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Allergy, Asthma, and Clinical... Apr 2024Alopecia areata (AA), a prevalent form of autoimmune hair loss, has a not well-defined relationship with atopic and allergic disorders, including eczema, hay fever, and...
BACKGROUND
Alopecia areata (AA), a prevalent form of autoimmune hair loss, has a not well-defined relationship with atopic and allergic disorders, including eczema, hay fever, and asthma.
OBJECTIVES
This study aims to elucidate the genetic relationship between atopy, allergies, and alopecia areata (AA) using Mendelian randomization. We hypothesize that atopic and allergic conditions contribute to the genetic predisposition of AA.
METHODS
We analyzed extensive genetic data from Genome-wide Association Studies (GWAS) involving over one million individuals. This analysis focused on assessing the genetic correlation between AA and various allergic conditions, including hay fever, eczema, asthma, and allergies to pollen, dust, and cats. The inverse variance weighted method served as our primary analytical tool, complemented by sensitivity analyses to verify the robustness of our results.
RESULTS
Our findings reveal a significant genetic correlation between atopy/allergies and an increased risk of AA. Notably, strong associations were observed for hay fever, eczema, asthma, and specific allergies (pollen, dust, and cats). The sensitivity analyses corroborated these associations, reinforcing the reliability of our primary results.
CONCLUSIONS
This study provides compelling genetic evidence of an association between atopic and allergic conditions and the development of AA. These findings suggest that individuals with such conditions may benefit from enhanced surveillance for early signs of AA.
PubMed: 38678274
DOI: 10.1186/s13223-024-00892-w -
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 -
International Journal of Molecular... Apr 2024Imbalances in gut microbiota reportedly contribute to the development of autoimmune diseases, but the association between the etiopathogenesis of alopecia areata (AA)...
Imbalances in gut microbiota reportedly contribute to the development of autoimmune diseases, but the association between the etiopathogenesis of alopecia areata (AA) and gut microbial dysbiosis remains unclear. This cross-sectional study was conducted to identify and compare the composition of the gut microbiome in patients affected by AA and those in a healthy control (HC) group, and to investigate possible bacterial biomarkers for the disease. Fecal samples were collected from 19 AA patients and 20 HCs to analyze the relationship with fecal bacteria. The three major genera constituting the gut microbiome of AA patients were , , and . The alpha diversity of the AA group was not statistically significant different from that of the HC group. However, bacterial community composition in the AA group was significantly different from that of HC group according to Jensen-Shannon dissimilarities. In patients with AA, we found an enriched presence of the genera and compared to the HC group ( < 0.05), whereas were less prevalent ( < 0.05). The gut microbiota of AA patients was distinct from those of the HC group. Our findings suggest a possible involvement of gut microbiota in in the as-yet-undefined pathogenesis of AA.
Topics: Humans; Alopecia Areata; Gastrointestinal Microbiome; Female; Male; Adult; Feces; Cross-Sectional Studies; Dysbiosis; Middle Aged; Young Adult; Case-Control Studies; Bacteria; RNA, Ribosomal, 16S; Bacteroides
PubMed: 38673841
DOI: 10.3390/ijms25084256 -
Journal of Clinical Medicine Apr 2024: A higher prevalence of ophthalmological alterations in systemic inflammatory diseases has been demonstrated. : Our objectives were to determine anterior segment...
: A higher prevalence of ophthalmological alterations in systemic inflammatory diseases has been demonstrated. : Our objectives were to determine anterior segment findings and corneal properties in alopecia areata (AA). : This is a case-control study. Severe AA patients (Severity of Alopecia Tool > 50%) and non-AA subjects underwent a general ophthalmological examination, a Pentacam and Corvis scheimpflug technology examination (Oculus Optikgeräte GmbH, Wetzlar, Germany). Visual acuity, refractive error, corneal aesthesiometry, and biomechanical and topographic variables were registered. : In total, 25 AA patients (50 eyes; 50.6 ± 8.1 years) and 29 controls (58 eyes; 49.4 ± 8.6 years) were included. AA patients had decreased corneal sensitivity, more corneal staining, and a more advanced cataract ( ≤ 0.004). The anterior topographic flat meridian, mean anterior keratometry, and maximum keratometric point were increased in AA ( ≤ 0.040), while pachymetry values were thinner ( ≤ 0.001). Keratoconus index and Belin/Ambrosio-enhanced ectasia total deviation display were increased ( ≤ 0.007). Two eyes with a topographic diagnosis of keratoconus and four eyes with subclinical keratoconus were detected in AA. Applanation lengths were smaller in AA ( ≤ 0.029). The Corvis Biomechanical Index was increased in AA ( = 0.022). : AA patients have reduced corneal sensitivity and increased corneal staining. Topographic and biomechanical parameters are altered, and there could be a higher risk of keratoconus, thus possibly requiring routine ophthalmological examination.
PubMed: 38673699
DOI: 10.3390/jcm13082426 -
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 -
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 -
Frontiers in Pharmacology 2024We performed a Bayesian network meta-analysis to indirectly compare the relative efficacy and safety of the latest JAK inhibitors for moderate-to-severe alopecia areata...
