Basal cell carcinoma (BCC) is the most common skin malignancy, and surgical excision remains the first-line treatment for most lesions. However, therapeutic options for elderly patients who are unsuitable for or decline surgery are limited. Acitretin, a systemic retinoid, has shown potential antitumor effects, while topical tretinoin may enhance local therapeutic efficacy. We herein report an elderly patient with facial BCC presenting as an ulcerative lesion on the right forehead. Reflectance confocal microscopy revealed basaloid cells arranged in cord-like structures, and histopathological examination demonstrated nests of basaloid tumor cells with peripheral palisading and retraction clefts, confirming the diagnosis of nodular BCC. The patient was treated with oral acitretin in combination with topical 0.1% tretinoin cream. After 12 weeks of treatment, the ulcerative lesion showed near-complete healing with marked clinical improvement. During the treatment course, only mild adverse events, including skin dryness and cheilitis, were observed, and no significant laboratory abnormalities occurred. This case suggests that oral acitretin combined with topical 0.1% tretinoin cream may represent a feasible and well-tolerated nonsurgical option for selected elderly patients with facial BCC, and no recurrence was observed during the 4-month follow-up.
Generalized pustular psoriasis (GPP) is a severe and potentially life-threatening form of psoriasis. Although spesolimab, an inhibitor of the interleukin (IL)-36 pathway, has been approved for the treatment of GPP, access to this agent remains limited. Vunakizumab, a humanized IgG1/κ monoclonal antibody that selectively neutralizes interleukin (IL)-17A inhibitors, is not yet approved for GPP. We herein report a 72-year-old male with a 40-year history of plaque psoriasis who developed GPP refractory to methotrexate combined with guselkumab and acitretin (20 mg/day). Following switching to vunakizumab (240 mg intravenously every 2 weeks) in combination with acitretin (40 mg/day), the patient achieved a GPPASI 75 response within 2 weeks and near-complete clearance (GPPASI ≈ 100) by week 12. Six induction doses of vunakizumab were administered, and acitretin was tapered to 20 mg/day for long-term maintenance. Throughout 36 weeks of follow-up, no disease relapse or drug-related adverse events were observed. This case, together with a review of the literature, provides support for IL-17A blockade combined with acitretin as a feasible and fast-acting regimen for refractory GPP in elderly patients.
Psoriasis is a complex chronic inflammatory disease with cutaneous manifestations, driven by intricate interactions between genetic, immunological, and metabolic dysregulations. However, the integrated molecular networks connecting transcriptional alterations to metabolic reprogramming remain incompletely elucidated. We performed a comprehensive integrated analysis of transcriptomics and targeted metabolomics using serum samples from 11 psoriasis vulgaris patients and 11 healthy controls to dissect the core gene-metabolite regulatory axes underlying psoriasis. RNA sequencing identified 5,186 differentially expressed genes (DEGs), with a striking predominance of downregulation (5,147 DEGs), and targeted metabolomic profiling detected 208 significantly altered metabolites, including upregulated propanoic acid and downregulated L-allysine. KEGG pathway enrichment analysis revealed six dysregulated metabolic pathways shared by DEGs and altered metabolites, notably lysine degradation, propanoate metabolism, and central carbon metabolism in cancer—with the latter identified as a novel pathogenic pathway in psoriasis vulgaris. Weighted Gene Co-expression Network Analysis (WGCNA) further delineated strong correlations between core genes (TP53, MTOR, AKT3) and key metabolites (propanoic acid, L-allysine), forming a functional network that links cellular energy metabolism to immune-inflammatory responses. Protein-protein interaction network analysis confirmed these core genes as hub regulators within the dysregulated pathways. In this exploratory pilot study, integrated transcriptomic and metabolomic profiling revealed preliminary associations between lysine degradation, propanoate metabolism, and psoriasis status. The observed crosstalk with central carbon metabolism, potentially involving TP53, MTOR, and AKT3, generates hypotheses that require validation in independent, larger cohorts before any clinical or mechanistic inferences can be drawn.
