Use Of Topical Therapy Research Articles

Atopic Dermatitis-Related Problems in Daily Life, Goals of Therapy and Deciding Factors for Systemic Therapy: A Review

Background/Objectives/Methods: Atopic dermatitis (AD) impacts various aspects of patients’ lives including personal life, psychological aspects/disturbances (e.g., depression, anxiety, or even suicidal thoughts), school, and work-related activities, including career advancement. The aim of this narrative review is to present the latest information available on how to best approach AD patient management, as well as decisions regarding standard/advanced systemic therapy, by gathering evidence from the relevant medical literature (PubMed and other prominent medical databases). Results: Thus, AD patient management and decisions regarding advanced/systemic therapy are complex, requiring the consideration of multiple disease-related factors: age; disease severity; patient medical history and comorbidities; previous topical therapy use and any adverse reactions; treatment efficacy concerns; patient preferences, expectations and fears; pregnancy planning; ability and willingness to adhere to the treatment regimen; impact on related risks; and any associated psychological or psychiatric issues. Current guidelines and systematic reviews support the safety and efficacy of systemic therapy including conventional drugs (cyclosporine, methotrexate, and azathioprine), biologics (dupilumab and tralokinumab), and JAK inhibitors (baricitinib, upadacitinib, and abrocitinib) recommended for treating moderate and severe AD. Recently, additional biologics have been evaluated in clinical trials, including lebrikizumab, nemolizumab, eblasakimab, and OX40/OX40L, among others. Conclusions: The most recently suggested approach to treating AD patients suggests focusing on therapy that targets and achieves minimal disease activity (MDA), where therapy decisions are informed by both the patient and the clinician. Available data also indicate the importance of a personalized, stepwise, and multidisciplinary approach. This type of approach promotes patient compliance, satisfaction with therapy, and increased engagement, which all lead to better patient outcomes.

Вылечить пиодерму без антибиотиков – возможно!

Pyoderma in various manifestations is one of the most common problems in veterinary practice. Multiple studies on the treatment and prevention of pyoderma, combined with an alarming increase in the incidence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) infections, have led to a shift from previous recommendations for the use of systemic antibiotics to the use of topical therapy. Antiseptics are primarily used in the treatment of bacterial infections. The most common component is chlorhexidine, which is available in various dosage forms. Benzoyl peroxide, chlorine solution, ethyl lactate, and miconazole can also be used for treatment. For local lesions, local antibiotics are sometimes prescribed – gentamicin, fusidine, silver sulfadiazine.

Capturing and reporting topical treatment use in childhood eczema: lessons for data collection in eczema trials.

Emollients and topical corticosteroids (TCS) prevent and treat flares in eczema. However, topical treatment use is poorly recorded and reported in clinical trials. There is no clear consensus of how best to capture and summarise topical treatment use. To explore different ways of capturing and reporting topical treatment use in childhood eczema. Secondary data analysis using 450 participants from the Best Emollients for Eczema (BEE) trial. Participants were allocated to use one type of emollient (lotion, cream, gel, or ointment) 'twice daily and when required' for 16 weeks. Otherwise, clinical management remained unchanged. Parents completed weekly questions about topical therapy use and eczema symptoms. Two versions of topical treatment use questionnaires were used. The first (n=202, 44.9%) asked parents to report treatment use on days 1-7, starting completion on the day they were randomised. The second (n=248, 55.1%) reported use by day of the week (Monday to Sunday), starting completion the first Monday after randomisation. Both underwent Patient and Public Involvement (PPI) review, but the second version was tested more thoroughly using cognitive interviewing techniques, following parent feedback that questions on the first version were confusing. Descriptive statistics compared questionnaire completion and differences in emollient and TCS use. Overall, questionnaire completion for both emollient and TCS use decreased with time: but at weeks 1 and 16 were 84.7% (381/450) and 58.9% (265/450) for emollient use, and 94.2% (424/450) and 80.4% (362/450) for TCS use, respectively. Fewer emollient use questionnaires were completed with first (33.5%) than the second (87.9%) version (p<0.001). TCS use questionnaire completion were similar for both (84.9% and 87.4%, p=0.002). We present different ways of summarising topical treatment use. While questionnaire completion was similar for TCS use, emollient use data completeness was higher in the second version. When designing questionnaires, balancing the detail and complexity of questions is important, especially if being collected as a secondary outcome measure. Numerous ways of summarising the same data can provide different information. Future collection and reporting of treatment use should reflect specific trial aims.

