Cantharidin Topical Solution 0.7%: First Approval.

Cantharidin (YCANTH™) is a proprietary drug-device combination product containing a formulation of cantharidin 0.7% topical solution (a vesicant naturally derived from blister beetles) delivered via a single-use applicator that has been developed by Verrica Pharmaceuticals Inc. for the treatment of molluscum contagiosum and is also being developed for the treatment of warts. In July 2023, YCANTH™ (cantharidin 0.7% topical solution) was approved for the topical treatment of molluscum contagiosum in adult and pediatric patients 2 years of age and older in the USA. This article summarizes the milestones in the development of cantharidin 0.7% topical solution leading to this first approval for the topical treatment of molluscum contagiosum in adult and pediatric patients 2 years of age and older.

N-Methyl-(2S,4R)-trans-4-hydroxy-L-proline isolated Sideroxylon obtusifolium attenuates TPA-induced irritant contact dermatitis in mice.

Dermatitis is defined as a set of inflammatory diseases that affect the skin, with varied causes. Among the different types of dermatitis, contact dermatitis is the most prevalent. Although the current therapy is often effective, it is associated with adverse effects and the possibility of drug tolerance. N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline is a L-proline amino acid derivative found in the leaves of Sideroxylon obtusifolium, a species traditionally used to treat inflammatory diseases. The aim of this study was to investigate the topical anti-inflammatory effect of N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline (NMP) in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced irritant contact dermatitis in mice. Topically administered NMP, at doses of 0.03 - 0.50 mg/ear, reduced TPA-induced ear edema and neutrophil migration, as evidenced by low tissue myeloperoxidase activity and verified by histological examination. In addition, NMP (0.06 mg/ear) reduced tissue levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, INF-γ and MCP-1) and of the anti-inflammatory cytokine IL-10, and reduced gene expression of TNF-α, IL-6 and IL-1ß increased by TPA. The data suggest that N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline acts as a topical anti-inflammatory agent that decreases the expression of inflammatory cytokines, making it useful for the treatment of skin inflammation. Further investigations are necessary for its development as a therapeutic agent.

Prognostic determinants in severe odontogenic space infections: a single-center retrospective analysis.

BACKGROUND: Odontogenic space infections are a common presentation in oral and maxillofacial surgery units worldwide. Multiple patient and treatment dependent variables may be used predict the outcomes of the disease process. This study was aimed at a retrospective evaluation of significant predictors of prognosis in terms of length of hospital stay and the need for re-exploration in cases of odontogenic space infections. METHODS: Patients who underwent incision and drainage of odontogenic space infections were identified from the hospital records of the Department of Oral and Maxillofacial Surgery, College of Dental Sciences, Davangere, Karnataka, India. The variables assessed included Diabetic status, pyrexia on admission, topical rubefacient agent application, hot fomentation, recent tooth extraction, trismus, dysphagia or dyspnea on presentation, white blood cell count, number of spaces involved, antibiotics used, organisms isolated, severity of the infection and the anesthesia technique used (local anesthesia [LA], conscious sedation or general anesthesia). RESULTS: The sample consisted of 259 patients (110 male, 159 female) with a mean age of 41±16.9 years. Space infections were preceded by tooth extractions in 53 (20%) cases, rubefacient balm application in 130 (40%) and hot fomentation in 58 (22%) cases. Trismus was noted in 140 patients with an average mouth opening of 21±10.3 mm. Dyspnea and dysphagia were noted in 55 (21%) and 96 (37%) patients each. Sixty-six patients were diabetic. The average length of hospital stay was 5.8±3 days and re-exploration was required in 75 (29%) patients. Significant predictors of hospital stay were severity (P<0.001), number of spaces affected (P<0.001), hot fomentation (P=0.04), trismus (P<0.001), dysphagia (P<0.001) and dyspnea (P<0.001). Predictors of re-exploration are an increased primary surgery under LA (P<0.001), white blood cell count (P<0.001), rubefacient balm application (P=0.045), dysphagia (P<0.001), dyspnea (P=0.018), and reduced mouth opening (P<0.001). No significant correlation between diabetes and length of hospital stay or the need for re-exploration were found in this study. CONCLUSIONS: Poorer outcomes can be predicted based on the severity of the infection, the number of spaces involved, an increased white blood cell count as well as clinical signs and symptoms like trismus, dysphagia and dyspnea. Hot fomentation and Rubefacient agent application were identified as significant determinants of poor prognosis in this study. The presence of these indicators warrants a more aggressive approach towards management of space infections.