Background:Acne is a chronic inflammatory skin disease affecting pilosebaceous unit. However, its specific mechanism remain incompletely understood. Objectives:This study aims to identify and analyze the differential expression of serum exosomal miRNA in severe acne, revealing new insights into the pathogenesis of acne. Methods:MiRNAs were extracted from serum exosomes of 15 patients with severe acne and 15 healthy controls. MiRNA libraries were constructed and sequenced using Illumina HiSeq 2500. The DESeq2R was applied to identify differentially expressed miRNAs. The candidate target genes were predicted using multiple miRNA databases. The DAVID database was used to enrich GO function and KEGG pathway analysis of target genes. Cytoscape3.10.0 was employed to construct a PPI interaction network and further screen hub genes. The most significantly differentially expressed miRNAs were validated using RT-qPCR detection. Results:Small RNA-Seq analysis identified a total of 96 serum exosome miRNAs, with 33 up-regulated and 63 down-regulated. Target prediction across four miRNA databases identified 10,569 target genes. GO analysis showed that target genes were mainly enriched in transcriptional regulation, signal transduction and protein binding; KEGG analysis revealed enrichment in 160 pathways including PI3K-Akt and MAPK signaling pathway. Cytoscape 3.10.0 identified 7 hub genes: PIK3R1, PIK3CA, SRC, EGFR, JAK2, ERBB2, and IGF1R, along with 35 corresponding differentially expressed miRNAs. RT-qPCR results indicated a significant reduction in exosomal miR-124-3p levels in severe acne. Conclusions:Serum exosomal miRNA expression in patients with severe acne significantly differed from that in healthy individuals. The exosomal miR-124-3p expression was markedly reduced in severe acne compared to healthy controls. Consequently, the increase of miR-124-3p expression may have potential therapeutic implications for severe acne.
Atopic dermatitis (AD) presents as a prevalent chronic, relapsing, inflammatory skin condition. While dupilumab has proven effective in treating moderate-to-severe AD, some patients still experience unsatisfactory outcomes with this therapy in clinical settings. Patients with AD receiving dupilumab were selected for inclusion in the present study for prospective observations. Over an 8-week period, the patients underwent monitoring and changes in serum biomarkers and circulating T helper (Th) cell levels were analyzed using questionnaires, ELISA and flow cytometry. The Scoring Atopic Dermatitis (SCORAD), Objective-SCORAD, Itch Numeric Rating Scale (NRS), Dermatology Life Quality Index, Patient Oriented Eczema measure and Atopic Dermatitis Control Tools scores in patients with AD significantly decreased at week 8 compared with those before treatment (P<0.05). Moderate positive correlations were demonstrated between serum thymus and activation-regulated chemokine (TARC) and human β-defensin 2 levels and Eczema Area and Severity Index (EASI) and SCORAD scores (P<0.05). A weak negative correlation was shown between serum IgE against Staphylococcus aureus enterotoxin A level and the EASI and SCORAD scores, although these were not statistically significant (P>0.05). There was a notable increase in the proportion of Th2 cells in peripheral blood at week 2 (P<0.05). The proportion of Th22 cells in the peripheral blood was weakly correlated with the NRS score (P>0.05). Patients were categorized into rapid or slow groups depending on whether they achieved EASI-75 scores by week 8. The proportion of Th17 cells in peripheral blood in the rapid group at week 8 of treatment was lower than that compared with the slow group at week 2 (P<0.05). The SCORAD scores of the rapid group were significantly lower compared with those of the slow group at week 8 of treatment (P<0.05). The conventional dupilumab treatment regimen led to a marked remission in patients with exogenous AD after 8 weeks of therapy. Significant correlations were observed between serum TARC levels and clinical disease scores (P<0.05), which changed notably during treatment and remained valuable for monitoring disease progression at follow-up. Additionally, the elevated ratio of Th17 cells in peripheral blood at week 2 of treatment showed potential for predicting the attainment of EASI-75 by week 8 after treatment.