[Translated article] Comparing the Use of Topical Therapy Along with Anti-IL-17 and Anti-IL-23 to Treat Moderate-to-Severe Psoriasis in the Routine Clinical Practice

BackgroundCombinations of topical (TT) and biological therapies (BT) are a common thing in the routine clinical practice. However, the scientific medical literature on how TT is, actually, used after the initiation of BT is scarce, particularly in combination with anti-IL17, or anti-IL23. ObjectivesTo describe the frequency of the concomitant use of TT + BT at baseline and after a 6-month course of several drugs (anti-IL17, ustekinumab, and anti-IL23). Our secondary endpoints are to describe the type of topical therapy used, compare the frequency of use of TT among the different groups of BT, describe the survival of topical therapy in these patients, and identify the factors that can impact the use or discontinuation of topical therapy in these patients (clinical response, quality of life, type of drug, etc.). Materials and methodsThis was a retrospective, observational, and single-center study of patients with moderate-to-severe psoriasis treated with anti-IL17 (secukinumab, ixekizumab), anti-IL17R (brodalumab), ustekinumab, and guselkumab from January 2015 through December 2020. ResultsWe included a total of 138 patients. When treatment started, 82.7% were on TT (55% daily), and after 6 months, 86.6% had discontinued TT. Regarding the analysis by type of drug, at 6 months, we found that 100% of the patients with BRO had discontinued topical treatment. We did not find any significant differences in the frequency of use of TT based on the BT used during the 6-month course of treatment. The estimated mean course of TT was 4.3 months (SD, 6.7). Also, the estimated mean course of TT was significantly shorter in the group of patients who achieved PASI100 (2.8 months vs. 8.1 months). ConclusionsIn our cohort, we saw a significant decrease in the frequency of use of TT at 6 months after starting BT in the routine clinical practice. This reduction occurred earlier in patients who improved their objective clinical response and quality of life.

Use of complementary and alternative medicine in vitiligo: a cross-sectional survey.

Vitiligo is characterized by skin depigmentation, which can lead to profound psychological effects and decreased quality of life, especially for those with skin of color. Individuals with vitiligo may utilize complementary and alternative medicine (CAM) due to limited treatment options with varying efficacy.An anonymous, multiple-choice, cross-sectional questionnaire was distributed to participants with vitiligo in the United States through online forums. Data on disease characteristics, use of prescription medications, use of topical therapies, supplements, and diets, and perceptions of CAM were collected.In total, 625 respondents completed the survey. Overall, 32.5% of participants (203/625) have tried CAM. Commonly reported CAM include supplements of vitamin D (57.7%, 116/203), vitamin B12 (46.3%, 93/203), vitamin C (27.4%, 55/203), topical Nigella sativa oil (26.4%, 53/203), oral omega-3 fatty acids (24.9%, 50/203), folic acid (22.9%, 46/203), and vitamin E (22.9%, 46/203). Frequently cited reasons for CAM use include desire to try "new" (40.4%, 82/203) or "more natural" (26.6%, 54/203) therapies, "frustration with conventional medicine" (24.6%, 50/203), and fear of "adverse side effects of conventional medicine" (23.6%, 48/203). Non-White participants were more likely than their White counterparts to report CAM use and have more positive perceptions of CAM therapies. Less than half (43.3%, 88/203) of CAM users reported that they disclosed their use of CAM with their physician.Dermatologists should be mindful of CAM and ask patients about their use. Further investigation of the role of CAM as adjuvant therapy for vitiligo is warranted to better advise patients.

"There is nothing that can prevent me from supporting her:" men's perspectives on their involvement and support of women's use of topical therapy for cervical precancer treatment in Kenya.

