Topical timolol, a novel therapeutic option for chronic hand eczema: a randomized double blind-controlled study

Topical timolol, a novel therapeutic option for chronic hand eczema: a randomized double blind-controlled study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Topical timolol, a novel therapeutic option for chronic hand eczema: a randomized double blind-controlled study Premjit Juntongjin, Pyrapa Jivanantapravat This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8079196/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Chronic hand eczema (CHE) is a relapsing inflammatory skin condition often treated with topical corticosteroids, which can cause long-term adverse effects. Topical timolol, a non-selective beta-blocker, has shown promise as an alternative therapy. This study aims to compare the efficacy and safety of topical timolol 0.5% versus desoximetasone 0.25% in CHE. In this randomized, double-blind study, CHE participants applied timolol and desoximetasone to opposite hands twice daily for 8 weeks, followed by 4 weeks of petrolatum application. The Hand Eczema Severity Index (HECSI), itching, disease severity, and adverse events were assessed. Total nineteen participants completed the study. Both treatments significantly reduced HECSI scores (p < 0.05) with no significant difference between groups. A rebound phenomenon occurred after desoximetasone discontinuation. Timolol was associated with dryness, itchiness, cracking, and stinging, while desoximetasone caused epidermal atrophy and hypopigmentation. No serious adverse events were reported. In conclusion, timolol is an effective and safe treatment and may be an alternative therapeutic option for CHE. chronic hand eczema topical timolol hand dermatitis topical therapy randomized controlled trial double-blind study Figures Figure 1 Figure 2 Figure 3 Figure 4 SIGNIFICANCE Timolol demonstrated efficacy comparable to high-potency topical corticosteroids in chronic hand eczema. With its good safety profile, easier availability, and lower cost, timolol may be considered a practical alternative topical therapy, particularly in patients where steroid use is limited by contraindications or long-term safety concerns. INTRODUCTION Chronic hand eczema (CHE) is defined as an eczematous process on the hands or wrists lasting over three months or relapsing at least twice a year[ 1 ]. It affects nearly 10% of the population annually[ 2 ], with significant impacts on quality of life comparable to psoriasis and asthma[ 3 ]. CHE also carries a considerable economic burden which is comparable with other dermatological conditions[ 4 ]. However, this data is likely underestimated due to outdated studies and increased cases during the COVID-19 pandemic. CHE have multifactorial etiologies, with skin barrier dysfunction playing a key role[ 5 , 6 ]. According to the guidelines, various classic treatments for hand eczema include topical corticosteroids, topical calcineurin inhibitors, phototherapy, oral corticosteroids, alitretinoin, acitretin, cyclosporin, azathioprine and methotrexate[ 1 , 7 ]. Moreover, dupilumab[ 8 ], topical and oral JAK inhibitors have been extensively reporting their favorable outcomes[ 9 – 11 ]. Although topical corticosteroids remain the first-line therapy, long-term use is associated with adverse effects such as skin atrophy, telangiectasia, and impaired barrier repair, making management challenging[ 12 ]. Timolol, a non-selective beta-adrenergic antagonist traditionally used for glaucoma, has emerged as an off-label dermatologic treatment. It has shown efficacy and significantly increases prescription in vascular tumors[ 13 , 14 ] and chronic wounds by promoting re-epithelialization and modulating inflammation through β2-adrenergic receptor blockade[ 15 ]. Also, Pawar reported timolol’s potential for treating recalcitrant CHE[ 16 ]. This study aims to compare the efficacy and safety of topical timolol 0.5% versus desoximetasone 0.25% in CHE treatment, proposing timolol as a possible alternatively effective and affordable therapy. MATERIALS AND METHODS This clinical study was designed as a prospective, randomized, double-blinded, intraindividual right–left comparative trial. The study was conducted between March 2021 and April 2022 at the Department of Dermatology, Benchakitti Park Hospital, and Thammasat University Hospital, Thailand. The research protocol was reviewed and approved by the Human Research Ethics Committee of Thammasat University. Written informed consent was obtained from all participants prior to enrollment. Subject Recruitment A total of twenty patients diagnosed with CHE were enrolled in the study. Inclusion criteria consisted of adults aged 20 to 65 years presenting with bilateral CHE of mild to moderate severity, as assessed by the Physician Global Assessment (PGA) score. Exclusion criteria were as follows: (1) a history of sinus bradycardia, second- or third-degree heart block, overt cardiac failure, or cardiogenic shock; (2) a history of bronchial asthma or chronic obstructive pulmonary disease; (3) use of topical immunosuppressants, retinoids, or corticosteroids within 2 weeks prior to study initiation; (4) use of systemic immunosuppressants, retinoids, corticosteroids, or phototherapy within 4 weeks prior to study initiation; (5) presence of other active dermatoses on the hands, such as psoriasis or acute skin infections; (6) pregnancy or lactation; (7) a previously positive patch test; and (8) known hypersensitivity to any components of timolol or desoximetasone. Intervention Timolol Maleate Eye Drop 0.5% solution (Alcon® Timolol Maleate Eye Drops; Alcon, Belgium) and desoximetasone 0.25% cream (Topicorte®; Sanofi, France) were repackaged into identical sterile tubes to ensure blinding. The products were assigned to either the left or right hand of each participant using computer-generated block randomization. Subjects were instructed to apply the assigned product to the designated hand twice daily for 8 weeks. This treatment phase was followed by a 4-week maintenance phase, during which petroleum ointment was applied to both hands twice daily. To prevent cross-contamination, a single-use cotton bud was used for each application. The use of any other topical products in the treated areas was not allowed throughout the study period. Outcome Measurement Outcome assessments were conducted at baseline, and at week 2, 4, and 8 during treatment period, as well as at week 12 (four weeks after treatment discontinuation). The Hand Eczema Severity Index (HECSI) was employed as an objective measure of disease severity. Standardized clinical photographs were captured at each visit using a full-frame mirrorless digital camera (Sony α7III; Sony Corp., Tokyo, Japan) under consistent lighting conditions. Subjective clinical outcomes were assessed using the Visual Analogue Scale (VAS). Subjects were instructed to rate the intensity of pruritus in each hand on a 10-cm VAS, where 0 represented no symptoms and 10 denoted the worst imaginable symptoms. Subject-perceived disease severity was also recorded using the same VAS method. Adverse reactions were monitored and assessed at every follow-up visit. Statistical Analysis All statistical analyses were performed using IBM SPSS Statistics, version 26 (IBM Corp., Armonk, NY, USA). Categorical variables were summarized as frequencies and percentages, while continuous variables were presented as mean ± standard deviation (SD). Nonparametric tests were used for intra- (Wilcoxon’s Sign Rank test) and inter- (Mann Whitney U-test) group comparisons. A p-value