Chemotherapy Extravasation: Incidence of and Factors Associated With Events in a Community Cancer Center.

BACKGROUND: The administration of chemotherapy is a high-risk and nurse-sensitive practice. One complication is extravasation. OBJECTIVES: The purpose of this study was to determine the incidence of and iatrogenic factors associated with extravasation in the ambulatory and inpatient settings of a community cancer center. METHODS: Events were reviewed by agent, route of administration, patient characteristics, and RNs administering the agent. A one-year, retrospective review of electronic health records and pharmacy and nursing reports was conducted. FINDINGS: The number of vesicants, irritants, and irritants with vesicant properties administered was 12,260 in the ambulatory setting and 612 on the inpatient unit, with 21 and 1 extravasation events, respectively. Incidence rates for both settings were 0.001%. The most common agent to extravasate was docetaxel, and all events occurred via peripheral route. The incidence of events was lower than the reported benchmark for National Cancer Institute-designated cancer centers.

Topical hydrogel containing Achyrocline satureioides oily extract (free and nanocapsule) has anti-inflammatory effects and thereby minimizes irritant contact dermatitis.

Inflammatory dermatoses are prevalent worldwide, with impacts on the quality of life of patients and their families. The aim of this study was to determine the anti-inflammatory effects of Achyrocline satureioides oily extracts and nanocapsules on the skin using a mouse model of irritant contact dermatitis induced by croton oil, and a skin inflammation model induced by ultraviolet B (UVB) radiation. The mice were treated with 15 mg/ear oily extract (HG-OLAS) or nanocapsules (HG-NCAS) of A. satureioides incorporated into Carbopol® 940 hydrogels. We found that HG-OLAS and HG-NCAS formulations reduced ear edema in croton oil-induced lesions with maximum inhibitions of 54±7% and 74±3%, respectively. HG-OLAS and HG-NCAS formulations decreased ear edema induced by UVB radiation (0.5 J/cm2), with maximum inhibitions of 68±6% and 76±2% compared to the UVB radiation group, respectively. HG-OLAS and HG-NCAS modulated myeloperoxidase (MPO) activity after croton oil induction. Furthermore, croton oil and UVB radiation for 6 and 24 h, respectively, stimulated polymorphonuclear cells infiltration. The topical treatments reduced inflammatory processes, as shown by histological analysis. Together, the data suggest that topical application of A. satureioides oily extracts and nanocapsules produced antiedematogenic and anti-inflammatory effects. They constitute a compelling alternative for treatment of skin injuries.

Recommendations for Management of Noncytotoxic Vesicant Extravasations.

To prepare clinicians to treat extravasation of noncytotoxic vesicants with antidotes and thermal compresses, a literature review was performed to identify noncytotoxic vesicants and to create evidence and consensus-based recommendations. The stage of injury and vesicant's mechanism of tissue injury dictate treatment. For a vasopressor extravasation, warm compresses and administration of a vasodilator are recommended. For osmolarity, pH, absorption refractory, and cytotoxic concentration-dependent vesicants, warm compresses and administration of hyaluronidase are recommended. Compared with potentially catastrophic costs of undertreatment, the cost of overtreatment is minimal.

Cantharidin is Superior to Trichloroacetic Acid for the Treatment of Non-mucosal Genital Warts: A Pilot Randomized Controlled Trial.

Condyloma Acuminatum is a sexually transmitted viral disease caused by the human papilloma virus (HPV). It is the most common viral sexually transmitted disease. In this randomized controlled trial, cantharidin was found to be more effective and better tolerated than trichloroacetic acid for the treatment of these lesions. Patients treated with cantharidin healed with less scarring than those treated with TCA (P<0.034), had less pain during treatment (P<0.01), and required fewer treatments to eradicate warts (P<0.01) when compared to Trichloroacetic acid.

Efficacy and Safety of Topical Cantharidin Treatment for Molluscum Contagiosum and Warts: A Systematic Review.

