagiosum. A biopsy of the skin was taken, and fragments of arthropod consistent with P. ventricosus were identified within umbilicated indentations of skin. The patient subsequently admitted to the onset of the rash immediately after carrying bales of straw while supporting each bale with his right side. The possibility of Pyemotes dermatitis mimicking a poxvirus-like eruption should be considered when encountering an unusual umbilicated papular eruption in the appropriate patient with occupational exposure.

Extended-release Formulation of Minocycline in the Treatment of Moderate-to-severe Acne Vulgaris in Patients Over the Age of 12 Years.

Oral antibiotics continue to play an important role in the treatment of moderate-to-severe acne. Minocycline is widely used in moderate-to-severe acne. Minocycline has anti-inflammatory properties, activity against Propionibacterium acnes and lipophilicity. An extended-release formulation of minocycline has been introduced. Extended-release minocycline is not bioequivalent to nonmodified release minocycline products and exhibits dose-proportional pharmacokinetics. Food or dairy products did not influence absorption. Efficacy is not dose-dependent, while the incidence of acute vestibular adverse events increases with dose suggesting an optimal dose of 1mg/kg. In two Phase 3 clinical trials, mean percent improvement in inflammatory lesions after 12 weeks of treatment with extended-release minocycline was 43.1 and 45.8 percent compared to 31.7 and 30.8 percent with placebo (P=0.001 and P<0.001, respectively) while the incidence of acute vestibular adverse events was comparable to placebo.

Safety and efficacy of micronized tretinoin gel (0.05%) in treating adolescent acne.

Tretinoin is widely used in the treatment of acne. Despite significant advances in formulation development, irritation and dryness can be particularly bothersome, especially during the first 3-4 weeks, impacting adherence. Dose titration and adjunct use of moisturizers have been commonly employed. Co-prescribing with benzoyl peroxide (BPO) or a BPO/antibiotic combination is also common practice. The tretinoin molecule is unstable and can be degraded by BPO, further complicating treatment regimens. Lately, formulation technology has focused on providing more efficient penetration of the tretinoin into the skin layers so that lower concentrations of tretinoin might afford better tolerability, but maintain good efficacy; incorporating moisturizing excipients to minimize irritation; and providing greater stability to the tretinoin molecule. This approach would be particularly relevant in a pediatric acne population where efficacy/tolerability balance is important and treatment regimens must take into account lifestyles, but little data exist on the use of tretinoin in this patient population. A micronized formulation of tretinoin (0.05%) gel has been developed that provides a more efficient delivery of tretinoin, because of its optimal particle size, no degradation by BPO and better cutaneous tolerability than tretinoin microsphere (0.1%) gel without compromising efficacy in a pediatric population.

Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline, USP capsules) administered once daily for treatment of rosacea.

BACKGROUND: Doxycycline monotherapy at antimicrobial doses has been shown to be effective for the treatment of rosacea. OBJECTIVE: To evaluate the efficacy and safety of once-daily anti-inflammatory dose doxycycline for the treatment of rosacea. METHODS: In two phase III, parallel-group, multicenter, randomized, double-blind, placebo-controlled studies (studies 301 and 302), patients received 40-mg of controlled-release doxycycline (n = 269) or placebo (n = 268) for 16 weeks. The primary efficacy end point was the mean change from baseline in facial inflammatory lesion count. RESULTS: The mean lesion count at baseline was approximately 20 in each study arm. At week 16, the mean change from baseline in lesion count in the active-treatment groups was -11.8 in study 301 and -9.5 in study 302 compared with -5.9 and -4.3, respectively, in the placebo groups (P < .001 for both comparisons). Anti-inflammatory dose doxycycline was well tolerated; the most common adverse events were nasopharyngitis (4.8%), diarrhea (4.4%), and headache (4.4%). LIMITATIONS: In both studies, the reduction of inflammatory lesion counts did not plateau within the 16-week time frame in either treatment group. Rosacea is often treated for a period of months or years. The duration of the studies did not allow for assessment of safety beyond 16 weeks or whether the progressive improvement seen with active treatment would continue beyond 16 weeks. Neither study assessed the effect of treatment in patients with only erythematotelangiectatic (subtype 1) rosacea. CONCLUSION: Once-daily anti-inflammatory dose doxycycline appears to be effective and safe for the treatment of rosacea.

Tazarotene 0.1 percent cream plus clindamycin 1 percent gel versus tretinoin 0.025 percent gel plus clindamycin 1 percent gel in the treatment of facial acne vulgaris.