of less than 0.05 was considered statistically significant. RESULTS Subjects Of the 20 subjects enrolled in the study, 19 completed the study as per protocol. One subject was lost to follow-up due to personal circumstances and was excluded from the final analysis. The majority were female (73.7%), with a mean age of 47.74 ± 10.06 years (range 28–63 years). The average duration of CHE was 70.00 ± 101.83 months, ranging from 10 to 360 months. At baseline, 57.9% of participants presented with mild disease and 42.1% with moderate disease based on the Physician Global Assessment (PGA). The most common clinical variant was chronic fissure hand eczema (63.2%), followed by hyperkeratotic hand eczema (21.1%), vesicular hand eczema (10.5%), and discoid eczema (5.3%). The most common occupations were office workers (36.84%) and maids/cleaners (26.32%). A history of atopy was reported in 63.16% of participants. (Table 1 ) Efficacy Objective evaluation The Hand Eczema Severity Index (HECSI) was used to objectively evaluate disease severity. At baseline, no significant difference was observed in mean HECSI scores between timolol- and desoximetasone-treated hands. Both regimens demonstrated significant improvement in HECSI scores following the 8-week treatment period (Fig. 1 ). At week 8, HECSI scores were gradually decreased by approximately 43% in timolol group (p < 0.001) and 53% in the desoximetasone group (p < 0.001). No significant difference in the magnitude of improvement between groups was revealed at any visit. Following treatment discontinuation, only petrolatum ointment was allowed to be applied on both hands for the later 4 weeks. At week 12, HECSI scores in both groups remained significantly lower than baseline (p < 0.05). Interestingly, the timolol-treated side showed a continued, though modest, reduction in HECSI scores while the desoximetasone-treated side exhibited an increase of approximately 24% from the 8th week. Nevertheless, the changes noticed during the follow-up period were not significantly difference when comparing the two treatment groups. Figure 2 demonstrates the clinical improvement observed during the study. Subjective evaluation The Visual Analogue Scale (VAS) was employed to assess itch intensity and overall disease severity at baseline, week 8, and week 12 (Fig. 3 and Fig. 4 ). Both timolol and desoximetasone significantly reduced itch and disease severity at week 8 (p < 0.05) with no statistically significant difference between groups. At the follow-up visit, the VAS scores remained stable or slightly decreased in timolol group; whereas, the scores of both itch intensity and overall disease severity increased in the desoximeasone group. Nonetheless, the differences were not statistically significant. Adverse events Dryness was the most frequent adverse event, reported in approximately 60% of the participants on the timolol-treated side and occurred significantly more often than on the desoximetasone-treated side (p < 0.001) (Table 2 ). Itchiness was reported with both treatments. Cracking and stringing were observed in the timolol group whereas skin atrophy and hypopigmentation were noticed in the desoximetasone group. No participants discontinued the protocol due to these adverse reactions. Table 2 Adverse reactions of the treatments Side effects Timolol Desoximetasone p-value N (%) N (%) Dryness 12 (63.16) 1 (5.26) < 0.001* Itchiness 7 (36.84) 2 (10.53) 0.060 Cracking 3 (15.79) 0 (0.00) 0.075 Stinging 2 (10.53) 0 (0.00) 0.152 Skin atrophy 0 (0.00) 1 (5.26) 0.317 Hypopigmentation 0 (0.00) 1 (5.26) 0.317 DISCUSSION/CONCLUSION The management of chronic hand eczema (CHE) remains a therapeutic challenge due to limitations in long-term tolerability and the lack of robust evidence supporting many available treatments. To our knowledge, this study represents the first prospective, randomized, double-blinded, intraindividual, right–left comparative trial directly evaluating the efficacy of topical timolol, a nonselective β-adrenergic receptor antagonist, against desoximetasone, a potent corticosteroid, in the treatment of CHE. Over the eight-week treatment period, both regimens demonstrated significant improvement in disease severity, as assessed by HECSI scores, visual analogue scale (VAS), and digital photographic evaluation. Timolol treatment resulted in a mean HECSI reduction of approximately 43% (p < 0.001), while desoximetasone achieved a slightly higher reduction of 53% (p = 0.001). These findings indicate that timolol, despite its distinct non-steroidal mechanism of action, exhibited a clinically meaningful effect comparable to that of a potent corticosteroid. Interestingly, the post-treatment follow-up phase revealed divergent trends between the two groups. In the timolol arm, mean HECSI scores continued to decline modestly, reaching an overall 46% reduction compared with baseline (p = 0.001). In contrast, the desoximetasone group showed a rebound in disease severity, with HECSI scores increasing by 24% following the discontinuation of topical medication. Nevertheless, this rebound did not reach statistical significance. Similarly, the itch score continued to show a decreasing trend even after discontinuation of timolol, whereas a slight increase was observed in the topical steroid group. These findings suggest that timolol may provide a more sustained therapeutic effect, while desoximetasone, despite its initial potency, may be associated with relapses once treatment is discontinued. Therefore, there might be the potential advantage of timolol in providing more durable symptom relief compared to conventional topical corticosteroids. Moreover, timolol could show less dryness and skin atrophy comparing to topical steroid application. Compared with the previous report by Pawar[ 16 ], in which a few drops of timolol applied at bedtime on recalcitrant fissures or erosions of hand eczema led to marked improvement within one week, our study demonstrated a more gradual improvement over an eight-week treatment period, with some continued benefit even after discontinuation of the topical medication. Importantly, no serious adverse reactions were observed. Beta-2 adrenergic receptors are abundantly expressed on keratinocytes and play a crucial role in maintaining cutaneous homeostasis. Timolol, a non-selective beta-adrenergic antagonist, has been shown to enhance extracellular signal-regulated kinase phosphorylation and promote keratinocyte migration, thereby facilitating re-epithelialization and wound healing[ 15 ]. In addition, topical timolol may accelerate the recovery of skin barrier function[ 17 ], further supporting its therapeutic potential in hand eczema. Tacrolimus, a topical calcineurin inhibitor, has been recommended as a second-line treatment[ 18 ] due to its efficacy being comparable to that of topical mometasone furoate[ 19 ]. It may be particularly useful for patients requiring long-term therapy, as it is considered safe and does not induce skin atrophy. However, its short-term effectiveness appears limited, with fewer than half of the subjects achieving clearance after two weeks of application[ 20 ]. Topical calcipotriol, a vitamin D analogue, has been proposed as an alternative treatment for CHE. Juntongjin and Pongprasert[ 21 ] demonstrated efficacy comparable to desoximetasone and significant HECSI reduction, with minimal side effects such as transient stinging and no rebound during follow-up. Its efficacy and safety appear similar to timolol in our study. Additionally, combination with 308-nm excimer light further enhances efficacy but commonly