Cervical cancer disproportionately impacts women in low- and middle-income countries (LMICs). The World Health Organization's (WHO) 90/70/90 strategy aims to eliminate cervical cancer by 2030 by increasing HPV vaccination coverage to 90%, screening 70% of eligible women, and effectively treating 90% of those with abnormal results by 2030, potentially preventing 62 million deaths in LMICs. LMICs, however, struggle with limited access to cervical precancer treatment, in part due to a lack of trained professionals and weak health systems. Effective non-surgical, self-administered, which have demonstrated efficacy in high-income countries, could bridge the treatment gap in LMICs and may be more scalable and cost-effective than provider-administered therapies. To inform feasibility studies in LMICs, data are needed on the role of male partners in influencing the acceptability and uptake of self-administered topical therapies, including their support of recommended abstinence and contraception guidelines associated with these therapies. Between November 2022 and April 2023, we conducted five focus group discussions (FGDs) with men aged 25 to 65 years in Kenya to explore their perspective and perceived support regarding their female partners using topical self-administered therapies for cervical precancer treatment. The FGDs were moderated by local qualitative research assistants and conducted in local languages, transcribed, coded, and analyzed using qualitative description. Thirty-nine male participants meeting the eligibility criteria participated in five FGDs. The mean age of participants was 42.5 years. Most participants, 79.5%, had a female partner with a history of cervical precancer treatment, 5.1% did not, and 15.4% were unsure of their female partner's prior precancer treatment history. The study aimed to assess men's support of their female partners' use of topical therapies for treating cervical precancer. We find that male participants strongly express acceptance and willingness to support their wives or partners in using such therapies, if available. Reported supportive behavior included permitting the use of the therapies and support of maintaining abstinence during the recommended times. Additionally, participants desired male involvement in clinic and community-based education about topical therapies to facilitate widespread support. The use of self-administered topical therapies for cervical precancer treatment, if supported by efficacy studies in LMICs, may support achieving the WHO's 2030 goal of 90% treatment access. We find that with adequate education, men express overwhelming support of their female partner's use of topical therapies, including adherence to abstinence and contraception guidelines.

Corneal wound healing-Pharmacological treatment

Physiological wound healing of the cornea is acomplex process and involves numerous multifactorial tissue processes. Aproper wound healing, especially without the formation of light-scattering scars, is essential to preserve the integrity and function of the cornea. Misdirected wound healing is of vast clinical relevance as it can lead to corneal fibrosis and the loss of optical transparency with subsequent reduction of visual acuity, up to blindness. In addition to the understanding of the pathophysiological mechanisms, the knowledge of therapeutic concepts and options for treating corneal wound healing disorders and fibrosis is essential to counteract apermanent damage of the cornea as early as possible. Nowadays, various pharmacological and surgical options are available for treatment. The decision, appropriate selection and indication for the optimal treatment depend primarily on the genesis and clinical appearance of the corneal wound, fibrosis or scar. The treatment of wound healing disorders ranges from the use of topical therapy and supportive measures up to tissue replacement procedures. As long as the mechanical stability of the cornea is intact and wound healing processes are still ongoing, apharmacological modulation is reasonable, which is discussed in this article.

Characteristics of Patients With Psoriasis Treated With Various Biologics – A Danish Cohort Study

Background Psoriasis is associated with several comorbidities and patients with psoriasis are more often obese than individuals without psoriasis. The excess disease burden is important to consider in choice of and response to treatment at the individual level. Objective To investigate whether patient characteristics differ across biologics for patients initiating biologic therapy and for patients still on biologic therapy after 1 year. Also, to quantify and compare the use of topical therapy among patients still on biologic therapy after 1 year. Methods This nationwide cohort study compared characteristics of patients prescribed adalimumab, etanercept, infliximab, secukinumab or ustekinumab for treatment of psoriasis by using data from the Danish registries. Results In the ustekinumab group, patients were younger and fewer had psoriatic arthritis. Patients treated with secukinumab and ustekinumab were less frequently co-treated with conventional systemics and topical therapy. All other patient characteristics such as sex, smoking and comorbidities other than psoriatic arthritis were similar across the biologic cohorts. Conclusion These results highlight the need to better understand which factors to consider when prescribing biologics to patients with psoriasis.

