Effect Of Topical Therapy Research Articles

BP-1107 [{2-[4-(2,4-Dioxo-thiazolidin-5-ylmethyl)-phenoxy]-ethyl}-methyl-amide]: A Novel Synthetic Thiazolidinedione That Inhibits Epidermal Hyperplasia in Psoriatic Skin-Severe-Combined Immunodeficient Mouse Transplants after Topical Application

Recent studies have demonstrated that orally administered thiazolidinedione ligands of the peroxisome proliferator-activated receptor-gamma can ameliorate clinical features of psoriasis in humans. Thiazolidinediones also inhibit the proliferation of psoriatic keratinocytes in monolayer and organ culture, and at least one of these agents (troglitazone) inhibits epidermal hyperplasia of human psoriatic skin transplanted to severe-combined immunodeficient (SCID) mice. In the present study, we show that a novel, synthetic, thiazoladinedione derivative, BP-1107 ({2-[4-(2,4-dioxo-thiazolidin-5-ylmethyl)-phenoxy]-ethyl}-methyl-amide), is capable of inhibiting psoriatic hyperplasia in the SCID mouse transplant model after topical application. Like other thiazolidinediones, BP-1107 inhibits proliferation of rapidly growing keratinocytes in monolayer culture, but compared with these agents, the effective dose of BP-1107 needed to suppress keratinocyte proliferation is much lower. Concentrations of BP-1107 that effectively inhibit keratinocyte function have no detrimental effect on dermal fibroblasts. These data suggest that effective topical antipsoriatic therapy may be provided with this agent.

Effective therapy of childhood atopic dermatitis allays food allergy concerns

Roughly one third of children with atopic dermatitis (AD) have IgE-mediated food allergy. Most parents and pediatricians assume foods also cause the eczema, a focus that diverts proper skin therapy and has negative outcomes including nutritional deficiency, costly referrals, and unnecessary testing. This project investigates the relationship between food allergy and AD, both before and after treatment in an established AD population. During an open trial of topical tacrolimus we observed a decrease in parental food allergy concern during good control of their child's eczema. We tested this observation by follow-up interviews and a questionnaire study to compare parental estimates of food allergy concerns after therapy with concerns before beginning the trial. Study subjects were children 11 years old and younger with AD and suspicion of food allergy. AD and food allergy parameters, pre- and post-treatment, were retrospectively assessed by a questionnaire given to the parents. Twenty-three patients were enrolled: 16 had positive food allergy tests (7 RAST and/or 10 skin prick tests) and 30% had a definite history of immediate IgE reactions to foods. Ninety-five percent of parents felt that food allergy exacerbated their child's AD. Treatment durations were 3 to 45 months. Parental concern of food allergy decreased significantly from 7.7 to 4.0 on a 10 point scale (P < .001). Additionally, estimated food reactions decreased by approximately 80% during 1- and 6-month periods (P = .001). In this selected university-based childhood AD population, nearly all parents were convinced their child had food allergy and further that the food contributed to the AD. The level of concern about food reactions was significantly decreased and the number of food reactions declined during effective topical therapy. This preliminary assessment of parental perceptions suggests that successful, stable therapy of AD reduces perceived food reactions and allays parental concerns about food allergy. Such therapy may encourage parents to refocus on direct skin care as the primary effort in AD therapy. We conclude that the effect of successful AD treatment on food allergy and food allergy concern are of interest and worthy of further study.

