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The Journal of Investigative Dermatology Jul 2018Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of ∼2%. In AA, the immune system targets the hair follicle, resulting in clinical hair loss.... (Clinical Trial)
Clinical Trial
Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of ∼2%. In AA, the immune system targets the hair follicle, resulting in clinical hair loss. The prognosis of AA is unpredictable, and currently there is no definitive treatment. Our previous whole genome expression studies identified active immune circuits in AA lesions, including common γ-chain cytokine and IFN pathways. Because these pathways are mediated through JAK kinases, we prioritized clinical exploration of small molecule JAK inhibitors. In preclinical trials in mice, tofacitinib successfully prevented AA development and reversed established disease. In our tofacitinib trial in 12 patients with moderate to severe AA, 11 patients completed a full course of treatment with minimal adverse events. Following limited response to the initial dose (5 mg b.i.d.), the dose was escalated (10 mg b.i.d.) for nonresponding subjects. Eight of 12 patients demonstrated ≥50% hair regrowth, while three patients demonstrated <50% hair regrowth, as measured by Severity in Alopecia Tool scoring. One patient demonstrated no regrowth. Gene expression profiles and Alopecia Areata Disease Activity Index scores correlated with clinical response. Our open-label studies of ruxolitinib and tofacitinib have shown dramatic clinical responses in moderate to severe AA, providing strong rationale for larger clinical trials using JAK inhibitors in AA. ClinicalTrials.gov ID NCT02299297.
Topics: Adult; Alopecia Areata; Autoimmune Diseases; Biopsy; Dose-Response Relationship, Drug; Female; Gene Expression Profiling; Hair Follicle; Humans; Janus Kinase Inhibitors; Janus Kinases; Male; Middle Aged; Nitriles; Photography; Pilot Projects; Piperidines; Pyrazoles; Pyrimidines; Pyrroles; Severity of Illness Index; Treatment Outcome; Young Adult
PubMed: 29452121
DOI: 10.1016/j.jid.2018.01.032 -
Proceedings of the Royal Society of... 1912
PubMed: 19975750
DOI: No ID Found -
The Journal of Investigative Dermatology Nov 1979Direct immunofluroescence studies were performed on hairy and alopecic areas of scalp in patients with alopecia areata, alopecia totalis and male pattern alopecia.... (Comparative Study)
Comparative Study
Direct immunofluroescence studies were performed on hairy and alopecic areas of scalp in patients with alopecia areata, alopecia totalis and male pattern alopecia. Abnormal deposits of C3 and occasionally of IgG and IgM were found in 92% of 12 patients with alopecia areata and in 21% of patients with male pattern alopecia. No abnormalities were seen in 4 patients with alopecia totalis. In both alopecia areata and male pattern alopecia, the deposits were most common along the basement zone of the inferior segment of hair follicles and occurred with equal frequency in alopecic and normal scalp. These observations suggest that immune factors may play a role in the pathogenesis of alopecia areata.
Topics: Alopecia; Alopecia Areata; Complement C3; Fluorescent Antibody Technique; Humans; Immunoglobulin G; Immunoglobulin M; Male
PubMed: 387883
DOI: 10.1111/1523-1747.ep12549703 -
EBioMedicine May 2016Alopecia areata (AA) is an autoimmune disease typified by nonscarring hair loss with a variable clinical course. In this study, we conducted whole genome gene expression...
Alopecia areata (AA) is an autoimmune disease typified by nonscarring hair loss with a variable clinical course. In this study, we conducted whole genome gene expression analysis of 96 human scalp skin biopsy specimens from AA or normal control subjects. Based on gene expression profiling, samples formed distinct clusters based on the presence or absence of disease as well as disease phenotype (patchy disease compared with alopecia totalis or universalis). Differential gene expression analysis allowed us to robustly demonstrate graded immune activity in samples of increasing phenotypic severity and generate a quantitative gene expression scoring system that classified samples based on interferon and cytotoxic T lymphocyte immune signatures critical for disease pathogenesis.
Topics: Alopecia Areata; Databases, Genetic; Gene Expression Profiling; Gene Expression Regulation; Genetic Markers; Humans; Oligonucleotide Array Sequence Analysis; Principal Component Analysis
PubMed: 27322477
DOI: 10.1016/j.ebiom.2016.03.036 -
Skin Appendage Disorders Aug 2017Alopecia areata is a common immune-mediated hair condition with limited treatment options and success rates. There is evidence that statins, which are used for reducing...
BACKGROUND/AIMS
Alopecia areata is a common immune-mediated hair condition with limited treatment options and success rates. There is evidence that statins, which are used for reducing atherogenesis and cardiovascular disease, have immunomodulatory activities and therefore may also be used for treatment of selected dermatologic conditions, including alopecia areata. Among treatments evaluated for alopecia areata, oral simvastatin/ezetimibe therapy is currently under the scrutiny of expert opinion.
METHODS
Prospective observational study of the efficacy and tolerability of simvastatin/ezetimibe 40/10 mg (Inegy; MSD Merck Sharp & Dohme AG, Lucerne, Switzerland) over a treatment period of 6 months in alopecia totalis, universalis, multipatch involvement of the scalp >30%, ophiasis, or diffuse alopecia areata.