P561 Reasons for low use of topical 5-ASA formulations in patients treated for ulcerative colitis: comparison of doctors and patients perspectives

Abstract Background Ulcerative colitis (UC) is a chronic relapsing inflammatory disorder of the colon. In patients with proctitis or left sided colitis, topical application of 5-ASA as suppository, enema or foam preparation has been shown more effective as compared to systemic treatment. In a study conducted 10 years ago, we observed an underuse of topical therapy in patients with UC. Objectives to assess the current use of topical 5-ASA for UC and compare it with previous findings. To evaluate perspectives on use of topical therapies, among physician and patients. Methods The study had two parts. We first conducted a retrospective cohort data analysis, among adult UC patients included in the SIBDCS. We included patients enrolled since 2012 (not included in our previous study), and to compare the results of the use of 5-ASA therapies from 2021-2021. We then conducted two parallel surveys: with patient and with gastroenterologists. The survey was independent from the cohort data analysis. We assessed potential reasons for low use of topical therapies. Results 721 patients were included in the retrospective study (329 (45.6%) females, age at diagnostic (median, IQR): 31 (23-42), disease duration: 6 (2-15)). Disease extension at last FU was 18.0% proctitis, 26.3% proctosigmoiditis; clinical activity was low to moderate in 18.6%, and high in 1.8% of patients. 16.4% of patients with proctitis received topical 5-ASA only (5-ASA top+oral (5ASA): 42.2%), 5.9% with proctosigmoiditis (16.6% 5ASA), 0% in left-sided colitis (9.3% 5ASA) (figure 1). Exclusive 5-ASA topical use was lower than observed 10 years ago (23.3%) in proctitis. The survey was completed by 142 patients: 89 females (63%), mean (SD) age 46 (13) and disease duration 15 (10), 15% had proctitis/proctosigmoiditis and 29% left-sided colitis. 63 gastroenterologists participated in the survey; 25% were females, 36.5% had a professional experience up to 10 years, 55% were in single/group practice. 76% of patients reported having ever been prescribed suppositories (S), 74% foam (F), 61% enema (E). Patients-reported top reasons for stopping topical therapy prematurely (1/3 of cases) were unpleasantness (51.3% F/E, 13.9% S), ineffectiveness (41.1% F/E, 60.5% S), and preference for tablets (51.3% F/E, 37.8% S). Physicians’ perspectives on compliance difficulties were unpleasantness (83.7% F/E, 56.3% S), and preference for tablets (76.4% F/E, 63.7% S). 85% of patients were well informed on rectal therapies, 76% of doctors would be open for training/update on rectal therapies. Conclusion The use of rectal therapies in UC patients that should benefit from is still low. Reasons for non-compliance were discordant between doctors and patients.

P881 Real-life vs trial access to biologic therapy differences: a 2019-2020 experience in an Italian tertiary IBD center

Abstract Background Inflammatory Bowel Diseases (IBD) are multifactorial diseases including Ulcerative Colitis (UC) and Crohn's Disease (CD). Up to 50% of IBD patients show a primary or secondary non-response to standard biological therapy. Hence, Randomized Clinical Trials (RCTs) represent a significant therapeutic opportunity for them. This study aims to describe the clinical characteristics of "trial IBD patients" vs. "real-life IBD". Methods We prospectively enrolled patients who started biologic therapy from August 2019 to August 2020. We divided patients into 3 sub-groups: (1) "real-life", patients treated according to clinical practice with biologic therapy that did not meet the inclusion and exclusion criteria for RCTs, (2) "real-life suitable for trial", patients potentially eligible in RCTs, but treated with standard of care, and (3) "trial", patients treated with drugs from 14 phases 2b and 3 studies actively recruiting in our center. Results We enrolled 134 patients (72 UC, 62 CD). "Real-life" patients were 41 in UC and 38 in CD, "real-life suitable for trial" were 6 in UC and 14 in CD, and "trial" were 25 in UC and 10 in CD. According to the existing inclusion and exclusion criteria, the study showed that 43% UC patients and 39% CD were suitable for enrollment in RCTs, however only 16% of CD were finally enrolled in RCTs. At the enrollment, patients were mainly excluded for topical therapy use, cancer, recent infections, low CDAI (&amp;lt;220) or SED-CD (&amp;lt;6), or presence of complication of diseases in CD or for limited extension of disease in UC. Both "trial" UC and CD patients presented more extraintestinal manifestations of disease, especially the articular ones (p&amp;lt;0,05) and a higher significant concomitant use of systemic corticosteroids (≤20mg/die (p &amp;lt; 0,05)). Percentages of patients treated previously with other biological drugs were superior in "trial" patients compared to "real-life" only in UC (88% vs 29%). We observed different baseline clinical disease activity scores in CD: the HBI of "real-life" patients was 4.8, and the HBI of "trial" patients was 9.1. In addition, patients enrolled in RCTs waited longer before accessing the proposed biological therapy. Conclusion This study highlights some differences between clinical practice and RCTs, particularly regarding criteria to start biologic therapy. Globally "trial patients" have more complex diseases that significantly impact their clinical status. Furthermore, RCTs use clinical scores (e.g. CDAI) as determinants for enrollment and decision-making, while endoscopy and radiological imaging are more widely used in clinical practice for decision making. These differences could cover the actual effectiveness of a new drug compared to the theoretical efficacy deriving from registration RCTs.

Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the international Vitiligo Task Force-Part 2: Specific treatment recommendations.

The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking. To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo. In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings. The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed. This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.

Hidradenitis suppurativa - current and promising non-surgical treatment

Introduction and purpose: Hidradenitis suppurativa (HS) also known as acne inversa is a chronic, inflammatory dermatosis with predilection to apocrine gland-rich regions. It is a multifactorial disease in which genetic and environmental factors play a key role. In this paper, we provide an overview of the current knowledge in most commonly used and emerging treatment options of HS. A brief description of the state of knowledge: The primary defect in HS pathophysiology involves follicular hyperkeratosis with occlusion of the pilosebaceous apparatus, followed by follicular rupture and immune responses. It typically develops after puberty with deep-seated painful nodules, abscesses, sinus tracts and scars. Due to the permanently painful, odorous lesions, hidradenitis suppurativa is one of the most distressing dermatological diseases with a substantial impact on patients’ quality of life. Inflammation in patients with HS is not limited to the skin but is systemic. Patients with HS frequently have significant comorbidities like metabolic syndrome, type 2 diabetes mellitus, spondyloarthropathy, inflammatory bowel disease and depression. Treatment is challenging and consists of pharmacological and surgical techniques, which must often be combined for best results. Materials and methods: A search was conducted using PubMed and GoogleScholar data bases. Articles were searched in English using the following key words: “hidradenitis suppurativa”, “acne invera”, “treatement”, “management”, “biological treatement”. Summary: Therapeutic options have rapidly evolved in the last decade and include the use of topical therapies, systemic antibiotics and a wide range of immunosuppressive medications such as anti-TNF-α biologics, but the number of therapies approved for HS is limited.

Effects of topical dehydroepiandrosterone therapy in women after pelvic organ prolapse surgery.

Pelvic organ prolapse (POP) occurs predominantly in postmenopausal women. Restoration of the proper estrogenization of vaginal mucosa is important in preoperative and postoperative treatment, increasing the effectiveness of this approach. The objective of this study was the development of intravaginal vaginal suppositories containing DHEA and comparison of the clinical effects of vaginal topical therapy with DHEA, estradiol, or antibiotic after POP surgery. Nine types of vaginal suppositories containing 6.5 mg DHEA in different bases were prepared to find optimal formulation for the vaginal conditions. Ninety women referred for POP surgery were randomly assigned to one of three groups receiving topical treatment in the postoperative period (estradiol, DHEA, or antibiotic). On admission to hospital and during follow-up vaginal pH, vaginal maturation index and vaginal symptoms were assessed. Vaginal suppositories with the base made from polyethylene glycol 1,000 without surfactants characterized the highest percentage of the released DHEA. In women treated with topical estradiol or DHEA a significant decrease in the number of parabasal cells, increase in superficial and intermediate cells in the vaginal smears, decrease in vaginal pH, and reduction of vaginal symptoms were observed. The use of topical therapy with DHEA or the use of topical therapy with estradiol in the postoperative period were both shown to improve maturation index, vaginal pH, and vaginal symptoms. The benefits of topical therapy with DHEA after pelvic organ prolapse repair brings similar results as estradiol, without potential systemic exposure to increased concentrations of sex steroids above levels observed in postmenopausal women.

Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: 52-week results of two randomized double-blinded placebo-controlled phase III trials.

