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Frontiers in Immunology 2024An unbiased screening of which proteins are deregulated in vitiligo using proteomics can offer an enormous value. It could not only reveal robust biomarkers for... (Review)
Review
An unbiased screening of which proteins are deregulated in vitiligo using proteomics can offer an enormous value. It could not only reveal robust biomarkers for detecting disease activity but can also identify which patients are most likely to respond to treatments. We performed a scoping review searching for all articles using proteomics in vitiligo. Eight manuscripts could be identified. Unfortunately, very limited overlap was found in the differentially expressed proteins between studies (15 out of 272; 5,51%) with variable degrees of the type of proteins and a substantial variety in the prevalence of acute phase proteins (range: 6-65%). Proteomics research has therefore brought little corroborating evidence on which proteins are differentially regulated between vitiligo patients and healthy controls or between active and stable vitiligo patients. While a limited patient size is an obvious weakness for several studies, an incomplete description of patient characteristics is an unfortunate and avoidable shortcoming. Additionally, the variations in the used methodology and analyses may further contribute to the overall observed variability. Nonetheless, more recent studies investigating the response to treatment seem to be more robust, as more differentially expressed proteins that have previously been confirmed to be involved in vitiligo were found. The further inclusion of proteomics analyses in clinical trials is recommended to increase insights into the pathogenic mechanisms in vitiligo and identify reliable biomarkers or promising drug targets. A harmonization in the study design, reporting and proteomics methodology could vastly improve the value of vitiligo proteomics research.
Topics: Vitiligo; Humans; Proteomics; Biomarkers; Proteome
PubMed: 38715599
DOI: 10.3389/fimmu.2024.1387011 -
JCEM Case Reports May 2024Malignancies may induce clinical sequelae distant from the sites of the tumor. Such paraneoplastic phenomena are known to affect many organs, including the skin....
Malignancies may induce clinical sequelae distant from the sites of the tumor. Such paraneoplastic phenomena are known to affect many organs, including the skin. Vitiligo is a disorder of patchy depigmentation, appearing as white macules with distinct margins. Rarely, vitiligo has been reported as a paraneoplastic occurrence, in the settings of pituitary adenoma, thymoma, gastric carcinoma, and lymphoma. We now describe a man presenting with the abrupt onset of vitiligo on the hands coinciding with recurrence of adrenocortical carcinoma (ACC) in the abdomen. The vitiligo rapidly dissipated following resection of his cancer. We believe this to be the first report of paraneoplastic vitiligo associated with ACC. Endocrinologists typically manage ACC and should be aware of this link, as the de novo observation of vitiligo may signal the onset or recurrence of underlying tumor. Other practitioners that encounter patients with new vitiligo should add ACC to their differential diagnosis of potential underlying conditions.
PubMed: 38707658
DOI: 10.1210/jcemcr/luae070 -
Cureus Apr 2024Abemaciclib is a cyclin-dependent kinase 4/6 inhibitor that is utilized to manage hormone-sensitive human epidermal growth factor receptor-2 positive metastatic breast...
Abemaciclib is a cyclin-dependent kinase 4/6 inhibitor that is utilized to manage hormone-sensitive human epidermal growth factor receptor-2 positive metastatic breast cancer. Palbociclib and ribociclib are types of other orally administered CDK4/6i that share similar safety and tolerability compared with Abemaciclib. Reported side effects include reversible neutropenia of a lower grade, gastrointestinal toxicity, and anemia. CDK4/6i could induce dermatological side effects. Although less frequent, cutaneous adverse effects of CDK4/6i account for 25% of medication discontinuation. Frequent cutaneous adverse events are rash and pruritus; nonetheless, hair loss, nail changes, vitiligo, and photosensitivity reactions, were also reported to a lesser extent. Herein, we report a case of hair, nail, and pigmentary disorder that occurred 10 months after initiating abemaciclib treatment.
PubMed: 38707105
DOI: 10.7759/cureus.57677 -
Frontiers in Medicine 2024Accumulating evidence reveals an association between circulating cytokine levels and vitiligo. However, the causal association between circulating cytokine levels and...
