Use of an alternative method to evaluate erythema severity in a clinical trial: difference in vehicle response with evaluation of baseline and postdose photographs for effect of oxymetazoline cream 1·0% for persistent erythema of rosacea in a phase IV study.

BACKGROUND: Once-daily topical oxymetazoline cream 1·0% significantly reduced persistent facial erythema of rosacea in trials requiring live, static patient assessments. OBJECTIVES: To evaluate critically the methodology of clinical trials that require live, static patient assessments by determining whether assessment of erythema is different when reference to the baseline photograph is allowed. METHODS: In two identically designed, randomized, phase III trials, adults with persistent facial erythema of rosacea applied oxymetazoline or vehicle once daily. This phase IV study evaluated standardized digital facial photographs from the phase III trials to record ≥ 1-grade Clinician Erythema Assessment (CEA) improvement at 1, 3, 6, 9 and 12 h postdose. RESULTS: Among 835 patients (oxymetazoline n = 415, vehicle n = 420), significantly greater proportions of patients treated with oxymetazoline vs. vehicle achieved ≥ 1-grade CEA improvement. For the comparison between phase IV study results and the original phase III analysis, when reference to baseline photographs was allowed while evaluating post-treatment photographs, the results for oxymetazoline were similar to results of the phase III trials (up to 85.7%), but a significantly lower proportion of vehicle recipients achieved ≥ 1-grade CEA improvement (up to 29.7% [phase 4] vs. 52.3% [phase 3]; P<0.001). In the phase IV study, up to 80·2% of patients treated with oxymetazoline achieved at least moderate erythema improvement vs. up to 22·9% of patients treated with vehicle. The association between patients' satisfaction with facial skin redness and percentage of erythema improvement was statistically significant. CONCLUSIONS: Assessment of study photographs, with comparison to baseline, confirmed significant erythema reduction with oxymetazoline on the first day of application. Compared with the phase III trial results, significantly fewer vehicle recipients attained ≥ 1-grade CEA improvement, suggesting a mitigated vehicle effect. This methodology may improve the accuracy of clinical trials evaluating erythema severity.

Rosacea: pathogenesis and therapy.

Rosacea is a chronic facial inflammatory disease. The pathogenesis, diagnosis and treatment are reviewed.

The effect of the menstrual cycle on acne.

Acne is a common disease with an underlying hormonal basis; however, there has never been a study to determine the ways in which the different stages of the menstrual cycle affect acne in women. Four hundred female participants, aged 12 to 52 years, were questioned whether their acne got worse before, during, or after their menstrual period and also asked whether it was unrelated to the menstrual period. Their age, severity of acne, ethnicity, and oral contraceptive use were also recorded. Overall 177 of 400 (44%) of those interviewed experienced premenstrual flares of their acne. Severity of acne, ethnicity, and oral contraceptive use did not affect the premenstrual flare rate. Women older than 33 years had a higher rate of premenstrual flares relative to women aged 20 to 33 years (P =.03 by chi(2) analysis). We concluded that almost half of all women experience premenstrual flares of their acne. Premenstrual flares may be more common in older women.

Treatment of rosacea.

Rosacea is an inflammatory disease of the face and eyes. Treatment is adjusted to the site of the disease and its severity.

Efficacy and tolerability of once-daily tazarotene 0.1% gel versus once-daily tretinoin 0.025% gel in the treatment of facial acne vulgaris: a randomized trial.

Tazarotene 0.1% gel and tretinoin 0.025% gel are both effective in the treatment of acne vulgaris. Results of a multicenter, double-blind, randomized, parallel-group study that compared the efficacy and tolerability of these drugs are presented here. A total of 143 patients with mild-to-moderate facial acne vulgaris were randomized to receive tazarotene 0.1% gel or tretinoin 0.025% gel once daily for 12 weeks. Tazarotene 0.1% gel was more effective than tretinoin 0.025% gel in reducing the open comedo count (P < or = .05), the total noninflammatory lesion count (P < or = .05), and the total inflammatory lesion count (not statistically significant). At some time points, tazarotene was associated with increased irritation, but peeling, erythema, dryness, burning, and itching never exceeded trace levels. We conclude that tazarotene 0.1% gel is more effective than tretinoin 0.025% gel in reducing noninflammatory lesions and similarly effective in reducing inflammatory lesions.