Background:Stable vitiligo, characterized by irreversible melanocyte loss, often resists conventional therapies. Non-cultured epidermal cell suspension (NCES) transplantation are increasingly used, and adjunctive autologous serum may enhance efficacy via growth factor-mediated cell survival and proliferation. This study evaluates the clinical outcomes of combined autologous serum and NCES therapy for stable vitiligo. Methods:This prospective case series enrolled 30 patients (61 sites) with stable vitiligo at the Guangzhou New Centre Institute of Vitiligo (2024-2025). Patients received autologous serum followed by NCES transplantation. Repigmentation was assessed using the Vitiligo Area Scoring Index (VASI) and color matching. Adverse events were monitored. Results:After 3 to 6 months, excellent repigmentation (> 90%) was achieved in 83.6% of treated sites (51/61), with particularly high efficacy on facial (90% efficacy in 9/10 sites) and neck regions (92.3% efficacy in 12/13 sites). The trunk, upper limbs, and hands/fingers exhibited excellent repigmentation in 80.0%, 77.8%, and 78.6% of sites, respectively. Poor repigmentation (< 25%) was observed in only one trunk site (1/61). Excellent color matching was achieved in 82.0% of treated sites (50/61), and no treatment-related adverse effects were reported. Conclusion:The combination of autologous serum and NCES transplantation is highly effective and safe for stable vitiligo. Autologous serum may synergize with NCES by supporting the microenvironment for melanocyte engraftment, offering a promising strategy for stable vitiligo.
Ustekinumab is an antibody targeting the common p40 subunit shared by interleukin (IL)-12 and IL-23, demonstrating favorable efficacy in the treatment of psoriasis. Herein, we report the case of a 69-year-old male with psoriasis, managed with ustekinumab, who presented with a new cutaneous eruption. Biopsy findings were consistent with lichenoid drug eruption (LDE). The patient's condition was promptly managed by upadacitinib, a selective Janus kinase (JAK) inhibitor. Physicians need not be overly concerned about this rare adverse reaction. JAK inhibitors may offer new treatment options with an advantage of rapid onset of action for patients experiencing LDE induced by biologic therapies for psoriasis.
We present a case series involving five patients with generalized pustular psoriasis (GPP) who received a single intravenous dose of 900 mg spesolimab in our department from September 2023 to January 2024. Spesolimab was effective in three patients, regardless of their IL-36RN gene mutation status. Two patients with concomitant plaque psoriasis, despite initially poor responses to spesolimab, achieved resolution of pustules after switching their therapy to ixekizumab or secukinumab. This study highlights the potential of spesolimab in managing GPP, especially in genetically distinct groups, and emphasizes the importance of tailored therapeutic approaches. These findings suggest that spesolimab can effectively treat GPP, regardless of IL-36RN gene mutation status. However, its therapeutic efficacy may be suboptimal in patients with concomitant plaque psoriasis, indicating the need for further investigation to optimize treatment outcomes in this subgroup.
Abrocitinib have been approved for patients with moderate to severe atopic dermatitis (AD), but its effectiveness and safety in adolescents, especially children is not established in both clinical trial and real-world studies. We aimed to analyze real-world data of abrocitinib in the treatment of children and adolescents. We prospectively enrolled children and adolescents with moderate to severe AD from 2 centers, who were stratified based on age groups (<6 years, 6–11 years, 12–17 years) and treated with oral abrocitinib at dosages of 25, 50, or 100 mg daily accordingly. The study assessed various parameters, including the eczema area and severity index (EASI), scoring of atopic dermatitis, investigator’s global assessment, numerical rating scale-itch, sleep-loss scores, children dermatology quality of life index/dermatology quality of life index, and safety at baseline and at weeks 2, 4, and 12 of treatment. This study included 28 children and adolescents with moderate to severe AD (4 patients aged < 6 years, 9 aged 6–11 years, and 15 aged 12–17 years). All patients combined exhibited a rapid and significant improvement in the clinical signs and symptoms of AD following the initial follow-up visit. By week 12, EASI-50, EASI-75, and EASI-90 responses were achieved by 100%, 60.7%, and 25.0% of all patients combined, respectively. 57.2% of all patients combined achieved investigator’s global assessment 0/1, and 85.7% had a reduction in numerical rating scale-itch score of at least 4 points. The sleep-loss score and children dermatology quality of life index/dermatology quality of life index score were reduced by 78.8% and 78.5% of all patients combined, respectively. Similar trends in the data were observed across various age groups, including patients aged < 6 years, 6–11 years, and 12–17 years. Two adolescents (7.1%) experienced mild adverse events, including Kaposi’s varicelliform eruption and nausea, with no occurrence of serious adverse events throughout the treatment period. The real-world application of age-based dosing of abrocitinib revealed favorable efficacy and well-tolerated safety profiles in treating moderate to severe AD among children and adolescents.
