Topical corticosteroids remain the mainstay of psoriasis management but are limited by skin atrophy and barrier impairment. Developing safer, steroid-sparing therapy represents an unmet need in topical pharmacology. The glucocorticoid receptor (GR) plays a central role in epidermal homeostasis, yet selective activation by natural phytochemicals has not been systematically explored. A molecular modeling framework integrating docking, molecular dynamics simulations, and pharmacophore conservation was established to evaluate GR engagement by four phytochemicals-sakuranetin, salvianolic acid B, lithospermic acid, and magnolol. Computational findings were compared with immunohistochemical analysis of total GR and phosphorylated Ser211-GR in psoriatic epidermal specimens derived from residual archived tissues. Salvianolic acid B and lithospermic acid displayed high docking affinity and stable retention of canonical GR contacts, whereas sakuranetin and magnolol exhibited moderate but consistent binding. Immunohistochemistry confirmed preserved GR abundance for all compounds, with lithospermic acid producing the greatest increase in Ser211 phosphorylation, consistent with differential receptor-associated signaling patterns. Computational and histological findings showed preliminary directional concordance between computational interaction profiles and tissue-level receptor-associated readouts. This study demonstrates that integrating molecular modeling with receptor-associated histological analysis may assist in prioritizing natural compounds with potential GR-engagement properties. The proposed framework provides an exploratory and reproducible strategy for receptor-engagement prioritization in topical pharmacology and may support future investigation of bioactive phytochemicals in dermatologic research.

BackgroundDermatitis cruris pustulosa et atrophicans (DCPA), a chronic skin inflammatory condition involving the shins, is a marginally recognized disorder in Uganda.PurposeTo describe the clinical manifestation of DCPA and risk factors among populations in southwestern Uganda.Patients and MethodsThe study was conducted in Mbarara and Kabale Regional Referral Hospital Skin Clinics. Demographic data and digital images of affected shins were taken and stored on remote server. In a descriptive cross-sectional study, data was collected from 405 participants from 02/November/2022 to 04/January/2024 and was analyzed using R, a data visualization and statistical computing programming language.ResultsMost patients (74.9%) were aged 0–25 years, with a mean age of 21.6 years (SD = 15.1). Females constituted 71.9% of cases. Patients were almost evenly distributed between Mbarara (46.2%) and Kabale (53.8%) Hospitals. The largest affected groups were students (38%) and pupils/infants (25.4%) followed by Farmers (16%) and semiskilled laborers (8.9%). Petroleum jelly was the most topical application (28.6%) while herbal remedies (11.9%), Systemic antibiotics (8.9%) and topical antifungal treatments (5.2%) were less frequently used.ConclusionDCPA presents with itching, pus discharge, and atrophic skin changes. In southwestern Uganda, it mainly affects young females. In its multifactorial etiopathogenesis oily cosmetic products is a contributory factor.These findings, supported by Mbarara University Data Science Research Hub (MUDSReH), highlight the need for improved diagnostic tools and targeted interventions for DCPA. Further research is needed to assess the broader impact of DCPA in Uganda.

Striae distensae (SD) is a prevalent dermatological disorder characterized by linear skin atrophy. It is associated with various factors, including mechanical tension, hormonal changes, and genetics. Many articles on SD have been published. Nevertheless, a systematic bibliometric analysis of global research trends in SD has not been conducted. To comprehensively analyze the field of SD using bibliometric tools, aiming to summarize the historical and current research progress in the field, identify global research hotspots and dynamic changes, and finally explore the potential direction of future research and clinical application. Records related to SD were collected in the Web of Science Core Collection database. Citation burst analysis was conducted to identify key authors who showed significant contributions in SD. A bibliometric analysis was applied to identify critical research trends in this field. A total of 234 records related to SD from 1 January 2015 to 31 December 2024 were collected. This study highlighted a steady growth in the number of publications from the United States and Egypt. Hague A., Lokhande AJ., and Hodeib AA. showed their significant contributions from their research on the treatment of SD. A bibliometric analysis showed therapy and management were the hotspots of this field. The temporal clustering analysis of 287 keywords indicated a transition from fundamental studies to increasing research themes. The bibliometric analysis of 234 SD publications from 2015 to 2024 has given us an insight into the trends and hotspots in the field, which are important for promoting international collaboration and driving improvements in clinical practice. More scientific breakthroughs in the prevention and treatment of SD are needed to meet the growing global demand for skin health.