Comparison of Azelaic Acid and Anthralin for the Therapy of Patchy Alopecia Areata

Although topical azelaic acid has been previously used for the treatment of alopecia, no controlled trials of azelaic acid for this condition have been conducted to date. The goal of this study was to determine the efficacy, tolerability, and safety of azelaic acid treatment in patients with patchy alopecia areata (AA) in comparison with anthralin (dithranol) treatment. This study included 31 subjects with patchy AA who did not receive any treatment for at least 1 month prior to the study. Demographic and clinical characteristics of these subjects were recorded at baseline. Subjects were randomized to apply either 20% azelaic acid (15 subjects) or 0.5% anthralin (16 subjects) for 12 consecutive weeks. In a subsequent 8-week follow-up period no cream was applied. Two independent investigators performed an efficacy evaluation with clinical examination using a terminal hair regrowth score (RGS) with a scale ranging from 0 (inadequate response) to 2 (complete response) at week 20. Partial response was accepted as score 1. Both groups were well matched for the relevant demographic and clinical indicators affecting treatment response at baseline. All subjects completed the trial. At week 20 the RGS was 1.27 +/- 0.9 in the azelaic acid group versus 1.37 +/- 0.8 in the anthralin group (p > 0.05). A complete response was observed in 53.3% of cases in the azelaic acid group (8 of 15) compared with 56.2% (9 of 16) in the anthralin group (p > 0.05). No serious adverse events were observed in either group during the study. The present pilot study showed that the use of azelaic acid gave similar results to anthralin with regard to hair regrowth, and that it can be an effective topical therapy for patchy AA. More extensive trials are necessary, however, to reach a definitive conclusion.

Topical agents and erectile dysfunction: is there a place?

Despite the proven efficacy of oral therapy for erectile dysfunction (ED), some patients are unable to take these medications because of drug interactions (ie, sildenafil and nitroglycerin) or a lack of response. Topical agents represent another minimally invasive option for the treatment of ED. This review discusses the impediments to effective topical therapy and examines the developmental status of several candidate drugs. Although still in the investigative stage, topical medications can be another tool in the urologist's armamentarium against ED.

Onychomycosis: diagnosis and topical therapy

Onychomycosis (true fungal infection of the nail plate) is a common malady that may present in several clinical patterns. Because many noninfectious disorders of the nail may masquerade as onychomycosis, the clinical diagnosis must be confirmed by wet mount (potassium hydroxide [KOH] examination), culture, or histology before treatment is begun. Although systemic therapy of onychomycosis with the newer drugs is more effective, the prospect of effective topical therapy is a welcome alternative in many situations. Choices for topical therapy are limited in the United States at this time. As new, improved choices are added to the therapeutic armamentarium, topical therapy my supersede systemic. In addition, the potential for synergism with systemic therapy and for prophylaxis of cleared infections is only now being explored.

Fluconazole versus ketoconazole in the treatment of tinea versicolor

BACKGROUND : A number of effective topical therapies are available for the treatment of tinea versicolor (TV). However, topical antifungals are difficult to apply to a large body surface area and for this reason TV is perhaps more easily treated with systemic agents. METHODS : A total of 128 patients with TV, aged 15-55 years, were entered into a randomized, double-blind, clinical trial comparing the efficacy and tolerance of two regimens of oral treatment for TV. The patients were randomly divided in two groups: group 1 received two 150 mg capsules of fluconazole in a single dose repeated weekly for 2 weeks; and group 2 received two 200 mg tablets of ketoconazole in a single dose repeated weekly for 2 weeks. Diagnosis of TV was made clinically by direct KOH preparation and Wood's lamp examination. RESULTS : Of 128 patients, 100 completed the study and no major side-effects were noted between the two treatment regimens. Results of the study showed no significant differences in efficacy, safety and tolerability between the two treatment regimens. The maximal cure rate was achieved at 8 weeks from the start of treatment and decreased slightly afterwards. CONCLUSIONS : Fluconazole and ketoconazole demonstrated similar efficacy in the treatment of TV. We also demonstrated a lack of correlation between mycological cure and hypopigmentation at the end of treatment (2 weeks) and the usefulness of Wood's lamp examination in detecting cure of TV.

