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Background: Myiasis by Cochliomyia hominivorax (Diptera: Calliphoridae) is a serious problem in animal health. Homeopathic Sulphur presents similarity with the clinical presentation verified in these cases and has already shown in vitro efficacy on the blowfly that causes this pathology. This article presents the report of a series of clinical cases of myiasis by C. hominivorax in sheep that underwent adjuvant treatment with homeopathic Sulphur and presents a theoretical-scientific discussion of biological events related to the clinical treatment of the condition., Patients: Seven naturally occurring myiases affecting sheep from an experimental farm were treated by an ointment impregnated with the homeopathic medicine Sulph 12cH, used as adjuvant after the manual removal of accessible larvae from the wound during wound cleaning. The animals were treated daily and evaluated clinically until complete healing of the lesions. Clinical information on the evolution of the inflammatory and scarring process was collected. Blood counts and bacteriological examinations were performed before and after topical homeopathic treatment., Results: The homeopathic ointment Sulph 12cH was able to inhibit the development of parasitic C. hominivorax larvae and promote tissue repair and healing in naturally occurring myiasis in the sheep of this study., Conclusion: The homeopathic medicine Sulphur , formulated as an ointment, may be a useful new and adjuvant therapeutic option for treating myiasis in animals., Competing Interests: G.P.B. and P.A.B. declare that they have one patent application pending on the intellectual property for the homeopathic ointment that is reported in this article. The registration of this patent is in co-authorship with the Federal University of Santa Catarina, in accordance with current legislation in Brazil., (Faculty of Homeopathy. This article is published by Thieme.)

Background: Crisaborole ointment, 2%, is a nonsteroidal topical phosphodiesterase 4 inhibitor approved for the treatment of mild-to-moderate atopic dermatitis., Objective: To evaluate the efficacy and safety of crisaborole in stasis dermatitis (SD)., Methods: In this randomized, double-blind, vehicle-controlled, decentralized phase 2a study (NCT04091087), 65 participants aged ≥45 years with SD without active ulceration received crisaborole or vehicle (1:1) twice-daily for 6 weeks. The primary end point was percentage change from baseline in total sign score at week 6 based on in-person assessment., Results: Crisaborole-treated participants had significantly reduced total sign score from baseline versus vehicle based on in-person (nondermatologist) assessment (-32.4% vs -18.1%, P = .0299) and central reader (dermatologists) assessment of photographs (-52.5% vs -10.3%, P = .0004). Efficacy according to success and improvement per Investigator's Global Assessment score and lesional percentage body surface area reached statistical significance based on central reader but not in-person assessments. Skin and subcutaneous tissue disorders were common all-causality treatment-emergent adverse events with crisaborole., Limitations: Small sample size and short treatment duration were key limitations. In-person assessment was not conducted by dermatologists., Conclusion: Crisaborole improved signs and symptoms of SD and was well tolerated. Central reader assessment represents a promising approach for siteless clinical research., Competing Interests: Conflicts of interest Dr Silverberg has received honoraria as a consultant and/or advisory board member for Pfizer Inc., AbbVie, Alamar, Aldena, Amgen, AObiome, Arcutis, Arena, Asana, ASLAN Pharmaceuticals, BioMX, Biosion, Bodewell, Boehringer Ingelheim, Bristol Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, Dermavant, Dermira, Dermtech, Eli Lilly and Company, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Menlo, Novartis, Optum, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Union, and UpToDate; served as a speaker for Pfizer Inc., AbbVie, Eli Lilly and Company, LEO Pharma, Regeneron, and Sanofi-Genzyme; and has received grants to his institution from Pfizer Inc., Galderma, and Incyte. Dr Kirsner was a paid consultant for Pfizer Inc for this trial. Dr Margolis has a current role as a consultant for Pfizer Inc., Bristol Myers Squibb, Insmed, Johnson & Johnson, and Palisave Bio. Author Myers, Author Annis, Dr Graham, Dr Zang, Author Vlahos, and Dr Sanders are employees and stockholders of Pfizer Inc. Dr Tharp has no conflicts of interest to declare., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

HY-072808 is a novel phosphodiesterase 4 inhibitor clinically used for topical atopic dermatitis treatment. Cytochrome P450 enzymes are involved in transforming it into major metabolite ZZ-24. An efficient UPLC-MS/MS method was established to detect HY-072808 and ZZ-24 in plasma and skin tissues of minipigs.One-step protein precipitation was performed with acetonitrile. Subsequently, elution was served with a methanol and water gradient containing 0.1% formic acid for 3.5 min. The plasma and skin tissue concentrations of HY-072808 and ZZ-24 showed good linearity from 0.200 to 200 ng/mL.The experimental minipigs exhibited low systemic exposure and bioavailability of 3.1-7.6% after transdermal application of 1-4% HY-072808 ointment. Multiple topical administrations over seven consecutive days showed a minor accumulation in systemic exposure, with accumulation factors of 2.3 and 4.0 for HY-072808 and ZZ-24, respectively.The distribution of HY-072808 ointment among different cortical layers in minipigs was studied for the first time. Following transdermal application of 2% HY-072808 ointment, the concentration in plasma and skin tissues in the order of epidermis > dermis > subcutaneous tissue ≈ subcutaneous muscle ≈ plasma; at 48 h after the administration, the epidermis and dermis still had a high concentration of the drug.

Background: Wound healing poses a challenging therapeutic scenario, requiring diverse clinical approaches., Objectives: This study aims to assess the wound-healing potential of Salix aegyptiaca's flower ointment compared to phenytoin, considering the active constituents of S. aegyptiaca and its traditional usage., Methods: Initially, the active components of S. aegyptiaca were isolated and identified through the GC-MS technique. Subsequently, for the experimental intervention, thirty-five rats were divided into five distinct groups: control (C), phenytoin (F), and three S. aegyptiaca ointment groups at different concentrations (5 % - S5, 25 % - S25, and 50 % - S50). Anesthesia was administered, and wounds were induced on the animals' necks following a standard procedure. These wounds were then treated for a duration of 21 days. Wound healing progress was quantified, and histopathological assessments were conducted using hematoxylin and eosin staining and Mason's trichrome staining., Results: The main active compounds of S. aegyptiaca, namely n-hexadecanoic acid and oleic acid, were identified via GC-MS analysis. Although the initial group weights did not show a significant difference (P = 0.271), a significant variation was observed in the final weights (P = 0.003). The S50 group exhibited a lower wound healing rate than the S25 group on the 7th and 14th days but surpassed it on the 21st day (C < F < S5≈S25

Objectives: Dyschromia is an understudied aspect of hypertrophic scar (HTS). The use of topical tacrolimus has successfully shown repigmentation in vitiligo patients through promotion of melanogenesis and melanocyte proliferation. It was hypothesized that HTSs treated with topical tacrolimus would have increased repigmentation compared to controls., Methodology: Full-thickness burns in red Duroc pigs were either treated with excision and meshed split-thickness skin grafting or excision and no grafting, and these wounds formed hypopigmented HTSs (n = 8). Half of the scars had 0.1% tacrolimus ointment applied to the scar twice a day for 21 days, while controls had no treatment. Further, each scar was bisected with half incurring fractional ablative CO 2 laser treatment before topical tacrolimus application to induce laser-assisted drug delivery (LADD). Pigmentation was evaluated using a noninvasive probe to measure melanin index (MI) at Days 0 (pretreatment), 7, 14, and 21. At each timepoint, punch biopsies were obtained and fixed in formalin or were incubated in dispase. The formalin-fixed biopsies were used to evaluate melanin levels by H&E staining. The biopsies incubated in dispase were used to obtain epidermal sheets. The ESs were then flash frozen and RNA was isolated from them and used in quantitative reverse transcription polymerase chain reaction for melanogenesis-related genes: Tyrosinase (TYR), TYR-related protein-1 (TYRP1), and dopachrome tautomerase (DCT). Analysis of variance test with Šídák's multiple comparisons test was used to compare groups., Results: Over time, within the grafted HTS and the NS group, there were no significant changes in MI, except for Week 3 in the -Tacro group. (+Tacro HTS= pre = 685.1 ± 42.0, w1 = 741.0 ± 54.16, w2 = 750.8 ± 59.0, w3 = 760.9 ± 49.8) (-Tacro HTS= pre = 700.4 ± 54.3, w1 = 722.3 ± 50.7, w2 = 739.6 ± 53.2, w3 = 722.7 ± 50.5). Over time, within the ungrafted HTS and the NS group, there were no significant changes in MI. (+Tacro HTS= pre = 644.9 ± 6.9, w1 = 661.6 ± 3.3, w2 = 650.3 ± 6.2, w3 = 636.3 ± 7.4) (-Tacro HTS= pre = 696.8 ± 8.0, w1 = 695.8 ± 12.3, w2 = 678.9 ± 14.0, w3 = 731.2 ± 50.3). LADD did not lead to any differential change in pigmentation compared to the non-LADD group. There was no evidence of increased melanogenesis within the tissue punch biopsies at any timepoint. There were no changes in TYR, TYRP1, or DCT gene expression after treatment., Conclusion: Hypopigmented HTSs treated with 0.1% tacrolimus ointment with or without LADD did not show significantly increased repigmentation. This study was limited by a shorter treatment interval than what is known to be required in vitiligo patients for repigmentation. The use of noninvasive, topical treatments to promote repigmentation are an appealing strategy to relieve morbidity associated with dyschromic burn scars and requires further investigation., (© 2024 Wiley Periodicals LLC.)