BACKGROUND AND OBJECTIVE: Topical cantharidin is routinely used for the treatment of molluscum contagiosum and warts. The objective of this systematic review is to assess the efficacy and safety of topical cantharidin treatment for molluscum contagiosum and warts. METHODS: We performed a systematic review of studies assessing topical cantharidin treatment of molluscum contagiosum or warts. We searched the databases of Cochrane, EMBASE, GREAT, LILACS, MEDLINE, and Scopus. Two authors performed the study selection and data extraction. RESULTS: Twenty studies (1958-2018) met inclusion/exclusion criteria. Twelve studies assessed warts, and eight studies assessed molluscum contagiosum. Overall, 1752 patients were included (range 0.3-62 years; specified in 15 studies). Clearance rates with topical cantharidin for molluscum contagiosum were variable (range 15.4-100%). Significant clearance of warts with maintenance of clearance was demonstrated with topical cantharidin alone. Topical cantharidin in combination with podophyllotoxin and salicylic acid demonstrated efficacy for plantar warts (pediatric and adult; clearance rate range 81-100%; four studies had 100% clearance), with the majority clearing after a single treatment. Satisfaction with cantharidin therapy was high, especially in molluscum contagiosum. Pain (7-85.7%), blistering (10-100%), and hyper-/hypopigmentation (1.8-53.3%) were the most commonly occurring adverse effects with cantharidin treatment. CONCLUSION: Topical cantharidin demonstrated clearance of warts, particularly in combination with podophyllotixin and salicylic acid, and modest benefit for pediatric molluscum contagiosum with good tolerability and safety.

Safety and efficacy of topical cantharidin for the treatment of pediatric molluscum contagiosum: a prospective, randomized, double-blind, placebo-controlled pilot trial.

Topical cantharidin is a commonly used treatment for molluscum contagiosum (MC). However, studies validating its safety and efficacy are limited. We conducted a 6-week, randomized, double-blind, placebo-controlled trial with subsequent open-label extension to assess the safety and effectiveness of cantharidin in treating pediatric MC. Ninety-four participants with MC were randomized to receive cantharidin or placebo, with or without occlusion. The primary outcome was complete lesion clearance. Secondary outcomes included post-treatment lesion count, adverse events, and side effects. No significant differences between the study arms, including baseline lesion count, were observed. The overall mean (SD) baseline lesion count was 22.2 (12.9). The number of participants achieving total clearance is as follows: 7/23 (30.4%) in the cantharidin only arm, 10/24 (41.7%) in the cantharidin with occlusion arm, 2/25 (8.0%) in the placebo with occlusion arm, and 3/22 (13.6%) in the placebo only arm. Post hoc analysis demonstrated that 17/47 (36.2%) participants in the combined cantharidin arms achieved clearance compared to 5/47 (10.6%) in the placebo arms (P = 0.0065). The mean (SD) lesion count change from baseline was -5.1 (12.2) in the placebo only arm; the mean change (SD) was -17.4 (12.8) in the cantharidin only arm (P = 0.0033) and -15.9 (11.6) in the cantharidin with occlusion arm (P = 0.0101). No serious adverse events or side effects were observed. Topical cantharidin was well-tolerated and associated with the resolution of MC.

[Rapidly growing squamous cell carcinoma after ingenol mebutate treatment]. / Carcinome épidermoïde de croissance rapide après traitement par mébutate d'ingénol.

INTRODUCTION: Ingenol mebutate is an actinic keratosis treatment, which has a dual action mechanism. It allows a rapid cellular death and a severe inflammation. OBSERVATION: We report the case of a 75 years old patient with a rapidly growing tumor 5 weeks after application of ingenol mebutate on typical actinic keratosis. Histological analysis after surgical excision showed an invasive squamous cell carcinoma (SCC); with aggressiveness signs: perineural infiltration and vascular permeation. DISCUSSION: Ingenol mebutate's common side effects are benign and regressive within 2 to 4 weeks. There are erythema, edema, crusts, and ulcerations/erosions. Squamous cell carcinoma development was rarely reported. We have tried to collect other cases in the literature and in pharmacovigilance centres: three similar cases were recently published in the literature, 21 cases were notified to the European Medicines Agency and we asked French pharmacovigilance centres and found 5 cases of SCC after ingenol mebutate application. The role of the molecule in SCC development is currently unknown. Induced inflammation could take part in the development of these tumors. We compare this case with other situations of inflammation, such skin graft donor site or surgical incision, complicated of rapidly growing SCC. Our case, literature's and pharmacovigilance's cases encourage us to follow ingenol mebutate's side effects. Careful follow-up and registration of such cases are important to gain further insight on this topic.