The use of the new oral antifungal agents, itraconazole, terbinafine, and fluconazole to treat onychomycosis and other dermatomycoses

Onychomycosis refers to a fungal infection of the nail bed and secondarily the nail plate. This could be caused by dermatophytes, Candida species, and nondermatophyte molds. Tinea unguium is infection of the nail bed/plate by dermatophytes. The modified classification of onychomycosis is distal and lateral subungual onychomycosis, proximal subungual onychomycosis, superficial onychomycosis, endonyx onychomycosis, and total dystrophic onychomycosis. In general, only about 50% of all abnormal-appearing toenails can be attributed to mycologically proven onychomycosis. The other causes for abnormally-appearing nails include psoriasis, trauma, and lichen planus. The newer oral antifungal agents itraconazole, terbinafine, and fluconazole have become primary treatments of onychomycosis and other superficial fungal infections; however, griseofulvin, is widely used to treat tinea capitis and ketoconazole, is preferred by some for the treatment of tinea versicolor. Each of the new oral agents has been shown to be effective and safe in dermatomycoses. Diabetic patients are more prone to development of onychomycosis compared with normal individuals. Because of the potential for morbidity, the feet in diabetic patients need to be examined carefully, with appropriate treatment of any fungal or bacterial infection. The management strategies with onychomycosis include no therapy, use of effective topical therapies if available, mechanical or chemical debridement, or oral antifungal therapy. In some instances the most appropriate approach is a combination of two of the above-mentioned therapy modes, for example, oral therapy and mechanical debridement. The preferred dosage regimens are itraconazole (pulse), terbinafine (continuous), and fluconazole (once-weekly). Once a cure has been achieved, management includes education and counseling of the patient to reduce the chances of recurrence of disease. There is a growing body of experience in which the new oral antifungal agents have been used to treat tinea capitis and other superficial infections in children. The data suggest that itraconazole, terbinafine, and fluconazole are effective and safe in children. (Curr Probl Dermatol 2001;13:213-48)

Vitamin B12 Cream Containing Avocado Oil in the Therapy of Plaque Psoriasis

Background: There are already many effective topical therapies available for use in the treatment of chronic plaque psoriasis. Unfortunately, these treatments are often associated with a rather significant risk of undesirable effects. Objective and Methods: In this randomized, prospective clinical trial, the effects of the vitamin D₃ analog calcipotriol were evaluated against those of a recently developed vitamin B₁₂ cream containing avocado oil in an intraindividual right/left-side comparison. The trial population consisted of 13 patients, 10 men and 3 women, with chronic plaque psoriasis. The observation period was 12 weeks; the effects of therapy were assessed on the basis of a PASI score adapted to the right/left-side comparison technique, the subjective evaluations of the investigator and patients and the results of 20-MHz sonography. Results: There was a more rapid development of beneficial effects with the use of calcipotriol in the initial 8 weeks, although differences in effects were significant only at the time point of therapy week 8 (p < 0.05). After 12 weeks, neither the PASI score nor 20-MHz sonography showed significant differences between the two treatments. While the efficacy of the calcipotriol preparation reached a maximum in the first 4 weeks and then began to subside, the effects of the vitamin B₁₂ cream containing avocado oil remained at a constant level over the whole observation period. This would indicate that the vitamin B₁₂ preparation containing avocado oil may be suitable for use in long-term therapy, a hypothesis further supported by the fact that the investigator and the patients assessed the tolerability of the vitamin B₁₂ cream containing avocado oil as significantly better in comparison with that of calcipotriol. Conclusion: The results of this clinical trial provide evidence that the recently developed vitamin B₁₂ cream containing avocado oil has considerable potential as a well-tolerated, long-term topical therapy of psoriasis.

Topical and surgical treatment of onychomycosis

Dermatophytes, yeasts, and molds can be the causative organisms of fungal nail infections. Alternatives to the systemic management of onychomycosis include topical and surgical treatments. Traditionally, topical agents used as monotherapy for onychomycosis are only able to inhibit the growth of fungal nail infections; clinical and mycologie cures have recently been observed after treatment with some of the newer preparations. In contrast, surgical treatments almost always need to be used in conjunction with either topical or systemic antifungal therapy. An efficacious topical treatment alternative for onychomycosis involves applying antifungal agents concurrently or sequentially with the removal or debridement of the infected nail structures. Alternatively, the application of antifungal lacquer to fingernail and toenail fungal infections may also be an effective topical therapy for the treatment of less severe forms of onychomycosis.