Importance: Atopic dermatitis (AD) and plaque psoriasis are inflammatory skin diseases with unmet need for effective topical treatments with few application site reactions., Objective: To assess the efficacy and safety of the topical phosphodiesterase 4 inhibitor PF-07038124 in patients with AD and plaque psoriasis., Design, Setting, and Participants: This phase 2a, randomized, double-blind clinical trial was conducted from December 21, 2020, to August 18, 2021, at 34 sites across 4 countries. Eligible patients (aged 18-70 years) had mild to moderate AD (covering 5%-20% body surface area) or plaque psoriasis (covering 5%-15% body surface area). Data were analyzed until December 15, 2021., Interventions: Patients were randomized (1:1) to PF-07038124, 0.01%, topical ointment or vehicle once daily for 6 weeks., Main Outcomes and Measures: The primary end point was the percent change from baseline (CFB) in the Eczema Area and Severity Index (EASI) total score among patients with AD and in the Psoriasis Area and Severity Index (PASI) score among patients with plaque psoriasis at week 6. Safety measures included treatment-emergent adverse events, including application site reactions., Results: Overall, 104 patients were randomized (mean [SD] age, 43.0 [15.4] years; 55 [52.9%] women; 4 [3.8%] Asian, 13 [12.5%] Black, and 87 [83.7%] White), including 70 with AD (41 women [58.6%]; mean [SD] ages, 41.4 [16.6] years in the PF-07038124 group and 36.1 [13.9] years in the vehicle group) and 34 with plaque psoriasis (20 men [58.8%]; mean [SD] ages, 51.8 [12.3] years in the PF-07038124 group and 51.2 [10.8] years in the vehicle group). Baseline characteristics were generally balanced. At week 6, the PF-07038124 groups showed significantly greater improvements compared with vehicle groups in EASI (least-squares mean CFB, -74.9% vs -35.5%; difference, -39.4% [90% CI, -58.8% to -20.1%]; P < .001) and PASI scores (CFB, -4.8 vs 0.1; difference, -4.9 [90% CI, -7.0 to -2.8]; P < .001). The number of patients with treatment-emergent adverse events was comparable between treatment groups in patients with AD (PF-07038124, 9 [25.0%]; vehicle, 9 [26.5%]) and plaque psoriasis (PF-07038124, 3 [17.6%]; vehicle, 6 [35.3%]). There were no application site reactions with PF-07038124 treatment., Conclusions and Relevance: Topical PF-07038124 was well tolerated and demonstrated superior efficacy compared with vehicle in patients with mild to moderate AD and plaque psoriasis., Trial Registration: ClinicalTrials.gov Identifier: NCT04664153.

Background and Objectives : Tirbanibulin 1% ointment is a novel synthetic anti-proliferative agent that inhibits tubulin polymerization. It is approved for treating actinic keratosis (AK) on the face and scalp in adults. It has demonstrated good efficacy, an adequate safety profile and excellent patient adherence in the phase 3 clinical trials, however data about its real-life efficacy and safety are lacking. Here we report the experience of the dermatology unit of the University Hospital of Messina. Materials and Methods : We performed a spontaneous open-label, prospective non-randomized study to assess the effectiveness and safety of tirbanibulin 1% ointment for the treatment of 228 AKs in 38 consecutive patients-28 males (73%) and 10 females (26%)-aged between 52 and 92 years (mean age: 72 ± 8.92 years). Results : Total clearance was recorded in 51% of lesions, while partial clearance was recorded in 73% of lesions. An excellent tolerability profile and high compliance rate were observed, with no treatment discontinuation due to the onset of adverse events. Conclusion: Our real-life experience confirms the effectiveness and safety of tirbanibulin ointment for the treatment of AKs.

Background: This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA)., Methods: This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded., Results: A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication., Conclusions: Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects., Trial Registration: ISRCTN34355813. Registered on 25/01/2021., (© 2024. The Author(s).)

Purpose: The purpose of this study was to assess the use of topical tacrolimus ointment in preventing rejection in high-risk corneal grafts, when added to the standard immunosuppressive regimen., Methods: We conducted an observational, retrospective study using clinical data of high-risk patients subjected to penetrating keratoplasty, who were treated with topical tacrolimus ointment 0.2 mg/g twice a day plus topical dexamethasone 0.1 mg/ml 6 id and compared it with a similar control group treated with topical dexamethasone 0.1 mg/ml 6 id alone. High-risk status was attributed to patients with previous ipsilateral corneal graft failure, two or more quadrants with corneal neovascularization or an infectious or inflammatory corneal disease., Results: We analysed 53 patients in the trial group versus 53 patients in the control group, with similar age, baseline diagnosis and risk factors, and median follow-up times of 30 and and 24 months, respectively. Survival analysis showed a higher graft survival rate at all follow-up periods for patients treated with topical tacrolimus ( p  < 0.01). No adverse reactions were reported., Discussion: This study shows that topical tacrolimus ointment increases the survival rate of the graft if added to the previous topical steroid regimen in high-risk patients., Conclusion: Topical tacrolimus is safe and effective in prolonging graft survival in high-risk patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The 31 st European Academy of Dermatology and Venereology (EADV) Congress took place between 7 th and 10 th of September 2022 in Milan, Italy., Objectives: We report presented clinical data on the efficacy/effectiveness, safety and tolerability of tirbanibulin 1% ointment that has recently been licensed for actinic keratosis (AK) of the face or scalp in adults., Methods: Summary of presentations given at the EADV Congress., Results: Prof. Pellacani presented two post hoc analyses from two phase-III trials with AK patients (NCT03285477 [N = 351] and NCT03285490 [N = 351]): A descriptive analysis of medical history, concomitant medications, and safety results confirming a favourable profile for tirbanibulin showing that number of baseline AK lesions was not correlated to severity of local skin reactions. The latter analysis showed that cases of tirbanibulin application site pain or pruritus were few, and most were found to be mild. Prof. Kunstfeld reported six real-life clinical cases in Austria showing good tirbanibulin effectiveness, safety and tolerability for the treatment of new or recurring AK lesions. Results demonstrated that after 2- to 4-month follow-up, tirbanibulin was well tolerated and effective in AK patients. Presentations by Dr. Patel confirmed good outcomes and tolerability of tirbanibulin in Olsen grade 1-2 AK (N = 12) and porokeratosis patients (N = 4) treated once daily for 5 consecutive days in the United Kingdom. Furthermore, real-world experience in solid organ transplant recipients (N = 2) demonstrated effectiveness of tirbanibulin in skin field cancerization treatment. A symposium sponsored by Almirall was conducted during the congress in which Dr. Hadshiew and Dr. Lear brought together their clinical experience in Germany and the United Kingdom respectively. Interesting clinical cases of 5 consecutive days of tirbanibulin treatment compared to other treatments were discussed with attendees, as well as current treatment needs of AK patients., Conclusions: This article provides an overview of presentations and symposium discussions, summarizing key phase-III results and real-life clinical experience with tirbanibulin shared by dermatologists across Europe., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Delgocitinib ointment, a topical Janus kinase inhibitor, is used as treatment of patients with atopic dermatitis (AD) aged ≥2 years in Japan. Although initiating appropriate and early treatment upon the onset of AD in childhood is important, the safety and efficacy of delgocitinib ointment in infants with AD have not been established., Methods: This phase 3 study was conducted from October 2020 to June 2022 (number JapicCTI-205412). Eligible Japanese infants with AD aged 6 to <24 months received 0.25% or 0.5% of delgocitinib ointment twice daily for 52 weeks in an open-label uncontrolled manner. Topical corticosteroids were allowed to apply for worsening AD during the treatment period at the investigators' discretion., Results: A total of 22 infants were enrolled. Adverse events (AEs) were reported in 21 (95.5%) infants and were mostly mild. No treatment-related AEs were reported. The Modified Eczema Area and Severity Index (mEASI) score continuously decreased until week 4, and the score reduction was maintained until week 52. The mean percent changes in the mEASI score from baseline were -73.5% at week 4, -81.7% at week 28, and -81.9% at week 52. Delgocitinib was not detected in the plasma of most infants (68.2%-95.2%)., Conclusions: Delgocitinib ointment is well tolerated and effective for up to 52 weeks when applied to Japanese infants with AD., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: Autonomic dysreflexia (AD) is a frequent complication of spinal cord injury (SCI), though current clinical practice patterns for medication management of this condition are unknown. Correspondingly, it is unclear if national differences in practice patterns exist., Objective: To determine trends in current pharmacologic management of AD throughout the Americas., Design: International survey of current physician practice patterns., Setting: Academic medical center., Participants: Sixty physicians managing patients with SCI and prescribing medications to manage AD., Interventions: Not applicable., Main Outcome Measures: Presence of a formal pharmacologic AD management protocol, first- and second-line medications, patient characteristics influencing pharmacologic management., Results: The majority of physicians (69%) had a formal AD management protocol for inpatient care, with nitroglycerin ointment (82%) being the most common first-line medication. Strong national differences existed regarding the use of nitroglycerin ointment, with 98% of U.S.-based physicians using this as first-line medication and 0% of physicians in Canada or Latin America using this due to recent lack of medication availability. Only 67% of physicians had a preferred second-line medication, with preferences split between hydralazine (48%) and nifedipine (28%). A systolic blood pressure threshold for pharmacologic management was used by 56% of physicians, wheres 26% considered neurological level of injury in decisions to use medications for AD. Heart rate was used by only 5% of physicians in their decision to manage AD with medications., Conclusions: As of 2023, U.S.-based physicians caring for individuals with SCI largely have formal inpatient protocols in place for medication management of AD, with nearly all relying on nitroglycerin ointment as their first-line medication. In areas outside of the United States where nitroglycerin ointment is unavailable, pharmacologic practice patterns significantly differ., (© 2023 American Academy of Physical Medicine and Rehabilitation.)