Transcriptome-guided development of a fibrosis-reversal compound reduces skin scarring and allows regeneration via mitochondrial uncoupling

The topical calcineurin inhibitors [TCIs] pimecrolimus and tacrolimus, offer an effective non-steroidal option for treating atopic dermatitis [AD], particularly in sensitive skin areas and for long-term use. There are several studies published on the effect of calcineurin inhibitors on the skin barrier but a comprehensive review on this topic is still missing. This review summarizes current evidence on the impact of TCIs on epidermal barrier structure and function. Clinical studies in patients with AD show that TCIs improve transepidermal water loss [TEWL], enhance stratum corneum [SC] hydration, and promote normalization of structural proteins such as filaggrin and loricrin. Unlike topical corticosteroids [TCS], TCIs do not induce skin atrophy and may even reverse steroid-induced epidermal thinning. Additionally, TCIs partially preserve antimicrobial peptide [AMP] expression in lesional AD skin, which may help reduce Staphylococcus aureus colonization and support microbial diversity. Positive effects on lipid lamellar organization and natural moisturizing factor [NMF] levels further support barrier restoration. Animal data suggesting impaired lipid synthesis under TCI treatment contrast with consistent positive findings in clinical studies. Importantly, emerging evidence indicates that TCIs may improve the skin microbiome in AD. TCIs exert their beneficial effects on skin inflammation through selective T-cell modulation without disrupting keratinocyte differentiation or dermal matrix components. For this reason, the general indirect positive effects on skin barrier associated with reduction of skin inflammation is not counterbalanced by intrinsic barrier damaging mechanisms as observed with topical steroids. Further studies are needed to evaluate long-term effects on skin structure, microbiome stability, and their integration into biologic treatment algorithms.

Allergic diseases are a heavy clinical and socioeconomic burden to human society. Dysregulated immune responses, especially a Th2 cytokine response and IgE-mediated hyperinflammation, are the main factors of the cascade of cellular and molecular events that underlie the immunopathogenesis of allergic diseases. The traditional antiallergic treatment is restricted today because of a wide variety of adverse effects (skin atrophy, growth retardation in children, hypertension, osteoporosis, and tachycardia). Thus, preclinical research should find other interventions that have fewer side effects and optimize the effectiveness of the treatment plan. Curcumin is a polytropic bioactive polyphenol derived from the rhizome of turmeric plant (strong anti-inflammatory, antioxidant, and immunomodulatory properties). The low water solubility, chemical instability, and rapid systemic metabolism have, however, limited its clinical use. Reportedly, nanotechnology has attempted to improve the pharmacokinetic and therapeutic targeting of nanocurcumin formulations using a number of methods. Therefore, this paper is a review of the immunopharmacological prospects of curcumin and nanocurcumin in allergic diseases, including preclinical and clinical evidence. The current review paper reviews the effects of curcumin in the inhibition of Th2 responses. Moreover, it has explored the Th1/Th2 balance, mast cell degranulation inhibition, decreasing proinflammatory mediators, and immune modulation. Conversely, it has recommended nanotechnological methods to enhance the solubility, cellular internalization, and release characteristics of nanocurcumin preparations to increase its efficacy. Lastly, the review gives future research directions by ranking limitations of the existing literature (methodological diversity and difficulties in applying the results to a clinical setting).

