Therapeutic studies with a new combination benzoyl peroxide/clindamycin topical gel in acne vulgaris.

Three independent clinical studies were conducted in more than 1250 patients with moderate to moderately severe acne vulgaris to evaluate the efficacy and safety of a new combination gel that stably combines 5% benzoyl peroxide and 1% clindamycin. The results indicated that the benzoyl peroxide/clindamycin combination product was an effective treatment for reducing the inflammatory and noninflammatory lesions of acne vulgaris. In overall improvement as rated by the physicians and patients, the combination gel was superior to clindamycin alone, and in 2 of the 3 studies, to benzoyl peroxide alone. The antimicrobial activity of the combination gel was significantly (each P < .01) superior to that seen with topical application of its individual constituents, 5% benzoyl peroxide or 1% clindamycin, and was numerically better than that found with topical application of a 5% benzoyl peroxide/3% erythromycin combination product. As with benzoyl peroxide, dry skin was the most frequent side effect with use of the combination gel, with isolated incidences of other localized irritation. No other safety or tolerability concerns were identified.

CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris.

Engagement of the B7 family of molecules on antigen-presenting cells with their T cell-associated ligands, CD28 and CD152 (cytotoxic T lymphocyte-associated antigen-4 [CTLA-4]), provides a pivotal costimulatory signal in T-cell activation. We investigated the role of the CD28/CD152 pathway in psoriasis in a 26-week, phase I, open-label dose-escalation study. The importance of this pathway in the generation of humoral immune responses to T cell-dependent neoantigens, bacteriophage phiX174 and keyhole limpet hemocyanin, was also evaluated. Forty-three patients with stable psoriasis vulgaris received 4 infusions of the soluble chimeric protein CTLA4Ig (BMS-188667). Forty-six percent of all study patients achieved a 50% or greater sustained improvement in clinical disease activity, with progressively greater effects observed in the highest-dosing cohorts. Improvement in these patients was associated with quantitative reduction in epidermal hyperplasia, which correlated with quantitative reduction in skin-infiltrating T cells. No markedly increased rate of intralesional T-cell apoptosis was identified, suggesting that the decreased number of lesional T cells was probably likely attributable to an inhibition of T-cell proliferation, T-cell recruitment, and/or apoptosis of antigen-specific T cells at extralesional sites. Altered antibody responses to T cell-dependent neoantigens were observed, but immunologic tolerance to these antigens was not demonstrated. This study illustrates the importance of the CD28/CD152 pathway in the pathogenesis of psoriasis and suggests a potential therapeutic use for this novel immunomodulatory approach in an array of T cell-mediated diseases.

The safety of etretinate as long-term therapy for psoriasis: results of the etretinate follow-up study.

BACKGROUND: Etretinate is an aromatic retinoid given orally to treat severe psoriasis, a chronic disease that often requires long-term therapy. OBJECTIVE: We assessed the safety of long-term therapy with etretinate for psoriasis. METHODS: This 5-year prospective study of a cohort of 956 patients with psoriasis treated with etretinate assessed the frequency of adverse events in relation to total use and in relation to the frequency of these events in control populations. RESULTS: Our data do not provide evidence for an increased risk of cardiovascular disease, cancer, diabetes, or inflammatory bowel disease in association with long-term etretinate use. Although some patients reported that joint problems improved with the use of etretinate, a greater number associated the use of etretinate with joint problems. CONCLUSION: With proper patient selection and monitoring, long-term etretinate therapy (up to 4 years) does not appear to be accompanied by a substantial increased risk of major adverse effects.

Topical tretinoin (retinoic acid) treatment of hyperpigmented lesions associated with photoaging in Chinese and Japanese patients: a vehicle-controlled trial.