Prevalence of parasitic skin diseases, cutaneous leishmaniasis is very frequent in Pakistan, especially in Baluchistan where occurrence of phelbotomine sand flies (vector of protozoan parasite of genus Leishmania) is very common. This study was conducted to assess the antileishmaniasis activity of Intericutol plus ointment (2% and 3%) made with ethanolic extract of bark and leaves of Holoptelea integrifolia (Roxb.)Planch. The antileishmaniasis effect was observed by applying the ointments on the lesions of leishmaniasis patients. 150 patients were included in the study that had single and multiple painful wet and dry ulcerative lesions on the exposed area of the body. The patients were divided into two groups of 75 patients each, applying 2% and 3% ointment respectively for 28 days. Dose of 10gm/week was applied topically on wounds. Excellent antileishmaniasis effect was observed with significant quick healing properties in the patients receiving 3% Intericutol plus ointment as compare to 2% showing 89% and 81% cure (p=0.02) respectively. It can be concluded that ointment made from medicinal plant proved to be very effective in treating cutaneous Leishmaniasis.

Scabies is considered an external parasite notorious for its high prevalence causing severe and contagious skin lesions in humans and animals worldwide. This study has introduced a medicine to treat dogs infested with scabies (variants of Demodex, Sarcoptes, Psoroptes, Otodectes, etc.). The present study offers a no-side-effect herbal formulation to treat dogs infested with scabies. Unlike oral and injectable medicines, which take the form of an ointment and are topically applied on-site, this medicinal formulation can be easily used without concerns over its side effects or consumption dosages. This medicinal formulation requires no skin rinsing due to its herbal and high skin absorption properties, as recovery may take less than a month with a maximum of two times of application. To carry out the experiment, 25 sick dogs with various breeds and ages suspected of scabies were gathered. Following accurate morphological examinations of all the samples, a deep skin chip of the lesion site was provided, which was examined by a microscope. Then, 13 dogs (Mix, Terrier, Pug, Husky, Spitz) were infested with Demodex scabies and 12 dogs (Pittbull, Mix, Shih Tzu, Terrier, Boxer, Setter) with Sarcoptic scabies. The prepared product was topically administered at a constant 2% dosage to the bodies of all the samples. To prepare the ointment, 1 g of Borax (Na 2 B 4 O 7 ·10H 2 O) was first dissolved in 35 g deionized water and heated to 70°C. Then, 45 g of liquid paraffin (C n H 2n+2 ) was mixed with 1 g of Carvacrol (C 10 H 14 O) and 1 g of geranium (C 10 H 18 O) and stirred well to become a phase. Later, 17 g of the melted beeswax (C 15 H 31 COOC3 0 H 61 ) was added to the liquid paraffin compound. In the end, the aqueous phase was added to the oil phase, and the mixture process immediately began in one direction with a glass stirrer and continued until the product cooled down. Essential oils (EO) was obtained by steam distillation of fresh Thyme and Rose-Acented Geranium in a stainless steel distillation apparatus (alembic) for 3 h. The main components of the essential oils used in the formulation were performed using a Hewlett-Packard GC system interfaced with a mass spectrometer equipped with an HP5-MS capillary column (30 m, 0.32 mm, 0.25 µm film thicknesses). For GC-MS detection, electron ionization with ionization energy of 70 eV was used. To examine the presence of scabies, weekly skin sampling was performed, and the treatment continued until 30 days, when no skin chip of the scabies was noted. The findings revealed that the formulation developed no side effects and removed the daily use, as it could be administered once or twice a week. Also, complete recovery of scabies in all the breeds was found to be less than a month at most. This medicinal formulationcan be easily used without concerns over its side effects or consumption dosages. This study introduced a herbal formulation with effective herbal ingredients without any side effects to treat the sarcoptes and demodex parasites; unlike other chemical compounds, this medicinal formulation has no side effects, while some other formulations could develop side effects., Competing Interests: The authors declare that they have no conflict of interest. This study not supported by any grant money from a pharmaceutical company or for-profit organization.

Introduction: Efficient postoperative pain control is important after hemorrhoidal surgery. Although several locally applied medications have been used, current evidence regarding the optimal strategy is still conflicting. This network meta-analysis assessed analgesic efficacy and safety of the various topical medications in patients submitted to excisional procedures for hemorrhoids., Methods: The present study followed the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. The last systematic literature screening was performed at 15 June 2023. Comparisons were based on a random effects multivariate network meta-analysis under a Bayesian framework., Results: Overall, 26 RCTs and 2132 patients were included. Regarding postoperative pain, EMLA cream (surface under the cumulative ranking curve (SUCRA) 80.3%) had the highest ranking at 12-h endpoint, while aloe vera cream (SUCRA 82.36%) scored first at 24 h. Metronidazole ointments had the highest scores at 7 and 14 days postoperatively. Aloe vera had the best analgesic profile (24-h SUCRA 84.8% and 48-h SUCRA 80.6%) during defecation. Lidocaine (SUCRA 87.9%) displayed the best performance regarding overall morbidity rates., Conclusions: Due to the inconclusive results and several study limitations, further RCTs are required., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Emollients are recommended for children with eczema (atopic eczema/dermatitis). A lack of head-to-head comparisons of the effectiveness and acceptability of the different types of emollients has resulted in a 'trial and error' approach to prescribing., Objective: To compare the effectiveness and acceptability of four commonly used types of emollients for the treatment of childhood eczema., Design: Four group, parallel, individually randomised, superiority randomised clinical trials with a nested qualitative study, completed in 2021. A purposeful sample of parents/children was interviewed at ≈ 4 and ≈ 16 weeks., Setting: Primary care (78 general practitioner surgeries) in England., Participants: Children aged between 6 months and 12 years with eczema, of at least mild severity, and with no known sensitivity to the study emollients or their constituents., Interventions: Study emollients sharing the same characteristics in the four types of lotion, cream, gel or ointment, alongside usual care, and allocated using a web-based randomisation system. Participants were unmasked and the researcher assessing the Eczema Area Severity Index scores was masked., Main Outcome Measures: The primary outcome was Patient-Oriented Eczema Measure scores over 16 weeks. The secondary outcomes were Patient-Oriented Eczema Measure scores over 52 weeks, Eczema Area Severity Index score at 16 weeks, quality of life (Atopic Dermatitis Quality of Life, Child Health Utility-9 Dimensions and EuroQol-5 Dimensions, five-level version, scores), Dermatitis Family Impact and satisfaction levels at 16 weeks., Results: A total of 550 children were randomised to receive lotion (analysed for primary outcome 131/allocated 137), cream (137/140), gel (130/135) or ointment (126/138). At baseline, 86.0% of participants were white and 46.4% were female. The median (interquartile range) age was 4 (2-8) years and the median Patient-Oriented Eczema Measure score was 9.3 (SD 5.5). There was no evidence of a difference in mean Patient-Oriented Eczema Measure scores over the first 16 weeks between emollient types (global p = 0.765): adjusted Patient-Oriented Eczema Measure pairwise differences - cream-lotion 0.42 (95% confidence interval -0.48 to 1.32), gel-lotion 0.17 (95% confidence interval -0.75 to 1.09), ointment-lotion -0.01 (95% confidence interval -0.93 to 0.91), gel-cream -0.25 (95% confidence interval -1.15 to 0.65), ointment-cream -0.43 (95% confidence interval -1.34 to 0.48) and ointment-gel -0.18 (95% confidence interval -1.11 to 0.75). There was no effect modification by parent expectation, age, disease severity or the application of UK diagnostic criteria, and no differences between groups in any of the secondary outcomes. Median weekly use of allocated emollient, non-allocated emollient and topical corticosteroids was similar across groups. Overall satisfaction was highest for lotions and gels. There was no difference in the number of adverse reactions and there were no significant adverse events. In the nested qualitative study ( n = 44 parents, n = 25 children), opinions about the acceptability of creams and ointments varied most, yet problems with all types were reported. Effectiveness may be favoured over acceptability. Parents preferred pumps and bottles over tubs and reported improved knowledge about, and use of, emollients as a result of taking part in the trial., Limitations: Parents and clinicians were unmasked to allocation. The findings may not apply to non-study emollients of the same type or to children from more ethnically diverse backgrounds., Conclusions: The four emollient types were equally effective. Satisfaction with the same emollient types varies, with different parents/children favouring different ones. Users need to be able to choose from a range of emollient types to find one that suits them., Future Work: Future work could focus on how best to support shared decision-making of different emollient types and evaluations of other paraffin-based, non-paraffin and 'novel' emollients., Trial Registration: This trial is registered as ISRCTN84540529 and EudraCT 2017-000688-34., Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (HTA 15/130/07) and will be published in full in Health Technology Assessment ; Vol. 27, No. 19. See the NIHR Journals Library website for further project information.