Over 15% of acne patients manifest moderate to severe clinical presentations, accompanied with bacterial infection, long-term inflammatory responses, dysregulated lipid metabolism, and post-acne skin atrophy. Although microneedles (MNs) represent an effective transdermal drug delivery system for acne treatment, the therapeutic effects on the restoration of dysregulated lipid metabolism and the prevention of atrophic acne scars are still lacking. Herein, we develop proteoglycan-mimetic comb polymer (HMC)-based dissolving microneedles (HMC-PEP MNs) with encapsulation of therapeutic peptides. This system effectively targets the acne pathophysiological pathways involving bacterial colonization, lipid dysregulation, chronic inflammation and impaired tissue repair. Specifically, HMC enables sustained release of antimicrobial and anti-inflammatory peptides via multiple non-covalent interactions. HMC-PEP MNs display significant efficacy via eradicatingCutibacterium acnes infection, suppressing pro-inflammatory mediator expression, and reducing the TREM2/M2 macrophage ratio. Integrated transcriptomic and metabolomic analysis reveals that HMC-PEP MNs effectively regulate cholesterol and linoleic acid metabolism, inhibit pro-inflammatory signaling transduction, and reduce keratinocyte proliferation and differentiation by inhibiting the IGF1/IGF1R/PI3K/AKT/mTOR signaling pathway. Interestingly, HMC-PEP MNs also promote collagen synthesis and ameliorate fibroblast dysfunction, thereby preventing the formation of post-acne dermal atrophy. This study presents an effective therapeutic strategy for acne and elucidates the underlying mechanisms of HMC-PEP MNs, demonstrating considerable promise for clinical translation.

Physical rehabilitation interventions for hand function in people with systemic sclerosis.

Hypertrophic scars (HTS) are common complications of wound healing characterized by excessive fibroblast proliferation and collagen deposition. HTS causes local elevation, pruritus, and pain, significantly impacting aesthetics and quality of life. While triamcinolone acetonide (TA) and compound betamethasone (CB) are standard treatments, direct comparative studies regarding their efficacy and recurrence rates remain limited. To evaluate the clinical efficacy, safety, and recurrence rate over 6 months of local injection of TA and CB monotherapy in the treatment of HTS. We retrospectively analyzed 126 patients with HTS who received intralesional injection therapy at our hospital between December 2021 and December 2024. Patients were divided into the TA group (n = 63) and the CB group (n = 63) based on the injected drug. All patients were observed during treatment and followed for at least 6 months to monitor adverse reactions and recurrence. Scar assessment was performed using the Vancouver Scar Scale (VSS), combined with high-frequency ultrasonography to measure scar thickness changes. Clinical efficacy was evaluated based on the percentage reduction in VSS scores. Baseline characteristics were not significantly different between the two groups. Both CB and TA significantly reduced VSS scores and ultrasonographically measured scar thickness in patients with HTS; however, the CB group exhibited greater reductions in both VSS scores and scar thickness compared with the TA group. Evaluation of clinical efficacy revealed a total effective rate of 93.65% in the CB group versus 80.95% in the TA group. The incidence of adverse reactions was similar between the two groups, primarily consisting of local skin atrophy, pigmentation changes, and telangiectasia. The 6-month recurrence rate was significantly lower for CB (3.17%) than for TA (15.87%, p = 0.015). Both CB and TA intralesional injections are effective in improving VSS scores, reducing scar thickness, and achieving high clinical efficacy rates in patients with HTS. However, CB demonstrates superior therapeutic outcomes and a significantly lower recurrence rate compared with TA, supporting its wider clinical application.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder requiring long-term topical therapy. While topical corticosteroids (TCS) remain the mainstay of treatment, their prolonged use is associated with adverse effects. Topical tacrolimus, a calcineurin inhibitor, offers a steroid-sparing alternative with a different safety profile. Aim: To compare the efficacy and safety of topical tacrolimus versus topical corticosteroids in the management of atopic dermatitis. Materials and Methods: A prospective, randomized, open-label, parallel-group study was conducted over one year in a tertiary care hospital. A total of 100 patients with mild to moderate AD were randomized into two groups: tacrolimus (Group A) and corticosteroids (Group B), with 50 patients each. Treatments were applied twice daily for 6 weeks. Disease severity was assessed using SCORAD score, along with pruritus score, adverse effects, and recurrence rates. Statistical analysis was performed using SPSS version 26. Results: Both groups showed significant improvement in SCORAD and pruritus scores. However, corticosteroids demonstrated a significantly faster and greater reduction in disease severity at all follow-up intervals (p<0.05). Burning sensation was more common with tacrolimus (20%), whereas skin atrophy was observed only in the corticosteroid group (12%) (p<0.05). Recurrence rates were lower in the tacrolimus group (12%) compared to corticosteroids (28%). Conclusion: Topical corticosteroids provide faster symptomatic relief in atopic dermatitis, making them suitable for acute flare management. However, tacrolimus offers comparable long-term efficacy with a superior safety profile and lower recurrence rates, making it a preferable option for maintenance therapy and use in sensitive skin areas.

