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Autoimmunity Reviews Jul 2016One of the most common human autoimmune diseases, alopecia areata (AA), is characterized by sudden, often persisting and psychologically devastating hair loss. Animal... (Review)
Review
One of the most common human autoimmune diseases, alopecia areata (AA), is characterized by sudden, often persisting and psychologically devastating hair loss. Animal models have helped greatly to elucidate critical cellular and molecular immune pathways in AA. The two most prominent ones are inbred C3H/HeJ mice which develop an AA-like hair phenotype spontaneously or after experimental induction, and healthy human scalp skin xenotransplanted onto SCID mice, in which a phenocopy of human AA is induced by injecting IL-2-stimulated PBMCs enriched for CD56+/NKG2D+ cells intradermally. The current review critically examines the pros and cons of the available AA animal models and how they have shaped our understanding of AA pathobiology, and the development of new therapeutic strategies. AA is thought to arise when the hair follicle's (HF) natural immune privilege (IP) collapses, inducing ectopic MHC class I expression in the HF epithelium and autoantigen presentation to autoreactive CD8+ T cells. In common with other autoimmune diseases, upregulation of IFN-γ and IL-15 is critically implicated in AA pathogenesis, as are NKG2D and its ligands, MICA, and ULBP3. The C3H/HeJ mouse model was used to identify key immune cell and molecular principles in murine AA, and proof-of-principle that Janus kinase (JAK) inhibitors are suitable agents for AA management in vivo, since both IFN-γ and IL-15 signal via the JAK pathway. Instead, the humanized mouse model of AA has been used to demonstrate the previously hypothesized key role of CD8+ T cells and NKG2D+ cells in AA pathogenesis and to discover human-specific pharmacologic targets like the potassium channel Kv1.3, and to show that the PDE4 inhibitor, apremilast, inhibits AA development in human skin. As such, AA provides a model disease, in which to contemplate general challenges, opportunities, and limitations one faces when selecting appropriate animal models in preclinical research for human autoimmune diseases.
Topics: Alopecia Areata; Animals; Autoantigens; Autoimmune Diseases; Disease Models, Animal; Humans; Mice, SCID
PubMed: 26971464
DOI: 10.1016/j.autrev.2016.03.008 -
The Journal of Investigative... Nov 2015Disease is not limited to humans. Rather, humans are but another mammal in a continuum, and as such, often share similar if not identical diseases with other mammalian... (Review)
Review
Disease is not limited to humans. Rather, humans are but another mammal in a continuum, and as such, often share similar if not identical diseases with other mammalian species. Alopecia areata (AA) is such a disease. Natural disease occurs in humans, nonhuman primates, many domestic animals, and laboratory rodents. However, to be useful as models of human disease, affected animals need to be readily available to the research community, closely resemble the human disease, be easy to work with, and provide reproducible data. To date, the laboratory mouse (most if not all of the C3H substrains) and the Dundee experimental bald rat fit these criteria. Manipulations using full-thickness skin grafts or specific immune cell transfers have improved the models. New mouse models that carry a variety of genetic-based immunodeficiencies can now be used to recapitulate the human immune system and allow for human full-thickness skin grafts onto mice to investigate human-specific mechanistic and therapeutic questions. These models are summarized here including where they can currently be obtained from public access repositories.