What Is This Summary About?: Atopic dermatitis (AD, also called atopic eczema) is a skin disease that that can affect a person for a long time and causes red or flaky skin that can be itchy and uncomfortable. Healthcare providers can prescribe medicated creams and ointments to reduce the visible signs and symptoms of AD, but these treatments are not always enough to keep it under control. A new medicine called abrocitinib is taken every day as a tablet. Abrocitinib works by slowing a part of the body's defense mechanism, called immune response, that is not functioning properly in AD. The clinical study described in this plain language summary, called JADE DARE, investigated how well and how safely 26 weeks of treatment with abrocitinib worked in adults with AD compared to an injected medicine, called dupilumab, that is also approved for AD., What Were the Results?: The study showed that abrocitinib was more effective than dupilumab in providing itch relief after 2 weeks. In addition, people who were taking abrocitinib for 4 and 16 weeks experienced greater improvement in the visible skin signs of AD than people who were taking dupilumab. The number of people who had health complaints while taking abrocitinib was similar to the number of people who had health complaints while taking dupilumab. Most of these complaints were minor., What Do the Results Mean?: Abrocitinib was more effective than dupilumab in quickly improving the signs and symptoms of moderate or severe AD in people who did not show improvement with prescribed medications like creams or ointments. Clinical Trial Registration: NCT04345367 (ClinicalTrials.gov).

Aim: Chronic anal fissure (CAF) is an extremely frequent finding in clinical practice. Several topical agents have been proposed for its treatment with the common goal of increasing anodermal blood flow to promote healing. The aim of this study was to compare the efficacy and safety of a Propionibacterium extract gel (PeG) and 0.4% glyceryl trinitrate ointment (GTN) in patients with CAF., Method: Patients were randomly allocated to a PeG or GTN group and medication was administered every 12 h for 40 days. The primary outcome was the success rate, as measured by a decrease in the REALISE scoring system for anal fissure at 10, 20 and 40 days after initiating either treatment. The secondary outcomes recorded at the same time points were healing rate, visual analogue scales for itching and burning, rate of complications and adverse events, patient quality of life and satisfaction, and cost analysis., Results: A total of 120 patients were enrolled, and 96 patients (PeG, n = 53; GTN, n = 43) completed the primary outcomes. A significant decrease over time in the REALISE score was observed in both groups. Adverse events occurred more frequently in the GTN group than in the PeG group, peaking at visit 1 [37 (63.8%) vs. 2 (3.4%), respectively], with headache being the most prevalent. The between-treatment cumulative average costs per patient were significantly higher for GTN than that for PeG at each follow-up visit. There were no other significant differences between the two groups for any of the other outcomes., Conclusion: While there was no difference in healing rates between the two treatments, PeG was more cost-effective and associated with fewer adverse events., (© 2023 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Radiodermatitis in breast cancer patients varies from mild irritation to life-threatening lesions. Several studies suggest a role for topical corticosteroid ointments in the treatment of radiodermatitis. Yet, to avoid the adverse effects of corticosteroids, many authors recommend the use of topical herbal products instead. The therapeutic role of herbal treatments has yet to be fully understood. This systematic review evaluates the role of topical or oral herbal medicines in radiodermatitis prevention and treatment. A systematic search of four databases (Embase, PubMed, Web of Science, and Scopus) was performed without language and time restrictions from their inception until April 2023. The bibliographies of potential articles were also searched manually. Studies evaluated and compared the effects of herbal preparations with the control group, on dermatitis induced by radiotherapy for breast cancer. The Cochrane risk of bias tool was used to assess the included studies. Thirty-five studies were included in the systematic review. Studies which used herbal drugs including topical and oral formulations were evaluated. Herbal monotherapy and combination therapy were reported, and their effects on radiodermatitis were explained in the systematic review. In conclusion, henna ointments, silymarin gel, and Juango cream were reported to reduce the severity of radiodermatitis. These agents should be considered for radiodermatitis prophylaxis and treatment. The data on aloe gel and calendula ointment were conflicting. Further randomized controlled trials of herbal medications and new herbal formulations are required to determine their effects on breast cancer radiodermatitis., (© 2023 John Wiley & Sons Ltd.)

Background: Safe and effective long-term topical treatments for atopic dermatitis (AD) remain limited., Objective: In this phase 2a, single-center, intrapatient, and vehicle-controlled study, we examine the mechanism of action of crisaborole 2% ointment, a topical nonsteroidal PDE4 (phosphodiesterase-4) inhibitor, in a proteomic analysis of 40 adults with mild to moderate AD and 20 healthy subjects., Methods: Within the AD cohort, 2 target lesions were randomized in an intrapatient (1:1) manner to double-blind crisaborole/vehicle applied twice daily for 14 days. Punch biopsy specimens were collected for biomarker analysis at baseline from all participants, then from AD patients only at day 8 (optional) and day 15., Results: Compared to the vehicle, crisaborole significantly reversed dysregulation of the overall lesional proteome and of key markers and pathways (eg, Th2, Th17/Th22, and T-cell activation) associated with AD pathogenesis toward both nonlesional and normal skin. Significant clinical correlations were observed with markers associated with nociception and Th2, Th17, and neutrophilic activation., Limitations: Study limitations include predominance of white patients in the cohort, relatively short treatment time, and regimented administration of crisaborole., Conclusion: Our results demonstrate crisaborole-induced normalization of the AD proteome toward a nonlesional molecular phenotype and further support topical PDE4 inhibition in the treatment of mild to moderate AD., Competing Interests: Conflicts of interest Dr Bissonnette is an Advisory Board Member, Consultant, Speaker and/or Investigator for and received honoraria and/or grants from AbbVie, Almirall, Amgen, AnaptysBio, Arcutis, Bausch Health, Boehringer-Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly, Escalier, Janssen, Kyowa Kirin, LEO Pharma, Nimbus, Pfizer, Regeneron, Sienna, and UCB. He is also an employee and shareholder of Innovaderm Research. Dr Guttman-Yassky has served as a consultant for AbbVie, Amgen, Allergan, Asana Bioscience, Celgene, Concert, Dermira, DS Biopharma, Escalier, Galderma, Glenmark, Kyowa Kirin, LEO Pharmaceuticals, Lilly, Mitsubishi Tanabe, Novartis, Pfizer, Regeneron, Sanofi, and Union Therapeutics; a member of advisory boards of Allergan, Asana Bioscience, Celgene, DBV, Dermavant, Dermira, Escalier, Galderma, Glenmark, Kyowa Kirin, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron, and Sanofi; and a recipient of research grants from AbbVie, AnaptysBio, AntibioTx, Asana Bioscience, Boehringer-Ingelheim, Celgene, DBV, Dermavant, DS Biopharma, Galderma, Glenmark, Innovaderm, Janssen Biotech, Kiniska Pharma, LEO Pharmaceuticals, Lilly, Medimmune, Sienna Biopharmaceuticals, Novan, Novartis, Ralexar, Regeneron, Pfizer, UCB, and Union Therapeutics. Dr Pavel is an employee of the Icahn School of Medicine at Mount Sinai and conducts research sponsored by Pfizer. Dr Werth is a full-time employee of and shareholder in Pfizer, Inc. Kim, Duca, Cheng, Carroll, Facheris, Estrada, Cha, Nocka, and Zhang have no conflicts of interest to declare., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Multikinase inhibitors (MKIs) treatment has been proven as a powerful strategy in cancer therapy. However, it is greatly hampered by its common adverse effect known as hand-foot skin reaction (HFSR), especially in patients with moderate-to-severe HFSR., Objective: To investigate the clinical characteristics, histopathological features, treatment response, and bio-indicators of HFSR., Methods: We retrospectively reviewed the medical records of 102 patients with moderate-to-severe HFSR resulting from MKIs therapy., Results: The median time to development of moderate-to-severe HFSR was 18 days, which would be significantly affected by the type of MKIs and the history of HFSR. Notably, we found that HFSR was classified into three consecutive stages: erythematous lesion, yellow hyperkeratotic lesion with surrounding erythema, and hyperkeratotic lesion. Inflammation was observed in the first two stages of HFSR, but disappeared in the third stage; in contrast, the hyperkeratosis gradually became thicker from stage one to stage three. Moreover, topical medications were demonstrated as an effective therapy for HFSR, among which, the topical steroids and urea ointment treatment response rate was 37.14%, the Shouzu Ning Decoction (SND) treatment response rate was 65%, and the SND in combination with urea ointment treatment response rate was 75%, meanwhile, systemic therapies did not improve the therapeutic efficacy of topical medications alone. In addition, the serum levels of HMGB1 were found to be a potential indicator for tracking the healing process as well as predicting the prognosis of HFSR., Conclusion: This study revealed the potential factors affecting the development of HFSR, evaluated the therapeutic response towards different strategies for treating HFSR, and identified a potential prognostic indicator of HFSR., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Much has changed since Credé reported that silver nitrate decreases the incidence of ophthalmia neonatorum. Prenatal screening and treatment of pregnant women for Neisseria gonorrhoeae became standard in the 1950s and for Chlamydia trachomatis in 1993. Neonatal gonococcal and chlamydial conjunctivitis are consequently uncommon today. Currently, only 0.5% erythromycin ophthalmic ointment is available in the United States (U.S.) for neonatal ocular prophylaxis, which is ineffective against C. trachomatis ., Areas Covered: This article addresses the altered epidemiology of ophthalmia neonatorum in the U.S. since prophylactic practices began, the lack of data supporting ophthalmic erythromycin for prevention of neonatal gonococcal and chlamydial conjunctivitis, and the impact of prenatal screening and treatment of pregnant women for N. gonorrhoeae and C. trachomatis on conjunctivitis incidence. The authors discuss why erythromycin ophthalmic ointment is likely ineffective against gonococcal ophthalmia, including the development of macrolide resistance. Physiologic limitations and pharmacokinetic properties are considered with respect to ophthalmic erythromycin for the prevention of gonococcal and chlamydial conjunctivitis., Expert Opinion: Administration of erythromycin ophthalmic ointment for the prevention of neonatal conjunctivitis is not literature-supported. Prenatal screening and treatment of pregnant women is the most effective way to prevent ophthalmia neonatorum. National mandates for prophylaxis should be withdrawn.

