ABSTRACT
This genetic association study examines the genetic aspects of necrobiotic xanthogranuloma in 3 patients in China.
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As one of the most prevalent chronic inflammatory skin diseases, atopic dermatitis (AD) increasingly affects the aging population. Amid the ongoing global aging trend, it's essential to recognize the intricate relationship between AD and aging. This paper reviews existing knowledge, summarizing clinical observations of associations between AD and aging-related diseases in various systems, including endocrine, cardiovascular, and neurological. Additionally, it discusses major theories explaining the correlation, encompassing skin-mucosal barriers, systemic inflammation and stress, genes, signal transduction, and environmental and behavioral factors. The association between AD and aging holds significant importance, both in population and basic perspectives. While further research is warranted, this paper aims to inspire deeper exploration of inflammation/allergy-aging dynamics and the timely management of elderly patients with AD.
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A woman in her 30s with myasthenia gravis diagnosed at age 27 years presented to the emergency department with severe erythroderma over the past 2 months. What is your diagnosis?
Subject(s)
Dermatitis, Exfoliative , Myasthenia Gravis , Thymoma , Thymus Neoplasms , Humans , Thymoma/complications , Thymoma/diagnosis , Dermatitis, Exfoliative/diagnosis , Dermatitis, Exfoliative/etiology , Thymus Neoplasms/complications , Thymus Neoplasms/diagnosis , Myasthenia Gravis/complications , Myasthenia Gravis/diagnosisABSTRACT
Cadonilimab is the first bi-specific antibody approved for certain malignancies in June 2022, which has a modified Fc structure to reduce immune-related adverse events. To date, no reports have described Cadonilimab-related toxic epidermal necrolysis (TEN). Here, we report the first case of TEN-like reactions occurring during the treatment of hepatocellular carcinoma with Cadonilimab in combination with Lenvatinib and transarterial chemoembolization, successfully treated with supplemental Adalimumab. We confirmed Cadonilimab as the culprit and observed significant improvement in the patient's condition following Adalimumab treatment. The case emphasizes the potential risk of Cadonilimab inducing TEN, and suggests that supplemental Adalimumab could be a favorable option for treating refractory Cadonilimab-related TEN.
Subject(s)
Adalimumab , Antibodies, Bispecific , Carcinoma, Hepatocellular , Immune Checkpoint Inhibitors , Liver Neoplasms , Stevens-Johnson Syndrome , Humans , Adalimumab/therapeutic use , Stevens-Johnson Syndrome/drug therapy , Stevens-Johnson Syndrome/etiology , Antibodies, Bispecific/adverse effects , Antibodies, Bispecific/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Male , Middle Aged , Withholding Treatment , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Treatment OutcomeABSTRACT
Introduction: To date, there is no standard treatment for Morbihan disease. Several studies have reported that Morbihan disease responds well to systemic corticosteroids (prednisone and prednisolone), systemic antibiotics (tetracyclines), antihistamines (ketotifen) and surgical therapy (Lymphaticovenous anastomosis). To our knowledge, Tofacitinib, as a Janus-activated kinase (JAK) inhibitor, plays a vital role in the treatment of inflammatory and autoimmune disorders. Therefore, Tofacitinib may be a promising medical option for patients with Morbihan disease. Case Presentation: The first case involves a 43-year-old Chinese man who presented a 12-month history of progressive painless swelling of the left upper eyelid. According to the skin biopsy, perivascular dermal edema with dilatation of lymphatic vessels and telangiectasia was observed, accompanied by mixed lymphocyte infiltrate, including histiocytes, plasma cells, and a few eosinophils. The second case involves a Chinese female patient who presented a 2-year history of progressive left-sided facial edema, which was eventually diagnosed as Morbihan disease. The skin biopsy revealed lymphocyte infiltration in the superficial vessels of dermis and some accessories. Based on patients' clinical presentation, skin biopsy results, and exclusion of differential diagnoses such as systemic lupus erythematosus (SLE), they were diagnosed with Morbihan disease. They were both treated with Tofacitinib (5mg, po twice daily). Outcomes: Patient 1 underwent a trial of Tofacitinib at a dosage of 5 mg twice daily for one month, with notable improvement. His edema and erythema present on the left face were alleviated. Patient 1 reduced the dosage of Tofacitinib by half (5mg, once daily) and continued using it for 5 months. During the 6-month follow-up, the facial erythema in the patient subsided, and there was a noticeable improvement in the swelling of the left eyelid compared to before. Patient 2, her lesions gradually improved after one-week treatment. She received a one-month treatment of Tofacitinib, and during the subsequent six-month follow-up, there was no evidence of eruption recurrence. Conclusion: We present the first cases of two patients receiving short-term Tofacitinib as therapy for Morbihan disease and retrieving huge succession. Tofacitinib may be a promising oral alternative for patients with Morbihan disease. However, its safety and efficacy require further assessment through clinical trials.
