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Journal of Cutaneous and Aesthetic... 2024Alopecia areata (AA) is an autoimmune disease characterized most commonly by patchy nonscarring hair loss which may progress to alopecia totalis which has poor...
Alopecia areata (AA) is an autoimmune disease characterized most commonly by patchy nonscarring hair loss which may progress to alopecia totalis which has poor prognosis. Platelet-rich plasma (PRP) therapy along with intralesional triamcinolone acetonide that is modified PRP proved to be beneficial in the case of alopecia totalis and helps in weaning patient off oral immunosuppression.
PubMed: 38800816
DOI: 10.4103/JCAS.JCAS_101_22 -
American Journal of Human Genetics Jan 2020Isolated complex III (CIII) deficiencies are among the least frequently diagnosed mitochondrial disorders. Clinical symptoms range from isolated myopathy to severe...
Isolated complex III (CIII) deficiencies are among the least frequently diagnosed mitochondrial disorders. Clinical symptoms range from isolated myopathy to severe multi-systemic disorders with early death and disability. To date, we know of pathogenic variants in genes encoding five out of 10 subunits and five out of 13 assembly factors of CIII. Here we describe rare bi-allelic variants in the gene of a catalytic subunit of CIII, UQCRFS1, which encodes the Rieske iron-sulfur protein, in two unrelated individuals. Affected children presented with low CIII activity in fibroblasts, lactic acidosis, fetal bradycardia, hypertrophic cardiomyopathy, and alopecia totalis. Studies in proband-derived fibroblasts showed a deleterious effect of the variants on UQCRFS1 protein abundance, mitochondrial import, CIII assembly, and cellular respiration. Complementation studies via lentiviral transduction and overexpression of wild-type UQCRFS1 restored mitochondrial function and rescued the cellular phenotype, confirming UQCRFS1 variants as causative for CIII deficiency. We demonstrate that mutations in UQCRFS1 can cause mitochondrial disease, and our results thereby expand the clinical and mutational spectrum of CIII deficiencies.
Topics: Alleles; Alopecia; Cardiomyopathies; Child; Electron Transport Complex III; Humans; Infant; Iron-Sulfur Proteins; Male; Mitochondrial Diseases; Mutation; Pedigree
PubMed: 31883641
DOI: 10.1016/j.ajhg.2019.12.005 -
Journal of Cutaneous Medicine and... 2023Alopecia areata (AA) is a T-cell driven autoimmune disease, which results in hair loss. This study aims to determine the efficacy, tolerability and safety of different...
BACKGROUND/OBJECTIVES
Alopecia areata (AA) is a T-cell driven autoimmune disease, which results in hair loss. This study aims to determine the efficacy, tolerability and safety of different concentrations of anthralin in the treatment of pediatric AA.
METHODS
A retrospective cohort study of patients < 18 yo diagnosed with AA treated with anthralin at SickKids Hospital, Toronto dermatology outpatient clinic in 2016 - 2018. Anthralin used at 0.1%, 0.2%, 0.5% and 1% in petrolatum at short contact, at increments of 15 minutes every week until a 1 hr maximum contact achieved. No other treatment was used in conjunction. Severity of Alopecia Tool (SALT) scores (SS) were determined using photographs and descriptions to assess severity of alopecia at baseline and post anthralin treatment.
RESULTS
A total of 11 charts were reviewed in this retrospective cohort. Hair loss pattern; 3 patients with patchy, 6 had mixed (patchy and ophiasis), and 2 were totalis. All except for 1 patient had failed traditional treatments. One patient had complete hair regrowth, 3 showed more than 85% hair re-growth and 7 patients showed more than 75% hair regrowth, the average time for this to occur was 6.5 months. None of the patients experience serious side effects.
CONCLUSIONS
Our study demonstrated the efficacy and tolerability of topical anthralin 0.1% to 1% in pediatric alopecia areata. In our study, anthralin 0.2% appears to offer the best performance and tolerability profile among the different concentrations used, with treatment course of at least 6 months in order to achieve more than 75% hair regrowth.
Topics: Humans; Child; Anthralin; Alopecia Areata; Retrospective Studies; Dermatologic Agents; Petrolatum; Administration, Topical; Alopecia
PubMed: 37559401
DOI: 10.1177/12034754231191060 -
Skin Appendage Disorders Apr 2018While most alopecia areata (AA) cases resolve spontaneously, the more severe types of AA, alopecia totalis (AT) and alopecia universalis (AU), can be highly resistant to...
