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Current Opinion in Allergy and Clinical... Jun 2024This review summarizes recent advances in identifying genetic risk factors for atopic dermatitis and how these genetic associations are being used to explore the causal...
PURPOSE OF REVIEW
This review summarizes recent advances in identifying genetic risk factors for atopic dermatitis and how these genetic associations are being used to explore the causal relationships between atopic dermatitis and potential risk factors and downstream outcomes.
RECENT FINDINGS
A recent large-scale GWAS meta-analysis has identified 91 genetic loci associated with atopic dermatitis. Rare variant studies have also identified new gain-of-function or loss-of-function variants implicated in atopic dermatitis, particularly for FLG and STAT6/JAK1. Finally, there has been a surge in utilizing genetic association data to investigate the causal relationships between atopic dermatitis and other traits. Mendelian randomization studies have found that various metabolites and gut microbiota are causal for atopic dermatitis and have causally implicate atopic dermatitis in the development of alopecia areata, diabetes, vascular dementia and some cancers.
SUMMARY
The past year has seen a huge increase in the genes implicated for atopic dermatitis and in the use of genetics to explore causal relationships. The latter requires caution in implementation and interpretation, but is a promising area of research. In the coming years, increasing the ethnic diversity of atopic dermatitis genetic studies would be very welcome and the translation of current genetic findings into new drugs will be an exciting area of development.
PubMed: 38920356
DOI: 10.1097/ACI.0000000000001005 -
Clinical Reviews in Allergy & Immunology Jun 2024Down syndrome is the most common genetic cause of intellectual disability and has previously been associated with a variety of autoimmune disorders affecting multiple... (Review)
Review
Down syndrome is the most common genetic cause of intellectual disability and has previously been associated with a variety of autoimmune disorders affecting multiple organ systems. The high prevalence of autoimmune disease, in conjunction with other inflammatory and infectious diseases, in this population suggests an intrinsic immune dysregulation associated with triplication of chromosome 21. Emerging data on the role of chromosome 21 in interferon activation, cytokine production, and activation of B-cell mediated autoimmunity are emerging hypotheses that may explain the elevated prevalence of autoimmune thyroid disease, celiac disease, type I diabetes, autoimmune skin disease, and a variety of autoimmune neurologic conditions. As the life expectancy for individuals with Down syndrome increases, knowledge of the epidemiology, clinical features, management and underlying causes of these conditions will become increasingly important. Disorders such as Hashimoto's thyroiditis are prevalent in between 13 and 34% of individuals with Down syndrome but only 3% of the neurotypical population, a pattern similarly recognized in individuals with Celiac Disease (5.8% v 0.5-2%), alopecia areata (27.7% v. 2%), and vitiligo (4.4% v. 0.05-1.55%), respectively. Given the chronicity of autoimmune conditions, early identification and management can significantly impact the quality of life of individuals with Down syndrome. This comprehensive review will highlight common clinical autoimmune conditions observed in individuals with Down syndrome and explore our current understanding of the mechanisms of disease in this population.
PubMed: 38913142
DOI: 10.1007/s12016-024-08996-2 -
European Journal of Dermatology : EJD Apr 2024Alopecia areata (AA) is a chronic autoimmune disease that causes non-scarring hair loss. Data are lacking on the epidemiology and clinical and economic burden of AA in... (Observational Study)
Observational Study
Alopecia areata (AA) is a chronic autoimmune disease that causes non-scarring hair loss. Data are lacking on the epidemiology and clinical and economic burden of AA in Spain. To estimate the prevalence and incidence of AA in Spain and describe sociodemographic and clinical characteristics, treatment patterns, healthcare resource utilization (HCRU) and associated costs. This was an observational, retrospective, descriptive study based on the Health Improvement Network (THIN®) database (Cegedim Health Data, Spain). Patients with ICD9-Code 704.01 for AA, registered between 2014 and 2021, were identified. Prevalence (%) and incidence rates per 1,000 patient-years (IR) of AA were calculated and clinical characteristics, treatment characteristics and HCRU/costs were assessed. A total of 5,488 patients with AA were identified. The point prevalence of AA in 2021 was 0.44 (95% confidence interval [CI]: 0.43-0.45) overall, 0.48 (0.47-0.49) in adults, and 0.23 (0.21-0.26) in children ≤12 years. The 2021 IR for AA in adults was 0.55 (0.51-0.60). Of 3,351 adults with AA, 53.4% were female, mean (standard deviation [SD]) age was 43.1 (14.7) years, and 41.6% experienced comorbidities. Among adults, 2.7% used systemic treatment (0.5% immunosuppressants, 2.5% oral corticosteroids, 0.3% both). Laboratory tests and health care professional visits were the principal drivers of cost, which was €821.2 (1065.6)/patient in the first year after diagnosis. The epidemiology of AA in Spain is comparable with that reported for other countries, being more prevalent among adults. There is a significant burden of comorbidities and cost for patients, with limited use of systemic treatments, suggesting an unmet treatment need in this population.