The discovery of new effective and safe antimalarial drugs is mandatory. In this report, we formulate and evaluate transdermal (td) 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) using the Plasmodium berghei rodent malaria parasite in vivo model. The selected solvent for the ointment type of td N-89 was polyethylene glycol (PEG) [PEG400:PEG 4000 = 8:1 (v/w)]. We tested different application areas of 4, 6, and 8 cm 2 on the shaved backs of mice. Pharmacokinetic (PK) analysis of N-89 parameters after a single 4 cm 2 transdermal application revealed that the T max was 2 h, the T 1/2 was 1.9 h, and the AUC was 1951.1 ng . h/mL. More than 10 ng/mL of plasma concentration was maintained for 12 h. The ED 50 values for the 4, 6, and 8 cm 2 application areas in a 4-day suppressive test were 18.9, 25.1, and 26.8 mg/kg, respectively. We additionally tested the cure effect of td N-89 in mice at a dose of 60 mg/kg, twice daily for 4 days at 0.2% parasitemia. Parasites disappeared following day 7 post-treatment in all td N-89 treated groups. Mice were cured without any parasite recurrence or dermal irritation. In conclusion, this study determined for the first time the PK parameters and effect of a new ointment type of td N-89. This suggests that transdermal treatment with N-89 is an effective and safe alternative route for the treatment of malaria, especially in children., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to examine the in vivo wound healing potential of Salvia huberi Hedge (endemic to Turkey) on excision and incision wound models in diabetic rats. Method: Male Wistar albino rats, 3-4 months old and weighing 180-240g were used. The animals were randomly divided into five groups including Control, Vehicle and Fito reference, and two different concentrations (0.5% and 1% weight/weight (w/w)) of ethanol extract of Salvia huberi were investigated in both wound models on streptozocin-induced diabetic rats using macroscopic, biomechanical, biochemical, histopathological, genotoxic and gene expression methods over both seven and 14 days. Fito cream (Tripharma Drug Industry and Trade Inc., Turkey) was used as the reference drug. Results: A total of 60 rats were used in this study. Salvia huberi ointments at 0.5% and 1% (w/w) concentrations and Fito cream showed 99.3%, 99.4% and 99.1% contraction for excision wounds, and 99.9%, 97.0% and 99% contraction for incision wounds, respectively. In Salvia huberi ointments and Fito cream groups, re-epithelialisation increased dramatically by both day 7 and day 14 (p<0.05). By day 14, low hydroxyproline and malondialdehyde (MDA) levels, and high glutathione (GSH) levels were observed in the Salvia huberi ointment groups. After two application periods, damaged cell percent and genetic damage index values and micronucleus frequency of Salvia huberi ointment treatment groups were lower than Control and Vehicle groups (p<0.001). A growth factor expression reached a high level by day 7 in the Control group; in Salvia huberi -treated groups it was decreased. Conclusion: The study showed that application of Salvia huberi ointments ameliorated the healing process in diabetic rats with excisional and incisional wounds and may serve as a potent healing agent.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome causing hamartomatous growths in multiple organs. Facial angiofibromas occur in up to 80% of patients and can be highly disfiguring. Treatment for these lesions is challenging. Recently, topical rapamycin has been proposed as an effective option to treat angiofibromas but a commercially available compound has not yet been developed in Europe. We conducted a retrospective review with the aim to update the current data on the use of topical rapamycin in the treatment of angiofibromas in TSC, focusing on the optimal concentration and trying to establish which vehicle should be preferred. Thirty-nine reports describing the use of topical rapamycin in the treatment of angiofibromas in TSC were considered, involving a total of 483 patients. An improvement of the lesions has been shown in over 90% of subjects, particularly if the treatment was started at early stages. Several different formulations (ointment, gel, solution and cream) with a wide range of concentrations (0.003%-1%) were proposed, of which a pharmacological analysis has also been performed. Topical rapamycin can be considered an effective and safe option for the treatment and the prevention of facial angiofibromas in younger patients, but the best formulation has yet to be established. Our review demonstrates that ointment and gel should be preferred, but it is not clear which concentration is optimal. However, according to this study, the 0.1% concentration represents the first choice. Long-term and comparative studies between topical rapamycin formulations are required in order to establish which treatment has a better outcome and lower recurrence rate., (© 2022 European Academy of Dermatology and Venereology.)

Alopecia areata/AA is an autoimmune cause of nonscarring hair loss. The pathogenesis of AA involves many immune axes, including Th1/Th2 pathways. Delgocitinib is a pan-Janus kinase/JAK inhibitor that broadly blocks pro-inflammatory cytokines and has been effective in other inflammatory skin conditions. Recent human studies/reports have shown that use of some systemic JAK inhibitors led to hair regrowth, suggesting this medication class as a potential therapy for AA. However, topical treatment is desirable due to potential systemic side effects. To assess the efficacy and safety of topical delgocitinib in AA, we conducted a double-blind, randomized, vehicle-controlled clinical trial in 31 moderate-to-severe AA patients that were randomized 2:1 to receive delgocitinib ointment 30 mg/g (n = 20) or ointment vehicle (n = 11) for 12 weeks. The primary endpoint was change in severity of Alopecia Tool/SALT score from baseline to week 12. The secondary endpoint included safety profile by reported adverse events. Twenty-three subjects completed the trial, with eight discontinuing mostly due to voluntary withdrawal. Ten patients receiving delgocitinib ointment and three patients receiving vehicle showed SALT score improvements after 12 weeks, but the mean percent SALT improvement at week 12 compared to baseline between the two arms was not significant (p = 0.92). Our study suggests that delgocitinib ointment is not effective in moderate-to-severe AA, likely due to its inability to penetrate sufficiently deeply into the dermis of the scalp, but larger studies are necessary to assess whether a different formulation of topical JAK inhibitors may be suitable to treat mild or more localized forms of AA., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The aim of this study was to evaluate the clinical efficacy of crisaborole ointment in the treatment of vulvar leukoplakia., Methods: A prospective, randomized controlled clinical trial was conducted, and a total of 100 patients with vulvar leukoplakia were divided into the observation group (n=50) treated with crisaborole ointment and the control group (n=50) treated with vitamin E. The symptom improvement and vulvar leukoplakia score after 2 weeks of treatment were analyzed, and the clinical efficacy of vulvar leukoplakia was evaluated by referring to the Guidelines for Clinical Research of New Drugs of Traditional Chinese Medicine (2018 Edition)., Results: After 2 weeks of treatment, the overall score of lesions in the observation group decreased, and the total treatment efficiency of patients in the observation group was 92% (46/50), which was significantly higher than that of 52% (26/50) in the control group P<0.05)., Conclusion: Crisaborole ointment can effectively treat vulvar leukoplakia, improving the symptoms and pathological changes of the vulvar skin.