Background: The long-term ingestion of external corticosteroids can lead to iatrogenic Cushing’s syndrome and are known to be adverse drug reactions that are prevented. There are many nonspecific symptoms associated with iatrogenic Cushing’s syndrome that often mimic other dermatologic or systemic conditions and may therefore go undetected. If there has been long-term use of an external corticosteroid, there are also considerations if the external corticosteroid is withdrawn suddenly. It can lead to a delayed crisis. Case Report: 53-year-old hypertensive female patient presented with skin thickening and hyperpigmentation over the abdomen and the lower extremities; generalized pruritus; exertional dyspnea; weakness; recent history of a chest pain; and fall. The patient reported medical history of taking chronic non-steroidal anti-inflammatory medication and external corticosteroids for joint pain. Clinical examination showed pallor, mild pedal edema, hypertension, skin atrophy, and scaliness. When laboratory tests were performed, low serum cortisol levels, concentric left ventricular hypertrophy with diastolic dysfunction Grade I, mild anemia, thrombocytopenia, hyperbilirubinemia, and mild renal impairment were obtained. Treatment/ Results: The patient was treated with antihypertensives, supportive care, gradual tapering of steroids and dermatology consult. Conclusion: This case demonstrates that there is chronic adrenal suppression from due to long-term exposure of corticosteroids. Low cortisol level confirms the diagnosis of Cushing’s syndrome due to exogenous steroid use as compared to endogenous causes. In the evaluation of abnormal skin or systemic changes, always ask the patient about use of corticosteroids; it is important to taper corticosteroids appropriately so sudden withdrawal does not result in a crisis

Background: Atopic dermatitis (AD) is a long-lasting inflammatory disease of the skin, which strikes up to 20% of the children and 7% of adults worldwide, and has yearly health care expenses estimated at over 5 billion dollars. Though traditional medicine has been the current method of treatment, there has been increasing interest in the use of plant-based therapies because of the adverse side effects that conventional drugs may have on the human body in the long term. Purpose: This paper will aim to examine the overall comparison between plant-based and conventional medicines to treat AD, which will involve the efficacy, safety profiles, mechanism of action and clinical use. This review summarize the existing literature, recent clinical trials, and emerging treatment modalities released up to 2025 with the TC, novel conventional therapies, and evidence-based plant medicines. Findings: Traditional interventions, especially topical corticosteroids, have strong short-term effects but have side effects of skin atrophy and systemic absorption in case of long-term use. Plant-based medicines, such as TCM formulations, or individual botanical extracts, demonstrate encouraging anti-inflammatory effects with an overall good safety record of high quality, although the evidence is more lacking. Conclusions: Each of the two methods has different merits, whereby conventional medicines are fast in controlling the symptoms and plant-based alternative has milder long-term management modalities. Combined strategies could maximize patient outcomes and reduce ill outcomes.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by dryness and itching. Steroids are the most common therapeutic agents, may induce skin atrophy, and damage the skin barrier. Therefore, we need to find a safer alternative option. Liquiritin (LQ), a flavonoid compound extracted from licorice rhizomes, possesses anticancer, anti-inflammatory, and antioxidant effects. This study aimed to investigate the therapeutic effects of LQ on AD, focusing on its potential skin barrier-protective and anti-inflammatory mechanisms. In this research, we prepared liquiritin carbomer gel (LQ-CG) and assessed its treatment effects on mice with AD triggered by 2,4-dinitrofluorobenzene (DNFB). It effectively attenuated AD progression by ameliorating skin lesions, decreasing epidermal thickness and mast cell infiltration, downregulating inflammatory cytokine levels, and restoring the expression of claudin-1, loricrin, and occludin. It also inhibited the release of TNF-α, IL-1β, and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and showed no significant toxicity to major organs in mice. In summary, our findings demonstrate that LQ-CG can effectively alleviate atopic symptoms by repairing the skin barrier and inhibiting inflammatory responses without causing significant changes in organ indices.