Topics: Humans; Spain; Alopecia Areata; Retrospective Studies; Female; Male; Adult; Prevalence; Cost of Illness; Child; Health Care Costs; Incidence; Middle Aged; Adolescent; Young Adult; Child, Preschool; Immunosuppressive Agents; Aged
PubMed: 38907547
DOI: 10.1684/ejd.2024.4654 -
Dermatology and Therapy Jun 2024Alopecia areata (AA) is an autoimmune disease associated with high rates of emotional and psychosocial distress. The analysis reported here describes the evolution of...
Improvement in Measures of Quality of Life and Symptoms of Anxiety and Depression in Patients with Severe Alopecia Areata Achieving Sustained Scalp Hair Regrowth with Baricitinib.
INTRODUCTION
Alopecia areata (AA) is an autoimmune disease associated with high rates of emotional and psychosocial distress. The analysis reported here describes the evolution of measures assessing health-related quality of life (HRQoL) and symptoms of anxiety and depression up to week 104 in patients who achieved sustained scalp hair regrowth during treatment with baricitinib in the BRAVE-AA phase III trials.
METHODS
This post-hoc analysis included data from the double-blind, parallel-group, randomized, placebo-controlled phase III trials BRAVE-AA1 (ClinicalTrials.gov number: NCT03570749) and BRAVE-AA2 (ClinicalTrials.gov number: NCT03899259). Adults with severe AA (defined as a Severity of Alopecia Tool [SALT] score ≥ 50) randomized to baricitinib 4 mg or baricitinib 2 mg at baseline who achieved SALT score ≤ 20 by week 36 and maintained SALT score ≤ 20 through week 104 on the same dose of baricitinib were included in this analysis of integrated data. Scalp hair regrowth (SALT score) and improvements in Skindex-16 AA Scale and Hospital Anxiety and Depression Scale (HADS) domain scores were analyzed over the 104-week period using descriptive statistics.
RESULTS
In total, 131 patients (88 on baricitinib 4 mg and 43 on baricitinib 2 mg) were included in this analysis. Across the two groups, the mean age (standard deviation) was 37.2 years (12.7), and 84 (64.1%) patients were female. The interquartile range) for time to achieve a SALT score ≤ 20 for patients treated with baricitinib 4 mg and baricitinib 2 mg was 13.1 and 19.6 weeks, respectively. By week 104, 91% (baricitinib 2 mg) and 96% (baricitinib 4 mg) of patients had achieved a SALT score ≤ 10 on baricitinib treatment. In both groups, progressive improvements in the Skindex-16 AA and HADS domain scores were observed up to week 104.
CONCLUSION
This analysis of adults with severe AA treated with baricitinib revealed that achievement of sustained clinically meaningful scalp hair regrowth (SALT score ≤ 20) was associated with improvements in both measures of HRQoL and symptoms of anxiety and depression up to week 104.
PubMed: 38904749
DOI: 10.1007/s13555-024-01208-x -
Frontiers in Immunology 2024An 8-year-old female child presented with patchy hair loss for 1 year, accompanied by eyebrow loss for 6 months. Microscopic examination of the hair confirmed the...
An 8-year-old female child presented with patchy hair loss for 1 year, accompanied by eyebrow loss for 6 months. Microscopic examination of the hair confirmed the features of active stage alopecia areata, with a Severity of Alopecia Tool (SALT) score of 70%. The diagnosis was severe alopecia areata. The patient had a history of atopic dermatitis since infancy, with recurrent episodes of scattered papules and pruritus for 8 years. Initial treatment involved subcutaneous injections of dupilumab 300mg every 2 weeks for 6 months, resulting in a reduction of SALT score to 20% and improvement of atopic dermatitis symptoms. Discontinuation of Dupilumab and initiation of daily oral Baricitinib at a dose of 2mg for a duration of 5 months. According to the SALT score evaluation, the severity of hair loss was less than 10% and there was significant regrowth of hair. No significant adverse reactions were observed during the treatment period.