Radiodermatitis is an inevitable side effect of radiotherapy in cancer treatment and there is currently no consensus on effective drugs for treating the condition. Vitamin B 12 is known to be effective for repairing and regenerating damaged skin. However, there are few studies on the use of Vitamin B 12 for treating radiodermatitis. This study explored the therapeutic efficacy and mechanism of action of Vitamin B 12 ointment on radiodermatitis. A porcine model of grade IV radiodermatitis was established. The ointment was applied for 12 weeks after which histological staining, transmission electron microscopy, RT-qPCR, western blotting, and gene sequencing were performed for the evaluation of specific indicators in skin samples. After 12 weeks of observation, the Vitamin B 12 treatment was found to have significantly alleviated radiodermatitis. The treatment also significantly reduced the expression levels of NF-κB, COX-2, IL-6, and TGF-β in the skin samples. The pathways involved in the effects of the treatment were identified by analysing gene expression. In conclusion, Vitamin B 12 ointment was found to be highly effective for treating radiodermatitis, with strong anti-radiation, anti-inflammatory, and anti-fibrosis effects. It is thus a promising drug candidate for the treatment of severe radiodermatitis., (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Background: Tacrolimus ointment is a recently developed topical immunomodulator that has been approved for use in patients with vitiligo older than 2 years. Concern regarding potential systemic toxic effects has limited treatment options for children younger than 2 years. We wanted to determine whether topical tacrolimus therapy is safe and effective in patients with vitiligo younger than 2 years., Methods: The present 6-month clinical trial was conducted to evaluate the efficacy and safety of 0.03% tacrolimus in the treatment of vitiligo in children under 2 years of age. Meanwhile, serum and urine samples were collected, and liquid chromatography-mass spectrometry was performed to generate the serum and urine metabolic profile data of patients and healthy controls., Results: The overall response rate at the sixth month, which was defined by the degree of re-pigmentation, was 100%. As revealed by blood monitoring and metabolite detection 6 months later, there was no difference between the treatment group and the control group. There is no evidence that long-term topical application of 0.03% tacrolimus ointment will cause metabolite or other physical changes in the body., Conclusions: Tacrolimus ointment appears to be effective and safe in the treatment of vitiligo in children younger than 2 year., Trial Registration: http://www.chictr.org.cn identifier: ChiCTR 2100045920., Impact: We first reported the efficacy and safety of topical application of 0.03% tacrolimus ointment in infants with vitiligo characterized by the metabolites. There is no evidence that long-term topical application of 0.03% tacrolimus ointment will cause metabolite or other physical changes in the body. This study provide evidence for the TCI treatment of infants with vitiligo., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Purpose: To evaluate the clinical efficacy and safety of different analgesic interventions in the treatment of pain after open hemorrhoidectomy by systematic review and network meta-analysis., Methods: Randomized controlled trials that met the inclusion criteria in PubMed, Cochrane Library, Embase, Web of Science, Scopus, CNKI, WANFANG DATA, and VIP were searched from the date of database construction to June 28, 2022., Results: Among the 13 randomized controlled trials (RCTs), 731 patients were included in the network meta-analysis. Most interventions are more effective than placebo in relieving postoperative pain. 24 h postoperative Visual Analogue Scale (VAS): glyceryl trinitrate (GTN) (mean difference (MD) - 4.20, 95% CI - 5.35, - 3.05), diltiazem (MD - 1.97, 95% CI - 2.44, - 1.51), botulinum toxin (BT) (MD - 1.50, 95% CI - 2.25, - 0.75), sucralfate (MD - 1.01, 95% CI - 1.53, - 0.49), and electroacupuncture (EA) (MD - 0.45, 95% CI - 0.87, - 0.04). 48 h postoperative VAS: diltiazem (MD - 2.45, 95% CI - 2.74, - 2.15), BT (MD - 2.18, 95% CI - 2.52, - 1.84), and sucralfate (MD - 1.41, 95% CI - 1.85, - 0.97). 7 d postoperative VAS: diltiazem (MD - 2.49, 95% CI - 3.20, - 1.78) and sucralfate (MD - 1.42, 95% CI - 2.00, - 0.85). The first postoperative defecation VAS: EA (MD - 0.70, 95% CI - 0.95, - 0.46). There are few data on intervention safety, and additional high-quality RCTs are expected to study this topic in the future., Conclusion: Diltiazem ointment may be the most effective medication for pain relief following open hemorrhoidectomy, and it can dramatically reduce pain within one week of surgery. The second and third recommended medications are BT and sucralfate ointment. GTN has a significant advantage in alleviating pain 24 h after open hemorrhoidectomy, but whether it causes headache is debatable; thus, it should be used with caution. EA's analgesic efficacy is still unknown. There was limited evidence on the safety of the intervention in this study, and it was simply presented statistically., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Transdermal scopolamine applied to the postauricular area is used to treat drooling. We investigated the duration of action of scopolamine ointment and the effect of the application site on drug efficacy and concentration in the salivary glands of rats. Scopolamine ointment was applied to the skin over the salivary glands (SSG) and back (SB). Saliva volume was measured after intraperitoneal administration of pilocarpine. Blood and salivary glands were collected after scopolamine ointment application, and scopolamine concentrations in the plasma and salivary glands were measured. Saliva volume after application in the SSG group was significantly lower at all time points than in the non-treated group, and the change in saliva volume in the SSG group was greater than that in the SB group at all time points. This suggests that applying scopolamine ointment to the SSG strongly suppresses salivary secretion. Scopolamine concentration in the salivary glands of the SSG group was significantly higher at 9 h. The change in the efficacy of scopolamine ointment depending on the application site was due to the difference in transfer to the salivary glands. Transdermal administration of scopolamine to the skin over the salivary glands may have high efficiency in treating drooling.

Wound-healing deficits of the skin, one of the most common complications in patients with diabetes, delay wound healing, significantly reducing the patient's QOL. Therefore, the topical treatment of wound areas with drug-containing ointments and dressings is important. In this study, we investigated the effect of various ointment bases on skin wound healing in normal and streptozotocin-induced diabetic rats (STZ rats). Three ointment bases were used: white ointment (oil-based), absorbent cream (emulsion-based, w/o), and macrogol ointment (water-based). Skin wound healing in STZ rats was delayed compared with that in normal rats. Each of the three ointment bases was applied to the skin wound area in normal rats, and there was no difference in the therapeutic effect. The therapeutic effect of both white ointment and absorbent cream was higher in the STZ rats group than that in the non-treated group, and delayed wound healing was observed in STZ rats treated with macrogol ointment. In conclusion, skin wound healing in STZ rats is affected by the properties of the ointment base, and it is important to use an ointment base that controls the drying of the wound area in STZ rats. These findings provide information for the selection of ointment bases useful for application to skin wounds in patients with diabetes.

Eucalyptol is a major volatile constituent among well-known wound healing medicinal plants. The current study evaluated eucalyptol wound healing activity in the rat's third-degree skin-burn model. The parameters, i.e., skin-healing, oxidative/antioxidant markers, pro-/anti-inflammatory markers, were evaluated after 1- and 2-weeks of treatment regimens with 5% eucalyptol ointment. Eucalyptol-loaded ointment base of 5% w/w strength was formulated using fusion method and physically evaluated for consistency, stability, and homogeneity. A 25-rats were divided randomly into intact, negative control (untreated), silver sulfadiazine (SS, positive control), 1-week, and 2-weeks treated eucalyptol groups. Using an aluminum cylinder (120℃, 10 second duration), 3 rd -degree skin burns were created on the rat's dorsum. Skin biopsies were collected at the end of the experiment for biochemical and histological investigations. Compared to the negative group; time-dependent wound size reduction and decreased edema were observed in eucalyptol-treated animals. Histopathological examinations demonstrated epidermis integrity, decreased neutrophil, and increased capillaries number in the 2-weeks and SS groups, compared to the negative and 1-week treated eucalyptol groups. Compared to the untreated animals, the 1- and 2-weeks eucalyptol treated groups' demonstrated significantly increased antioxidant superoxide dismutase (SOD, p=0.002 and p=0.003, respectively) and reduced lipid peroxide (LP, p=0.005 and p=0.0006, respectively). However, a significant increment of catalase (CAT, p=0.0009) was found only in the 2-weeks of eucalyptol group at a level of 2.42 ± 0.39 ng/g compared to 1.14 ± 0.04 ng/g in the untreated animals. Also, significant reductions in the cytokines, IL-1b, IL-6, and TNF-α (p < 0.05); and increase in the pro-angiogenic marker, IL-10, were detected in the 2-weeks (p=0.001) and SS (p=0.002) treated animals compared to the negative and 1-week eucalyptol treated groups. The study concluded that eucalyptol induced significant duration-based wound healing properties attributed to its antioxidant and anti-inflammatory effects.

Background: Hemorrhoidal disease (HD) is one of the most common anorectal benign disorder affecting millions of people around the world. Grade I-II HD are generally treated with a conservative approach with topical products such as creams and ointments considered a safe and effective option to treat mild symptoms. The aim of the present study was to assess the safety and efficacy of a topical medical device (Lenoid ™ ; International Health Science [IHS] - Biofarma Group, Mereto di Tomba, Udine, Italy) in patients affected by symptomatic HD., Methods: This study is a randomized, double blind, placebo-controlled, 2-weeks clinical trial. Patients affected by I-II grade symptomatic HD were enrolled in the study and then randomly assigned to Lenoid ™ arm (LA) or placebo arm (PA), respectively. Patients were evaluated before and after intervention through clinical examination and disease-specific questionnaires assessing symptoms such as pain, tenesmus, pruritus and anal discharge., Results: A total of 68 patients were screened and 60 (30 in each group) were enrolled into the study. All patients belonging to LA showed a statistically significant improvement of each symptom after 7 and 14 days of treatment when compared to PA (P<0.001). Furthermore, subjective improvement of change in overall assessment of disease was observed in the LA but not in the PA. No serious adverse events were recorded., Conclusions: The tested product was found safe and effective in improving clinical signs and symptoms in patients with grade I-II HD.