Background Psoriasis is a chronic, inflammatory, immune-mediated skin disorder characterized by abnormal keratinocyte proliferation and systemic inflammation. Limited plaque psoriasis, defined as involving less than a specified portion of the body surface area (BSA), presents as localized, erythematous, and scaly plaques. Though milder in extent, it significantly impairs quality of life due to physical discomfort and psychological distress. Topical therapies remain the primary treatment approach for this subtype. Potent topical corticosteroids, such as clobetasol propionate 0.05% ointment, offer rapid relief but pose long-term risks, like skin atrophy. In contrast, topical methotrexate 1% gel is emerging as a safer, sustained alternative. Objective The primary objective of this study was to compare the efficacy and safety of topical methotrexate 1% gel versus clobetasol propionate 0.05% ointment in patients with limited plaque psoriasis. Secondary objectives included the assessment of disease severity scores and adverse effects. Methods This prospective comparative, open-label study involved a per-protocol cohort of 70 patients. Patients were divided into two groups: clobetasol, 35 (50%) patients, and methotrexate, 35 (50%) patients, and were followed for 12 weeks. Results Clobetasol demonstrated faster initial clinical improvement by Week 4, but methotrexate yielded significantly better sustained results. By Week 12, 13 (37.1%) patients in the methotrexate group achieved Psoriasis Area and Severity Index (PASI)-75, compared to five (14.3%) in the clobetasol group (p = 0.026). Endline Physician's Global Assessment (PGA) scores showed seven (20%) methotrexate patients achieved clear skin, and 19 (54.3%) were almost clear, contrasting favorably against clobetasol (two (5.71%) clear; nine (25.7%) almost clear). Methotrexate significantly improved Beer Sheva Psoriasis Severity Score (BSPSS) values without serious adverse events. The clobetasol group reported atrophy in eight (22.9%) patients and tachyphylaxis in one (2.9%) patient at Week 10. Conclusion Topical methotrexate 1% gel is significantly superior to clobetasol propionate for sustained treatment. It provides high clinical efficacy and avoids steroid-associated adverse effects, making it a highly recommended, safer, long-term option for limited plaque psoriasis.