Subject(s)
Erythema , Janus Kinase Inhibitors , Humans , Male , Female , Adult , Erythema/diagnosis , Skin/pathology , Edema , Piperidines/therapeutic use , Anti-Bacterial Agents , Janus Kinase Inhibitors/therapeutic useSubject(s)
Erythema , Pruritus , Male , Humans , Erythema/diagnosis , Erythema/drug therapy , Pruritus/diagnosis , Pruritus/etiologyABSTRACT
Background: Treatment for pediatric psoriasis is challenging because of the lack of real-world evidence, especially for biological therapies. Objectives: This study evaluated the efficacy and safety of biologics in children with psoriasis based on real-world evidence. Methods: Pediatric psoriasis patients aged <18 years who were treated with biologics in our hospital (2020-2022) were prospectively analyzed. Patients treated with adalimumab, secukinumab, or ixekizumab were followed up for at least 16 weeks, and 22 of 38 patients completed the 52-week observation period. Dermatologist raters were blinded to ensure the reliability of the PASI, BSA, and PGA score assessments. PASI 75 or PGA 0/1 at week 12 represented an efficient indicator. Results: Thirty-eight patients (20 males and 18 females; median age, 12.6 ± 4.1 years) were enrolled, and none were lost to follow-up. All participants were diagnosed with psoriasis, including plaque psoriasis (n = 36), nail psoriasis (n = 1), and pustular psoriasis (n = 1). Within 12 weeks, all patients achieved scores above PASI 75 and PGA 0/1. The average time to reach PASI 75 was 4.3 ± 2.0, 3.2 ± 1.8, and 2.4 ± 0.4 weeks in patients using adalimumab, secukinumab, and ixekizumab, respectively, and, 27.2% (3/11), 86.4% (19/22), and 75.0% (3/4) of these patients achieved PASI 100 at week 12, respectively. Moreover, 18 of 20 patients with plaque psoriasis maintained ≥PASI 75 after 52 weeks. The most commonly reported adverse effect was upper respiratory tract infection, and no severe adverse effects were reported. Conclusions: Our real-world data demonstrated the safety and effectiveness of adalimumab, secukinumab, and ixekizumab in children with psoriasis.
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Electronic skins are currently in huge demand for health monitoring platforms and personalized medicine applications. To ensure safe monitoring for long-term periods, high-performance electronic skins that are softly interfaced with biological tissues are required. Stretchability, self-healing behavior, and biocompatibility of the materials will ensure the future application of electronic skins in biomedical engineering. This mini-review highlights recent advances in mechanically active materials and structural designs for electronic skins, which have been used successfully in these contexts. Firstly, the structural and biomechanical characteristics of biological skins are described and compared with those of artificial electronic skins. Thereafter, a wide variety of processing techniques for stretchable materials are reviewed, including geometric engineering and acquiring intrinsic stretchability. Then, different types of self-healing materials and their applications in electronic skins are critically assessed and compared. Finally, the mini-review is concluded with a discussion on remaining challenges and future opportunities for materials and biomedical research.
