Common Topical Agents Research Articles

Assessing the Validity of Clinician Advice That Patients Avoid Use of Topical Agents Before Daily Radiotherapy Treatments

Radiation dermatitis is common and often treated with topical therapy. Patients are typically advised to avoid topical agents for several hours before daily radiotherapy (RT) out of concern that topical agents might increase the radiation dose to the skin. With modern RT's improved skin-sparing properties, this recommendation may be irrelevant. To assess whether applying either metallic or nonmetallic topical agents before radiation treatment alters the skin dose. A 24-question online survey of patients and clinicians was conducted from January 15, 2015, to March 15, 2017, to determine current practices regarding topical therapy use. In preclinical studies, dosimetric effect of the topical agents was evaluated by delivering 200 monitor units and measuring the dose at the surface and at 2-cm depth in a tissue-equivalent phantom with or without 2 common topical agents: a petroleum-based ointment (Aquaphor, petrolatum 41%) and silver sulfadiazine cream, 1%. Skin doses associated with various photon and electron energies, topical agent thicknesses, and beam incidence were assessed. Whether topical agents altered the skin dose was also evaluated in 24 C57BL/6 mice by using phosphorylated histone (γ-H2AX) immunofluorescent staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Preclinical studies took place at the University of Pennsylvania. Patient and clinician survey responses; surface radiation dose readings in tissue-equivalent phantom; and γ-H2AX and TUNEL intensity measured in mice. The 133 patients surveyed received RT for cancer and had a median (range) age of 60 (18-86) years; 117 (87.9%) were women. One hundred eight clinicians completed the survey with 105 reporting that they were involved in managing patient skin care during RT. One hundred eleven (83.4%) of the patients and 96 (91.4%) of the 105 clinicians received or gave the advice to avoid applying topical agents before RT treatments. Dosimetric measurements showed no difference in the delivered dose at either the surface or a 2-cm depth with or without a 1- to 2-mm application of either topical agent when using en face 6- or 15-megavoltage (MV) photons. The same application of topicals did not alter the surface dose as a function of beam incident angle from 15° to 60°, except for a 6% increase at 60° with the silver sulfadiazine cream. Surface dose for 6- and 15-MV beams were significantly increased with a thicker (≥3-mm) topical application. For 6 MV, the surface dose was 1.05 Gy with a thick layer of petroleum-based ointment and 1.02 Gy for silver sulfadiazine cream vs 0.88 Gy without topical agents. For 15 MV, the doses were 0.70 Gy for a thick layer of petroleum-based ointment and 0.60 Gy for silver sulfadiazine cream vs 0.52 Gy for the controls. With 6- and 9-MeV electrons, there was a 2% to 5% increase in surface dose with the use of the topical agents. There were no dose differences at 2-cm depth. Irradiated skin in mice showed no differences in γ-H2AX-positive foci or in TUNEL staining with or without topical agents of varying thickness. Thin or moderately applied topical agents, even if applied just before RT, may have minimal influence on skin dose regardless of beam energy or beam incidence. The findings of this study suggest that applying very thick amounts of a topical agent before RT may increase the surface dose and should be avoided.

Current and Emerging Topical Antibacterials and Antiseptics: Agents, Action, and Resistance Patterns.

Bacterial skin infections represent some of the most common infectious diseases globally. Prevention and treatment of skin infections can involve application of a topical antimicrobial, which may be an antibiotic (such as mupirocin or fusidic acid) or an antiseptic (such as chlorhexidine or alcohol). However, there is limited evidence to support the widespread prophylactic or therapeutic use of topical agents. Challenges involved in the use of topical antimicrobials include increasing rates of bacterial resistance, local hypersensitivity reactions (particularly to older agents, such as bacitracin), and concerns about the indiscriminate use of antiseptics potentially coselecting for antibiotic resistance. We review the evidence for the major clinical uses of topical antibiotics and antiseptics. In addition, we review the mechanisms of action of common topical agents and define the clinical and molecular epidemiology of antimicrobial resistance in these agents. Moreover, we review the potential use of newer and emerging agents, such as retapamulin and ebselen, and discuss the role of antiseptic agents in preventing bacterial skin infections. A comprehensive understanding of the clinical efficacy and drivers of resistance to topical agents will inform the optimal use of these agents to preserve their activity in the future.