We read with great interest Bitar et al.'s case series of 12 patients from two US centers with cutis marmorata telangiectatica congenita (CMTC) and leg length discrepancy (LLD) [1]. CMTC is a rare congenital vascular anomaly with persistent telangiectasia in a reticulate erythema pattern, typically present at birth and often with atrophy, ulcerations, or erosions and underlying limb hypoplasia [2]. Historically, the term CMTC has been used for a variety of conditions in which a reticulate capillary malformation is a part. This has led to the misnomer “macrocephaly-cutis marmorata telangiectatica congenita” [3] and possible inclusion of patients with PIK3CA-related overgrowth syndrome and diffuse capillary malformation with overgrowth and undergrowth, which are associated with pathogenic variants in PIK3CA and GNA11. Further clouding the picture are patients with mosaic AKT3 p.E17K variants who have cutaneous features that resemble CMTC but often have megalencephaly that clinically resembles megalencephaly-capillary malformation syndrome [4]. Earlier literature has examined the relationship between CMTC and LLD [2]. However, representative photos from reports have depicted pink-red reticulate stains that lack well-defined borders, atrophy, or obvious textural changes. Whether this is labeled as a reticulate CM or the newly described GNA11 CMTC variant [5], this morphology is quite distinct from the reticulated, well-demarcated violaceous plaques, with a coarse fixed livedo pattern and areas of skin atrophy and erosion, as depicted in this publication by Bitar et al. (in this issue). However, for clinical precision, it is important to tease apart the characteristics of patients that are more clinically homogeneous. To that end, we would like to commend and highlight the work done by Bitar et al., where they include patients that seem to meet the clinical phenotype of congenital, reticulated, well-demarcated dark blue, red-purple, or violaceous macules or plaques with a coarse fixed livedo pattern with contiguous areas of skin atrophy or ulceration, as proposed by Schuart et al. [5]. At the very least, this study will help us risk stratify the patients with the classic CMTC phenotype and provide useful numbers on the high incidence of LLD in patients with lower extremity CMTC. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Despite decades of control interventions in sub-Saharan Africa, morbidity associated with Onchocerca volvulus infection still exerts a substantial burden of disease, arising from cutaneous, ocular and neurological manifestations. We developed and integrated a morbidity sub-model into our previously published individual-based, stochastic transmission model, EPIONCHO-IBM, including both reversible (severe itch, reactive skin disease (RSD)), and irreversible (skin atrophy, depigmentation, hanging groin) cutaneous sequelae, and eye disease (blindness, visual impairment). We modelled the relationship between onchocerciasis skin disease (OSD) and infection prevalence using pre-intervention data from northern Nigeria, and between onchocerciasis ocular disease (OOD) and infection intensity using data from the Onchocerciasis Control Programme in West Africa. We simulated the impact of ivermectin mass drug administration (MDA) upon OSD and OOD using data from Cameroon, Central African Republic, Nigeria, Sudan and Uganda. Modelled age-specific OSD and OOD prevalence at baseline align well with reported prevalence estimates across the simulated range of endemicity levels but underestimate irreversible OSD in older age groups. Under MDA, we capture trends in infection prevalence, severe itch and irreversible OSD but underestimate reductions in RSD and blindness prevalence. Integrating morbidity outcomes into transmission dynamics modelling will help improve estimates of onchocerciasis disease burden and inform the effectiveness and cost-effectiveness of current and alternative interventions.

Hyaluronic acid fillers in systemic sclerosis and localized scleroderma: A systematic review.

Erosive pustular dermatosis of the lower legs (EPDL) is a rarely diagnosed, chronic inflammatory skin disease that occurs predominantly in elderly people. Predisposing factors include skin atrophy, chronic venous insufficiency, and trauma. Although the pathogenesis of EPDL has not yet been conclusively clarified, there are ongoing discussions on its nature as a neutrophilic dermatosis in which exogenous triggers lead to immunological dysregulation with local skin damage. Clinically, EPDL manifests with superficial, sterile pustules from which sharply defined erosions develop. The predilection sites are the middle third of the lower leg extensor sides. It is a diagnosis of exclusion, which makes diagnostic differentiation more difficult. Potent topical glucocorticoids with a high therapeutic index (TIX) and calcineurin inhibitors are used therapeutically. Systemic immunomodulating therapies are reserved for refractory courses. Optimization of wound care is also important. In the long term, education and skin care are at the forefront of the complex and often long-term treatment. Due to the chronic recurrent course and the risk of secondary ulcerations and superinfections, early diagnosis and individual treatment planning is important. Interdisciplinary and interprofessional collaboration can make a decisive contribution to improve quality of life of affected patients and reduce the risk of complications.

Hallermann-Streiff syndrome (HSS) is a rare genetic condition characterized by seven cardinal findings comprising congenital cataracts, microphthalmia, recognizable facial features, sparse hair with hypotrichosis, skin atrophy, dental anomalies, and short stature. Around 200 patients have been reported and almost all cases have been sporadic. Several reviews have described the clinical findings in patients reported to have HSS, but the lack of a genetic test or other biomarker has complicated an accurate delineation of the condition. Although HSS is suspected to have a genetic basis and non-recurrent deleterious variants in genes such as GJA1, CHD6, and ZMPSTE24 have been noted in patients diagnosed with HSS, the etiology for almost all cases remains unknown. Our findings reveal a consistent phenotype but highlight the diagnostic challenges associated with HSS, including clinical overlap with other genetic conditions. It is also likely that the original reports of HSS described patients with heterogeneous conditions. Further research to identify the cause(s) of HSS and to develop best practices for patient care are needed.

A pragmatic roadmap toward personalized vitiligo care.