BackgroundAcne vulgaris is a prevalent chronic inflammatory disorderof the skin and oral isotretinoin is one of the most effective treatments forsevere acne with incompletely understood mechanisms. The aim of thisstudy was to investigate the pathogenesis of acne and the therapeuticmechanisms underlying isotretinoin treatment from integrated human plasma metabolomics and proteomics.MethodsLiquid chromatography-tandem mass spectrometry (LC-MS/MS) full-spectrum metabolomics and four-dimensional data-independent acquisition (4D-DIA) quantitative proteomics were employed to analyze plasma samples from patients with group AG (severe acne group), group AG1 (severe acne group1, before isotretinoin treatment), group TG (isotretinoin treatment group) and group CG (control group). Bioinformatics statistical analysis were employed to analyze the metabolomic and proteomic data.Results489 differentially expressed metabolites (DEMs) were detected in the plasma from patients with severe acne compared to controls. Isotretinoin treatment normalized the dysregulation of 94 metabolites, including inositol 1,3,4-trisphosphate (Ins(1,3,4)P3), 11-cis-retinol, thyroxine (T4), androstenediol, estrone 3-sulfate, bovinicacid, n-oleoylethanolamine, LPS(20:1), Cer(d16:1/23:0) and TG(17:1 18:2 18:3). Additionally, 36 differentially expressed proteins (DEPs) were identified in patients before and after isotretinoin treatment. Notably, downregulation of acyl-CoA synthetase long-chain family member 4 (ACSL4) suggests a potential therapeutic mechanism for isotretinoin, while upregulation of monoacylglycerol O-acyltransferase 2 (MOGAT2) may mediate the elevation of blood lipids and the correction of some abnormal lipids. Isotretinoin modulates multiple pathways, including inositol phosphatemetabolism, glycerolipid metabolism, thyroid hormone synthesis and insulin resistance.ConclusionImportant DEMs, DEPs and metabolic pathways were identified in this study, which will help clarify the pathogenesis of acneand the potential mechanisms of isotretinoin in the treatment of acne, andidentify novel targets for severe acne treatment and side effect reduction.
Objectives To assess the efficacy and safety of topical compound flumethasone pivalate-salicylic acid cream for verrucous epidermal nevus (VEN), a benign keratinocytic hamartoma with limited current treatment options.Methods A 25-year-old male with 20-year VEN (right buttock/lower limb plaques) was treated with the compound cream (0.2 mg flumethasone pivalate + 30 mg salicylic acid/gram) twice daily for over 2 months, followed by 14-week follow-up.Results Lesions showed progressive thinning, significantly reduced hyperpigmentation, and no adverse events. The Dermatology Life Quality Index score improved from 13 to 3, with no recurrence at follow-up.Conclusions Topical compound flumethasone pivalate-salicylic acid cream is effective and safe for VEN, potentially via inhibiting abnormal keratinocyte proliferation, serving as a practical topical option.
Janus kinase (JAK) inhibitors are increasingly being used in dermatology due to their broad potential in managing both local and systemic inflammation. More recently, abrocitinib, an oral JAK 1 inhibitor, has shown promising clinical efficacy in the treatment of various skin disorders beyond moderate to severe atopic dermatitis (AD). We firstly presented three cases, each with diagnosis of pyoderma gangrenosum (PG), livedoid vasculopathy (LV), or hidradenitis suppurativa (HS), and conducted a comprehensive scoping review of the available literature on the use of abrocitinib in the treatment of diverse skin disorders. We summarized a total of 16 skin disorders, including our cases. The results indicated that abrocitinib, whether used as monotherapy or in combination with other treatments, was effective and well-tolerated in these disorders. These findings expanded the range of diseases for which abrocitinib may serve as an alternative therapeutic choice.
Aim: To evaluate the therapeutic efficacy and safety of JAK inhibitor abrocitinib in patients with localized granuloma annulare (GA) and to review the available cases documented in English.Methods: We presented a patient who had a persistent, localized granuloma anulare (GA) for one year and did not respond to traditional therapies. This patient was treated with oral abrocitinib at a dosage of 150 mg daily.Results: After 6 weeks of treatment with abrocitinib, the patient exhibited notable symptom improvement with no new lesions. No adverse events or recurrences were reported during the 5-month follow-up period.Conclusions: Abrocitinib may be a promising and safe treatment option for patients with localized GA who do not respond to traditional therapies.