Topical retinoids are the cornerstone of therapy for acne vulgaris. Nevertheless, the adjunctive use of other anti-acne agents can help enhance the efficacy of topical retinoids still further. Given that tazarotene 0.1 percent gel has previously shown significantly greater efficacy than tretinoin 0.025 percent gel, it is likely that tazarotene plus clindamycin offers superior efficacy to tretinoin plus clindamycin, which has recently become available as a combination product. A total of 150 patients with facial acne vulgaris were randomly assigned to receive either tazarotene 0.1 percent cream plus clindamycin 1 percent gel, or tretinoin 0.025 percent gel plus clindamycin 1 percent gel. Each medication was applied once daily in the evening (clindamycin followed by the retinoid 5-10 minutes later) for up to 12 weeks. At week 12, the reduction from baseline in lesion counts was greater with tazarotene/clindamycin than tretinoin/clindamycin for both the non-inflammatory lesion count (71% vs. 52%, p< or =.01) and the inflammatory lesion count (77% vs. 67%, P=.053). Tazarotene/clindamycin also resulted in a significantly higher incidence of patients achieving > or = 50 percent global improvement (incidence of 88% vs. 75% at week 12; p< or =.05). Both regimens were similarly well tolerated. In the treatment of facial acne vulgaris, tazarotene plus clindamycin offers significantly greater efficacy than tretinoin plus clindamycin and has comparable tolerability.

A comprehensive review of the long-term and short-term treatment of melasma with a triple combination cream.

Melasma is a common disorder of hyperpigmentation and generally involves areas of the face and neck. Hyperpigmentation is especially prevalent in darker complected patients and is often difficult to treat. Hydroquinone, tretinoin, and topical corticosteroids are well established monotherapeutic agents for treating melasma and hyperpigmentation; however, a stable, once-daily formulation triple combination cream containing 0.05% tretinoin, 4.0% hydroquinone, and 0.01% fluocinolone acetonide (Tri-Luma) represents the only commercially available combination of all three agents. This product is approved by the US FDA for the treatment of facial melasma. A number of publications have described the safety and efficacy of triple combination cream in over 2000 patients with melasma, some of whom were treated for >12 months. In the initial 8-week study, 29% of patients experienced complete clearing of melasma by week 8, and 77% were clear or almost clear by week 8. Similarly, good results were seen in the two long-term studies, with the clear/mild rate ranging from 78% to 84% of patients at month 6 and from 81% to 94% of patients at month 12. Adverse events were almost always mild in severity and typically occurred only at the application site. The primary concern for most physicians using corticosteroid-containing products on the face is skin atrophy. However, only two cases of skin atrophy were reported across the three published studies. Overall, the results of these extensive studies indicate that triple combination cream is efficacious in treating melasma and exhibits a safe profile with low potential for adverse events.

The Nicomide Improvement in Clinical Outcomes Study (NICOS): results of an 8-week trial.

The Nicomide Improvement in Clinical Outcomes Study (NICOS) was an open-label, multicenter, prospective cohort study designed to assess the clinical utility of oral pharmacologic doses of nicotinamide and zinc in 198 patients with acne vulgaris and/or rosacea. The study's primary efficacy measures were patient global evaluation and patient evaluation of the percentage of reduction in inflammatory lesions after 4 and 8 weeks of treatment; overall patient satisfaction also was recorded. The study formulation consisted of nicotinamide 750 mg, zinc 25 mg, copper 1.5 mg, and folic acid 500 microg, marketed as Nicomide (Nic/Zn). Nic/Zn was designed to deliver adequate concentrations of nicotinamide and zinc to effectively treat inflammatory cutaneous conditions with a safety profile suitable for long-term administration. After a relatively short treatment period of 4 weeks, the number of patients enrolled in NICOS who reported improvement was significantly greater (P<.0001) than the number who reported either no change in or worsening of their condition. Of the patients studied, 79% reported their improvement in appearance as moderately better or much better, as measured by patient global evaluation, and 55% reported moderate (26%-50% reduction in lesions) or substantial (>50% reduction in lesions) improvement after 4 weeks of treatment (P<.0001). The percentage of patients who responded to therapy continued to increase through the 8 weeks of treatment. When comparing patients who received concomitant oral antibiotic therapy (51/198, 26%) with those who received Nic/Zn tablets as their only oral therapy (147/198, 74%), the percentage of patients who responded to treatment was not significantly different between treatment groups (P=. 13). This finding was particularly interesting given that most patients studied considered their condition to be of at least moderate severity (143/198, 72%). It appears that the addition of an oral antibiotic to a treatment regimen that includes Nic/Zn tablets may not be necessary because the combination did not significantly increase the percentage of patients responding. Nic/Zn tablets appear to be an effective oral therapy for the treatment of acne vulgaris and rosacea when used alone or with other topical therapies and should be considered a useful alternative approach to oral antibiotics for the treatment of acne vulgaris and rosacea.