Topics: Alopecia Areata; Animals; Disease Models, Animal; Heterografts; Humans; Mice; Rats; Skin Transplantation
PubMed: 26551940
DOI: 10.1038/jidsymp.2015.35 -
Acta Dermato-venereologica Sep 2023Alopecia areata (AA) is a common cause of hair loss in children. Despite numerous therapeutic options for paediatric AA, none have been found to be both effective and... (Review)
Review
Alopecia areata (AA) is a common cause of hair loss in children. Despite numerous therapeutic options for paediatric AA, none have been found to be both effective and safe. Recent studies have demonstrated the efficacy and safety of the Janus kinase (JAK) inhibitor tofacitinib in adult patients with AA, whereas data on paediatric patients with AA in real-world practice are limited. This was a single-centre, retrospective study that included 11 pre-adolescent patients with AA treated with tofacitinib between December 2021 and September 2022. Clinical characteristics of patients, clinical response and adverse events were evaluated. Overall, 82% (9/11) of patients experienced hair regrowth and 64% (7/11) of patients experienced over 50% improvement in their Severity of Alopecia Tool (SALT) scores. Adverse events were mild. In the literature, tofacitinib has been used to treat AA in 31 children ≤12 years of age who failed to respond to prior treatments. Eighty-seven percent (27/31) of these patients showed significant responses based on changes in their SALT scores. This case series demonstrates that oral tofacitinib is an effective and safe treatment option for paediatric AA, particularly for children who have failed to respond to traditional treatments or are not suitable for such treatments.
Topics: Adult; Humans; Adolescent; Child; Alopecia Areata; Retrospective Studies; Piperidines; Janus Kinase Inhibitors
PubMed: 37731213
DOI: 10.2340/actadv.v103.13418 -
Frontiers in Immunology 2022No comprehensive studies have been published on the global burden of alopecia areata since 2010.
BACKGROUND
No comprehensive studies have been published on the global burden of alopecia areata since 2010.
OBJECTIVE
We aimed to measure the global, regional, and national incidence of alopecia areata and disability-adjusted life-years (DALYs) by age, sex, and socio-demographic index (SDI) value from 1990 to 2019.
METHODS
Data were extracted from the Global Burden of Disease Study 2019. Estimated annual percentage changes (EAPCs) were calculated to quantify temporal trends in the age-standardized rates of alopecia areata incidence and DALYs. The correlations between EAPCs in the age-standardized rates and SDI values were also analyzed.
RESULTS
From 1990 to 2019, the alopecia areata incidence number and the associated number of DALYs increased globally by 49.14%, and 49.51%, respectively. The global age-standardized incidence rate decreased (EAPC, -0.13; 95% confidence interval [CI], -0.13 to -0.12) and the age-standardized DALY rate showed a downward trend (EAPC, -0.12; 95% CI, -0.13 to -0.11). The largest increases in the age-standardized incidence rate and age-standardized DALY rate were observed in Low SDI quintile and Western Sub-Saharan Africa regions. The regions with the greatest changes in the incidence of alopecia areata were Central Sub-Saharan Africa and Western Sub-Saharan Africa. The three countries with the largest increases in alopecia areata incidence from 1990 to 2019 were Kuwait (EAPC, 0.15), South Sudan (EAPC, 0.12), and Nigeria (EAPC, 0.11). The age-standardized incidence rate was higher in females than in males.
CONCLUSION
Globally, both the age-standardized incidence rate and age-standardized DALY rate of alopecia areata showed decreasing trends. Future preventive strategies should focus on low-income countries, Central Sub-Saharan Africa, Western Sub-Saharan Africa, Kuwait, South Sudan, Nigeria.
Topics: Alopecia Areata; Female; Global Burden of Disease; Global Health; Humans; Male; Quality-Adjusted Life Years
PubMed: 35911734
DOI: 10.3389/fimmu.2022.874677 -
The British Journal of Dermatology Jul 2022Macbeth 2022; 187:73–81.
Macbeth 2022; 187:73–81.
Topics: Alopecia Areata; Humans; Psychological Distress
PubMed: 35562779
DOI: 10.1111/bjd.21597 -
JAMA Dermatology Apr 2023Prevalences of alopecia areata (AA), alopecia totalis (AT), and alopecia universalis (AU) are poorly established.
IMPORTANCE
Prevalences of alopecia areata (AA), alopecia totalis (AT), and alopecia universalis (AU) are poorly established.