Topical 0.050% betamethasone dipropionate. Pharmacokinetic and pharmacodynamic dose-response studies in humans.

Effective topical drug therapy requires drug delivery into the skin to produce the desired pharmacodynamic response. For topical corticosteroids, the visual skin-blanching assay has been used to rank the potency of the corticosteroids and their overall efficacy. While vehicles have been shown to influence the resulting blanching response, the dose of drug applied has not always produced proportional differences in the blanching assay. The mechanism of the nonproportional pharmacodynamic response to the corticosteroid dose is unclear. We describe four methods for assessing the dose-response relationship of topical betamethasone dipropionate on the ventral forearm of six human subjects: duration, concentration, film thickness, and surface area. Drug uptake analysis in human stratum corneum and the resulting pharmacodynamic response, measured visually and with a chromameter, were performed with each method to quantify the dose-response relationship. Only the concentration and duration methods demonstrated an increase in mean drug uptake with increasing dose. The maximal mean pharmacodynamic response reflected the mean drug uptake with all four methods. Application conditions for maximal pharmacodynamic activity of topical betamethasone dipropionate in the skin include short duration of treatment (< or = 2 hours), a lower concentration than commercially marketed, and thin film thicknesses (1 to 5 microns). A dose response can be produced by increasing the drug concentration or the duration of application time. Achievement of steady-state betamethasone dipropionate uptake into the stratum corneum was not commensurate with the maximal pharmacodynamic response. Very small amounts of this potent corticosteroid within the skin appear to maximize the receptor response to drug.

Topical 0.050% Betamethasone Dipropionate

<h3>Background and Design:</h3> Effective topical drug therapy requires drug delivery into the skin to produce the desired pharmacodynamic response. For topical corticosteroids, the visual skin-blanching assay has been used to rank the potency of the corticosteroids and their overall efficacy. While vehicles have been shown to influence the resulting blanching response, the dose of drug applied has not always produced proportional differences in the blanching assay. The mechanism of the nonproportional pharmacodynamic response to the corticosteroid dose is unclear. We describe four methods for assessing the dose-response relationship of topical betamethasone dipropionate on the ventral forearm of six human subjects: duration, concentration, film thickness, and surface area. Drug uptake analysis in human stratum corneum and the resulting pharmacodynamic response, measured visually and with a chromameter, were performed with each method to quantify the dose-response relationship. <h3>Results:</h3> Only the concentration and duration methods demonstrated an increase in mean drug uptake with increasing dose. The maximal mean pharmacodynamic response reflected the mean drug uptake with all four methods. Application conditions for maximal pharmacodynamic activity of topical betamethasone dipropionate in the skin include short duration of treatment (≤2 hours), a lower concentration than commercially marketed, and thin film thicknesses (1 to 5 μm). <h3>Conclusion:</h3> A dose response can be produced by increasing the drug concentration or the duration of application time. Achievement of steady-state betamethasone dipropionate uptake into the stratum corneum was not commensurate with the maximal pharmacodynamic response. Very small amounts of this potent corticosteroid within the skin appear to maximize the receptor response to drug. (Arch Dermatol. 1994;130:740-747)

Phenoxyethanol is effective topical therapy of Gram-negative cellulitis in neutropenic patients

In neutropenic patients cellulitis caused by Gram-negative organisms may prove difficult to control and cause considerable tissue damage. Phenoxyethanol has activity against a range of bacteria, including Pseudomonas aeruginosa, and is absorbed by intact skin. Three severely neutropenic patients are described in whom cellulitis failed to respond to appropriate intravenous antibiotics. However the topical application of phenoxyethanol solution gave prompt local control. This cheap and nontoxic agent may give dramatic improvement in this difficult clinical situation.