BACKGROUND
Accumulating evidence reveals an association between circulating cytokine levels and vitiligo. However, the causal association between circulating cytokine levels and vitiligo remains unrevealed.
METHODS
We performed a two-sample Mendelian randomization (MR) analysis using a genome-wide association study of the 41 cytokines dataset, which was conducted with 3 Finnish cohorts ( = 8,293). Vitiligo data were acquired from strictly defined vitiligo data collected by FinnGenbiobank analysis, which included 207,613 European ancestors (131 vitiligo patients, 207,482 controls). The inverse-variance weighted (IVW) method, weighted median (WME), simple model, weighted model, and MR-Egger were used to determine the changes in vitiligo pathogenic cytokine taxa, followed by sensitivity analysis, including horizontal pleiotropy analysis. The MR Steiger test evaluated the strength of a causal association, and the leave-one-out method was used to assess the reliability of the results. The possibility of reverse causality was also investigated using a reverse MR study.
RESULTS
We observed that rising IL-4 levels generated an enhanced probability of vitiligo in IVW (OR 2.72, 95%CI 1.19-6.22, = 0.018). According to the results of the MR analysis, there were causal links between IL-4 and vitiligo. Results were steady after sensitivity and heterogeneity analyses.
CONCLUSION
Our research reveals that a genetically determined increased level of circulating IL-4 may be linked to a higher risk of developing vitiligo. The development of innovative treatment approaches (such as tofacitinib or dupilumab) that focus on blocking IL-4 as a novel way of preventing and treating vitiligo is significantly impacted by our findings.
PubMed: 38695020
DOI: 10.3389/fmed.2024.1375339 -
Frontiers in Immunology 2024The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a meta-analysis.
METHODS
PubMed, Web of Science, OVID, EMBASE, and Cochrane central register of controlled trials were searched. Information and data were screened and extracted by 2 researchers. The obtained data were analyzed using the R software meta package. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger's test.
RESULTS
The search retrieved a total of 3530 papers from the databases. After screening, a total of 37 studies were included in the meta-analysis. The analysis results indicate that the pooled incidence rate of overall secondary autoimmune events (SAEs) in the included studies was 0.2824 [0.2348, 0.3300] (I²=94%, p<0.01). The overall incidence of autoimmune thyroid events (ATE) was 0.2257 [0.1810, 0.2703] (I²=94%, p<0.01). Among them, the rate of serious autoimmune thyroid events (SATE) was 0.0541 [0.0396, 0.0687] (I²=0%, p=0.44). The incidence rates of different thyroid events were as follows: Graves' disease (GD), 0.2266 [0.1632, 0.2900] (I²=83%, p<0.01); Hashimoto thyroiditis (HT), 0.0844 [0.0000, 0.2262] (I²=81%, p=0.02); Hashimoto thyroiditis with hypothyroidism (HTwH), 0.0499 [0.0058, 0.0940] (I²=37%, p=0.21); fluctuating thyroid dysfunction (FTD), 0.0219 [0.0015, 0.0424] (I²=0%, p=0.40); transient thyroiditis (TT), 0.0178 [0.0062, 0.0295] (I²=0%, p=0.94). The overall incidence of hematological events was 0.0431 [0.0274, 0.0621] (I²=70%, p<0.01). The incidence rates from high to low were as follows: lymphopenia, 0.0367 [0.0000, 0.0776] (I²=81%, p=0.02); Idiopathic thrombocytopenic purpura (ITP), 0.0258 [0.0199, 0.0323] (I²=25%, p=0.15); Hemolytic anemia (HA), 0.0177 [0.0081, 0.0391] (I²=29%, p=0.23); pancytopenia, 0.0136 [0.0000, 0.0314] (I²=0%, p=0.67); Neutropenia, 0.0081 [0.0000, 0.0183] (I²=0%, p=0.42). After excluding thyroid and hematological diseases, the combined incidence of other related SAEs was 0.0061 [0.0014, 0.0109] (I²=50%, p=0.02). The incidence of each disease ranked from highest to lowest as: skin psoriasis (SP), 0.0430 [0.0000, 0.0929] (I²=0%, p=0.57); alopecia areata (AA), 0.0159 [0.0024, 0.0372] (I²=19%, p=0.29); vitiligo, 0.0134 [0.0044, 0.0223] (I²=0%, p=0.81); inflammatory atrichia (IA), 0.0103 [0.0000, 0.0232] (I²=0%, p=0.43); chronic urticaria (CU), 0.0107 [0.0000, 0.0233] (I²=0%, p=0.60); and nephropathy, 0.0051 [0.0000, 0.0263] (I²=62%, p=0.02).