BACKGROUND: Hyperpigmented lesions are a predominant component of photoaging in Chinese and Japanese persons. Topical 0.1% tretinoin cream improves the hyperpigmentation associated with photoaging in Caucasian persons. OBJECTIVE: Our purpose was to assess the efficacy of 0.1% tretinoin cream treatment of hyperpigmented lesions associated with photoaging in Chinese and Japanese patients. METHODS: Forty-five photoaged patients (23 Chinese, 22 Japanese) completed a double-blind, randomized study in which 21 applied 0.1% tretinoin cream and 24 applied vehicle cream once daily to face and/or hands for 40 weeks. Patients' hyperpigmented lesions were evaluated clinically and by colorimetry throughout the study and by histologic analysis of skin biopsy specimens taken before therapy and at the end of treatment. RESULTS: At the end of treatment, hyperpigmented lesions of the face and hands were lighter or much lighter in 90% of patients receiving tretinoin compared with 33% receiving vehicle (p < 0.0001). Colorimetry demonstrated significant lightening of lesions after tretinoin compared with vehicle (p < 0.05). Histologic analysis of hyperpigmented lesions demonstrated a statistically significant 41% decrease in epidermal pigmentation with tretinoin therapy as compared with a 37% increase in the vehicle group (p = 0.0004). No patient withdrew for adverse effects. CONCLUSION: By clinical, colorimetric, and histologic evaluation, 0.1% tretinoin cream significantly lightens the hyperpigmentation of photoaging in Chinese and Japanese patients.

Oral cyclosporine for severe chronic idiopathic urticaria and angioedema.

Three patients with chronic urticaria, two of whom also had angioedema, were treated with oral cyclosporine, 6 mg/kg per day. In each patient, complete resolution of symptoms occurred within the first week of therapy; however, all patients eventually had to stop therapy as a result of side effects. On stopping therapy, all side effects resolved and the urticaria and angioedema recurred. Although cyclosporine therapy is not an appropriate treatment of urticaria, the results of this preliminary study suggest that cyclosporine and related drugs should be investigated in the treatment of mast cell-mediated diseases.

Office therapy for human papillomavirus infection in nongenital sites.

The many different treatment possibilities for the eradication of warts provide evidence that no single method that is completely effective has been found. Although the various methods described herein are usually successful therapies for warts, they are all associated with treatment failures and side effects. Until the perfect cure for warts is discovered, the physician must evaluate every wart carefully before deciding on a course of action.

Short-term changes in renal function, blood pressure, and electrolyte levels in patients receiving cyclosporine for dermatologic disorders.

We compared the changes in renal function, blood pressure (BP), and concentrations of serum potassium, magnesium, and urate (uric acid) in two groups of patients not given transplants. Group 1, comprising 21 psoriatic patients, was treated with 14 mg/kg per day of oral cyclosporine for 4 weeks in a prospective, placebo-controlled study; group 2, comprising 28 patients with diverse cutaneous diseases, was given 6 mg/kg per day of oral cyclosporine for 1 to 3 months in a prospective, open-labeled study. Renal function (determined by serum urea nitrogen [SUN] and creatinine levels and urinalysis), BP, serum electrolyte levels (potassium and magnesium), and urate level were measured weekly for the first 4 weeks in both groups, and then, after 2 and 3 months of therapy, in group 2 only. During the first 4 weeks in group 1 patients, there were significant increases in values of SUN, creatinine, BP, potassium, and urate, and a significant decrease in the serum magnesium value. When data for the two groups were combined, the changes from pretherapy values in each of the above measures (except systolic BP) during the first 4 weeks correlated significantly with cyclosporine trough levels. In group 2, the changes that occurred in the first 4 weeks in the SUN value, SUN/creatinine ratio, and BP were magnified over the subsequent 8 weeks of treatment. In the combined group for the first 4 weeks of therapy, duration of therapy, independent of cyclosporine trough levels, correlated with changes in SUN, creatinine, and urate levels, but not with changes in the potassium or magnesium level or in BP. We conclude that the cyclosporine blood level was a better discriminant than cyclosporine dosage in the analysis of renal dysfunction and hypertension in these patients.

Tretinoin treatment of photodamaged skin. Cosmesis through medical therapy.