Lebrikizumab is a novel, high-affinity monoclonal antibody that selectively binds to interleukin (IL)-13. To evaluate the efficacy and safety of lebrikizumab monotherapy in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD) over 52 weeks of treatment in ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). Patients who responded to lebrikizumab 250 mg every 2 weeks (Q2W) at the end of the 16-week induction period were re-randomized 2 : 2 : 1 to receive lebrikizumab Q2W, lebrikizumab 250 mg every 4 weeks (Q4W) or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. Response at week 16 was defined as achieving a 75% reduction in Eczema Area Severity Index (EASI 75) or an Investigator's Global Assessment (IGA) of 0 or 1, with a ≥ 2-point improvement and no rescue medication use. Multiple imputation was used to handle missing data. Intermittent use of topical therapy was permitted during the maintenance period. After 52 weeks, an IGA of 0 or 1 with a ≥ 2 point improvement was maintained by 71.2% of patients treated with lebrikizumab Q2W, 76.9% of patients treated with lebrikizumab Q4W and 47.9% of patients in the lebrikizumab withdrawal arm. EASI 75 was maintained by 78.4% of patients treated with lebrikizumab Q2W, 81.7% of patients treated with lebrikizumab Q4W and 66.4% of patients in the lebrikizumab withdrawal arm at week 52. Across treatment arms, proportions of patients using any rescue therapy were 14.0% (ADvocate1) and 16.4% (ADvocate2). During the combined induction and maintenance periods of ADvocate1 and ADvocate2, 63.0% of lebrikizumab-treated patients reported any treatment emergent adverse event, with most events (93.1%) being mild or moderate in severity. After a 16-week induction period with lebrikizumab Q2W, lebrikizumab Q2W and Q4W maintained similar improvement of the signs and symptoms of moderate-to-severe AD, with a safety profile consistent with previously published data.

Nasal washes in chronic rhinosinusitis, review article

Chronic rhinosinusitis (CRS) is a chronic condition of inflammation in the mucosa of the paranasal sinuses that is associated with a significantly impaired quality of life, which motivates the constant study of therapies for its control and cost reduction. The cutting edge of clinical management for CRS is topical therapy. The advantages of topical medical therapy include direct administration of the drug into the diseased tissue, the possibility of administering higher local concentrations of the drug and minimizing systemic absorption which is not without adverse effects, thus becoming an important strategy in the management of CRS. The objective of this literature review is to formally review and identify topical medical therapy strategies and promote an evidence-based approach to their use. A literature review was conducted based on a keyword search. The computerized databases of PubMed, ElSevier and ResearchGate were accessed. We included articles highlighting the results of the use of topical therapies in CRS and that the type of study was a clinical trial. This review identified and evaluated the literature on topical therapy strategies for CRS: saline irrigation, topical antibiotics, topical steroids, and topical antifungals. Topical therapy has become an important tool in the treatment arsenal for CRS. Based on a review of the literature, nasal irrigation with saline and topical steroid sprays are the most evidence supportive. Nonstandard topical nasosinusal steroid therapies may be an option for managing CRS.

Nasal washes in chronic rhinosinusitis, review article

Chronic rhinosinusitis (CRS) is a chronic condition of inflammation in the mucosa of the paranasal sinuses that is associated with a significantly impaired quality of life, which motivates the constant study of therapies for its control and cost reduction. The cutting edge of clinical management for CRS is topical therapy. The advantages of topical medical therapy include direct administration of the drug into the diseased tissue, the possibility of administering higher local concentrations of the drug and minimizing systemic absorption which is not without adverse effects, thus becoming an important strategy in the management of CRS. The objective of this literature review is to formally review and identify topical medical therapy strategies and promote an evidence-based approach to their use. A literature review was conducted based on a keyword search. The computerized databases of PubMed, ElSevier and ResearchGate were accessed. We included articles highlighting the results of the use of topical therapies in CRS and that the type of study was a clinical trial. This review identified and evaluated the literature on topical therapy strategies for CRS: saline irrigation, topical antibiotics, topical steroids, and topical antifungals. Topical therapy has become an important tool in the treatment arsenal for CRS. Based on a review of the literature, nasal irrigation with saline and topical steroid sprays are the most evidence supportive. Nonstandard topical nasosinusal steroid therapies may be an option for managing CRS.

Deucravacitinib, a TYK2 inhibitor, safety in psoriasis and psoriatic arthritis: What should a dermatologist know?