Topical treatment of New World cutaneous leishmaniasis in Belize: A clinical study

Many studies have been performed during the past decade to find an effective topical therapy for cutaneous leishmaniasis (CL). Our purpose was to evaluate the effect of paromomycin ointment (P-ointment) containing 15% paromomycin sulfate and 12% methylbenzethonium chloride on Belizean patients with New World CL. Fifty-three patients were treated twice daily for 14 to 21 days with P-ointment. Sixty-eight percent of the patients healed, 6% had a delayed cure, and 26% did not respond. No toxic effects from the ointment were observed. Topical paromomycin is as efficacious in the treatment of New World CL as other currently accepted modalities that are potentially more toxic.

Antimicrobial effects of azelaic acid

Azelaic acid has been shown to be an effective topical acne therapy. Cream containing 20% azelaic acid significantly reduces the skin surface and follicular propionibacteria and staphylococci by at least 96% after 8 weeks of treatment. In vitro, azelaic acid reduces the growth rate of, and inhibits and kills Propionibacterium acnes and Staphylococcus epidermidis. The effect is dependent on the concentration of azelaic acid and the pH of the environment. Azelaic acid is more effective at low pH values. Azelaic acid is actively transported into P. acnes and S. epidermidis and its mode of action is directed to protein synthesis with 50% inhibition at 313 and 457 μM respectively. Follicular concentrations of azelaic acid reached those sufficient to inhibit both P. acnes and S. epidermidis after one application to the skin. No mutants resistant to azelaic acid appeared in P. acnes or S. epidermidis when they were grown for 9.8 × 1013 and 5.5 × 1013 cell generations, respectively, in its presence.

DMSO protects against adriamycin-induced tissue necrosis.

Inadvertent extravasation of Adriamycin (Adria) can result in severe tissue necrosis. The mechanism of this tissue damage is believed to be the release of free radicals into the tissue. Topical applications of dimethylsulfoxide (DMSO) used after Adria extravasation have been shown to decrease ulcer size. This may be due to DMSO's ability to scavenge free radicals. However, effective topical therapy requires prompt recognition of extravasation, which is often difficult. We hypothesized that the delivery of Adria in low concentrations DMSO would reduce Adria-induced ulcer size and ulcer incidence caused by Adria extravasation. To test this hypothesis, 180, male Sprague-Dawley rats were randomly allocated into three treatment groups of 60 each. All three groups received intradermal injections of Adria (1 mg) diluted in 0.5 cc of saline (Group 1), 10% DMSO (Group 2), or 20% DMSO (Group 3). Rats were observed for 4 weeks. Ulcer incidence (%) and size of ulcers (mm2) were assessed over time. Area of skin ulceration was calculated as the product of the two greatest diameters. Statistical evaluation of the differences in incidence and ulcer size between Group 1 and Groups 2 or 3 were evaluated using analysis of variance. Delivery of Adriamycin in 10 or 20% DMSO resulted in a statistically significant (P less than 0.001) decrease in the incidence of ulceration caused by intentional Adria extravasation.

Tinea versicolor: Epidemiologic, clinical, and therapeutic aspects

Age of the patient, climate, season, and local environmental factors influence the onset and course of tinea versicolor (pityriasis versicolor). A number of effective topical therapies are available. In addition, a single dose of 400 mg of oral ketoconazole eliminates the disease and can be used prophylactically in some cases to prevent recurrence.

Evaluation of Oral Minoxidil in the Treatment of Alopecia Areata

A dose-response effect has previously been demonstrated in topical minoxidil treatment of alopecia areata. Limitations in minoxidil solubility and percutaneous absorption have impaired the development of more effective topical therapy. Oral minoxidil (5 mg every 12 hours), a dose demonstrated to be relatively well tolerated if a 2-g sodium diet is strictly followed, was given to 65 patients with severe, treatment-resistant alopecia areata in an attempt to bypass the limitations of topical treatment and increase efficacy. Although hair regrowth progressed more rapidly and was more extensive with oral than topical 5% minoxidil, cosmetic response was seen only in 18% of the patients. Neither serum nor tissue levels of minoxidil correlated with response. These findings suggest that improved preparations of topical minoxidil, when used as a single therapeutic agent, are unlikely to be cosmetically effective in the majority of patients with severe alopecia areata.