CONCLUSION
The occurrence of secondary autoimmune diseases in patients with MS treated with ALZ is noteworthy, particularly in the form of thyroid events and hematological events. Clinicians should monitor the overall condition of patients promptly for early management and avoid delayed diagnosis and treatment.
SYSTEMATIC REVIEW REGISTRATION
inplasy.com/inplasy-2024-4-0048/, identifier INPLASY202440048.
Topics: Humans; Alemtuzumab; Multiple Sclerosis; Autoimmune Diseases; Incidence; Hashimoto Disease
PubMed: 38690271
DOI: 10.3389/fimmu.2024.1343971 -
Frontiers in Immunology 2024Autophagy is a cellular process that functions to maintain intracellular homeostasis via the degradation and recycling of defective organelles or damaged proteins. This... (Review)
Review
Autophagy is a cellular process that functions to maintain intracellular homeostasis via the degradation and recycling of defective organelles or damaged proteins. This dynamic mechanism participates in various biological processes, such as the regulation of cellular differentiation, proliferation, survival, and the modulation of inflammation and immune responses. Recent evidence has demonstrated the involvement of polymorphisms in autophagy-related genes in various skin autoimmune diseases. In addition, autophagy, along with autophagy-related proteins, also contributes to homeostasis maintenance and immune regulation in the skin, which is associated with skin autoimmune disorders. This review aims to provide an overview of the multifaceted role of autophagy in skin autoimmune diseases and shed light on the potential of autophagy-targeting therapeutic strategies in dermatology.
Topics: Humans; Autophagy; Autoimmune Diseases; Skin Diseases; Animals; Skin; Homeostasis
PubMed: 38690268
DOI: 10.3389/fimmu.2024.1343987 -
International Journal of Molecular... Apr 2024Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment... (Review)
Review
Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment loss, respectively. In AA, inflammatory cell infiltrates are in the deep reticular dermis close to the hair bulb (swarm of bees), whereas in vitiligo the inflammatory infiltrates are in the epidermis and papillary dermis. Immune privilege collapse has been extensively investigated in AA pathogenesis, including the suppression of immunomodulatory factors (e.g., transforming growth factor-β (TGF-β), programmed death-ligand 1 (PDL1), interleukin-10 (IL-10), α-melanocyte-stimulating hormone (α-MSH), and macrophage migration inhibitory factor (MIF)) and enhanced expression of the major histocompatibility complex (MHC) throughout hair follicles. However, immune privilege collapse in vitiligo remains less explored. Both AA and vitiligo are autoimmune diseases that share commonalities in pathogenesis, including the involvement of plasmacytoid dendritic cells (and interferon-α (IFN- α) signaling pathways) and cytotoxic CD8+ T lymphocytes (and activated IFN-γ signaling pathways). Blood chemokine C-X-C motif ligand 9 (CXCL9) and CXCL10 are elevated in both diseases. Common factors that contribute to AA and vitiligo include oxidative stress, autophagy, type 2 cytokines, and the Wnt/β-catenin pathway (e.g., dickkopf 1 (DKK1)). Here, we summarize the commonalities and differences between AA and vitiligo, focusing on their pathogenesis.