Optimization and therapeutic effects of PDT mediated by ALA and MAL in the treatment of cutaneous malignant lesions: A comparative study.

5-aminolevulinic acid (ALA) and its methylated ester (MAL) are the most common topical agents used in photodynamic therapy (PDT) as precursors of the photosensitizer protoporphyrin IX (PpIX). The induction of newly PpIX depends on incubation time of each photosensitizer in the tissue and the presence of high intralesional porphyrin levels is an important parameter for the PDT effectiveness. This study used laser-induced fluorescence (LIF) spectroscopy to evaluate the optimum time to light exposure of PDT mediated by ALA (20% w/w) and MAL (10% w/w) to treat malignant lesions precursors of cutaneous squamous cell carcinoma induced in mice. The therapeutic effects obtained by optimized ALA- and MAL-PDT were assessed 10 and 20 days after treatments. Higher PpIX levels were evidenced in the lesions photosensitized by ALA than MAL and according to LIF measurements the PDT irradiation was performed, respectively, at 300 and 330 minutes after ALA and MAL incubation. Histopathological analysis evidenced necrosis and epithelial atrophy after 10 days of PDT using both prodrugs, as well as reepitelization and collagen deposition at 20 days. Thus, despite the distinct concentration of ALA and MAL used in the formulation of each photosensitizing cream, PDT mediated by both photosensitizing agents obtained similar therapeutic outcomes.

Management of Ocular Surface Tumors: Excision vs. Topical Treatment

Ocular surface squamous neoplasia (OSSN) encompasses a range of corneal and conjunctival lesions from intraepithelial dysplasia to invasive squamous cell carcinoma. The mainstay of treatment for OSSN has traditionally been surgical excision with wide margins and cryotherapy. Increasing evidence on the efficacy and safety of medical therapy and the avoidance of surgical complications has made topical chemotherapy increasingly popular among corneal specialists. The most common topical agents used for the treatment of OSSN include mitomycin C, 5-fluorouracil, and interferon a 2b. Herein, we review recent advances in the surgical and medical management of OSSN and discuss advantages and disadvantages of each approach. The role of ultra highresolution optical coherence tomography in the diagnosis and treatment of primary and recurrent OSSN lesions is also discussed.

Does experience doing lumbar punctures result in expertise?

With any open wound infection may occur. Many factors such as age and general health status may increase the likelihood of infection, but the size and depth of the wound are critical factors in determining the chronicity of any wound. Infection greatly adds to the morbidity associated with open wounds. An infected wound not only heals more slowly, there is also the risk of systemic infection and even death. Infected wounds also scar more severely and are associated with more prolonged rehabilitation. Topical therapeutic agents have been shown to be effective in the management of open skin wounds. These agents may assist less complicated healing and decrease the conversion of a partial-thickness injury to a full-thickness injury, and thereby reduce wound-related morbidity. Common topical agents with suggestions for application are discussed in this review.

Efficacy and Safety of Imiquimod Versus Podophyllotoxin in the Treatment of Anogenital Warts