Topics: Humans; Alopecia Areata; Dermatitis, Atopic; Female; Purines; Child; Azetidines; Pyrazoles; Sulfonamides; Antibodies, Monoclonal, Humanized; Treatment Outcome; Severity of Illness Index; Drug Therapy, Combination
PubMed: 38903518
DOI: 10.3389/fimmu.2024.1395288 -
Diagnostics (Basel, Switzerland) May 2024This survey represents the first endeavor to assess the clarity of the dermoscopic language by a chatbot, unveiling insights into the interplay between dermatologists...
This survey represents the first endeavor to assess the clarity of the dermoscopic language by a chatbot, unveiling insights into the interplay between dermatologists and AI systems within the complexity of the dermoscopic language. Given the complex, descriptive, and metaphorical aspects of the dermoscopic language, subjective interpretations often emerge. The survey evaluated the completeness and diagnostic efficacy of chatbot-generated reports, focusing on their role in facilitating accurate diagnoses and educational opportunities for novice dermatologists. A total of 30 participants were presented with hypothetical dermoscopic descriptions of skin lesions, including dermoscopic descriptions of skin cancers such as BCC, SCC, and melanoma, skin cancer mimickers such as actinic and seborrheic keratosis, dermatofibroma, and atypical nevus, and inflammatory dermatosis such as psoriasis and alopecia areata. Each description was accompanied by specific clinical information, and the participants were tasked with assessing the differential diagnosis list generated by the AI chatbot in its initial response. In each scenario, the chatbot generated an extensive list of potential differential diagnoses, exhibiting lower performance in cases of SCC and inflammatory dermatoses, albeit without statistical significance, suggesting that the participants were equally satisfied with the responses provided. Scores decreased notably when practical descriptions of dermoscopic signs were provided. Answers to BCC scenario scores in the diagnosis category (2.9 ± 0.4) were higher than those with SCC (2.6 ± 0.66, = 0.005) and inflammatory dermatoses (2.6 ± 0.67, = 0). Similarly, in the teaching tool usefulness category, BCC-based chatbot differential diagnosis received higher scores (2.9 ± 0.4) compared to SCC (2.6 ± 0.67, = 0.001) and inflammatory dermatoses (2.4 ± 0.81, = 0). The abovementioned results underscore dermatologists' familiarity with BCC dermoscopic images while highlighting the challenges associated with interpreting rigorous dermoscopic images. Moreover, by incorporating patient characteristics such as age, phototype, or immune state, the differential diagnosis list in each case was customized to include lesion types appropriate for each category, illustrating the AI's flexibility in evaluating diagnoses and highlighting its value as a resource for dermatologists.
PubMed: 38893694
DOI: 10.3390/diagnostics14111165 -
Journal of Clinical Medicine Jun 2024Alopecia areata (AA) is a common form of non-scarring alopecia characterized by acute hair loss. Nail involvement, though not always present, can occur in AA patients.... (Review)
Review
Alopecia areata (AA) is a common form of non-scarring alopecia characterized by acute hair loss. Nail involvement, though not always present, can occur in AA patients. Nail changes are more frequent in severe forms of AA and in children. Literature related to nail changes in AA was comprehensively reviewed after a search on the PubMed database without time restrictions in order to identify common clinical presentations and associated factors to aid clinicians with the correct evaluation and management of these dystrophies. Nail changes in AA include pitting, trachyonychia, leukonychia, red lunula, and miscellaneous alterations such as longitudinal ridging and brittle nails. Nail changes are usually asymptomatic but, nevertheless, sometimes cosmetically disfiguring and can be associated with a reduced quality of life and impaired daily activities. Nail changes in AA may precede or follow hair loss and can occur as an isolated finding. Diagnosis may require a biopsy for definitive identification. Spontaneous improvement is possible, particularly in children, and treatment is not always necessary. Further research is, however, needed to establish a consensus on treatment approaches according to age and severity.
PubMed: 38893003
DOI: 10.3390/jcm13113292 -
Journal of Clinical Medicine May 2024Depressive disorders are a growing problem worldwide. They are also characterized by high comorbidity, including from the circle of dermatological diseases. Autoimmune... (Review)
Review
Depressive disorders are a growing problem worldwide. They are also characterized by high comorbidity, including from the circle of dermatological diseases. Autoimmune diseases seem to be particularly correlated with depressive comorbidity, raising the question of their possible common pathomechanism. The PubMed database was searched, focusing on results published after 2016. A particular reciprocal correlation of depressive disorders with psoriasis, atopic dermatitis, alopecia areata, impetigo, lupus and systemic scleroderma was found. One possible explanation for the co-occurrence of the above diseases is that the inflammatory theory may be applicable to depression, the various elements of which also apply to autoimmune diseases.