induces post-inflammatory hyperpigmentation[ 22 ]. Delgocitinib, the first topical pan-JAK inhibitor recently approved by the FDA for moderate to severe CHE, exerts its effect by suppressing the release of inflammatory cytokines implicated in disease pathogenesis. Clinical evidence from the DELTA1 and DELTA2 trials[ 23 ] demonstrated significantly greater efficacy of delgocitinib compared with placebo, and further study[ 24 ] has shown superior outcomes relative to oral alitretinoin in patients with severe CHE. Nevertheless, its widespread use remains limited due to restricted availability, high cost and the lack of long-term safety data, underscoring the need for further real-world studies to determine its optimal role in clinical practice. Alitretinoin, an oral vitamin A derivative, is the only first-line systemic therapy recommended by European guidelines[ 1 , 7 ] for CHE, with treatment courses of up to 24 weeks. Owing to its teratogenicity, strict pregnancy prevention measures are required, and adverse effects such as headache, hypertriglyceridemia, elevated liver enzymes, and reduced thyroid function necessitate regular monitoring. In cases unresponsive or contraindicated to alitretinoin, off-label use of agents such as acitretin, azathioprine, methotrexate, or ciclosporine may be considered; however, their use is constrained by limited evidence and safety concerns. Emerging biologics targeting IL-4/IL-13, such as dupilumab, have shown favorable outcomes in patients with CHE even refractory to highly potent topical corticosteroids. Nevertheless, dupilumab-associated ocular surface disease remains the most notable adverse event[ 25 ]. Systemic JAK inhibitors, including abrocitinib[ 26 ], baricitinib[ 27 ], and upadacitinib[ 10 ], have also been evaluated in CHE, particularly among patients with concomitant moderate to severe atopic dermatitis. However, evidence for their efficacy in CHE without atopic dermatitis is limited, and concerns persist regarding potential risks associated with long-term use. This study has some limitations, including a small sample size, short duration, and reliance on clinical scoring without histopathologic confirmation. Conducted shortly after the COVID-19 pandemic, when frequent handwashing and sanitizer use were widespread, the findings may reflect reduced treatment responsiveness compared with pre-pandemic conditions. In consideration of the systemic adverse effects, limited availability, and high cost of systemic therapies, as well as the safety concerns associated with long-term use of high-potency topical corticosteroids in CHE, this study highlights timolol as a novel and effective topical option. Timolol demonstrated comparable efficacy to topical corticosteroids, promoted wound healing, and maintained prolonged benefit even after treatment discontinuation, in contrast to the rebound phenomenon commonly observed with corticosteroids. These findings suggest that timolol may serve as a safe, cost-effective, and clinically valuable alternative for the topical management of CHE. Declarations ACKNOWLEDGEMENTS This study was supported by Chulabhorn International College of Medicine, Thammasat University Research Fund, Contract No. B 4/2567 DATA AVAILABILITY STATEMENT The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. ETHICS DECLARATIONS AND TRIAL REGISTRY INFORMATION The study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Ethics Committee of Thammasat University (Ethics approval number: MTU-EC-OO-6-097/64, May 25, 2021). Written informed consent was obtained from all participants prior to inclusion in the study. This trial was prospectively registered with the Thai Clinical Trials Registry (TCTR20210704004). DISCLOSURE STATEMENTS The authors have no conflicts of interest to declare. References Thyssen JP et al (2022) Guidelines for diagnosis, prevention, and treatment of hand eczema. Contact Dermat 86(5):357–378 Thyssen JP et al (2010) The epidemiology of hand eczema in the general population–prevalence and main findings. Contact Dermat 62(2):75–87 Moberg C, Alderling M, Meding B (2009) Hand eczema and quality of life: a population-based study. Br J Dermatol 161(2):397–403 Armstrong A et al (2022) Economic Burden of Chronic Hand Eczema: A Review. Am J Clin Dermatol 23(3):287–300 Tauber M et al (2020) Latent class analysis categorizes chronic hand eczema patients according to skin barrier impairment. J Eur Acad Dermatol Venereol 34(7):1529–1535 Wang X et al (2020) Altered Epidermal Permeability Barrier Function in the Uninvolved Skin Supports a Role of Epidermal Dysfunction in the Pathogenesis of Occupational Hand Eczema. Skin Pharmacol Physiol 33(2):94–101 Bauer A et al (2023) S2k guideline diagnosis, prevention, and therapy of hand eczema. J Dtsch Dermatol Ges, 21(9): pp. 1054–1074 Asamoah N et al (2025) Efficacy and safety of dupilumab in chronic hand eczema: a systematic review. Arch Dermatol Res 317(1):441 Abdelhalim A et al (2025) Topical delgocitinib for the treatment of chronic hand eczema. J Dermatolog Treat 36(1):2479126 Alani O et al (2025) Treating Chronic Hand Eczema with Upadacitinib: Insights from Clinical Trials and Real-World Experience. J Drugs Dermatol 24(7):702–707 Zalewski A, Szepietowski JC (2023) Topical and systemic JAK inhibitors in hand eczema - a narrative review. Expert Rev Clin Immunol 19(4):365–373 Niculet E, Bobeica C, Tatu AL (2020) Glucocorticoid-Induced Skin Atrophy: The Old and the New. Clin Cosmet Investig Dermatol 13:1041–1050 Xia M et al (2025) The timing and safety of topical timolol treatment for superficial infantile hemangioma: a retrospective cohort study. Eur J Pediatr 184(2):151 Afarideh M, Anderson KR, Tollefson MM (2025) Trends in Healthcare Utilization and Treatments of Infantile Hemangioma in the United States: Analysis of the National Ambulatory Medical Care Survey (NAMCS) 2009–2019. Pediatr Dermatol Elsharkawy MM et al (2025) Efficacy of Topical Timolol in Chronic Unhealed Ulcers: A Systematic Review and Meta-Analysis. Int J Low Extrem Wounds, : p. 15347346251345249 Pawar M (2021) Topical timolol in chronic, recalcitrant fissures and erosions of hand eczema. J Am Acad Dermatol 84(3):e125–e126 Denda M, Fuziwara S, Inoue K (2003) Beta2-adrenergic receptor antagonist accelerates skin barrier recovery and reduces epidermal hyperplasia induced by barrier disruption. J Invest Dermatol 121(1):142–148 Weidinger S, Novak N (2024) Hand eczema. Lancet 404(10470):2476–2486 Katsarou A et al (2012) Tacrolimus 0.1% vs mometasone furoate topical treatment in allergic contact hand eczema: a prospective randomized clinical study. Eur J Dermatol 22(2):192–196 Schliemann S et al (2008) Tacrolimus ointment in the treatment of occupationally induced chronic hand dermatitis. Contact Dermat 58(5):299–306 Juntongjin P, Pongprasert R (2019) Calcipotriol ointment shows comparable efficacy to topical steroids in chronic hand eczema. Dermatol Ther 32(4):e12956 Juntongjin P, Chunhakham P (2021) Synergistic Effects of the 308-nm Excimer Light and Topical Calcipotriol for the Treatment of Chronic Hand Eczema: A Randomized Controlled Study. Dermatology 237(1):31–38 Bissonnette R et al (2024) Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 1 and DELTA 2): results from multicentre, randomised, controlled, double-blind, phase 3 trials. Lancet 404(10451):461–473 Gimenez-Arnau AM et al (2025) Efficacy and safety of topical delgocitinib cream versus oral alitretinoin capsules in adults with severe chronic hand eczema (DELTA FORCE): a 24-week, randomised, head-to-head, phase 3 trial. Lancet 405(10490):1676–1688 Riva HR et al (2024) Dupilumab for Chronic Hand Eczema: A Systematic Review and Meta-Analysis. Dermatitis Kamphuis E et al (2024) Real-world Experience of Abrocitinib Treatment in Patients with Atopic Dermatitis and Hand Eczema: Up to 28-week Results from the BioDay Registry. Acta Derm Venereol 104:adv19454 Khurana A et al (2025) Baricitinib in severe and recalcitrant hyperkeratotic chronic hand eczema and associated tissue cytokine patterns: are pan JAK inhibitors a more suitable choice? Arch Dermatol Res 317(1):443 Table 1 Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 20 Jan, 2026 Editor assigned by journal 11 Nov, 2025 Submission checks completed at journal 11 Nov, 2025 First submitted to journal 10 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8079196","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":577923068,"identity":"6823a1ac-ddfc-4867-8f9c-623859a62f4f","order_by":0,"name":"Premjit Juntongjin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYLACCQMgwd7AwEyKFqAengOkaGFgAGqRSCBSi7n04aMbLAr+JG6XfGP4uaDChoG/vTsBrxbLvrS0G0CHJe6cnWMsPeNMGoPEmbMb8LvoDI8ZSIuxwe0cA2netsMMBhK5hLTwf4NouXnG+DeRWnjYQFrkDG7wmBFni2UPG8hhxnKWPWll1jxn0ngI+sWch/nZbYk/cjzm7Ic33+apsJHjb+8l4DAgZpYAMzhAbAYevMphWhg/gBnsDwiqHgWjYBSMgpEJAGEEQOciT2EVAAAAAElFTkSuQmCC","orcid":"","institution":"Chulabhorn International College of Medicine, Thammasat University","correspondingAuthor":true,"prefix":"","firstName":"Premjit","middleName":"","lastName":"Juntongjin","suffix":""},{"id":577923069,"identity":"4a6611c4-3104-45c1-9a2b-b98a4bb03a3b","order_by":1,"name":"Pyrapa Jivanantapravat","email":"","orcid":"","institution":"Chulabhorn International College of Medicine, Thammasat University","correspondingAuthor":false,"prefix":"","firstName":"Pyrapa","middleName":"","lastName":"Jivanantapravat","suffix":""}],"badges":[],"createdAt":"2025-11-10 16:38:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8079196/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8079196/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100876856,"identity":"ea7768bc-599a-4271-b816-cd17d36409f5","added_by":"auto","created_at":"2026-01-22 10:26:46","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1735650,"visible":true,"origin":"","legend":"","description":"","filename":"submitArchDermResearchCHEtimolol.docx","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/51efa7b2635bb61edd8deaf7.docx"},{"id":100876909,"identity":"41e70d45-a038-4a0e-8c0a-5fb01a802a69","added_by":"auto","created_at":"2026-01-22 10:26:53","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":4269,"visible":true,"origin":"","legend":"","description":"","filename":"cada8f128fe74e2ca5491cfc19966f9c.json","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/680ffcdb2396422e6358c4fa.json"},{"id":100952719,"identity":"25c74c8e-ee98-4865-8f96-cab5f132f7e3","added_by":"auto","created_at":"2026-01-23 07:17:44","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":65681,"visible":true,"origin":"","legend":"","description":"","filename":"cada8f128fe74e2ca5491cfc19966f9c1enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/c5a5cb35108a44f0d186d858.xml"},{"id":100876859,"identity":"7799ec04-1280-452a-b202-6766c292fe2a","added_by":"auto","created_at":"2026-01-22 10:26:46","extension":"jpeg","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":114898,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/5112ee84bfe36b0721c1ed05.jpeg"},{"id":100876891,"identity":"274a3703-0658-4606-aaa8-c3a33dfac515","added_by":"auto","created_at":"2026-01-22 10:26:46","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1293597,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/219db876043f3a50c04f0ba0.png"},{"id":100876854,"identity":"8573b191-aa92-4ce5-a43a-c56df1d78de0","added_by":"auto","created_at":"2026-01-22 10:26:45","extension":"jpeg","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":121798,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/e19fe043b59b8061e9465ca2.jpeg"},{"id":100950390,"identity":"486c28f5-5471-4d42-b2cf-660c318970a0","added_by":"auto","created_at":"2026-01-23 07:07:55","extension":"jpeg","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":109350,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/a5a80e88920ba9a8f2c83513.jpeg"},{"id":100876879,"identity":"f042977a-8927-4e95-87ad-ee6ebe172287","added_by":"auto","created_at":"2026-01-22 10:26:46","extension":"png","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":34867,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/68ac29ab4ab411c214b0f81f.png"},{"id":100876899,"identity":"4f5b3b9a-c178-42aa-9a74-c3a747e3497f","added_by":"auto","created_at":"2026-01-22 10:26:46","extension":"png","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":153975,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/1ebbaa0950d815d837f7b9be.png"},{"id":100876916,"identity":"563f5cb3-a633-43fc-aee2-72a1810fcef7","added_by":"auto","created_at":"2026-01-22 10:26:53","extension":"png","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":29838,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/7e33f1ed19bf3f7dcc41745a.png"},{"id":100876913,"identity":"c55a6ad6-6e23-4d93-a76f-bb1339348d28","added_by":"auto","created_at":"2026-01-22 10:26:53","extension":"png","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":34918,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/43127703ba03ca841fba0a7b.png"},{"id":100949723,"identity":"cd7c3769-7087-4929-8566-ed2ed20fce55","added_by":"auto","created_at":"2026-01-23 07:05:13","extension":"xml","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":62584,"visible":true,"origin":"","legend":"","description":"","filename":"cada8f128fe74e2ca5491cfc19966f9c1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/4a8753c94c33cfd9f6437dfc.xml"},{"id":100950543,"identity":"54352b23-8eb4-4e64-b5ae-e3107dd48e27","added_by":"auto","created_at":"2026-01-23 07:08:33","extension":"html","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":72511,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/fa79456a99669513703321ed.html"},{"id":100876858,"identity":"966599a4-6781-4d6d-812e-c24296d0ea5b","added_by":"auto","created_at":"2026-01-22 10:26:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":283835,"visible":true,"origin":"","legend":"\u003cp\u003eMean HECSI scores in participants treated with Timolol 0.5% and Desoximetasone 0.25%\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/d720e37b804cf821f11e04b4.png"},{"id":100876867,"identity":"f94855bb-a5fa-437c-9758-b33aec65d15f","added_by":"auto","created_at":"2026-01-22 10:26:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1293597,"visible":true,"origin":"","legend":"\u003cp\u003eClinical improvement following Timolol 0.5% and Desoximetasone 0.25%\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/426b4c8939e61a49546de003.png"},{"id":100949590,"identity":"12765e41-2434-4b31-a7b7-b42169fa804a","added_by":"auto","created_at":"2026-01-23 07:04:32","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":254776,"visible":true,"origin":"","legend":"\u003cp\u003eVAS scores of itch severity\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/8b006642a9a1e86a7bfe00e6.png"},{"id":100876901,"identity":"80adb50b-9782-41fa-a452-af08f1f834d3","added_by":"auto","created_at":"2026-01-22 10:26:46","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":283008,"visible":true,"origin":"","legend":"\u003cp\u003eVAS scores of disease severity\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/faa95d5ca6052491d8db7962.png"},{"id":100953415,"identity":"93a4613a-0b63-4894-a2a9-ed11661a01b1","added_by":"auto","created_at":"2026-01-23 07:21:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2411682,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/1978a461-8c17-41a3-8b9f-a7a189d61fc8.pdf"},{"id":100876855,"identity":"b7d98612-c734-4a37-a0f5-7eb622cfc43d","added_by":"auto","created_at":"2026-01-22 10:26:46","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16354,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8079196/v1/c90a4bd7c567a1b28bfce207.