RESULTS
Of the 12 patients included in the study, 67% had no hair regrowth, 24% transient diffuse or patchy hair regrowth, and 24% patchy regrowth of pigmented hair which was not considered cosmetically satisfactory. Adverse effects were observed in 24% of patients, who reported myalgia. One patient showed elevation of creatine phosphokinase.
CONCLUSION
Simvastatin/ezetimibe is not effective for treatment of alopecia areata, at least in severe and/or cases refractory to other treatments, either as monotherapy or as adjuvant. Ultimately, in choosing such a treatment with questionable benefit, one must take the risk of serious adverse effects into careful consideration.
PubMed: 28879192
DOI: 10.1159/000468991 -
JAAD Case Reports Sep 2022
PubMed: 35937957
DOI: 10.1016/j.jdcr.2022.07.027 -
The Journal of Investigative Dermatology Nov 2003Alopecia in women is a common problem, and conflicting observational data have failed to determine whether an association exists between alopecia and iron deficiency in...
Alopecia in women is a common problem, and conflicting observational data have failed to determine whether an association exists between alopecia and iron deficiency in women. We therefore utilized an analytical cross-sectional methodology to evaluate whether common types of alopecia in women are associated with decreased tissue iron stores, as measured by serum ferritin. We studied patients with telogen effluvium (n = 30), androgenetic alopecia (n = 52), alopecia areata (n = 17), and alopecia areata totalis/universalis (n = 7). The normal group consisted of 11 subjects without hair loss from the same referral base and source population as those patients with alopecia. We analyzed the data utilizing the unpaired Student's t test assuming unequal variances with an alpha adjustment for multiple comparisons to assess whether the mean ages, ferritin levels, and hemoglobin levels of women without hair loss differed from the means in each alopecia group. The mean age of patients and normals did not differ significantly. We found that the mean ferritin level (ng per ml [95% confidence intervals]) in patients with androgenetic alopecia (37.3 128.4, 46.1]) and alopecia areata (24.9 [17.2, 32.6]) were statistically significantly lower than in normals without hair loss (59.5 [40.8, 78.1]). The mean ferritin levels in patients with telogen effluvium (50.1 [33.9, 66.33]) and alopecia areata totalis/universalis (52.3 [23.1, 81.5]) were not significantly lower than in normals. Our findings have implications regarding therapeutics, clinical trial design, and understanding the triggers for alopecia.
Topics: Adolescent; Adult; Age Factors; Aged; Alopecia; Female; Ferritins; Hemoglobins; Humans; Iron; Iron Deficiencies; Middle Aged
PubMed: 14708596
DOI: 10.1046/j.1523-1747.2003.12540.x -
Acta Dermato-venereologica Jul 1997Psychosocial stress has been reported to play a role in the onset and/or exacerbation of alopecia areata. Little is known about the clinical characteristics of alopecia...
Psychosocial stress has been reported to play a role in the onset and/or exacerbation of alopecia areata. Little is known about the clinical characteristics of alopecia areata patients whose alopecia is stress-reactive. We examined the relation between the stress reactivity of alopecia areata and a wide range of psychosocial measures among 16 patients with alopecia areata/totalis and 28 patients with alopecia universalis. The degree to which the alopecia was exacerbated by stress was measured by patient ratings on a 10-point scale. A wide range of psychologic measures correlated (p<0.05) with the stress reactivity score. Stepwise logistic regression analysis revealed that patients with higher depression scores were more likely to be in the high-stress reactor group. Patients whose alopecia is stress-reactive may suffer from depressive illness, a potentially important consideration in the overall management of such patients.
Topics: Adult; Alopecia Areata; Female; Humans; Life Change Events; Male; Middle Aged; Personality Tests; Regression Analysis; Stress, Psychological
PubMed: 9228223
DOI: 10.2340/0001555577296298 -
Sultan Qaboos University Medical Journal Feb 2019
PubMed: 31198601
DOI: 10.18295/squmj.2019.19.01.015 -
The Journal of Investigative Dermatology Feb 2002Alopecia areata affects 1%-2% of the population and is hypothesized to be an autoimmune, organ specific T-cell mediated reaction directed against the human hair...
Alopecia areata affects 1%-2% of the population and is hypothesized to be an autoimmune, organ specific T-cell mediated reaction directed against the human hair follicle. It is characterized by loss of hair in patches (alopecia areata) with progression in some individuals to total loss of scalp hair (alopecia totalis) or to loss of all scalp and body hair (alopecia universalis). The interleukin-1 receptor antagonist (IL-1RN) gene was found to be associated with more severe clinical outcome in several chronic inflammatory diseases, including alopecia areata. The IL-1RN*2 allele was found to be associated with alopecia areata severity in a British case-control study. In this paper, we analyzed alopecia areata probands in a family-based sample (n = 131 parent-offspring trios) to study the association between alleles of the IL-1RN and various phenotypes of alopecia areata. In considering all patients with any form of alopecia areata, no association was found with IL-1RN. IL-1RN*2 allele was not associated with alopecia totalis and alopecia universalis. A borderline association was observed between IL-1RN and patchy alopecia areata but it was not statistically significant (p =0.06). We also observed an association between IL1-RN*1 allele and patchy alopecia areata (p =0.045).
Topics: Alleles; Alopecia Areata; Gene Frequency; Humans; Interleukin 1 Receptor Antagonist Protein; Severity of Illness Index; Sialoglycoproteins
PubMed: 11841553
DOI: 10.1046/j.0022-202x.2001.01676.x