Nail psoriasis is a chronic nail disorder that commonly affects psoriatic patients causing severe distress despite the limited body surface area. Treatments for nail psoriasis are limited, as nails are often difficult to treat with topical therapies, and among different systemic agents responses are unpredictable. We carried out a prospective study in order to analyze the effectiveness and tolerability of topical cyclosporine hydrogel ointment in nail psoriasis. Three patients, for a total of 44 nails, were treated with topical cyclosporine hydrogel ointment. All nails were evaluated, before starting the treatment, every 28 days and after 12 weeks of therapy, by the same dermatologists, through clinical and onychoscopic evaluations. The patients were also asked to assess on the compliance with product use. Complete response (CR) was observed in 2 of 3 patients; a partial response (PR) was observed in the other patient. Overall, 24 of 44 nails had CR and 20 had a PR. Cyclosporine hydrogel ointment has shown efficacy and safety in the treatment of nail psoriasis. The product has also been shown to be stable in composition, easy to apply and not discomfortable for the patient., (© 2022 Wiley Periodicals LLC.)

Despite the considerably high prevalence of cutaneous warts, no optimally effective and safe treatment is available. Leaves of date palm (Phoenix dactylifera L.; Arecaceae) have long been used in Iran's folk medicine as a remedy for warts. To assess the state-of-the-art evidence on using P. dactylifera L. for warts, we conducted a systematic review using CINAHL (via EBSCO), Embase, Medline (via PubMed), ProQuest, Scopus, and Web of Science. We conducted an open-label uncontrolled pilot clinical study to evaluate the efficacy and safety of a proprietary topical date palm leaf-based ointment for the treatment of various types of nongenital warts. This study consisted of an 8-week treatment phase and a 4-week follow-up phase. The assessed outcomes included complete clearance, patient satisfaction (on Likert scale), and the occurrence of any adverse effect. The systematic review demonstrated that the effects of date palm on warts have not been scientifically studied. Thirty patients entered the study with a mean age of 29.5 years (SD = 14.04); among which 17 were female and 13 were male. The patients presented diverse types of warts: verruca vulgaris 15 (50%), plantar 9 (30%), plane 2 (7%), periungual 2 (7%), and warts at multiple sites 2 (7%). In this trial, 19 patients (63.3%) experienced complete clearance and 5 patients (16.6%) experienced partial clearance. Eight patients (26.67%) dropped out during the study. 21 (70%) patients were very satisfied (score on Likert scale = 5) while 1 (3.3%) patient with partial clearance was somewhat satisfied (score on Likert scale = 4). No adverse effect was observed. The results of this pilot study indicate that the date palm leaf-based ointment is a promising treatment whose efficacy and safety should be further investigated in a randomized controlled clinical trial., (© 2022 Wiley Periodicals LLC.)

Introduction: Psoriasis is a kind of chronic inflammatory skin disease characterized by erythema, skin hyperplasia, scales and keratinocyte hyperproliferation. Psoriasis Vulgaris, the most common kind of psoriasis, severely deteriorates the life quality of patients. Traditional Chinese Medicine (TCM) is a good choice for the treatment of psoriasis, which has been proved to be safe and effective, and may reduce the recurrence rate. In clinical practice, Liangxue Jiedu Runzhi (LJR) ointment can effectively treat mild and moderate psoriasis with blood-heat syndrome, but there is a lack of evidence-based medical evidence. This trial aims to evaluate the efficacy and safety of LJR ointment for the treatment of mild and moderate psoriasis with blood-heat syndrome., Methods: A multicenter, randomized, double-blind, placebo-controlled, and self-controlled clinical trial was carried out according to this paper. The symmetrical rashes of each subject were regarded as the target lesions and were randomly divided into a treatment group (LJR ointment group) and a control group (placebo group). The LJR ointment or placebo ointment were externally administered on bilateral symmetric rashes, twice a day for eight weeks. The follow-up examination was made for subjects every two weeks. The primary research finding was conveyed by Psoriasis Area and Severity Index (PASI) in 8 weeks. The secondary research finding includes adverse events., Results: 46 subjects undergo this research project. The difference between PASI scores of the target lesions in the treatment group and control group is statistically significant were in 8 weeks (P < .001). The percentage of PASI 75 in treatment group and control group were 48% and 15% in week 8, respectively (x2 = 11.33, P < .05). No severe adverse events were reported., Conclusions: LJR ointment was proved to have efficacy in the treatment of mild and moderate psoriasis with the blood-heat syndrome., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease that involves damage to the peripheral nervous system. The course of the disease can progress for more than 8 weeks, with frequent incidences of relapse-remission courses. This article reported a rare combination of CIDP with fluctuating symptoms, recurrence-remission, and comorbidity with psoriasis., Case Presentation: A 29-year-old male patient with repeated limb weakness and numbness was admitted to the hospital several times in the past six months. He had a history of psoriasis for 6 years, and the medications (clobetasol propionate ointment and calcipotriol ointment) treated for psoriasis were discontinued 1 year ago. During the hospitalization, repeated intravenous injections of human immunoglobulin G (IVIg), immunoadsorption, and secukinumab were performed. Nerve electrophysiology tests, ganglioside autoantibody spectrum tests, and clinical MRC muscle strength scores were performed on a regular basis to confirm the diagnosis of CIDP. The patient was regularly followed up., Results: After repeated rounds of human IVIg and immunoadsorption, the patient's MRC score was increased by ≥ 6 points. The first ganglioside autoantibody spectrum test showed anti-GQ1b IgG ( +) and anti-GM1 IgM ( +) antibodies, and all were negative after re-examination. Finally, the patient was treated with the IL-17A inhibitor secukinumab for psoriasis. During 7 months of follow-up, the CIDP and psoriasis symptoms are relatively stable., Conclusion: Combination of IVIg and immunoadsorption was highly effective in treating CIDP complicated with psoriasis. The clinical manifestations of CIDP are diverse. When relapse-remission occurs in the course of the disease, it is necessary to clarify whether it is combined with other autoimmune diseases and should control the autoimmune diseases as soon as possible., (© 2022. The Author(s).)

Psoriasis is a chronic inflammatory disease whereby long-term disease control remains a challenge for the patients. Latest evidence suggests that combined topical treatment with steroids and vitamin D analogue foam (Calcipotriol/Betamethasone) is efficient in long-term management of the disease and reducing the number of relapses. Its effects on cellular inflammation and cytokine production remain to be explored. We set out to examine the effect of topical therapies on cellular infiltrate and cytokine profile in the lesional skin of psoriasis patients. This was a monocentric, double-blind, randomized trial with 30 patients. Patients were treated with the combined Calcipotriol/Betamethasone foam, Betamethasone foam alone, Clobetasol Propionate ointment or placebo. 4 mm skin biopsies from lesional and non-lesional sites were taken before and 4 weeks after treatment. Cellular infiltrate, IFNγ and IL-17 were studied by immunofluorescence. Each patient was their own control. Evolution in skin inflammation was studied in parallel with changes in patient's epidermal thickness and their tPASI clinical score. Lesional skin was characterized by increased epidermal thickness, increased number of IL-17 and IFNγ producing CD8+ T cells, NK cells and neutrophils. All treatment reduced epidermal thickness and improved patients tPASI scores. Only the combined Calcipotriol/Betamethasone foam completely abolished epidermal and dermal influx of CD8+ T cells, reduced number of CD8 + IFNγ+ cells (but not CD8 + IL-17+ cells) and significantly reduced the number of MPO+ neutrophils which were predominantly IL-17+. None of the treatments had effect on NK cells. We have shown the combined topical treatment with Calcipotriol/Betamethasone foam to be effective in reducing cellular influx into lesional skin of psoriasis patients and this effect to be superior to emollient or Betamethasone alone. Its previously described efficacy in the clinic may be attributed to its unique and rapid ability to inhibit both adaptive CD8+ T cell and innate immune neutrophilia influx into the skin, which was not observed for the other treatments., (© 2022 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Background: Psoriasis Vulgaris is a common immune-mediated skin disease. Its high prevalence, disability, chronicity, disfiguration, and associated comorbidities make it a challenge for physicians. Topical agents remain the mainstay of treatment for patients with mild to moderate psoriasis., Aim: To evaluate the efficacy and tolerability of topical methotrexate 1% gel (MTX) versus topical calcipotriol 0.005% cream (CPL) in the treatment of localized plaque psoriasis., Methods: This prospective comparative study included 40 patients with localized plaque psoriasis instructed to apply MTX to one side (group A) and CPL to the other side lesions (group B) twice daily for 12 weeks. Clinical and dermoscopic evaluations before, weekly during and after 3 months of treatment were done. The immunohistopathological assessment was done for skin biopsies from 10 patients in each group before and after treatment., Results: At the end of 12 weeks, there was marked-complete improvement in 97.5% of group A lesions treated with MTX 1% gel compared with 37.5% of group B lesions treated with calcipotriol 0.005% cream (p < 0.001). There was a very high statistically significant improvement in erythema that was cleared totally in 67.5% vs 22.5%, scaling in 75% vs 17.5%, and infiltration in 72.5% vs 27.5% in group A vs B, respectively (p < 0.001). These results were confirmed by dermoscopic and immunohistopathological findings., Conclusion: Methotrexate 1% gel is a marvelous promising well-tolerated effective topical agent that can be used safely in the treatment of localized plaque psoriasis., (© 2022 Wiley Periodicals LLC.)