While most alopecia areata (AA) cases resolve spontaneously, the more severe types of AA, alopecia totalis (AT) and alopecia universalis (AU), can be highly resistant to therapy. We report on a 33-year-old ultraorthodox Jewish man with an 11-year history of AA that resulted in complete loss of the scalp and body hair 7 years ago. Previous treatments with intralesional and systemic corticosteroids had only partial and temporary effects. The patient was treated with ruxolitinib, 20 mg twice daily, resulting in complete growth of the beard after 4 months of treatment. The beard has a special significance for ultraorthodox Jews, and loss of the beard hair can have marked social and psychological consequences in AA patients. The Janus kinase (JAK) inhibitors have recently emerged as an effective treatment modality in AA, including the more severe forms, such as AT or AU. This report highlights the beneficial effects of the JAK inhibitors, especially in populations where the hair has a special importance due to cultural and religious backgrounds.
PubMed: 29765973
DOI: 10.1159/000479722 -
Skin Appendage Disorders Mar 2023Alopecia areata (AA) is an autoimmune condition that results in nonscarring hair loss. There is currently only one Food and Drug Administration (FDA)-approved treatment...
INTRODUCTION
Alopecia areata (AA) is an autoimmune condition that results in nonscarring hair loss. There is currently only one Food and Drug Administration (FDA)-approved treatment for AA; as a result, a wide range of treatments are commonly administered. This study aimed to determine how patients with AA prioritize treatment characteristics when choosing a therapy.
METHODS
A cross-sectional national survey was distributed using the National Alopecia Areata Foundation's (NAAF) email list. This study was approved by the Mass General Brigham Institutional Review Board. Participants were asked to rank the importance of five treatment domains.
RESULTS
Of the 1,074 completed surveys (completion rate 77.4%), most respondents were female (85.4%) and white (77.8%) with an average age of 49.3 ± 15.4 years. Respondents had AA for an average of 17.7 ± 15.4 years, with 90.0% experiencing current active hair loss. 95.6% of respondents considered the treatment's ability to achieve hair regrowth as important, 93.9% listed the availability of information about the treatment (e.g., via doctor or online) as important, 89.1% ranked the treatment side effects as important, 75.7% the cost, and 68.0% the convenience of use. A sub-analysis was performed examining responses between respondents who identify as white versus nonwhite, which showed that while the order of importance was the same between groups, a significantly larger proportion of nonwhite respondents attributed higher importance to cost (white: 73.8%, nonwhite: 82.4%; = 0.006) and convenience (white: 65.3%, nonwhite: 77.3%; < 0.001) than their white counterparts.
DISCUSSION/CONCLUSION
These findings identify key domains that can serve as a starting point in shared decision-making between patients and physicians. This knowledge can streamline dermatologist delivery of key information and highlight areas of improvement for future therapeutics. Limitations include the nonrandomized NAAF population with most participants being white females. Future studies should confirm these findings in other patient populations.
PubMed: 36937159
DOI: 10.1159/000527251 -
International Journal of Trichology 2018Alopecia areata (AA) is a chronic autoimmune disorder characterized by patchy loss of hair from scalp, beard, eyebrows, or rarely even body hair. Rarely, the disease can...
BACKGROUND
Alopecia areata (AA) is a chronic autoimmune disorder characterized by patchy loss of hair from scalp, beard, eyebrows, or rarely even body hair. Rarely, the disease can be widespread and severe leading to loss of entire scalp and body hair causing apprehension and psychological stress in patients. Management of such cases is equally difficult with the available options of topical and systemic immunosuppressant. Tofacitinib, JAK3 inhibitor, is emerging as a promising drug for the management of severe and resistant cases of AA/totalis/universalis.
OBJECTIVE
Our study aims to show the effectiveness of oral tofacitinib in the treatment of alopecia universalis (AU).
METHODS
Six patients diagnosed with AU/alopecia totalis duration of disease 6 months-15 years refractory to other treatments were selected and were started on oral tofacitinib 5 mg twice daily up to 10 mg BID and were followed up every 4 weeks. The efficacy was measured by hair regrowth using photographic assessment, Severity of Alopecia Tool score, and physical examination. Patients will be followed up for 6 months after stopping treatment for assessing disease relapse.