Acute intensive care unit management of mustard gas victims: the Turkish experience.

PURPOSE: Sulphur mustard (SM) is an highly toxic and vesicant chemical weapon that was used in various military conflicts several times in the history. The severity of ocular, dermal, and pulmonary symptoms that may appear following a characteristic asymptomatic period are depending on the SM concentration and exposure duration. The aim of this study is to present the clinical features and share the intensive care unit (ICU) experiences for the medical management of mustard gas victims. MATERIALS AND METHODS: Thirteen Free Syrian Army soldiers near Al-Bab region of North Syria were reportedly exposed to oily blackish smoke with garlic smell due to the explosion of a trapped bomb without causing any blast or thermal effect on 26th November 2016. None of them wore any chemical protective suits or gas masks during explosion. Since they observed skin lesions including bullous formation next day, they were admitted to the Turkish Field Hospital at the Turkish - Syrian border and then evacuated to the State Hospital of Gaziantep Province, Turkey for further management. Eight victims who were very close to point of explosion suffered burning eyes, sore throat, dry cough and dyspnoea after the chemical attack. RESULTS: On admission to hospital, all cases had conjunctivitis, hoarseness and bullae on various body areas. Blepharospasm and opacity were found in 8 patients and 5 of them had corneal erosions and periorbital oedema. Temporary loss of vision in 4 cases lasted for 24 h. Multiple fluid-filled blisters were observed especially on the scalp, neck, arms and hands, where direct skin exposure to the agent occurred. A definitive clinical care and infection prophylaxis measures along with the burn treatment and bronchodilators for respiratory effects were applied in ICU. Two patients received granulocyte-colony-stimulating factor due to the SM-mediated bone marrow suppression on the 16th day of exposure and one of them died because of necrotic bronchial pseudomembrane obstruction resulting in cardiopulmonary arrest. CONCLUSIONS: SM was first used during the First World War and it is still considered one of the major chemical weapons recently used by non-state actors in Syria and Iraq. In case of SM exposure, medical treatment of SM-induced lesions is symptomatic because no antidote or causal therapy does exist even though SM is very well known for over 100 years. However, clinical management in intensive care medicine of SM victims have improved since the 1980s, this study which is one of the largest recent SM-exposed case series since that time is important for the contribution to the clinical experience.

Measuring niacin-associated skin toxicity (NASTy) stigmata along with symptoms to aid development of niacin mimetics.

Though cardioprotective, niacin monotherapy is limited by unpleasant cutaneous symptoms mimicking dermatitis: niacin-associated skin toxicity (NASTy). Niacin is prototypical of several emerging drugs suffering off-target rubefacient properties whereby agonizing the GPR109A receptor on cutaneous immune cells provokes vasodilation, prompting skin plethora and rubor, as well as dolor, tumor, and calor, and systemically, heat loss, frigor, chills, and rigors. Typically, NASTy effects are described by subjective patient-reported perception, at best semi-quantitative and bias-prone. Conversely, objective, quantitative, and unbiased methods measuring NASTy stigmata would facilitate research to abolish them, motivating development of several objective methods. In early drug development, such methods might better predict clinical tolerability in larger clinical trials. Measuring cutaneous stigmata may also aid investigations of vasospastic, ischemic, and inflammatory skin conditions. We present methods to measure NASTy physical stigmata to facilitate research into novel niacin mimetics/analogs, detailing characteristics of each technique following niacin, and how NASTy stigmata relate to symptom perception. We gave niacin orally and measured rubor by colorimetry and white-light spectroscopy, plethora by laser Doppler flowmetry, and calor/frigor by thermometry. Surprisingly, each stigma's abruptness predicted symptom perception, whereas peak intensity did not. These methods are adaptable to study other rubefacient drugs or dermatologic and vascular disorders.

An innovative polysaccharide nanobased nail formulation for improvement of onychomycosis treatment.