The search for therapeutic options in psoriasis that are effective, safe and convenient for patients has led to the development of new drugs. Selective tyrosine kinase 2 (TYK2) inhibitors, namely deucravacitinib, are recent therapeutic weapons, whose role is to inhibit key cytokines, such as interleukin (IL)-12, IL-23 and type I interferon, involved in the pathogenesis of immune-mediated diseases, such as psoriasis and psoriatic arthritis. This new small molecule acts by allosteric binding to the regulatory rather than the active catalytic domain of TYK2, being more selective for TYK2 than to other JAKs, thus not affecting the JAK 1, 2 or 3 signalling pathway.1 Because of its higher selectivity, better therapeutic effects can be achieved with fewer associated adverse effects (AEs). Given the recent information available on this promising drug, this letter aims to alert dermatologists to the most frequent and relevant AEs associated with deucravacitinib. Deucravacitinib demonstrated a favourable safety profile in phase 2 and 3 clinical trials in 1723 patients with moderate-to-severe plaque psoriasis and psoriatic arthritis (Table 1). In two phase 2 trials,2, 3 the most commonly reported AEs included nasopharyngitis, upper respiratory tract infection (URTI), headache, diarrhoea and nausea. The rates of serious AEs (SAEs) and AEs leading to discontinuation were similar between placebo and active-treatment groups. No cases of clinically meaningful laboratory changes or herpes zoster were reported. When considering dermatological AEs, the occurrence of mild-to-moderate acne was higher in patients in the active-treatment group, mostly in the highest-dose group (9%), showing a dose-dependent correlation. This is in accordance and expected as other JAK inhibitors, mainly upadacitinib, present the same cutaneous AEs.4 In a 52-week phase 3 trial (POETYK PSO-1),5 which compared the efficacy and safety of deucravacitinib with apremilast and placebo in patients with psoriasis, the types and rates of AEs and SAEs were similar across the groups. The most frequent AEs were nasopharyngitis and URTI, and the frequency of discontinuations due to AEs was lower in the deucravacitinib-treated patients. Except for pericarditis and cholecystitis which occurred in 2 deucravacitinib-treated patients, all SAEs occurred in single patients, with no deaths reported in the active-treatment group. The most common laboratory abnormality was an increase in creatine phosphokinase, however, all cases were mild and resolved without treatment. There was an increase in viral infections, especially herpes zoster reactivation, with five cases reported. Nevertheless, every event was mild to moderate, localized, and followed a benign course. The phase 3 trial (POETYK PSO-2)6 showed similar results in AEs, SAEs and AEs-related discontinuation rates. There were two deaths reported in deucravacitinib-treated patients, none of which was considered treatment-related, and all SAEs occurred in single patients, except for pneumonia in three patients. Besides a slight increase in creatine phosphokinase, there were no clinically relevant laboratory changes. Herpes zoster reactivation rates were higher in the active-treatment group, with no severe cases reported. Regarding skin events, there was also an increase in acne and folliculitis. In all of the above clinical trials, no tuberculosis or opportunistic infections were reported, and malignancy, thrombosis, and cardiovascular event rates were similar between groups and in the general population. The described safety profile was consistent with a long-term extension, with no emerging safety signals.7 Overall, the use of the new TYK2 inhibitor appears to be well tolerated. Its mechanism of action provides a high degree of selectivity and reduces the off-target effects associated with other JAK inhibitors, such as laboratory changes (namely haematological parameters, lipid level or other chemistry parameters),1 which limits their use. Of note, this drug is associated with increased cutaneous AEs, mostly in the form of mild-to-moderate acne. The use of topical therapy alone for acne (e.g., adapalene and combination with benzoyl peroxide as first-line) seems to be an effective treatment for these patients, with no need to discontinue treatment with deucravacitinib.8 As this is an oral drug administered once daily, it combines convenience with a favourable efficacy and safety profile. Further clinical trials and real-world evidence are essential to support the scientific data available. Data collection: Inês Pereira Amaral. Research design: Inês Pereira Amaral. Manuscript write-up and review: Inês Pereira Amaral, Joana Antunes, Ivânia Soares, Madalena Pupo Correia, Paulo Filipe. Manuscript submission: Inês Pereira Amaral. Overall supervision: Inês Pereira Amaral, Joana Antunes, Paulo Filipe. Data validation: Joana Antunes, Ivânia Soares, Madalena Pupo Correia, Paulo Filipe. Critical revision and approval of the final version of the manuscript: Joana Antunes, Ivânia Soares, Madalena Pupo Correia, Paulo Filipe. Research idea: Paulo Filipe. No funding source. The authors declare no conflict of interest. Not applicable. The data that support the findings of this study are available from the corresponding author upon reasonable request.