Vascular diseases are the most common cutaneous manifestations of reflex sympathetic dystrophy.

Reflex sympathetic dystrophy (RSD) is a chronic pain syndrome with prominent cutaneous findings. Atrophy has been considered to be the most common manifestation of the disease. We catalogued the abnormal skin conditions in RSD by means of chart review. Vascular problems were most common, followed by inflammatory diseases, infections, and atrophic diseases. Atrophic disease accounts for a minority of the skin problems seen in RSD. Most cutaneous complaints were related to vascular disease, particularly edema.

Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part II, safety.

In two randomized, double-blind, multicenter studies, a total of 631 adult patients with moderate to severe atopic dermatitis applied tacrolimus ointment (0.03% or 0.1%) or vehicle twice daily for up to 12 weeks. The mean percent body surface area (%BSA) affected at baseline was 45%, and 56% of patients had severe atopic dermatitis. As previously reported, these studies showed that tacrolimus ointment was superior to vehicle for all efficacy parameters measured. This report focuses on the safety of tacrolimus ointment in these studies. The most common adverse events were the sensation of skin burning, pruritus, flu-like symptoms, skin erythema, and headache. Skin burning and pruritus were more common among patients with severe or extensive disease; these events were usually brief and were resolved during the first few days of treatment. Common adverse events with a significantly higher incidence in one or both of the tacrolimus ointment groups than in the vehicle group included skin burning, flu-like symptoms, and headache. More patients in the vehicle group discontinued the study because of an adverse event than in either of the tacrolimus ointment groups. There were no notable or consistent changes in any laboratory variables. Tacrolimus was not detected in 80% of blood samples collected. Measurable concentrations of tacrolimus were transitory and were not associated with adverse events. Tacrolimus ointment is a safe therapy for the treatment of adult patients with atopic dermatitis on the face, neck, or other body regions.

Acne vulgaris and rosacea: evaluation and management.

Acne vulgaris, commonly termed acne, is an extremely common disease. It can be found in nearly all teenagers to some degree as well as in women in their 30s. Regardless of severity, acne often has a greater psychologic effect than cutaneous effect. Indeed, most patients overestimate the severity of their disease, while most physicians underestimate its impact on their patients. Studies have shown that people with severe acne as teens are less employable as adults and that self-esteem is low. When combined with other adolescent tensions, acne can be a difficult disease to treat. Rosacea, which usually starts in the late 20s, may affect the eyes as well as the skin. This article describes the pathogenesis of acne and rosacea and treatment approaches the primary care physician can use.

Topical medications: a focus on antifungals and topical steroids.

Because skin disease is accessible, it can be treated with locally applied medication, which offers great advantages--exposure to a drug is limited to the affected skin and systemic effects of potentially toxic drugs are minimized. Ointments, creams, antifungals, and antibiotics all have their place in treating various skin diseases. Topical steroids, the largest group of topical medications, are effective but present the potential for side effects. This article discusses current and new topical medications that can be used to treat a range of skin diseases.

Common skin disorders in the elderly.

Skin diseases commonly seen in the elderly are more often than not the effects of sun damage or vascular disease. The effects of a lifetime of even casual sun exposure can be dramatic. Chronically sun-exposed skin becomes thin, loses collagen, and has disrupted elastin and decreased glycosaminoglycans. The result is skin that breaks easily, bruises, sags, irritates easily, and itches. The spots and bumps that patients associate with age are all sun-induced. Consider how lesionless a 60-year-old's buttock is compared to the extensor forearm. The reason that bruising attributed to anticoagulation seems to occur exclusively on the extensor forearm and not the volar aspect of the arm is that sun-induced elastin degradation is greatest on the extensor forearm. Even trivial trauma will cause unsupported capillaries to shear and bleed whether the patient is anticoagulated or not. This article reviews the primary skin disorders associated with the elderly and some of the management approaches that the primary care physician can use.