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Abstract Psoriasis is a chronic skin inflammation, characterized by impaired differentiation, hyperproliferation of keratinocytes involving pro-inflammatory factors interleukin (IL)-13/17A, tumor necrosis factor (TNF)-α, interferon (IFN)-γ. Among the integrin family, α5 is important for blood vessel formation, and ß4 for proliferation, differentiation of keratinocytes. To investigate the expression and regulation of integrin α5 and ß4 in psoriatic keratinocytes. Skin biopsies were obtained from 14 psoriatic patients and 12 normal volunteers. We compared the immunolocalization and regulation of α5 and ß4 between the psoriatic and normal ones, before and after incubation with MEK/ERK pathway inhibitor U0126 by immunohistochemistry and western blot separately. Immunohistochemistry showed psoriatic keratinocytes had higher α5 than normal ones. According to western blot, IL-17A and IL-13 increased normal keratinocytes' α5 and ß4 respectively, but psoriatic keratinocytes were the exact opposite. Incubated with U0126, normal keratinocytes' α5 was enhanced by the 5 cytokines ; while IL-13/17A, IFN-γ suppressed ß4. Psoriatic keratinocytes' α5 was increased by IL-13/17A, decreased by IFN-γ; but ß4 increased by IL-17A, IFN-γ. IL-13/17A, TNF-α, IFN-γ regulate α5 and ß4 through ERK pathway whether normal or psoriasis. The normal and psoriatic keratinocytes respond to the same cytokines differently
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Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Integrins/analysis , Keratinocytes/classification , Patients/classification , Psoriasis/pathology , Blotting, Western/instrumentation , Cytokines/agonists , Interleukins/analysisABSTRACT
Objectives: To investigate the effect of suppressor of fused (Sufu) on epidermal and dermal cellular properties and in wound healing. Approach: Transgenic (TG) mice overexpressing human Sufu (hSufu) in the epidermis were applied to investigate the effects of Sufu on epidermal and dermal cellular properties and in wound healing. Results: Histological staining revealed a reduction of epidermal and dermal thickness and an increase of hypodermal adipose tissue in homozygous K14-hSufu TG mice when compared with wild-type (WT) controls. TG mice exhibited significantly delayed skin wound healing. Moreover, the migratory and proliferative capabilities of cultured keratinocytes were decreased in K14-hSufuTG mice. Transforming growth factor-ß treatment increased the expression of α-smooth muscle actin more in WT than in TG fibroblasts. Sufu overexpression significantly decreased the expression of ß-catenin, glioma transcription factor 1 (Gli1), and matrix metalloproteinase-3 in wounds of K14-hSufu TG mice when compared with controls, probably indicating a delaying effect of Sufu on wound healing via blocking the hedgehog (Hh)/Gli and Wnt/ß-catenin pathway. Innovation: Our results indicate a new property of Sufu in the process of skin wound healing. It provides an important basis for Sufu as a potential target for skin wound healing. Conclusion: Our findings suggest that Sufu overexpression in the epidermis impairs wound healing via dampening the Hh/Gli and Wnt/ß-catenin signaling pathway. These data provide an important basis for further analyses of Sufu in skin wound healing.
Subject(s)
Fibroblasts/metabolism , Keratinocytes/metabolism , Repressor Proteins/metabolism , Wnt Signaling Pathway , Wound Healing , Animals , Cell Differentiation , Disease Models, Animal , Epidermal Cells , Epidermis/growth & development , Epidermis/metabolism , Fibroblasts/cytology , Hedgehog Proteins/metabolism , Keratinocytes/cytology , Male , Mice , Mice, Transgenic , Skin Aging/pathology , Skin Aging/physiology , Transforming Growth Factor beta/metabolismABSTRACT
BACKGROUND Ustekinumab, a human-derived monoclonal antibody that targets the p40 subunit of interleukin (IL)-12 and IL-23, has excellent clinical efficacy and safety in treating psoriasis, with a long half-life. However, no reports have described the use of human skin/serum samples to elucidate its molecular mechanisms. MATERIAL AND METHODS Twenty-four psoriasis patients were enrolled in our double-blind study and randomly divided into placebo and ustekinumab-administered groups. Dynamic changes in psoriasis area-severity index scores, and mRNA and protein levels of p35 and p40 were analyzed at 3 time points (before treatment and during the 12th and 24th weeks of treatment). RESULTS Ustekinumab initially increased and then decreased p35 mRNA expression, but increased p40 mRNA levels throughout the study. The p35 protein levels were not significantly altered, while p40 protein levels were increased after the first 2 injections but decreased after the third injection. CONCLUSIONS We concluded that 2 equilibria influence the efficacy of ustekinumab against psoriasis. First, because of the dual roles of p35 in psoriasis pathogenesis, homeostasis occurs between p35 and p40 expression levels. The second balance lies between the upregulation of p40 mRNA levels and the ability of ustekinumab to neutralize the function of the elevated p40 protein.
