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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 -
Autoimmunity Reviews Jul 2016Squaric acid dibutylester (SADBE) is a commonly used contact sensitizer in immunotherapy for alopecia areata (AA). Severe contact dermatitis is induced by the currently... (Review)
Review
Squaric acid dibutylester (SADBE) is a commonly used contact sensitizer in immunotherapy for alopecia areata (AA). Severe contact dermatitis is induced by the currently high recommended sensitization dose of 1%-2% SADBE, often decreasing patient compliance. We assessed a modified immunotherapy for AA using SADBE at a starting concentration of 0.01% without sensitization. After one or two weeks of initial 0.01% SADBE application, the concentration of SADBE was increased gradually to 0.025%, 0.05%, 0.1%, 0.25%, 0.5%, 1% and 2% until the patients felt itching or erythema at the AA lesion site. The modified immunotherapy showed a response rate of 69.4% (25/36), equivalent to conventional immunotherapy using SADBE starting at 1%-2% sensitization. Furthermore, we investigated the combination therapy of SADBE and multiple courses of steroid pulses for AA. The response rate for combination therapy was 73.7% (28/38); however, the group receiving combination therapy showed a significant prevalence of severe AA compared with the group receiving modified immunotherapy only. We reviewed the efficacy and safety of modified immunotherapy without initial sensitization and combination therapy with immunotherapy and multiple courses of pulses for AA.
Topics: Adjuvants, Immunologic; Alopecia Areata; Autoimmunity; Combined Modality Therapy; Cyclobutanes; Humans; Immunotherapy
PubMed: 26932732
DOI: 10.1016/j.autrev.2016.02.021 -
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 2023
Topics: Humans; Alopecia Areata; Cost of Illness
PubMed: 36857064
DOI: 10.1001/jamadermatol.2023.0001 -
Pharmacology & Therapeutics Nov 2017This review aims to address the mechanisms of compromised immune tolerance contributing to the development and maintenance of Alopecia Areata (AA). Our goal is to also... (Review)
Review
This review aims to address the mechanisms of compromised immune tolerance contributing to the development and maintenance of Alopecia Areata (AA). Our goal is to also highlight future treatment opportunities and therapeutics that will safely and efficiently restore hair growth and maintain patients in remission. AA is a presumptive autoimmune disorder that coincides and genetically clusters to several other autoimmune diseases. In this review, we pay attention to the learnings from the mechanistic research and drug development in these other autoimmune conditions. Interestingly, most of these diseases have been linked to compromised central and peripheral tolerance, and increased intestinal inflammation with enhanced gut permeability. Break of tolerance and priming of the autoreactive T-cells to attack antigenic epitopes in the hair follicle most likely requires several steps which include escape from negative selection and compromised peripheral tolerance. Local skin-related changes are also of importance due to the patchy manifestation of the skin areas with loss of hair, particularly in the early disease. Here, we discuss the defective mechanisms of tolerance, both central and peripheral, and hypothesize that the disease is driven by areas of tolerance break, and that these could be targeted for successful therapeutic interventions.
Topics: Alopecia Areata; Animals; Autoimmunity; Gastrointestinal Microbiome; Helminthiasis; Humans; Immune Tolerance
PubMed: 28546083
DOI: 10.1016/j.pharmthera.2017.05.008 -
Cutis Jan 2023
Topics: Humans; Alopecia Areata; Ethnic and Racial Minorities
PubMed: 36947770
DOI: 10.12788/cutis.0685 -
The Journal of Investigative... Nov 2015Selection of a therapy for a patient with alopecia areata (AA) is frequently based on the age of the patient, disease extent, perhaps disease duration, patient... (Review)
Review
Selection of a therapy for a patient with alopecia areata (AA) is frequently based on the age of the patient, disease extent, perhaps disease duration, patient expectations, cost of therapy in terms of time commitment, and financial resources, as well as the results of screening laboratory studies that rule out the presence of other co-morbidities such as anemia, low iron stores, thyroid abnormalities, low vitamin D, or other autoimmune diseases. Although there is currently no cure for AA and no universally proven therapy that induces and sustains remission, many therapies are available which can be of benefit to both affected children and adults. Before selecting a treatment for patients with extensive long-standing AA, a scalp biopsy may provide useful information about the degree of inflammation and follicle differentiation. Recent clinical and translational research observations with the systemic Janus kinase (JAK) inhibitors and interleukin-2 (IL-2) have excited the clinical and AA patient communities and have led to clinical trials, as well as to the off-label use of these more expensive and targeted systemic therapies.