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Topical timolol, a novel therapeutic option for chronic hand eczema: a randomized double blind-controlled study","fulltext":[{"header":"SIGNIFICANCE","content":"\u003cp\u003eTimolol demonstrated efficacy comparable to high-potency topical corticosteroids in chronic hand eczema. \u0026nbsp; With its good safety profile, easier availability, and lower cost, timolol may be considered a practical alternative topical therapy, particularly in patients where steroid use is limited by contraindications or long-term safety concerns.\u003c/p\u003e\n"},{"header":"INTRODUCTION","content":"\u003cp\u003eChronic hand eczema (CHE) is defined as an eczematous process on the hands or wrists lasting over three months or relapsing at least twice a year[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It affects nearly 10% of the population annually[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], with significant impacts on quality of life comparable to psoriasis and asthma[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. CHE also carries a considerable economic burden which is comparable with other dermatological conditions[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, this data is likely underestimated due to outdated studies and increased cases during the COVID-19 pandemic.\u003c/p\u003e \u003cp\u003eCHE have multifactorial etiologies, with skin barrier dysfunction playing a key role[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. According to the guidelines, various classic treatments for hand eczema include topical corticosteroids, topical calcineurin inhibitors, phototherapy, oral corticosteroids, alitretinoin, acitretin, cyclosporin, azathioprine and methotrexate[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Moreover, dupilumab[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], topical and oral JAK inhibitors have been extensively reporting their favorable outcomes[\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Although topical corticosteroids remain the first-line therapy, long-term use is associated with adverse effects such as skin atrophy, telangiectasia, and impaired barrier repair, making management challenging[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTimolol, a non-selective beta-adrenergic antagonist traditionally used for glaucoma, has emerged as an off-label dermatologic treatment. It has shown efficacy and significantly increases prescription in vascular tumors[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and chronic wounds by promoting re-epithelialization and modulating inflammation through β2-adrenergic receptor blockade[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Also, Pawar reported timolol\u0026rsquo;s potential for treating recalcitrant CHE[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study aims to compare the efficacy and safety of topical timolol 0.5% versus desoximetasone 0.25% in CHE treatment, proposing timolol as a possible alternatively effective and affordable therapy.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003eThis clinical study was designed as a prospective, randomized, double-blinded, intraindividual right\u0026ndash;left comparative trial. The study was conducted between March 2021 and April 2022 at the Department of Dermatology, Benchakitti Park Hospital, and Thammasat University Hospital, Thailand. The research protocol was reviewed and approved by the Human Research Ethics Committee of Thammasat University. Written informed consent was obtained from all participants prior to enrollment.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSubject Recruitment\u003c/h2\u003e \u003cp\u003eA total of twenty patients diagnosed with CHE were enrolled in the study. Inclusion criteria consisted of adults aged 20 to 65 years presenting with bilateral CHE of mild to moderate severity, as assessed by the Physician Global Assessment (PGA) score. Exclusion criteria were as follows: (1) a history of sinus bradycardia, second- or third-degree heart block, overt cardiac failure, or cardiogenic shock; (2) a history of bronchial asthma or chronic obstructive pulmonary disease; (3) use of topical immunosuppressants, retinoids, or corticosteroids within 2 weeks prior to study initiation; (4) use of systemic immunosuppressants, retinoids, corticosteroids, or phototherapy within 4 weeks prior to study initiation; (5) presence of other active dermatoses on the hands, such as psoriasis or acute skin infections; (6) pregnancy or lactation; (7) a previously positive patch test; and (8) known hypersensitivity to any components of timolol or desoximetasone.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eIntervention\u003c/h3\u003e\n\u003cp\u003eTimolol Maleate Eye Drop 0.5% solution (Alcon\u0026reg; Timolol Maleate Eye Drops; Alcon, Belgium) and desoximetasone 0.25% cream (Topicorte\u0026reg;; Sanofi, France) were repackaged into identical sterile tubes to ensure blinding. The products were assigned to either the left or right hand of each participant using computer-generated block randomization. Subjects were instructed to apply the assigned product to the designated hand twice daily for 8 weeks. This treatment phase was followed by a 4-week maintenance phase, during which petroleum ointment was applied to both hands twice daily. To prevent cross-contamination, a single-use cotton bud was used for each application. The use of any other topical products in the treated areas was not allowed throughout the study period.\u003c/p\u003e\n\u003ch3\u003eOutcome Measurement\u003c/h3\u003e\n\u003cp\u003eOutcome assessments were conducted at baseline, and at week 2, 4, and 8 during treatment period, as well as at week 12 (four weeks after treatment discontinuation). The Hand Eczema Severity Index (HECSI) was employed as an objective measure of disease severity. Standardized clinical photographs were captured at each visit using a full-frame mirrorless digital camera (Sony α7III; Sony Corp., Tokyo, Japan) under consistent lighting conditions. Subjective clinical outcomes were assessed using the Visual Analogue Scale (VAS). Subjects were instructed to rate the intensity of pruritus in each hand on a 10-cm VAS, where 0 represented no symptoms and 10 denoted the worst imaginable symptoms. Subject-perceived disease severity was also recorded using the same VAS method. Adverse reactions were monitored and assessed at every follow-up visit.