Tioconazole-loaded nanocapsule suspensions and its coating with a cationic polymer were developed for nail drug delivery. The colloidal systems presented a nanometric size around 155nm for uncoated nanoparticles and 162nm for those with the cationic coating, with negative and positive zeta potential values, respectively. Both nanosuspensions showed drug content close to theoretical values (1mgmL-1), association efficiency close to 100% (HPLC) and were able to control tioconazol release. The developed formulations showed in vitro antifungal activity (agar diffusion method) against C. albicans. The cationic nanocapsules were considered bioadhesive, showed higher viscosity and were chosen to be incorporated into an ungueal formulation. Pullulan nanobased nail formulation showed adequate viscosity for nail application and drug content close to the theoretical values. It was equivalent to the commercial formulation Trosid® in preventing nail infection by T. rubrum in an in vitro onychomycosis model. The nanocapsule suspensions and Pullulan nanobased nail formulation showed lower irritant potential than the commercial formulation and than free drug in an in vitro evaluation. Pullulan nanobased nail formulation is promising for the treatment of onychomycosis.

Cantharidin in Dermatology.

Cantharidin is natural toxin produced by the blistering beetle. It has both vesicant and keratolytic features by inducing acanthloysis through targeting the desmosomal dense plaque, leading to detachment of the desmosomes from the tonofilaments. There are two available liquid preparations for dermatologic use, Canthacur (0.7% cantharidin) and Canthacur PS (1% cantharidin 30%/salicylic acid/2% podophylotoxin). The former preparation is indicated for the treatment of common warts, periungual warts, and molluscum contagiosum, while the more potent latter preparation is indicated only for plantar warts. Both preparations provide painless applications with outcomes similar to other treatment modalities for warts and molluscum contagiosum; however, neither is approved by the Food and Drug Administration (FDA). The lack of FDA approval could be related to its toxic effects following oral ingestion, which include ulceration of the gastrointestinal and genitourinary tracts, along with electrolyte and renal function disturbance in humans and animals. The mechanism of action, dermatologic indications, application techniques, and complications of cantharidin preparations are discussed.

Dietary Supplements and Alternative Therapies for Pain Management.

The use of complementary and alternative medicines (CAM) continues to grow in North America. The most recent National Health Interview Survey found that in 2012, 33.2 percent of respondents reported usage of some form of CAM in the previous 12 months. A survey of adult patients in a U.S. dental school clinic found that 24 percent reported the use of herbal supplements. Dietary supplements and alternative therapies are often used for pain management.

Modified dextrose prolotherapy for recurrent temporomandibular joint dislocation.

Conservative interventions with simple procedures and predictable benefits are expected by patients with recurrent dislocation of the temporomandibular joint (TMJ). We have introduced a modified technique of prolotherapy that comprises injection of lignocaine and 50% dextrose at a single site in the posterior periarticular tissues. We studied the effects in 45 younger patients (age range 17-59 years) with non-neurogenic recurrent dislocation of the TMJ, and confirmed the therapeutic effect after more than a year's follow-up. There were appreciable improvements in the number of episodes of dislocation and clicking after the injection. The overall success rate, defined as the absence of any further dislocation or subluxation for more than 6 months, was 41/45 (91%). Of the 41 rehabilitated patients, 26 (63%) required a single injection, 11 (27%) had 2 treatments, and 4 (10%) needed a third injection. All patients tolerated the injections well. The modified dextrose prolotherapy is simple, safe, and cost-effective for the treatment of recurrent dislocation of the TMJ.

Cantharidin combined with chemotherapy for Chinese patients with metastatic colorectal cancer.

BACKGROUND: This systematic analysis was conducted to evaluate the efficacy and safety of cantharidin combined with chemotherapy in treating Chinese patients with metastatic colorectal cancer. METHODS: Clinical studies evaluating the efficacy and safety of cantharidin combined with chemotherapy on response and safety for Chinese patients with colorectal cancer were identified using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. RESULTS: When cantharidin combined with chemotherapy, 4 clinical studies which included 155 patients with advanced colorectal cancer were considered eligible for inclusion. The systematic analysis suggested that, in all patients, pooled RR was 46.5% (72/155) in cantharidin combined regimens. Major adverse effects were neutropenia, leukopenia, fatigue, and anemia with cantharidin combined treatment; no treatment related deaths occurred. CONCLUSION: This systematic analysis suggests that cantharidin combined regimens are associated with high response rate and accepted toxicity in treating Chinese patients with metastatic colorectal cancer suggesting that randomized clinical trials are now warranted.