OBJECTIVE
To estimate overall and subgroup prevalences of AA and its subtypes.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study using electronic records comprising the Explorys database (Watson Health, IBM Corporation) included children, adolescents, and adults seeking healthcare across the 4 census regions in the US between January 1, 2019, and December 31, 2019. The statistical analysis was conducted between July 21, 2022, and December 22, 2022.
MAIN OUTCOMES AND MEASURES
Prevalent cases of AA, AT, and AU.
RESULTS
Of the 1 093 176 patients who met inclusion criteria, 1812 had at least 1 code for AA, 1216 female (67%) and 596 male (33%) patients. Overall age-and-sex standardized prevalences among adults and among children and adolescents were observed to be 0.18% and 0.10%, respectively. The age-standardized prevalence ratio in women to men was 1.32. Standardized prevalence was highest in those aged 30 to 39 (297 per 100 000; 95% CI, 263-335) and 40 to 49 (270 per 100 000; 95% CI, 240-303) years. The highest standardized prevalence was observed among Asian patients (414 per 100 000; 95% CI, 306-548), followed by patients reporting another race or multiple races (314 per 100 000; 95% CI, 266-368), Black (226 per 100 000; 95% CI, 199-255), and Hispanic/Latino (212 per 100 000; 95% CI, 129-328) patients. White patients had the lowest standardized prevalence (168 per 100 000; 95% CI, 157-179) among racial and ethnic subgroups. Relative to White patients, standardized prevalence ratios for Asian, Black, and Hispanic/Latino patients were 2.47 (95% CI, 2.17-2.81), 1.35 (95% CI, 1.26-1.44), and 1.26 (95% CI, 1.03-1.55), respectively. Cases of AT and AU comprised approximately 9% of patients diagnosed with AA.
CONCLUSIONS AND RELEVANCE
The findings of this cross-sectional study suggest that there is a significant burden of AA, AT, and AU in the US in which people of color, particularly Asian Americans, appear to be disproportionately affected.
Topics: Adult; Child; Adolescent; Female; Male; Humans; Alopecia Areata; Prevalence; Cross-Sectional Studies; Cost of Illness
PubMed: 36857044
DOI: 10.1001/jamadermatol.2023.0016 -
The Journal of Investigative... Jan 2018In the absence of an approved treatment by the US Food and Drug Administration, choosing one of the many off-label treatments available for a child, teen, or adult with... (Review)
Review
In the absence of an approved treatment by the US Food and Drug Administration, choosing one of the many off-label treatments available for a child, teen, or adult with alopecia areata (AA) can be challenging. The physician or midlevel provider treating a patient with AA needs to take into consideration the age of the patient, location of hair loss, disease extent and activity, and any ongoing medical or psychological issues. Many patients and their families have now also heard the "buzz" about evolving research, particularly with JAK inhibitors, for the treatment of AA. This means that today's clinic visit with the AA patient should include not only a discussion about traditionally used off-label treatments but also evolving therapies and clinical research opportunities.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Alopecia Areata; Child; Humans; Immunotherapy; Janus Kinase Inhibitors; Off-Label Use; Research
PubMed: 29273111
DOI: 10.1016/j.jisp.2017.10.015 -
Frontiers in Immunology 2023JAK inhibitors treat various autoimmune diseases, but an updated systematic review in treating alopecia areata is currently lacking. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
JAK inhibitors treat various autoimmune diseases, but an updated systematic review in treating alopecia areata is currently lacking.
OBJECTIVE
Evaluate the specific efficacy and safety of JAK inhibitors in alopecia areata by systematic review and meta-analysis.
METHODS
Eligible studies in PubMed, Embase, Web of Science, and Clinical Trials up to May 30, 2022, were searched. We enrolled in randomized controlled trials and observational studies of applying JAK inhibitors in alopecia areata.