Topical tretinoin is an effective therapy for the treatment of photodamaged skin. Clinically, patients experience decreased wrinkling, improved texture, and pinkening of sallow skin. However, the changes induced by topical tretinoin extend beyond simple cosmesis. Microscopic, ultrastructural, and biochemical alterations indicate that topical tretinoin is a significant medical therapy. Its successful use requires the guidance of an experienced physician.

The use of sulfasalazine in atrophie blanche.

Atrophie blanche can be a chronic condition for which there is no satisfactory treatment. Two patients with atrophie blanche who had not responded to various therapeutic modalities were given a trial of sulfasalazine 1 g three times daily. The ulcers healed within 3 months in both cases. In view of these positive results, patients should be treated with sulfasalazine to determine the efficacy of this drug in atrophie blanche.

The role of fish oil in psoriasis. A randomized, double-blind, placebo-controlled study to evaluate the effect of fish oil and topical corticosteroid therapy in psoriasis.

In a randomized, double-blind, placebo-controlled study, patients received 10 fish or olive oil capsules three times daily for the whole study in addition to applying betamethasone diproprionate to their psoriatic plaques for the first 3 weeks. Most patients gradually worsened upon discontinuation of corticosteroids. Using survival analysis methods, no significant difference was found between the fish and olive oil groups. The authors attempt to put the role of fish oil in the therapy of psoriasis into perspective and discuss the efficacy of fish oil when used alone versus in combination therapy.

Topical tretinoin: its use in daily practice to reverse photoageing.

The effect of 0.1% tretinoin cream for the treatment of photoageing was studied in a double-blind, placebo-controlled trial. All patients applied tretinoin cream to one forearm and the vehicle cream to the other, and half of the patients also applied tretinoin cream to the face and the other half used the vehicle cream. Tretinoin treatment produced an improvement in the signs of extrinsic ageing compared with the vehicle-treated areas. Fine wrinkling was improved most, although coarse wrinkling, brown spots, tactile roughness and overall skin colour also showed clear improvement. The majority of lentigines and sun-induced freckles showed some reduction in coloration with extended treatment. It is important when using tretinoin that the treatment procedure is carefully explained to the patients and that they are warned about a retinoid reaction. It should be stressed that improvement is gradual and that regular application of the cream must continue even after improvement has been achieved. Patients should be assured that there is no evidence of carcinogenicity in humans. Although no teratogenic effects of tretinoin have been reported when applied topically, it is not advisable to use the cream when trying to conceive or when pregnant.

Oral cyclosporine in the treatment of inflammatory and noninflammatory dermatoses. A clinical and immunopathologic analysis.

Cyclosporine is known to be effective in the treatment of psoriasis. In this study, we have used oral cyclosporine (6 mg/kg per day) given for 5 to 30 weeks to 24 patients for the treatment of 12 different dermatoses. Patients with the following diseases demonstrated a marked response or total clearing: 1 patient each with pyoderma gangrenosum, pityriasis lichenoides chronica, and psoriasis of the acrodermatitis continua of Hallopeau type. Moderate to marked response occurred in both patients with epidermolysis bullosa acquisita and the patient with hidradenitis suppurativa. Minimal to moderate responses were obtained in both patients with granuloma annulare, 1 of 2 with acrodermatitis continua of Hallopeau, both patients with Darier's disease, and 1 of 6 patients with vitiligo. Little or no response was noted in both patients with sarcoidosis, all 3 patients with pityriasis rubra pilaris, 5 of 6 patients with vitiligo, 1 patient with pemphigus foliaceous, and 1 with pemphigus vulgaris. Clinical side effects were mild and transient and included dysesthesia, fatigue, hypertrichosis, nausea, and flushing. The most frequent clinically significant abnormalities were hypertension and renal dysfunction, with all factors normalizing within 1 month of discontinuation of cyclosporine therapy.

Tretinoin therapy: practical aspects of evaluation and treatment.