Onycholysis associated with weekly administration of paclitaxel.

OBJECTIVE: To report an unusual reaction associated with weekly administration of paclitaxel. CASE SUMMARIES: Onycholysis was seen in four women with recurrent ovarian cancer being treated with low-dose, weekly paclitaxel. Two of the patients had previously received higher doses of paclitaxel on an every-three-week schedule without similar reactions. Onycholysis developed between weeks 10-13 of treatment in three of the patients. In the fourth patient, it developed shortly after initiation of weekly paclitaxel. None of the reactions required dose adjustments or discontinuation of therapy. Direct toxicity to the nail bed or inhibition of angiogenesis are possible mechanisms for this reaction. DISCUSSION: Onycholysis, separation of the nail from the nail bed, is an infrequent adverse effect of drug therapy. Antineoplastic drugs have previously been reported to cause onycholysis, pigmentation, bands, thickening or thinning of the nail bed, and nail shedding. Nail changes with the taxanes, primarily docetaxel, are reported in up to 30-40% of patients. Paclitaxel is not commonly associated with dermatologic reactions, although localized skin reactions and tissue necrosis have been reported. Nail changes, pigmentation or discoloration of the nail bed, occur in 2% of patients receiving paclitaxel. CONCLUSIONS: Onycholysis is an uncommon reaction that may occur in some patients receiving weekly, low-dose paclitaxel therapy. The reaction is not life-threatening and does not warrant discontinuation of therapy. However, clinicians should be aware of the possibility of this effect and be prepared to advise patients who develop signs of nail changes.

Acne and rosacea.

The diagnosis of acne and rosacea are reviewed in this article, and specific therapeutic strategies are discussed for these extremely common diseases.

Inflammatory acne represents hypersensitivity to Propionibacterium acnes.

Hypersensitivity to P. acnes may account for the great variation in acne severity. Alternative explanations such as hyperandrogenism fail to account for disease severity in large numbers of patients.

Intralesional fluorouracil/epinephrine injectable gel for treatment of condylomata acuminata. A phase 3 clinical study.

BACKGROUND AND DESIGN: A new intralesional sustained-release chemotherapy is under development as a treatment for condylomata acuminata; it is administered as an injectable gel that consists of fluorouracil and epinephrine with a purified bovine collagen as the gellant (fluorouracil/epinephrine gel). In this randomized, double-blind study, we evaluated the safety and efficacy of this intralesional treatment in 401 patients, using 2 active drug formulations (fluorouracil/epinephrine gel and fluorouracil gel alone) and a placebo. Each lesion was injected once a week for up to 6 weeks, and patients were followed up for 3 months. RESULTS: A total of 359 patients with 1926 condylomata underwent evaluation. For all lesions treated with fluorouracil/epinephrine gel, the complete response (CR) rate was 77%. For all patients treated with fluorouracil/epinephrine gel, the CR rate was 61%. The fluorouracil/epinephrine gel was significantly more effective (P < .002) in treating condylomata than the fluorouracil gel without epinephrine (CR rate, 43%); both were superior to placebo (CR rate, 5%). At 3 months after completion of treatment, recurrence rates in patients with CRs were as follows: fluorouracil/epinephrine gel group, 50%; fluorouracil gel group, 58%. No clinically significant drug-related systemic reactions occurred. Finally, the type and severity of local tissue reactions of patients with a positive pretreatment collagen skin test result (6/401 [1.5%]) were similar to those of patients with a negative collagen skin test result. CONCLUSION: The fluorouracil/epinephrine injectable gel is a safe and effective treatment for condylomata acuminata.