Background: Alveolar osteitis (AO) is one of the most commonly encountered complication following tooth extraction, however, to date there is no standard methods of prevention and treatment. The study aims to investigate the efficiency of minocycline hydrochloride ointment (MHO) for the treatment of alveolar osteitis compared with traditional treatment with iodoform gauze (IG)., Methods/design: STROBE checklist was followed to report this study. All patients underwent tooth extraction either in our department or other hospitals, whom presented with postoperative pain, were screened out to meet the inclusion and exclusion criteria of this study about AO. Patients who fulfilled the inclusion criteria were enrolled in our prospective cohort study, and MHO or IG was administered. The Visual analog scale scores were used to assess the pain score of patients. The healing status of the extraction sockets was followed up. Differences in responses between groups were analyzed using Mann-Whitney U tests. Chi-square test was performed to explore the differences in the teeth position of AO., Results: Of 41,371 patients underwent tooth extraction with post-operative follow-up in our departments, only 20 patients (0.05%) suffered from AO. 31 patients with AO, whose teeth were extracted in other places, were also enrolled. The incidence of AO was significantly higher in third molars than other teeth (P < 0.01). In 28 patients that were treated with MHO, the pain was relieved substantially on day 3 and almost painless on day 7. And only 25% of cases required dressing change more than once. Whilst 23 patients treated with IG, the pain was relieved on day 5, and 56.5% of cases required multiple dressing change. The difference between the two groups of VAS scores had statistical significance during treatment at 8 h, 24 h, 3d, 5d, and 7d. No allergic reaction or further infection occurred., Conclusion: MHO has a safer and higher therapeutic effect in the treatment of AO compared with traditional treatment with IG. MHO may become a preferred treatment modality for AO., (© 2022. The Author(s).)

The objective of study was to evaluate the clinical outcome of topical 0.2% Glyceryl trinitrate topical (GTN) ointment in the treatment of chronic anal fissure. This randomized control trial was carried out in the Colorectal Surgery Unit, Department of Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh from May 2015 to April 2016. Total 94 patients were included in this trial, where 47(50.0%) patients were treated by 0.2% GTN ointment as Trial group 12 hourly for 8 weeks and 47(50.0%) patients by lateral internal sphincterotomy (LIS) as Control group in this study. Patients were randomized in two groups by lottery following purposive sampling. Post-procedural outcome variables with 6 months follow up were evaluated. Majority of the patients were found in between 20 to 40 years of age in both groups. The mean age was 34.6±10.4 years and 33.2±8.6 years in GTN and LIS respectively. Overall male female ratio was 0.88:1. All (100.0%) patients presented with pain in anus and 86.15% patients presented with per rectal bleeding. Pain relief in GTN arm versus LIS arm in 2nd and 6th week was 55.31% vs. 76.6%, 74.5% vs. 87.23% with no significant difference between two groups. But at 6 month it was 57.44% vs. 93.6% respectively. The fall in pain relief at 6th month in GTN arm was due to recurrence of fissure. At the end of 2nd, 6th week and 6month, cessation of bleeding improved gradually in both groups after treatment but the improvement was significantly better in LIS group than in GTN group indicating sphincterotomy stops bleeding better. Healing after 2nd week in both groups was minimum but equal 2(4.26%) patients. After 6 weeks LIS group had significant better healing than GTN 40(85.1%) versus 26(55.3%) with p value <0.001. In 6 month time GTN group had increased healing but LIS group had significant better healing than GTN group 42(89.36) vs. 32(68.08) with p value 0.004. Transient flatus and liquid incontinence were 8.51% and 6.4% respectively in LIS group with 0.0% in GTN group. Headache and recurrence were significantly higher in GTN group 61.7% and 34.04% with p<0.001. Lateral internal anal sphincterotomy is superior to the topical application of 0.2% nitroglycerin ointment in the treatment of chronic anal fissure with the advantages of good symptomatic relief, high rate of healing and a very low rate of transient continence disturbances.

This is the English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, descriptions of three new drugs, namely, dupilumab, delgocitinib, and baricitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice., (© 2022 Japanese Dermatological Association.)

Vitamin B12, a water-soluble vitamin, plays a vital role in the formation of hematopoietic stem cells and has been associated with oral mucosal diseases, mainly recurrent aphthous stomatitis (RAS). The latter is a debilitating condition, and B12 was proposed as a potential treatment given its role in regenerating oral mucosal tissue. There is conflicting evidence that B12 deficiency causes RAS. Five of the seven randomized controlled trials reviewed used the inactive form of B12 (cyanocobalamin) as intervention, while the other two used the active form (methylcobalamin). Of the latter two, buccal discs (500 μg B12) showed significant improvement and reduced perceived pain in 77% of the subjects, and submucosal injections showed a significant difference in pain, starting from the second day. Moreover, three studies administered vitamin B12 sublingually with different dosages, which revealed that the higher dose (1000 μg) achieved a significant reduction in outbreaks, number, and duration of ulcers, especially after six months. Multivitamins showed no difference in new RAS episodes and duration. Injectable B12 was compared with the oral form, and nearly 50% of the injection group reported a desired response by the eighth week. An ointment form (500 μg) showed a significant reduction in pain levels after two days of treatment. Based on the available literature, we suggest that a daily dose of 1000 μg of vitamin B12 sublingually for six months can be used to treat RAS. Nevertheless, this conclusion should be considered tentative due to the lack of high quality, large scale studies.

This is an abridged edition of English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, the description about three new drugs, namely, dupilumab, delgocitinib, and baricitinib, has been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice., (Copyright © 2022 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Black salve is a controversial complementary and alternative medicine (CAM) associated with skin toxicity and skin cancer treatment failures. Black salve formulations vary between manufacturers and contain a number of botanical and synthetic constituents. The skin cancer cytotoxicity of a number of these constituents has not been assessed to date. The alkaloids from the rhizomes of Sanguinaria canadensis, a key black salve ingredient, have had their single compound cytotoxicity assessed; however, whether they possess synergistic cytotoxicity with other compounds has not been studied and is of direct clinical relevance. This research aimed to improve our understanding of the skin cancer cytotoxicity of black salve constituents., Methods: The cytotoxicity of individual and combination black salve constituents were assessed against the A375 melanoma and A431 squamous cell carcinoma cell lines. Cytotoxicity was determined using the Resazurin assay with fluorescence measured using a Tecan Infinite 200 Pro Microplate reader, compound cytotoxicity being compared to that of the topical cancer therapeutic agent, 5- fluouracil. Docetaxal was used as a positive control. Dunnetts p value was used to determine whether significant synergistic cytotoxicity was present., Results: Sanguinarine was the most cytotoxic compound tested with a 24-hour IC 50 of 2.1 μM against the A375 Melanoma cell line and 3.14 μM against the A431 SCC cell line. All black salve constituents showed greater cytotoxicity against the two skin cancer cell lines tested than the skin cancer therapeutic 5-Fluouracil with 24 hours of compound exposure. Chelerythrine and minor Quaternary Benzophenanthridine Alkaloids (QBAs) present in black salve, at concentrations not having a cytotoxic effect by themselves, boosted the cytotoxic effects of sanguinarine. This could be a synergistic rather than additive cytotoxic effect although the synergistic effect was cell line and concentration dependent., Conclusions: Black salve contains several cytotoxic compounds, a number of which have been found to possess synergistic cytotoxicity for the first time against skin cancer cell lines. In addition, these compounds together increase the overall cytotoxic effect. Assessing multi-compound cytotoxicity in herbal medicine can provide additional information about both their therapeutic and toxicity potential. As black salve is currently being used by patients, further cytotoxicity work should be undertaken to assess whether synergistic cytotoxicity exists when tested in normal skin cells., (© 2022. The Author(s).)

We report a case of a 7-year-old male patient with vaccine-induced erythrodermic psoriasis (EP) complicated by pulmonary infection, hypoproteinemia, and liver dysfunction successfully treated with secukinumab in combination with symptomatic and supportive therapy. The patient presented with diffuse flushing on the head, face, trunk, and limbs, which were covered with chaff-like white scales in the rash-affected area, with no blisters, pustules, and no apparent abnormalities in the palms, soles, nails, and joints. Histopathology analysis revealed hyperkeratosis, focal parakeratosis, thinning or effacement of the granular layer, psoriasiform hyperplasia of the epidermis, neutrophilic microabscess formation in the upper part of the epidermis, edema of the dermal papilla, dilation of blood vessels, and lymphocyte infiltration. The patient was eventually diagnosed with EP. At weeks 0, 1, and 2, the patient received a subcutaneous injection of 150 mg secukinumab (three injections). Fluticasone propionate ointment, taccathitol ointment, yellow vaseline, and other drugs were also given topically. Following 2 weeks of treatment, the child's skin lesions resolved significantly with only slight pigmentation remaining and the Psoriasis Area and Severity Index (PASI) score decreased from 37.5 to 7.5 (PASI 75). Thereafter, 150 mg secukinumab was injected every 4 weeks until the last dose at 18 weeks (four more injections). After 18 weeks, the child's lesion resolved entirely (PASI 100), and no adverse effects were reported., (© 2022 Wiley Periodicals LLC.)