We performed a Bayesian network meta-analysis to indirectly compare the relative efficacy and safety of the latest JAK inhibitors for moderate-to-severe alopecia areata (AA). 13 trials totaling 3,613 patients were included. Two low-dose groups of oral formulations (ritlecitinib 10mg and ivarmacitinib 2mg) and two topical formulations (delgocitinib ointment and ruxolitinib cream) appeared to be relatively ineffective against moderate-to-severe AA. Ranking analysis suggested that brepocitinib 30mg has the best relative effect in reducing the SALT score (sucra = 0.9831), and demonstrated comparable efficacy to deuruxolitinib 12mg (sucra = 0.9245), followed by deuruxolitinib 8mg (sucra = 0.7736). Regarding the SALT response, brepocitinib 30mg ranked highest (sucra = 0.9567), followed by ritlecitinib 50mg (sucra = 0.8689) and deuruxolitinib 12mg (sucra = 0.7690). For achieving the SALT response, deuruxolitinib 12mg had the highest probability (sucra = 0.9761), followed by deuruxolitinib 8mg (sucra = 0.8678) and brepocitinib 30mg (sucra = 0.8448). Deuruxolitinib 12mg might be the most effective therapy for patients with severe AA (sucra = 0.9395), followed by ritlecitinib 50mg (sucra = 0.8753) and deuruxolitinib 8mg (sucra = 0.8070). Deuruxolitinib 12mg/8mg demonstrated notable efficacy for moderate-to-severe AA, and is expected to be a new treatment option for AA. It was worth noting that deuruxolitinib exhibit a greater likelihood of causing adverse events in comparison to other JAK inhibitors. Ritlecitinib 50mg seemed to exhibit fewer adverse effects in the high-dose groups of oral JAK inhibitors and might be an optimal choice to balance safety and efficacy. The majority of JAK inhibitors exhibited acceptable short-term safety profiles. To enhance the applicability and accuracy of our research, further head-to-head trials with longer follow-up periods are needed. identifier [CRD42022368012].
PubMed: 38659584
DOI: 10.3389/fphar.2024.1372810 -
Italian Journal of Dermatology and... Apr 2024This real-world analysis aimed at characterizing patients hospitalized for alopecia areata (AA) in Italy, focusing on comorbidities, treatment patterns and the economic...
BACKGROUND
This real-world analysis aimed at characterizing patients hospitalized for alopecia areata (AA) in Italy, focusing on comorbidities, treatment patterns and the economic burden for disease management.
METHODS
Administrative databases of healthcare entities covering 8.9 million residents were retrospectively browsed to include patients of all ages with hospitalization discharge diagnosis for AA from 2010 to 2020. The population was characterized during the year before the first AA-related hospitalization (index-date) and followed-up for all the available successive period. AA drug prescriptions and treatment discontinuation were analyzed during follow-up. Healthcare costs were also examined.
RESULTS
Among 252 patients with AA (mean age 32.1 years, 40.9% males), the most common comorbidities were thyroid disease (22.2%) and hypertension (21.8%), consistent with literature; only 44.4% (112/252) received therapy for AA, more frequently with prednisone, triamcinolone and clobetasol. Treatment discontinuation (no prescriptions during the last trimester) was observed in 86% and 88% of patients, respectively at 12 and 24-month after therapy initiation. Overall healthcare costs were 1715€ per patient (rising to 2143€ in the presence of comorbidities), mostly driven by hospitalization and drugs expenses.
CONCLUSIONS
This first real-world description of hospitalized AA patients in Italy confirmed the youth and female predominance of this population, in line with international data. The large use of corticosteroids over other systemic therapies followed the Italian guidelines, but the high discontinuation rates suggest an unmet need for further treatment options. Lastly, the analysis of healthcare expenses indicated that hospitalizations and drugs were the most impactive cost items.
Topics: Humans; Italy; Alopecia Areata; Male; Female; Adult; Retrospective Studies; Hospitalization; Adolescent; Young Adult; Middle Aged; Child; Health Care Costs; Comorbidity; Child, Preschool; Thyroid Diseases; Hypertension; Aged
PubMed: 38650498
DOI: 10.23736/S2784-8671.24.07785-5 -
Journal of Translational Medicine Apr 2024JAK-STAT signalling pathway inhibitors have emerged as promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 has become an...
JAK-STAT signalling pathway inhibitors have emerged as promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 has become an ideal target for drug discovery because it only regulates a narrow spectrum of γc cytokines. Here, we report the discovery of MJ04, a novel and highly selective 3-pyrimidinylazaindole based JAK3 inhibitor, as a potential hair growth promoter with an IC of 2.03 nM. During in vivo efficacy assays, topical application of MJ04 on DHT-challenged AGA and athymic nude mice resulted in early onset of hair regrowth. Furthermore, MJ04 significantly promoted the growth of human hair follicles under ex-vivo conditions. MJ04 exhibited a reasonably good pharmacokinetic profile and demonstrated a favourable safety profile under in vivo and in vitro conditions. Taken together, we report MJ04 as a highly potent and selective JAK3 inhibitor that exhibits overall properties suitable for topical drug development and advancement to human clinical trials.
Topics: Mice; Animals; Humans; Mice, Nude; Hair; Drug Development; Drug Discovery; Janus Kinase 3
PubMed: 38637842
DOI: 10.1186/s12967-024-05144-4