Topics: Adult; Alopecia Areata; Child; Dermatologic Agents; Holistic Health; Humans; Immunotherapy; Minoxidil; Phototherapy; Steroids
PubMed: 26551946
DOI: 10.1038/jidsymp.2015.41 -
Human Psychopharmacology Jan 2022To review the literature on valproate-associated hair abnormalities and the available treatment options. (Review)
Review
OBJECTIVE
To review the literature on valproate-associated hair abnormalities and the available treatment options.
METHODS
We searched PubMed and Google Scholar with keywords including "valproate", "valproic acid", "hair", "alopecia", and "effluvium," supplemented with hand search from cross-references. We included all types of studies including case reports in this review.
RESULTS
The pathophysiology of hair loss includes telogen effluvium, biotin, mineral deficiency, and possibly hyperandrogenism. Diagnosis is based on history of hair loss or abnormalities following valproate treatment, and is confirmed by use of simple clinical tests such as pull test and modified wash test. Treatment involves reassurance and advice on hair care, and if possible drug discontinuation or dose reduction. Medications such as biotin and other vitamins with minerals supplementation is effective for most individuals with hair loss. Other treatment options are agomelatine, topical valproate or minoxidil, though these lack evidence.
CONCLUSION
Hair abnormalities with valproate are common, benign adverse effects, and management includes general measures and specific treatment options.
Topics: Alopecia Areata; Hair; Humans; Minoxidil; Valproic Acid
PubMed: 34532891
DOI: 10.1002/hup.2814 -
International Journal of Dermatology May 2024While observational studies have suggested a link between gut microbiota diversity and alopecia areata (AA), the causal relationship remains unclear.
BACKGROUND
While observational studies have suggested a link between gut microbiota diversity and alopecia areata (AA), the causal relationship remains unclear.
METHODS
We leveraged data from the MiBioGen and FinnGen consortiums' Genome-wide association studies (GWAS) encompassing gut microbiota (n = 13,266) and AA (n = 211,428) datasets. A comprehensive Mendelian randomization (MR) and reverse MR approach were employed, utilizing five statistical methods to evaluate causality. Sensitivity analyses were also conducted to corroborate the MR results.
RESULTS
Inverse variance weighted (IVW) analysis indicated a protective effect against AA from Butyricimonas (OR = 0.37, 95% CI: 0.18-0.77, P = 0.01), Enterorhabdus (OR = 0.40, 95% CI: 0.16-0.95, P = 0.04), Eubacterium (xylanophilum group) (OR = 0.36, 95% CI: 0.15-0.84, P = 0.02), and Phascolarctobacterium (OR = 0.37, 95% CI: 0.15-0.91, P = 0.03), while Ruminococcaceae UCG003 posed as a risk factor (OR = 2.79, 95% CI: 1.27-6.14, P = 0.01). Reverse MR showed no significant causal link between AA and gut microbiota, with no significant heterogeneity or horizontal pleiotropy.
CONCLUSIONS
Our analysis suggests probable causality between certain gut microbiota and AA, shedding light on its pathogenesis and potential intervention strategies.
Topics: Humans; Mendelian Randomization Analysis; Gastrointestinal Microbiome; Alopecia Areata; Genome-Wide Association Study; Risk Factors
PubMed: 38240406
DOI: 10.1111/ijd.17032 -
Expert Opinion on Emerging Drugs Mar 2018Alopecia Areata is a common form of non-scarring hair loss that usually starts abruptly with a very high psychological impact. Due to the still not completely understood... (Review)
Review
Alopecia Areata is a common form of non-scarring hair loss that usually starts abruptly with a very high psychological impact. Due to the still not completely understood etiopathogenesis, at present there is no treatment that can induce a permanent remission and there is no drug approved for the treatment of this disorder. Areas covered: Leading existing treatment are briefly overviewed and then ongoing research on Janus Kinases Inhibitors is discussed, reviewing trials with oral and topical formulations so as new opportunities for other forms of alopecia, such as cicatricial alopecia. Expert opinion: JAK inhibitors represent a promise among alopecia treatments, but further studies are needed on long term safety. There is still no validated dosage for alopecia areata and the vehicles used for topical formulations seem not yet ideal in terms of skin penetration and reduced systemic absorption. Hopefully several studies are ongoing and we hope, in the near future, that JAK inhibitors will become part of the armamentarium to treat alopecia areata patients in terms of safety and costs.
Topics: Administration, Oral; Administration, Topical; Alopecia Areata; Animals; Drug Design; Humans; Janus Kinase Inhibitors
PubMed: 29466675
DOI: 10.1080/14728214.2018.1444750