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using IBM SPSS Statistics, version 26 (IBM Corp., Armonk, NY, USA). Categorical variables were summarized as frequencies and percentages, while continuous variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). Nonparametric tests were used for intra- (Wilcoxon\u0026rsquo;s Sign Rank test) and inter- (Mann Whitney U-test) group comparisons. A p-value of less than 0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eSubjects\u003c/h2\u003e\n \u003cp\u003eOf the 20 subjects enrolled in the study, 19 completed the study as per protocol. One subject was lost to follow-up due to personal circumstances and was excluded from the final analysis. The majority were female (73.7%), with a mean age of 47.74\u0026thinsp;\u0026plusmn;\u0026thinsp;10.06 years (range 28\u0026ndash;63 years). The average duration of CHE was 70.00\u0026thinsp;\u0026plusmn;\u0026thinsp;101.83 months, ranging from 10 to 360 months. At baseline, 57.9% of participants presented with mild disease and 42.1% with moderate disease based on the Physician Global Assessment (PGA). The most common clinical variant was chronic fissure hand eczema (63.2%), followed by hyperkeratotic hand eczema (21.1%), vesicular hand eczema (10.5%), and discoid eczema (5.3%). The most common occupations were office workers (36.84%) and maids/cleaners (26.32%). A history of atopy was reported in 63.16% of participants. (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eEfficacy\u003c/h3\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003eObjective evaluation\u003c/h2\u003e\n \u003cp\u003eThe Hand Eczema Severity Index (HECSI) was used to objectively evaluate disease severity. At baseline, no significant difference was observed in mean HECSI scores between timolol- and desoximetasone-treated hands.\u003c/p\u003e\n \u003cp\u003eBoth regimens demonstrated significant improvement in HECSI scores following the 8-week treatment period (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). At week 8, HECSI scores were gradually decreased by approximately 43% in timolol group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 53% in the desoximetasone group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No significant difference in the magnitude of improvement between groups was revealed at any visit.\u003c/p\u003e\n \u003cp\u003eFollowing treatment discontinuation, only petrolatum ointment was allowed to be applied on both hands for the later 4 weeks. At week 12, HECSI scores in both groups remained significantly lower than baseline (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Interestingly, the timolol-treated side showed a continued, though modest, reduction in HECSI scores while the desoximetasone-treated side exhibited an increase of approximately 24% from the 8th week. Nevertheless, the changes noticed during the follow-up period were not significantly difference when comparing the two treatment groups. Figure \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e demonstrates the clinical improvement observed during the study.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eSubjective evaluation\u003c/h2\u003e\n \u003cp\u003eThe Visual Analogue Scale (VAS) was employed to assess itch intensity and overall disease severity at baseline, week 8, and week 12 (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). Both timolol and desoximetasone significantly reduced itch and disease severity at week 8 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) with no statistically significant difference between groups. At the follow-up visit, the VAS scores remained stable or slightly decreased in timolol group; whereas, the scores of both itch intensity and overall disease severity increased in the desoximeasone group. Nonetheless, the differences were not statistically significant.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003eAdverse events\u003c/h2\u003e\n \u003cp\u003eDryness was the most frequent adverse event, reported in approximately 60% of the participants on the timolol-treated side and occurred significantly more often than on the desoximetasone-treated side (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Itchiness was reported with both treatments. Cracking and stringing were observed in the timolol group whereas skin atrophy and hypopigmentation were noticed in the desoximetasone group. No participants discontinued the protocol due to these adverse reactions.\u003c/p\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAdverse reactions of the treatments\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSide effects\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTimolol\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDesoximetasone\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDryness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (63.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (5.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eItchiness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7 (36.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (10.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.060\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCracking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (15.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.075\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStinging\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (10.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.152\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSkin atrophy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (5.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.317\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypopigmentation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (5.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.317\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION/CONCLUSION","content":"\u003cp\u003eThe management of chronic hand eczema (CHE) remains a therapeutic challenge due to limitations in long-term tolerability and the lack of robust evidence supporting many available treatments. To our knowledge, this study represents the first prospective, randomized, double-blinded, intraindividual, right–left comparative trial directly evaluating the efficacy of topical timolol, a nonselective β-adrenergic receptor antagonist, against desoximetasone, a potent corticosteroid, in the treatment of CHE.\u003c/p\u003e\u003cp\u003eOver the eight-week treatment period, both regimens demonstrated significant improvement in disease severity, as assessed by HECSI scores, visual analogue scale (VAS), and digital photographic evaluation. Timolol treatment resulted in a mean HECSI reduction of approximately 43% (p \u0026lt; 0.001), while desoximetasone achieved a slightly higher reduction of 53% (p = 0.001). These findings indicate that timolol, despite its distinct non-steroidal mechanism of action, exhibited a clinically meaningful effect comparable to that of a potent corticosteroid.\u003c/p\u003e\u003cp\u003eInterestingly, the post-treatment follow-up phase revealed divergent trends between the two groups. In the timolol arm, mean HECSI scores continued to decline modestly, reaching an overall 46% reduction compared with baseline (p = 0.001). In contrast, the desoximetasone group showed a rebound in disease severity, with HECSI scores increasing by 24% following the discontinuation of topical medication. Nevertheless, this rebound did not reach statistical significance. Similarly, the itch score continued to show a decreasing trend even after discontinuation of timolol, whereas a slight increase was observed in the topical steroid group. These findings suggest that timolol may provide a more sustained therapeutic effect, while desoximetasone, despite its initial potency, may be associated with relapses once treatment is discontinued. Therefore, there might be the potential advantage of timolol in providing more durable symptom relief compared to conventional topical corticosteroids. Moreover, timolol could show less dryness and skin atrophy comparing to topical steroid application.