Community-based trial of a triple-combination agent for the treatment of facial melasma.

Melasma is a common hyperpigmentation disorder that is frequently recalcitrant to treatment. An 8-week, multicenter, open-label, community-based study evaluated a new therapeutic approach that combines tretinoin 0.05%, hydroquinone 4.0%, and fluocinolone acetonide 0.01% (RA+HQ+FA) in a hydrophilic cream formulation. The trial enrolled 1290 patients of diverse races/ethnicities with a full range of Fitzpatrick skin types (I through VI). The mean Melasma Area and Severity Index (MASI) decreased significantly at both weeks 4 and 8 compared with baseline in the overall study population and across all Fitzpatrick skin types and races/ethnicities (P<.0001). The mean MASI darkness and homogeneity scores likewise fell significantly at weeks 4 and 8 in all facial regions involved (forehead, right and left malar regions, and chin) and in all Fitzpatrick skin types (P<.0001). By week 8, investigators' global evaluations showed that 75% of patients had "moderate or marked improvement" or were "almost clear" or "clear." The study medication was found to be safe and well tolerated. The results of this study demonstrate that RA+HQ+FA produces significant rapid improvement of melasma across the range of patients seen in daily practice, including whites, Hispanics, blacks, Asians, American Indians, Alaskan natives, and Pacific Islanders.

Dose-ranging efficacy of new once-daily extended-release minocycline for acne vulgaris.

A multicenter, 12-week, randomized, double-blinded, placebo-controlled, dose-ranging study was conducted in 233 subjects with moderate to severe facial acne vulgaris to determine the lowest effective once-daily oral dose of a new extended-release (ER) minocycline hydrochloride formulation with the safest adverse effect profile. Subjects randomly were assigned to treatment with daily dosages of ER-minocycline 1-, 2-, or 3-mg/kg tablets, or daily placebo tablets, for 84 days. At the end of the 12 weeks, the number of inflammatory lesions decreased approximately 50% from baseline levels in the dose groups. No dose-dependent effect was observed, with the percentage decrease in the number of inflammatory lesions in the 1-mg/kg treatment group being equal to or greater than higher doses. The pairwise difference between the ER-minocycline 1 mg/kg and placebo groups in the percentage decrease in inflammatory lesions was statistically significant (P = .015). Acute vestibular adverse events (AVAEs) appeared to be dose proportional, with the incidence being similar in the lowest (1 mg/kg) dosing group (24%) and in the placebo group (26%). Higher-dose regimens were associated with a higher incidence of central nervous system side effects and AVAEs. A 1-mg/kg daily dosage of the new ER-minocycline formulation is the lowest effective dose with the safest side effect profile, with higher-dose regimens offering no substantial therapeutic advantages.

A large 12-month extension study of an 8-week trial to evaluate the safety and efficacy of triple combination (TC) cream in melasma patients previously treated with TC cream or one of its dyads.

This was a 12-month extension of a randomized, investigator-blinded, multicenter, 8-week trial with triple combination (TC) cream in facial melasma. A total of 585 patients were enrolled in the study and 569 patients received study medication. Three hundred eighty-nine patients completed 6 months of treatment and 327 patients completed 12 months of treatment. TC cream demonstrated a favorable safety profile: only 14 patients (2.5%) discontinued the study due to treatment-related adverse events (AEs). The 2 cases of skin atrophy were mild and did not lead to withdrawal. From the 23 cases of mild telangiectasia, only 2 resulted in discontinuation. All others were transient. Results confirmed those of a previous smaller study, with both physicians and patients reporting clinically significant improvements in melasma. By month 12, 80% of patients had lesions completely cleared or nearly cleared. Once daily application of TC cream applied intermittently over a long period is a safe, tolerable, and effective treatment for moderate to severe melasma of the face.