Subject(s)
Interleukin-12 Subunit p40/metabolism , Psoriasis/drug therapy , Ustekinumab/therapeutic use , Adult , Dermatologic Agents/therapeutic use , Double-Blind Method , Female , Humans , Interleukin-12 Subunit p40/genetics , Male , Middle Aged , Psoriasis/genetics , Psoriasis/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Severity of Illness IndexABSTRACT
OBJECTIVES: Sprouty (SPRY) 1 is one of the SPRY proteins that inhibits signalling from various growth factors pathways and has also been known as a tumour suppressor in various malignancies. However, no study elucidates the role of SPRY1 in the skin. Our study was conducted to determine the function of SPRY1 in human keratinocytes and the epidermis. MATERIALS AND METHODS: In vitro primary cultured epidermal keratinocytes were used to investigate the proliferation, differentiation and apoptosis of these cells. We also established overexpression of SPRY1 in vitro and K14-SPRY1 transgenic mice. RESULTS: SPRY1 was mainly located in the cytoplasm of the epidermal keratinocytes from the granular epidermal layer of the skin and cultured cells. Overexpressed SPRY1 in keratinocytes resulted in up-regulation of P21, P27 and down-regulation of cyclin B1; decrease in MMP3 and integrin α6. SPRY1-overexpressed primary keratinocytes exhibited a lower proliferation and migration capability and higher rates of apoptosis. Epidermis of SPRY1-TG mice represented delayed wound healing. Proteomics analysis and GO enrichment showed DEPs of SPRY1 TG mice epidermis is significantly enriched in immune- and inflammatory-associated biological process. CONCLUSIONS: In summary, SPRY1 expression was inversely correlated with cell proliferation, migration and promote cell apoptosis of keratinocytes. SPRY1 maybe a negative feedback regulator in normal human epidermal keratinocytes and cutaneous inflammatory responses. Our study raised the possibility that enhancing expression of SPRY1 may have the potential to promote anti-inflammatory effects.
Subject(s)
Apoptosis/genetics , Cell Differentiation/genetics , Cell Proliferation/genetics , Epidermis/metabolism , Keratinocytes/metabolism , Membrane Proteins/genetics , Phosphoproteins/genetics , Adult , Animals , Cell Line , Down-Regulation/genetics , HEK293 Cells , Humans , Inflammation/genetics , Inflammation/metabolism , Mice , Mice, Inbred C57BL , Mice, Transgenic/genetics , Signal Transduction/genetics , Skin/metabolism , Up-Regulation/geneticsABSTRACT
Vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) have been shown to keep angiogenesis activation and inhibition in balance in normal and pathological conditions. In this study, we examined the expression of VEGF and PEDF in keratinocytes and fibroblasts from normal and psoriatic skin to evaluate their potential roles and interactions in the development of psoriasis. The expression of VEGF and PEDF was detected in normal and psoriatic skin ex vivo and in co-cultured keratinocytes and fibroblasts in vitro, and increased in keratinocytes and fibroblasts from psoriatic skin compared with those cells from normal skin. Our results suggest that PEDF act as a multipotent factor in the skin and the imbalance of PEDF and VEGF may be responsible for the transformation from normal skin to psoriasis.
Subject(s)
Dermis/metabolism , Epidermis/metabolism , Eye Proteins/biosynthesis , Gene Expression Regulation , Keratinocytes/metabolism , Nerve Growth Factors/biosynthesis , Psoriasis/metabolism , Serpins/biosynthesis , Vascular Endothelial Growth Factor A/biosynthesis , Adult , Aged , Dermis/pathology , Epidermis/pathology , Female , Humans , Keratinocytes/pathology , Male , Middle Aged , Psoriasis/pathologyABSTRACT
Psoriasis is a T-cell mediated disease that involves IL-23/Th17 and IL-12/Th1 axes. Ustekinumab, a fully human monoclonal antibody targeting the p40 subunit of both IL-12 and IL-23, has proven to be efficient and safe for treating patients with psoriasis. Yet, there have been no reports with human skin/blood samples that would elucidate the molecular mechanisms by which ustekinumab calms psoriasis skin lesions. To investigate the efficacy and molecular pathway (RORC, t-BOX and GATA) of ustekinumab in treating patients with psoriasis skin lesions. A total of 30 patients with psoriasis were randomized into placebo group and treatment group. PASI of each patient was calculated at 0, 12 and 24 weeks post-treatment. The mRNA levels of RORC, t-BOX and GATA in peripheral blood mononuclear cells separated from patients' whole blood were analyzed using qPCR. Decreased mRNA of RORC, t-BOX and GATA were observed after continuous injections, indicating that ustekinumab exerts its effect by interacting with these molecules; while no significant difference in foxp3 mRNA levels were found between placebo group and treatment group.