\u003c/p\u003e\u003cp\u003eCompared with the previous report by Pawar[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], in which a few drops of timolol applied at bedtime on recalcitrant fissures or erosions of hand eczema led to marked improvement within one week, our study demonstrated a more gradual improvement over an eight-week treatment period, with some continued benefit even after discontinuation of the topical medication. Importantly, no serious adverse reactions were observed.\u003c/p\u003e\u003cp\u003eBeta-2 adrenergic receptors are abundantly expressed on keratinocytes and play a crucial role in maintaining cutaneous homeostasis. Timolol, a non-selective beta-adrenergic antagonist, has been shown to enhance extracellular signal-regulated kinase phosphorylation and promote keratinocyte migration, thereby facilitating re-epithelialization and wound healing[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In addition, topical timolol may accelerate the recovery of skin barrier function[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], further supporting its therapeutic potential in hand eczema.\u003c/p\u003e\u003cp\u003eTacrolimus, a topical calcineurin inhibitor, has been recommended as a second-line treatment[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] due to its efficacy being comparable to that of topical mometasone furoate[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. It may be particularly useful for patients requiring long-term therapy, as it is considered safe and does not induce skin atrophy. However, its short-term effectiveness appears limited, with fewer than half of the subjects achieving clearance after two weeks of application[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTopical calcipotriol, a vitamin D analogue, has been proposed as an alternative treatment for CHE. Juntongjin and Pongprasert[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] demonstrated efficacy comparable to desoximetasone and significant HECSI reduction, with minimal side effects such as transient stinging and no rebound during follow-up. Its efficacy and safety appear similar to timolol in our study. Additionally, combination with 308-nm excimer light further enhances efficacy but commonly induces post-inflammatory hyperpigmentation[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e Delgocitinib, the first topical pan-JAK inhibitor recently approved by the FDA for moderate to severe CHE, exerts its effect by suppressing the release of inflammatory cytokines implicated in disease pathogenesis. Clinical evidence from the DELTA1 and DELTA2 trials[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] demonstrated significantly greater efficacy of delgocitinib compared with placebo, and further study[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] has shown superior outcomes relative to oral alitretinoin in patients with severe CHE. Nevertheless, its widespread use remains limited due to restricted availability, high cost and the lack of long-term safety data, underscoring the need for further real-world studies to determine its optimal role in clinical practice.\u003c/p\u003e\u003cp\u003eAlitretinoin, an oral vitamin A derivative, is the only first-line systemic therapy recommended by European guidelines[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] for CHE, with treatment courses of up to 24 weeks. Owing to its teratogenicity, strict pregnancy prevention measures are required, and adverse effects such as headache, hypertriglyceridemia, elevated liver enzymes, and reduced thyroid function necessitate regular monitoring. In cases unresponsive or contraindicated to alitretinoin, off-label use of agents such as acitretin, azathioprine, methotrexate, or ciclosporine may be considered; however, their use is constrained by limited evidence and safety concerns.\u003c/p\u003e\u003cp\u003eEmerging biologics targeting IL-4/IL-13, such as dupilumab, have shown favorable outcomes in patients with CHE even refractory to highly potent topical corticosteroids. Nevertheless, dupilumab-associated ocular surface disease remains the most notable adverse event[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Systemic JAK inhibitors, including abrocitinib[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], baricitinib[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], and upadacitinib[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], have also been evaluated in CHE, particularly among patients with concomitant moderate to severe atopic dermatitis. However, evidence for their efficacy in CHE without atopic dermatitis is limited, and concerns persist regarding potential risks associated with long-term use.\u003c/p\u003e\u003cp\u003eThis study has some limitations, including a small sample size, short duration, and reliance on clinical scoring without histopathologic confirmation. Conducted shortly after the COVID-19 pandemic, when frequent handwashing and sanitizer use were widespread, the findings may reflect reduced treatment responsiveness compared with pre-pandemic conditions.\u003c/p\u003e\u003cp\u003eIn consideration of the systemic adverse effects, limited availability, and high cost of systemic therapies, as well as the safety concerns associated with long-term use of high-potency topical corticosteroids in CHE, this study highlights timolol as a novel and effective topical option. Timolol demonstrated comparable efficacy to topical corticosteroids, promoted wound healing, and maintained prolonged benefit even after treatment discontinuation, in contrast to the rebound phenomenon commonly observed with corticosteroids. These findings suggest that timolol may serve as a safe, cost-effective, and clinically valuable alternative for the topical management of CHE.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch6\u003eACKNOWLEDGEMENTS\u003c/h6\u003e\n\u003cp id=\"_Toc472330568\"\u003eThis study was supported by Chulabhorn International College of Medicine, Thammasat University Research Fund, Contract No.\u0026nbsp;B 4/2567\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eDATA AVAILABILITY STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eETHICS DECLARATIONS AND TRIAL REGISTRY INFORMATION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Ethics Committee of Thammasat University (Ethics approval number: MTU-EC-OO-6-097/64, May 25, 2021). \u0026nbsp; Written informed consent was obtained from all participants prior to inclusion in the study. This trial was prospectively registered with the Thai Clinical Trials Registry (TCTR20210704004).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eDISCLOSURE STATEMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eThyssen JP et al (2022) Guidelines for diagnosis, prevention, and treatment of hand eczema. Contact Dermat 86(5):357\u0026ndash;378\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThyssen JP et al (2010) The epidemiology of hand eczema in the general population\u0026ndash;prevalence and main findings. Contact Dermat 62(2):75\u0026ndash;87\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoberg C, Alderling M, Meding B (2009) Hand eczema and quality of life: a population-based study. Br J Dermatol 161(2):397\u0026ndash;403\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArmstrong A et al (2022) Economic Burden of Chronic Hand Eczema: A Review. Am J Clin Dermatol 23(3):287\u0026ndash;300\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTauber M et al (2020) Latent class analysis categorizes chronic hand eczema patients according to skin barrier impairment. J Eur Acad Dermatol Venereol 34(7):1529\u0026ndash;1535\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang X et al (2020) Altered Epidermal Permeability Barrier Function in the Uninvolved Skin Supports a Role of Epidermal Dysfunction in the Pathogenesis of Occupational Hand Eczema. Skin Pharmacol Physiol 33(2):94\u0026ndash;101\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBauer A et al (2023) \u003cem\u003eS2k guideline diagnosis, prevention, and therapy of hand eczema.