Background: The association between psoriasis and hyperthyroidism/hypothyroidism remains inconclusive, with conflicting findings in prior studies. Objectives: This study employs Mendelian randomization methods to assess the potential relationship. Methods: Given the inability to accurately observe the link between psoriasis and thyroid dysfunction, we prioritized utilizing known genetic variants to investigate the potential impacts of the disease.We analyzed data from genome-wide association studies (GWASs), FinnGen, and UK Biobank to extract information on psoriasis, hyperthyroidism, and hypothyroidism. Three MR approaches (MR Egger, weighted median, and inverse variance weighted) were used to scrutinize the causal link. Results: Our analysis revealed no correlation between psoriasis and hyperthyroidism/hypothyroidism. However, vulgar psoriasis and guttate psoriasis were associated with hypothyroidism/myxedema (IVW odds ratio (OR) = 1.00, 95
Darier's disease (DD) is a rare chronic keratinizing skin disease characterized by dyskeratosis of epidermal cells. We report a case of DD with a medical history spanning over 20 years and recurring symptoms. Pathologically confirmed DD was treated with a combination of abrocitinib and acitretin, resulting in rapid symptom resolution within 2 weeks. No recurrence was noted in an 11- week follow-up. The mechanism may involve acitretin's inhibition of proliferation and anti-inflammation, while abrocitinib acts on IL- 6 implicated in DD pathogenesis, exerting an immunomodulatory and anti-inflammatory effect, leading to rapid symptom relief. The combination of abrocitinib and acitretin is an effective therapy for DD, offering a promising new option for refractory patients.
Prurigo nodularis (PN) is a debilitating chronic neuroimmunologic skin condition due to the intense pruritus and difficult to treat. The pruritogenic cytokines, particularly IL-4, IL-13, IL-22, IL-31, and oncostatin M (OSM), play a crucial role in the pathogenesis of PN, potentially involving the JAK1-STAT pathway. An oral JAK1 inhibitor, abrocitinib, is presently undergoing Phase 2 trials for the treatment of PN. We evaluated the efficacy of abrocitinib at a daily dosage of 100 mg in treating two patients with PN affecting both lower limbs: a 50-year-old male with a 16-year disease history and a 38-year-old female with over three years of disease history, both of whom had failed to respond to multiple conventional treatments. Both patients responded rapidly after one week of treatment and exhibited a marked improvement. Following eight weeks of therapy, near-complete resolution of both pruritus and lesions was achieved, and no adverse effects were reported. Additionally, there were no reported side effects during the initial four months of continued treatment. Abrocitinib is an effective targeted therapy for PN, offering a promising new option for refractory patients.
Vitiligo is a chronic autoimmune disorder characterized by depigmented patches of the skin. The treatment of vitiligo remains challenging, partly owing to the lack of efficient drug delivery system. Microneedles (MNs), an ideal transdermal drug delivery system, have emerged as promising drug delivery platform for vitiligo. Recently, the emergence of novel MNs with increased biocompatibility, including hydrogel and hollow MNs, further enhance the translational value of MNs in the treatment of vitiligo. However, up-to-date review of these advancements remains lacking. This review aims to summarize the most recent studies of MN-based drug delivery systems for vitiligo, highlighting the translational potential of MNs as a therapeutic platform for the treatment of vitiligo in the near future.
Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disorder characterized by abnormal skin barrier function, immune inflammation, and disrupted skin microbiome. The dynamic alterations of staphylococcus aureus (S. aureus) superantigens, kallikreins (KLKs), and β-defensin 2 (β-HBD2) in keratinocytes play pivotal roles in the pathogenesis of AD. However, the mechanisms of their action remain poorly understood. In our study, we utilized staphylococcal enterotoxin gene B (SEB) to stimulate HaCaT cells. Although SEB did not significantly alter the proliferation of HaCaT cells nor increase cell apoptosis, KLKs were increased and β-HBD2 was decreased to varying degrees, indicating that KLKs activation and β-HBD2 reduction may facilitate the induction of AD and the colonization of S. aureus. Our investigation into the in vitro cellular mechanisms of SEB on AD progression provides a theoretical foundation for future AD therapies.