Herpesvirus.

Herpesvirus (HSV) infection of the genital tract is a sexually transmitted disease that is increasing at an epidemic rate. 2 types of virus, Type 1 (HSV-1) and Type 2 (HSV-2) have been identified, of which HSV-2 is the major cause of genital and neonatal infection. Type 2 herpes infections may be the 2nd most common venereal disease in the US. More than 60% of the adult US population has antibodies to HSV, and socioeconomic factors have been found to influence the incidence of HSV infection. The precise incidence of genital herpes in the US is not known, but in 1979 there were 29.2/100,000 consultations for genital herpes, compared to 3.4/100,000 in 1966. As many as 20 million people have herpes, and there are 5 million new cases/year. Genital herpes occurs more frequently in a sexually active population. Clinical manifestations depend on the immune status of the individual and may be 1st episode primary genital herpes, 1st episode nonprimary genital herpes, or recurrent disease. 85% of primary 1st episode genital herpes are caused by HSV-2, the attack rate for susceptible sexual contacts from individuals with active genital lesions is approximately 75%, and the incubation period averages 6 days. 1st episode primary disease may produce severe localized symptoms as well as systemic symptoms. Complete resolution of lesions takes up to 6 weeks, and symptoms persist for an average of 13.8 days. 1st episode nonprimary genital herpes and recurrent disease have similar clinical courses, with ususally mild local symptoms lasting on average 6.9 days, no systemic symptoms, 1-3 lesions, complete resolution of lesions in 8 days, short duration of viral shedding, and presence of preexisting HSV antibodies. Possible complications of genital herpes infections include urethral and bladder infections and secondary bacterial skin infections, inflammatory radiculomyelitis, transverse myelitis, and aseptic meningitis. Humoral and cell-mediated immune responses are important. The majority of infections are diagnosed clinically. Viral culture is the most reliable laboratory technique. Other venereal diseases commonly coexist with genital herpes. To date there is no effective topical therapy for recurrent genital herpes. Cesarean section has been recommended to avoid infecting infants of infected mothers during delivery. Psychological and emotional problems caused by fears of infecting a sexual partner and increased risk of genital cancer in women are among longterm sequelae of genital herpes.

The effect of steroid and dithranol therapy on cyclic nucleotides in psoriatic epidermis.

Absolute values of both cAMP and cGMP leves were measured in the involved and uninvolved skin of psoriatic patients, and also the effect of topical therapy on these levels in the involved skin was studied. The mean cGMP level in the untreated psoriatic plaque was increased by 300% compared to the non-involved skin (which did not differ from normal skin), but no significant difference in cAMP levels was found. Epidermal stripping of uninvolved skin, which stimulates cell proliferation, did not change the cGMP level. Treatment of the psoriasis with dithranol caused the cGMP levels to return to normal, but a potent topical glucocorticoid, in contrast, produced no such decrease. This may imply that the two drugs act at different levels in suppressing cell replication, and dithranol may be a useful tool for the further investigation of cyclic nucleotide metabolism.

Allergy to various components of topical preparations in stasis dermatitis and leg ulcer.

Patients suffering from stasis dermatitis and leg ulcers (192) were found to give an allergic reaction in epicutaneous tests to one or more components of topical preparations in 69.2% of cases. The most common reactions were obtained with neomycin 34.0% and its component framycetin 31.2%, wool alcohols 22.9%, balsam of Peru 21.4%, chlorquinaldon 16.7%, bacitracin 13.1%, chinoform 10.9%, dequalin 9.9%, formaldehyde 4.2% and parabens 3.6%. The incidence of allergic reactions reflects local use of preparations containing various allergens as well as their capacity to produce alllergy. Allergy may in some cases interfere with effective topical therapy. Debrisan dextran polymer beads were found to be suitable for treatment of ulcers of multiallergic patients without risk of contact allergy.