Topics: Alopecia Areata; Humans; Vitiligo; Animals; Immune Privilege; Cytokines
PubMed: 38673994
DOI: 10.3390/ijms25084409 -
Life (Basel, Switzerland) Apr 2024Immuno-correlated dermatological pathologies refer to skin disorders that are closely associated with immune system dysfunction or abnormal immune responses.... (Review)
Review
Immuno-correlated dermatological pathologies refer to skin disorders that are closely associated with immune system dysfunction or abnormal immune responses. Advancements in the field of artificial intelligence (AI) have shown promise in enhancing the diagnosis, management, and assessment of immuno-correlated dermatological pathologies. This intersection of dermatology and immunology plays a pivotal role in comprehending and addressing complex skin disorders with immune system involvement. The paper explores the knowledge known so far and the evolution and achievements of AI in diagnosis; discusses segmentation and the classification of medical images; and reviews existing challenges, in immunological-related skin diseases. From our review, the role of AI has emerged, especially in the analysis of images for both diagnostic and severity assessment purposes. Furthermore, the possibility of predicting patients' response to therapies is emerging, in order to create tailored therapies.
PubMed: 38672786
DOI: 10.3390/life14040516 -
Life (Basel, Switzerland) Apr 2024Skin conditions are numerous and often have a major impact on patients' quality of life, and effective and safe treatment is very important. The conventional drugs used... (Review)
Review
Skin conditions are numerous and often have a major impact on patients' quality of life, and effective and safe treatment is very important. The conventional drugs used for skin diseases are usually corticosteroids and antimicrobial products that can induce various side effects, especially with long-term use, which is why researchers are studying alternatives, especially biologically active natural products. Three products caught our attention: bee venom (BV), due to reported experimental results showing anti-inflammatory, antibacterial, antiviral, antioxidant, antimycotic, and anticancer effects, (FC) due to its demonstrated antioxidant, antibacterial, and anti-inflammatory action, and finally essential oil (GEO), with proven antifungal, antibacterial, anti-inflammatory, and antioxidant effects. Following a review of the literature, we produced this paper, which presents a review of the potential therapeutic applications of the three products in combating various skin conditions and for skin care, because BV, FC, and GEO have common pharmacological actions (anti-inflammatory, antibacterial, and antioxidant). We also focused on studying the safety of the topical use of BV, FC, and GEO, and new approaches to this. This paper presents the use of these natural therapeutic agents to treat patients with conditions such as vitiligo, melasma, and melanoma, as well as their use in treating dermatological conditions in patients with diabetes.
PubMed: 38672762
DOI: 10.3390/life14040492 -
Current Issues in Molecular Biology Mar 2024The evolution of personalized medicine in dermatology signifies a transformative shift towards individualized treatments, driven by the integration of biomarkers. These... (Review)
Review
The evolution of personalized medicine in dermatology signifies a transformative shift towards individualized treatments, driven by the integration of biomarkers. These molecular indicators serve beyond diagnostics, offering insights into disease staging, prognosis, and therapeutic monitoring. Specific criteria guide biomarker selection, ensuring attributes like specificity, sensitivity, cost feasibility, stability, rapid detection, and reproducibility. This literature review, based on data from PubMed, SCOPUS, and Web of Science, explores biomarkers in Hidradenitis Suppurativa (HS), Psoriasis, Atopic Dermatitis (AD), Alopecia Areata (AA), Vitiligo, and Chronic Spontaneous Urticaria (CSU). In HS, TNF-α, IL-1β, and MMPs serve as biomarkers, influencing targeted therapies like adalimumab and anakinra. Psoriasis involves biomarkers such as TNF-α, IL-23, and HLA genes, shaping treatments like IL23 and IL17 inhibitors. AD biomarkers include ECP, IL-4, IL-13, guiding therapies like dupilumab and tralokinumab. For AA, lipocalin-2, cytokines, and genetic polymorphisms inform JAK inhibitors' use. Vitiligo biomarkers range from cytokines to genetic markers like TYR, TYRP1, guiding treatments like JAK inhibitors. CSU biomarkers encompass IgE, cytokines, and autologous serum tests, influencing therapies like omalizumab and cyclosporine. Comparing conditions, common proinflammatory markers reveal limited specificity. While some biomarkers aid diagnosis and standard treatments, others hold more scientific than clinical value. Precision medicine, driven by biomarkers, has shown success in skin malignancies. Future directions involve AI-powered algorithms, nanotechnology, and multi-omics integration for personalized dermatological care.
PubMed: 38666916
DOI: 10.3390/cimb46040186