Tretinoin has previously been used for the treatment of acne. Recent studies, however, demonstrating the efficacy of topical tretinoin in the treatment of photodamaged skin have led to its widespread use for this entirely new indication. When prescribing tretinoin for photodamaged skin rather than acne, physicians must take into consideration a new set of issues. Patients must be selected based on their commitment to a total sun-avoidance regimen. Evaluation of photodamage must be careful and thorough prior to initiating topical tretinoin therapy. Global assessment of a patient's photodamaged skin should be made before therapy and at all follow-up visits. The patient population treated for photodamage tends to be older than that using topical tretinoin for acne; therefore, the treatment regimen must account for the different clinical and physiological characteristics of older patients' skin.

Topical tretinoin therapy: its use in photoaged skin.

Tretinoin cream has been used extensively to reverse the changes of photoaging. It is the first topical therapy to undergo controlled clinical testing and proved to be efficacious. These results have been substantiated with photography, histopathologic examination, and skin surface replicas. The mechanism of action of retinoic acid is unknown, but it may bind to a specific receptor that alters the gene expression of the cell. Therapy is most successful when a liberal amount of tretinoin 0.1% cream is applied to the skin daily. Tretinoin cream has an excellent safety record; a local cutaneous hypervitaminosis A reaction is the only common problem.

Side-effect profile of acitretin therapy in psoriasis.

Acitretin, the principal and free acid metabolite of etretinate, was used to treat patients with stable, plaque-type psoriasis. For the first 8 weeks, 38 patients received placebo or acitretin, 10, 25, 50, or 75 mg daily, in a double-blind manner. After the double-blind phase, the patients were allowed to continue for a total of 6 months of acitretin therapy at an average dosage of 50 mg/day. When the patients flared after stopping therapy, an additional 6-month course of acitretin therapy was offered. Acitretin, which was as effective as etretinate, had to be given at a dosage of 50 mg/day or more to obtain a significant benefit. Side effects frequently occurred in patients receiving acitretin, 25 mg/day or more, but were generally mild and did not warrant discontinuation of therapy. They were similar to those of etretinate therapy; cheilitis, peeling of palms and soles, and alopecia occurred most frequently. The most common abnormal laboratory test results were elevations in serum triglycerides and, to a lesser extent, serum cholesterol and liver transaminase levels. Acitretin, in view of its much shorter half-life and similar efficacy and side-effect profile compared with etretinate, may be a preferable therapy for psoriasis, especially in women of childbearing age.

Topical tretinoin and photoaged skin.

Topical tretinoin has been proposed for the treatment of photoaged skin in recent years. In both open and double-blind trials, it has been successful in reversing some of the histologically and clinically apparent changes of photoaging. Many patients will experience a dermatitis due to retinoids during therapy, but are usually able to tolerate the treatment. Although clinical improvement may be modest, most patients are pleased with the result. We have found that optimal improvement is achieved by using tretinoin 0.1 percent cream to the limit of tolerance. By carefully instructing the patient on the application of the medication, the occurrence of initial dermatitis with therapy, and the type of improvement to expect, compliance with and tolerance of tretinoin therapy are greatly enhanced.

A morphometric and histologic study of the scalp in psoriasis. Paradoxical sebaceous gland atrophy and decreased hair shaft diameters without alopecia.

A histologic study was designed to evaluate the pilosebaceous unit of the scalp in nonpustular patch- and plaque-stage psoriasis. Punch biopsy specimens from involved and uninvolved areas of 28 patients were sectioned in a horizontal plane for qualitative and quantitative study. All samples were evaluated in a blind mode, and data were analyzed for statistical significance. There was no evidence for alopecia of any type. Sebaceous gland atrophy was a frequent concomitant in the psoriatic lesion, with probable down-sizing of the hair follicle and thinner hair shafts. Paradoxical sebaceous gland atrophy and down-sized hair follicles in psoriasis may be due to possible inhibiting effects of yet unidentified factors produced by the epidermal lesion.