PubMed: 38892934
DOI: 10.3390/jcm13113224 -
International Journal of Molecular... May 2024Alopecia areata (AA) is an autoimmune-mediated disorder in which the proximal hair follicle (HF) attack results in non-scarring partial to total scalp or body hair loss.... (Review)
Review
Alopecia areata (AA) is an autoimmune-mediated disorder in which the proximal hair follicle (HF) attack results in non-scarring partial to total scalp or body hair loss. Despite the growing knowledge about AA, its exact cause still needs to be understood. However, immunity and genetic factors are affirmed to be critical in AA development. While the genome-wide association studies proved the innate and acquired immunity involvement, AA mouse models implicated the IFN-γ- and cytotoxic CD8+ T-cell-mediated immune response as the main drivers of disease pathogenesis. The AA hair loss is caused by T-cell-mediated inflammation in the HF area, disturbing its function and disrupting the hair growth cycle without destroying the follicle. Thus, the loss of HF immune privilege, autoimmune HF destruction mediated by cytotoxic mechanisms, and the upregulation of inflammatory pathways play a crucial role. AA is associated with concurrent systemic and autoimmune disorders such as atopic dermatitis, vitiligo, psoriasis, and thyroiditis. Likewise, the patient's quality of life (QoL) is significantly impaired by morphologic disfigurement caused by the illness. The patients experience a negative impact on psychological well-being and self-esteem and may be more likely to suffer from psychiatric comorbidities. This manuscript aims to present the latest knowledge on the pathogenesis of AA, which involves genetic, epigenetic, immunological, and environmental factors, with a particular emphasis on immunopathogenesis.
Topics: Alopecia Areata; Humans; Animals; Hair Follicle
PubMed: 38891839
DOI: 10.3390/ijms25115652 -
Stem Cell Research & Therapy Jun 2024The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as...
AIMS AND OBJECTIVES
The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as platelet-rich plasma, stromal vascular fraction, cell therapy, conditioned media, etc.) in treating specific dermatologic diseases. Rejuvenation, scarring, wound healing, and other secondary conditions of skin damage were not investigated in this study.
METHOD
Major databases, including PubMed, Scopus, and Web of Science, were meticulously searched for RCTs up to January 2024, focusing on regenerative medicine interventions for specific dermatologic disorders (such as androgenetic alopecia, vitiligo, alopecia areata, etc.). Key data extracted encompassed participant characteristics and sample sizes, types of regenerative therapy, treatment efficacy, and adverse events.
RESULTS
In this systematic review, 64 studies involving a total of 2888 patients were examined. Women constituted 44.8% of the study population, while men made up 55.2% of the participants, with an average age of 27.64 years. The most frequently studied skin diseases were androgenetic alopecia (AGA) (45.3%) and vitiligo (31.2%). The most common regenerative methods investigated for these diseases were PRP and the transplantation of autologous epidermal melanocyte/keratinocyte cells, respectively. Studies reported up to 68.4% improvement in AGA and up to 71% improvement in vitiligo. Other diseases included in the review were alopecia areata, melasma, lichen sclerosus et atrophicus (LSA), inflammatory acne vulgaris, chronic telogen effluvium, erosive oral lichen planus, and dystrophic epidermolysis bullosa. Regenerative medicine was found to be an effective treatment option in all of these studies, along with other methods. The regenerative medicine techniques investigated in this study comprised the transplantation of autologous epidermal melanocyte/keratinocyte cells, isolated melanocyte transplantation, cell transplantation from hair follicle origins, melanocyte-keratinocyte suspension in PRP, conditioned media injection, a combination of PRP and basic fibroblast growth factor, intravenous injection of mesenchymal stem cells, concentrated growth factor, stromal vascular fraction (SVF), a combination of PRP and SVF, and preserving hair grafts in PRP.
CONCLUSION
Regenerative medicine holds promise as a treatment for specific dermatologic disorders. To validate our findings, it is recommended to conduct numerous clinical trials focusing on various skin conditions. In our study, we did not explore secondary skin lesions like scars or ulcers. Therefore, assessing the effectiveness of this treatment method for addressing these conditions would necessitate a separate study.
Topics: Adult; Female; Humans; Male; Platelet-Rich Plasma; Randomized Controlled Trials as Topic; Regenerative Medicine; Skin Diseases
PubMed: 38886861
DOI: 10.1186/s13287-024-03800-6