RESULTS
6 randomized controlled trials with 1455 patients exhibited SALT (odd ratio [OR], 5.08; 95% confidence interval [CI], 3.49-7.38), SALT (OR, 7.40; 95% CI, 4.34-12.67) and change in SALT score (weighted mean difference [WSD], 5.55; 95% CI, 2.60-8.50) compared to the placebo. The proportion of 26 observational studies with 563 patients of SALT was 0.71(95% CI, 0.65-0.78), SALT was 0.54(95% CI 0.46-0.63), SALT was 0.33(95% CI, 0.24-0.42), and SALT score (WSD, -2.18; 95% CI, -3.12 to -1.23) compared with baseline. Any adverse effects occurred in 921 of 1508 patients; a total of 30 patients discontinued the trial owing to adverse reactions.
LIMITATIONS
Few randomized controlled trials met the inclusion criteria and insufficiency of eligible data.
CONCLUSION
JAK inhibitors are effective in alopecia areata, although associated with an increased risk.
Topics: Humans; Janus Kinase Inhibitors; Alopecia Areata; Autoimmune Diseases; Odds Ratio
PubMed: 37334349
DOI: 10.3389/fimmu.2023.1195858 -
Expert Review of Clinical Immunology 2015Alopecia areata (AA) development is associated with both innate and adaptive immune cell activation, migration to peri- and intra-follicular regions, and hair follicle... (Review)
Review
Alopecia areata (AA) development is associated with both innate and adaptive immune cell activation, migration to peri- and intra-follicular regions, and hair follicle disruption. Both CD4(+) and CD8(+) lymphocytes are abundant in AA lesions; however, CD8(+) cytotoxic T lymphocytes are more likely to enter inside hair follicles, circumstantially suggesting that they have a significant role to play in AA development. Several rodent models recapitulate important features of the human autoimmune disease and demonstrate that CD8(+) cytotoxic T lymphocytes are fundamentally required for AA induction and perpetuation. However, the initiating events, the self-antigens involved, and the molecular signaling pathways, all need further exploration. Studying CD8(+) cytotoxic T lymphocytes and their fate decisions in AA development may reveal new and improved treatment approaches.
Topics: Alopecia Areata; Autoantigens; Autoimmune Diseases; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Humans; Signal Transduction
PubMed: 26548356
DOI: 10.1586/1744666X.2015.1085306 -
Cells Dec 2021Alopecia areata is a type of non-scarring hair loss. The dysregulation of numerous systemic Th1 (IL-2, IFN-γ, TNF, IL-12, and IL-18), Th2 (IL-4, IL-5, IL-6, IL-9,... (Review)
Review
Alopecia areata is a type of non-scarring hair loss. The dysregulation of numerous systemic Th1 (IL-2, IFN-γ, TNF, IL-12, and IL-18), Th2 (IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17E, IL-31 and IL-33) and Th17 (IL-17, IL-17F, IL-21, IL-22, IL-23 and TGF-β) cytokines was observed in patients with alopecia areata. Positive correlations between the severity of alopecia areata and an increased serum level of various cytokines including IL-2, TNF, IL-12, IL-17, and IL-17E were reported in the literature. An increased serum level of numerous cytokines, such as IL-2, IL-6, TNF, IL-12, IL-17E, and IL-22, was described as positively correlated with the duration of the disease. Moreover, it was shown that increased pre-treatment serum level of IL-12 was a positive, while increased serum levels of IL-4 and IL-13 were negative prognostic markers for the efficacy of diphenylcyclopropenone. In conclusion, alopecia areata is associated with the dysregulation of systemic Th1, Th2 and Th17 cytokines with their role in the pathogenesis, clinical manifestations and prognosis of the disease. Available data indicate the most significant role of serum IL-2, TNF, IL-12, IL-17, and IL-17E as markers of disease activity. The serum levels IL-4, IL-12 and IL-13 may be useful as potential predictors of diphenylcyclopropenone efficacy.
Topics: Alopecia Areata; Cytokines; Humans; Interleukin-12; Interleukin-17; Interleukin-2; Th1 Cells; Th17 Cells; Th2 Cells; Tumor Necrosis Factor-alpha
PubMed: 34943905
DOI: 10.3390/cells10123397