A Systematic Review of Aquagenic Urticaria—Subgroups and Treatment Options

Aquagenic urticaria (AquaU) is a rare variant of chronic inducible urticaria where wheals occur after skin contact with water. Information on clinical manifestations and treatment outcomes is limited, which makes the management of AquaU challenging. To systematically review disease features and relevant triggers of AquaU and patients' response to treatment. Related articles were searched by use of the terms "aquagenic urticaria" and "aquagenic angioedema" until June 2021 and reviewed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. A total of 77 patients with AquaU were investigated in 59 studies including 47 case reports and 12 case series. AquaU predominantly presented in women (47 patients, 61%), and the mean age of onset of the disease was 19.6 ± 10.8 years (range: 0-54 years). Wheals commonly occurred in localized areas and regardless of the water temperature. Based on the reviewed evidence, AquaU can be classified as familial AquaU (FAquaU, 18.2%) and acquired AquaU (AAquaU, 81.8%). Although many treatments were used in both subtypes of AquaU, the use of second-generation H1 antihistamines (2ndAH1) was reported most often to achieve marked improvement in both subtypes. The use of topical therapies in AquaU, which most commonly use hydrophobic vehicles, is poorly documented and of controversial efficiency. AquaU is proposed to be classified into 2 subtypes, FAquaU and the more common AAquaU. Treatment with a 2ndAH1 is recommended as the first-line treatment for both types of AquaU. Further studies are required to fill knowledge gaps.

POSC138 The Burden Due to Moderate-to-Severe Paediatric Atopic Dermatitis Treated with Systemic Immunosuppressants on the Healthcare System in England

Children and adolescents with moderate-to-severe atopic dermatitis (AD) which cannot be managed despite optimal use of topical therapies often require intervention with systemic immunosuppressants (IMs), almost all of which are used off-label in the UK. These patients must be closely monitored due to the adverse effect profile of these broad-spectrum therapies. The objective of this study is to quantify the healthcare burden associated with clinical interactions and monitoring of children with moderate-to-severe AD receiving IM therapies.

The effectiveness of antibacterial therapeutic clothing based on silver or chitosan as compared with non-antibacterial therapeutic clothing in patients with moderate to severe atopic dermatitis (ABC trial): study protocol for a pragmatic randomized controlled trial

BackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disease that affects 10 to 20% of children and between 2 and 15% of the adults in Western Europe. Since 2000, therapeutic clothing or functional textiles based on silver or chitosan as antibacterial agents were introduced for AD. These agents aim to reduce skin colonization with Staphylococcus (S.) aureus. Increased colonization with S. aureus is correlated with increased AD severity. The antimicrobial effects of silver and chitosan have been demonstrated before. At this point, there is insufficient evidence for the effectiveness of antibacterial therapeutic clothing in patients with AD.MethodsThis is a pragmatic randomized controlled double-blind multi-center trial comparing the effectiveness of antibacterial therapeutic clothing based on silver or chitosan as compared with non-antibacterial therapeutic clothing in patients with moderate to severe AD. A total of 165 participants, aged 0 to 80, diagnosed with moderate to severe AD are included. The study is performed in the Erasmus MC University Medical Center, University Medical Center Groningen, University Medical Center Utrecht, Amsterdam University Medical Centers, and St. Antonius Hospital Nieuwegein. Patients will be randomized 1:1:1 into one of the three intervention groups: group A will receive therapeutic clothing without antimicrobial agents, group B will receive microbial growth reducing therapeutic clothing based on chitosan, and group C will receive antimicrobial clothing based on silver. All therapeutic clothing is to be worn at night during the 12-month intervention period. Usual care is continued. The primary objective is to assess the effectiveness of antibacterial clothing (silver and chitosan group) as compared to non-antibacterial clothing assessed with the Eczema Area and Severity Index at 12 months compared to baseline. Secondary outcomes include between-group differences in physician- and patient-reported outcome measures, topical therapy use, S. aureus skin colonization, and safety. Data will be collected at baseline and after 1 month, 3 months, 6 months, and 12 months. A cost-effectiveness analysis will be performed.DiscussionThis trial will provide data on the effectiveness, cost-effectiveness, and safety of antibacterial therapeutic clothing for patients with AD.Trial registrationClinicalTrials.gov NCT04297215. Registered on 5 March 2020