Combination sodium sulfacetamide 10% and sulfur 5% cream with sunscreens versus metronidazole 0.75% cream for rosacea.

Topical metronidazole and combination sodium sulfacetamide and sulfur commonly are used to treat rosacea. Recently, the relative efficacy and safety of sodium sulfacetamide 10% and sulfur 5% cream with sunscreens (Rosac Cream) (n = 75) and metronidazole 0.75% cream (Metrocream) (n = 77) were compared in an investigator-blinded, randomized, parallel-group study at 6 sites. After 12 weeks of treatment with sodium sulfacetamide 10% and sulfur 5% cream with sunscreens, there was a significantly greater percentage reduction (80%) in inflammatory lesions compared with metronidazole 0.75% cream (72%)(P = .04), as well as a significantly greater percentage of subjects with improved erythema (69% vs 45%, respectively; P = .0007). In addition, the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens group had a significantly greater proportion of subjects with success in global improvement at week 12 compared with the metronidazole 0.75% cream group (79% vs 59%, respectively; P = .01). There was no significant difference between treatment groups in the percentage of subjects with improvement in investigator global severity. Overall tolerance was good or excellent in 85% of subjects in the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens group and in 97% of subjects in the metronidazole 0.75% cream group. Seven subjects had poor tolerance to the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens, possibly caused by a sulfa drug allergy.

Hydroquinone 4%, tretinoin 0.05%, fluocinolone acetonide 0.01%: a safe and efficacious 12-month treatment for melasma.

This article describes a long-term, multicenter, open-label, 12-month study of once-daily fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05% (Tri-Luma Cream, hereinafter called TC [triple combination]) application in the treatment of melasma. A total of 228 patients with facial melasma were enrolled and treated; 173 patients (76%) completed the study. Most patients had 1 to 2 courses of treatment lasting approximately 6 months in total. TC cream showed a favorable safety profile. only 3 patients (1%) withdrew from the study due to treatment-related adverse events (AEs). A total of 129 patients (57%) experienced at least one treatment-related AE. Most AEs were expected application-site reactions that were mild and transient in nature and did not require remedial therapy. There were no cases of skin atrophy or skin thinning and only 6 cases of telangiectasia (5 mild and 1 moderate), most of which had improved by the end of the study. Results of the efficacy assessments were positive, with both the patient and the physician assessing melasma to be either completely or nearly cleared by the end of the study in more than 90% of cases. In this study, a once-daily application of TC cream over an extended period of 12 months showed no notable safety concerns and offered an effective treatment for melasma.

Clocortolone pivalate cream 0.1% used concomitantly with tacrolimus ointment 0.1% in atopic dermatitis.

This study was designed to evaluate the safety and efficacy of concomitant therapy with the corticosteroid clocortolone pivalate cream 0.1% (Cloderm Cream 0.1%) and the topical immunosuppressive agent tacrolimus ointment 0.1% (Protopic Ointment 0.1%) and to compare each drug alone for the treatment of atopic dermatitis in adolescents and adults. Concomitant therapy may minimize the potential adverse effects of both treatments taken alone and may potentially improve overall response. In this 21-day study with 57 patients with atopic dermatitis, groups of 19 patients were randomized to 1 of 3 treatments: concomitant treatment with clocortolone pivalate cream 0.1% and tacrolimus ointment 0.1% (CPC+ TO), monotherapy with clocortolone pivalate cream 0.1% (CPC), or monotherapy with tacrolimus ointment 0.1% (TO). CPC+ TO was statistically superior to TO alone in the percentage change for dermatologic sum score at days 14 (P = .024) and 21 (P = .033), excoriation at day 21 (P = .028), induration at day 21 (P = .033), and erythema at day 14 (P = .048). The dual therapy was also superior to CPC alone in excoriation at days 7 (P = .045) and 14 (P = .037), oozing or crusting at days 3 (P = .034) and 7 (P = .012), and lichenification at day 3 (P = .031). In addition, unlike the 2 single-therapy treatment groups, percentage reductions from baseline in scores for the sensation of transient pruritus and burning or stinging were statistically significant for the concomitant treatment at days 14 (P = .016) and 21 (P = .016).

Efficacy and safety of a new triple-combination agent for the treatment of facial melasma.

Treatment of melasma, a hyperpigmentation disorder, remains a challenge. The primary objective of two 8-week, multicenter, randomized, 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 randomized to the various treatment groups. Due to the similarity of the study designs, 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.