Anogenital warts are a common sexually transmitted disease caused by human papillomaviruses. Despite the fact, that imiquimod and podophyllotoxin represent common topical agents, direct comparative studies lack. This work compares the effectiveness and safety of self-applied imiquimod 5% cream and podophyllotoxin 0.5% solution. Within 2 years, consecutive patients presenting with untreated anogenital warts were included in a randomized, open label trial. The primary endpoint was complete clearance at the end of treatment (4 weeks after the start with podophyllotoxin, 16 weeks after the start of imiquimod therapy). Side effects were evaluated as a secondary endpoint. A total of 45 patients, 7 women and 35 men, of whom 5 were circumcised, concluded the treatment and were eligible for evaluation. The rates of clearance of baseline warts among treatment groups were 72% (95% confidence interval [CI], 52%-86%) in the podophyllotoxin group and 75% (95% CI, 53%-98%) in the imiquimod group. Statistically, clearance rates were identical (P=1). The differences in side effects between treatment groups were statistically not significant (P=0.24). The current study, a direct comparison of both, confirms the previously obtained mathematical data, that imiquimod 5% cream and podophyllotoxin 0.5% solution have an identical beneficial effect on anogenital warts and are associated with identical and acceptable side effects. Both substances constitute effective and safe treatments of untreated anogenital warts in immunocompetent individuals.

Taurine bromamine: a new therapeutic option in inflammatory skin diseases

Acne vulgaris is a multifactorial inflammatory skin disease. One of the pathogenic factors in acne is Propionibacterium acnes (P. acnes). Traditional treatment of acne lesions involves topical application of antibiotics with anti-bacterial and anti-inflammatory properties. However, a failure of this therapy is widely associated with emergence of resistant bacteria. Therefore, a search for alternative topical anti-acne drugs is necessary. Taurine bromamine (TauBr), the physiological product of hypobromous acid reaction with taurine, shows antioxidant, anti-inflammatory, and anti-bacterial properties. Importantly, P. acnes, a potential pathogenic agent for acne vulgaris, is extremely sensitive to TauBr. In addition, TauBr inhibits the generation of H(2)O(2) by activated neutrophils, which seems to be crucial for reducing the number and severity of inflammatory acne lesions. All these data strongly support the concept of using TauBr for topical anti-acne therapy. In our pilot clinical study, we have compared the efficacy of TauBr cream with clindamycin gel, one of the most common topical agents used in the treatment of acne. After 6 weeks, both treatments produced comparable, beneficial results. More than 90% of patients improved clinically with similar reductions in a number of acne lesions (approximately 65%). Therefore, the results from clinical studies are consistent with previous in vitro data and strongly suggest that TauBr could be considered a new therapeutic option in inflammatory acne.

Hypoallergenic and non-toxic emollient therapies for children

There are many anatomical and functional differences between the skin of young children and adult skin. As a consequence, the skin is more easily irritated by topical agents. There is also increased transcutaneous absorption; the latter effect is amplified by underlying conditions such as ichthyoses and atopic dermatitis with defects of the epidermal barrier. Common topical agents such as salicylic acid and lactic acid can cause life-threatening intoxications. The relevance of transcutaneous absorption of "hidden" ingredients such as polyethylene glycol and preservatives is unknown at present. By emulsifying endogenous barrier lipids, emulsifiers can promote skin dryness. We review the effects of common emollients and their suitability for skin care in children, particularly with the aim to reduce exposure to potential contact allergens and inadvertent emollient activity.

Meta-Analysis of 5% Imiquimod and 0.5% Podophyllotoxin in the Treatment of Condylomata Acuminata