\u003c/em\u003e J Dtsch Dermatol Ges, 21(9): pp. 1054\u0026ndash;1074\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAsamoah N et al (2025) Efficacy and safety of dupilumab in chronic hand eczema: a systematic review. Arch Dermatol Res 317(1):441\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbdelhalim A et al (2025) Topical delgocitinib for the treatment of chronic hand eczema. J Dermatolog Treat 36(1):2479126\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlani O et al (2025) Treating Chronic Hand Eczema with Upadacitinib: Insights from Clinical Trials and Real-World Experience. J Drugs Dermatol 24(7):702\u0026ndash;707\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZalewski A, Szepietowski JC (2023) Topical and systemic JAK inhibitors in hand eczema - a narrative review. Expert Rev Clin Immunol 19(4):365\u0026ndash;373\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNiculet E, Bobeica C, Tatu AL (2020) Glucocorticoid-Induced Skin Atrophy: The Old and the New. Clin Cosmet Investig Dermatol 13:1041\u0026ndash;1050\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXia M et al (2025) The timing and safety of topical timolol treatment for superficial infantile hemangioma: a retrospective cohort study. Eur J Pediatr 184(2):151\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAfarideh M, Anderson KR, Tollefson MM (2025) Trends in Healthcare Utilization and Treatments of Infantile Hemangioma in the United States: Analysis of the National Ambulatory Medical Care Survey (NAMCS) 2009\u0026ndash;2019. Pediatr Dermatol\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElsharkawy MM et al (2025) Efficacy of Topical Timolol in Chronic Unhealed Ulcers: A Systematic Review and Meta-Analysis. Int J Low Extrem Wounds, : p. 15347346251345249\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePawar M (2021) Topical timolol in chronic, recalcitrant fissures and erosions of hand eczema. J Am Acad Dermatol 84(3):e125\u0026ndash;e126\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDenda M, Fuziwara S, Inoue K (2003) Beta2-adrenergic receptor antagonist accelerates skin barrier recovery and reduces epidermal hyperplasia induced by barrier disruption. J Invest Dermatol 121(1):142\u0026ndash;148\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWeidinger S, Novak N (2024) Hand eczema. Lancet 404(10470):2476\u0026ndash;2486\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatsarou A et al (2012) Tacrolimus 0.1% vs mometasone furoate topical treatment in allergic contact hand eczema: a prospective randomized clinical study. Eur J Dermatol 22(2):192\u0026ndash;196\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchliemann S et al (2008) Tacrolimus ointment in the treatment of occupationally induced chronic hand dermatitis. Contact Dermat 58(5):299\u0026ndash;306\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJuntongjin P, Pongprasert R (2019) Calcipotriol ointment shows comparable efficacy to topical steroids in chronic hand eczema. Dermatol Ther 32(4):e12956\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJuntongjin P, Chunhakham P (2021) Synergistic Effects of the 308-nm Excimer Light and Topical Calcipotriol for the Treatment of Chronic Hand Eczema: A Randomized Controlled Study. Dermatology 237(1):31\u0026ndash;38\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBissonnette R et al (2024) Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 1 and DELTA 2): results from multicentre, randomised, controlled, double-blind, phase 3 trials. Lancet 404(10451):461\u0026ndash;473\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGimenez-Arnau AM et al (2025) Efficacy and safety of topical delgocitinib cream versus oral alitretinoin capsules in adults with severe chronic hand eczema (DELTA FORCE): a 24-week, randomised, head-to-head, phase 3 trial. Lancet 405(10490):1676\u0026ndash;1688\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRiva HR et al (2024) \u003cem\u003eDupilumab for Chronic Hand Eczema: A Systematic Review and Meta-Analysis.\u003c/em\u003e Dermatitis\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKamphuis E et al (2024) Real-world Experience of Abrocitinib Treatment in Patients with Atopic Dermatitis and Hand Eczema: Up to 28-week Results from the BioDay Registry. Acta Derm Venereol 104:adv19454\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhurana A et al (2025) Baricitinib in severe and recalcitrant hyperkeratotic chronic hand eczema and associated tissue cytokine patterns: are pan JAK inhibitors a more suitable choice? Arch Dermatol Res 317(1):443\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Table 1","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"chronic hand eczema, topical timolol, hand dermatitis, topical therapy, randomized controlled trial, double-blind study","lastPublishedDoi":"10.21203/rs.3.rs-8079196/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8079196/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eChronic hand eczema (CHE) is a relapsing inflammatory skin condition often treated with topical corticosteroids, which can cause long-term adverse effects. Topical timolol, a non-selective beta-blocker, has shown promise as an alternative therapy. This study aims to compare the efficacy and safety of topical timolol 0.5% versus desoximetasone 0.25% in CHE. In this randomized, double-blind study, CHE participants applied timolol and desoximetasone to opposite hands twice daily for 8 weeks, followed by 4 weeks of petrolatum application. The Hand Eczema Severity Index (HECSI), itching, disease severity, and adverse events were assessed. Total nineteen participants completed the study. Both treatments significantly reduced HECSI scores (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) with no significant difference between groups. A rebound phenomenon occurred after desoximetasone discontinuation. Timolol was associated with dryness, itchiness, cracking, and stinging, while desoximetasone caused epidermal atrophy and hypopigmentation. No serious adverse events were reported. In conclusion, timolol is an effective and safe treatment and may be an alternative therapeutic option for CHE.\u003c/p\u003e","manuscriptTitle":"Topical timolol, a novel therapeutic option for chronic hand eczema: a randomized double blind-controlled study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-22 10:26:37","doi":"10.21203/rs.3.rs-8079196/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-01-20T20:56:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-11T07:30:49+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-11T07:28:16+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Dermatological Research","date":"2025-11-10T16:31:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"120aa301-d519-4520-95fc-ec1211add33e","owner":[],"postedDate":"January 22nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-22T10:26:38+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-22 10:26:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8079196","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8079196","identity":"rs-8079196","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}