Background: Genital warts are a common sexually transmitted disease caused by human papillomaviruses. Podophyllotoxin 0.5%, approved for patient self-administration, has been used most extensively in the treatment of genital warts. Imiquimod, a novel immune response modifier capable of inducing interferon-α and a variety of cytokines, has been examined as a potential treatment for genital warts. But 0.5% podophyllotoxin and 5% imiquimod have not been compared in any extensive and formal studies, although they are the common topical agents for genital warts. Objective: To evaluate the efficacy and safety of topical 5% imiquimod and 0.5% podophyllotoxin in the treatment of genital warts. Methods: We searched Medline (1966 to June 2005), Embase (1974 to June 2005) and the Cochrane Controlled Trials Register (issue 3, 2005). Randomized controlled trials of 5% imiquimod or 0.5% podophyllotoxin in the treatment of genital warts were collected. Two reviewers extracted the data and independently assessed the quality of the included medical literature. Then, meta-analysis was conducted. Results: Twelve studies including 3 placebo-controlled trials of imiquimod and 9 placebo-controlled trials of podophyllotoxin were included. The clinical cure rates of imiquimod and podophyllotoxin were 50.34 and 56.41%, respectively, without statistically significant differences between the two (p > 0.05). A combined analysis of the 3 studies on imiquimod showed a statistically significant difference to the placebo group [pooled odds ratio (OR) 11.65, 95% confidence interval (CI) 6.05–22.44], as did a combined analysis of the 9 studies on podophyllotoxin (pooled OR 16.70, 95% CI 7.06–39.48). The most common adverse events of imiquimod were erythema, erosion, excoriation, itching and burning; those of podophyllotoxin were burning, pain, erosion, itching and inflammation. Conclusion: Imiquimod and podophyllotoxin possess similar curative effects on condylomata acuminata but podophyllotoxin has more serious adverse effects.

Effect of topical nasal pharmaceuticals on sodium and chloride transport by human airway epithelia.

The human airway epithelium lines the respiratory tract from the nasal mucosa to the bronchioles. Electrolyte transport by these epithelia is crucial in maintaining the appropriate volume and salt composition of the airway surface fluid. When this epithelium becomes functionally impaired, the airways are more prone to respiratory infections. We studied the effect of six common topical agents that are commonly used to treat rhinorrhea and nasal inflammation on the transepithelial resistance, sodium, and chloride transport of primary cultures of human airway epithelia grown at the air-liquid interface. The pharmaceuticals fluticasone propionate, cromolyn sodium, ipratropium bromide, azelastine, oxymetazoline, and normal saline were used and the electrical function of the epithelia was studied in Ussing chambers. Azelastin and ipratropium bromide-treated epithelia were found to have a significant decrease in transepithelial resistance. Both normal saline and fluticasone propionate resulted in significant increases in amiloride-sensitive short circuit currents that reflect sodium transport. Finally, normal saline resulted in a significant increase in bumetanide-sensitive short circuit current that reflects chloride transport across the epithelia. The data presented may explain a mechanism by which some topical pharmaceuticals help reduce rhinorrhea, and may point to some unwanted side effects of some pharmaceuticals on the electrolyte transport of the airway epithelia. In summary, several of the common topical nasal agents alter the electrolyte transport of the nasal airway epithelia. The in vivo significance of these findings is to be determined.

Topical Agents in Burn and Wound Care

With any open wound infection may occur. Many factors such as age and general health status may increase the likelihood of infection, but the size and depth of the wound are critical factors in determining the chronicity of any wound. Infection greatly adds to the morbidity associated with open wounds. An infected wound not only heals more slowly, there is also the risk of systemic infection and even death. Infected wounds also scar more severely and are associated with more prolonged rehabilitation. Topical therapeutic agents have been shown to be effective in the management of open skin wounds. These agents may assist less complicated healing and decrease the conversion of a partial-thickness injury to a full-thickness injury, and thereby reduce wound-related morbidity. Common topical agents with suggestions for application are discussed in this review.

Laboratory and clinical procedures for assessing photosensitizing potential of topical agents

Contact photosensitization to certain plant materials, chemicals, and drugs has been known for a long time. Attention in recent years has been drawn to acceptable topical antibacterial agents employed in soaps and cosmetics as being involved in occasional but rare cases of photodermatitis. Evidence is presented documenting the safety of these agents, such as tribromsalan, trichlocarban, and hexachlorophene, for consumer use, based on a long history of successful mass marketing and the failure to elicit adverse reactions in repeat insult tests realistically conducted on animals and humans. Instances of photodermatitis implicating common topical agents are usually associated with patients possessing metabolic or genetic aberrations or exposed to undue environmental stress. Data are given of studies on guinea pigs and man which support this view.