RESULTS
All our six patients showed dramatic response to oral tofacitinib. Patients were followed up every 4 weeks, and results were assessed. Significant hair regrowth was evident in all the patients by the end of 12 weeks. Currently, four of our patients are on oral tofacitinib 10 mg BID and are under follow-up. There was no relapse in one patient after stopping drug for 4 months. Another patient started developed AA patches in the eyebrows within 2 months of stopping tofacitinib. Acneiform eruptions were seen in two patients which were managed with topicals.
CONCLUSION
In our patients, tofacitinib successfully alleviated AU in the absence of significant adverse side effects. We recommend that further controlled studies be required to establish safety and confirm efficacy.
PubMed: 30034188
DOI: 10.4103/ijt.ijt_21_18 -
Skin Appendage Disorders Sep 2022Alopecia areata (AA) is a type of nonscarring alopecia that has autoimmune etiology, in which the hair follicle, usually an immune-privileged site, becomes the target of...
INTRODUCTION
Alopecia areata (AA) is a type of nonscarring alopecia that has autoimmune etiology, in which the hair follicle, usually an immune-privileged site, becomes the target of attack. Alopecia totalis (AT) is a subset of AA in which patients completely lose hair on the scalp. Initial hair regrowth is often fine and without pigment. We present a case of AT in which pigmented hair grew only overlying superficial veins, a finding which has not been previously reported.
CASE PRESENTATION
An adult female with brown hair presented with AA that progressed to AT despite the use of triamcinolone ointment and topical 2% tofacitinib ointment. She was treated with nightly augmented betamethasone dipropionate 0.05% ointment under occlusion. Two months later, she noticed diffuse regrowth of thin hair on her scalp, most of which was depigmented. However, linear bands of darkly pigmented hairs were noted overlying superficial scalp veins.
DISCUSSION/CONCLUSION
Loss of pigmentation and subsequent repigmentation of the hair shaft in regrowing AA is not entirely understood. Initial hair regrowth in AA tends to be fine and depigmented, although the hair will usually regain normal texture and color. Pigmentation following a vein suggests that local temperature may play a role, possibly augmented by corticosteroid induced reduced expression of inflammatory cytokines and endothelial release of the vasoconstrictor hormone endothelin, which stimulates melanogenesis.
PubMed: 36161076
DOI: 10.1159/000524247 -
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 -
Annals of Dermatology Dec 2017Simvastatin belongs to the statin family, whose members have immunomodulatory activities. Ezetimibe have synergetic effects when co-administered with simvastatin. In...
BACKGROUND
Simvastatin belongs to the statin family, whose members have immunomodulatory activities. Ezetimibe have synergetic effects when co-administered with simvastatin. In several case reports, alopecia totalis and alopecia universalis were successfully treated with simvastatin/ezetimibe, suggesting that this combination could be a new efficient therapy for recalcitrant alopecia areata (AA).
OBJECTIVE
To verify the efficacy of the simvastatin/ezetimibe combination therapy for recalcitrant AA and investigate the relationship between various treatment responses and prognostic factors.
METHODS
This prospective open study was performed in patients with recalcitrant AA with the bald surface exceeding 75%. All patients took simvastatin (40 mg) and ezetimibe (10 mg) daily. The extent of hair regrowth expressed as percentage of the bald area was used to evaluate the effectiveness of the therapy.
RESULTS
Of 14 enrolled patients, 4 patients (28.6%) were judged as responders showing regrowth of 30% to 80% after 3 months of treatment. The mean age of onset in non-responders was significantly lower than in responders. The total score of prognostic factors, calculated as a sum of factors related to poor prognosis, was much lower in responders than in non-responders.
CONCLUSION
The remission rate in this study was unsatisfactory. However, since the recruited patients had not responded to any other treatments for AA, simvastatin/ezetimibe can still be considered as an alternative treatment for recalcitrant AA. The total scores of the prognostic factors were statistically different between responders and non-responders. These results can be used to predict the outcome of treatment with simvastatin/ezetimibe and anticipate prognosis.
PubMed: 29200765
DOI: 10.5021/ad.2017.29.6.755 -
Circulation Research Dec 2017Arrhythmogenic cardiomyopathy is caused primarily by mutations in genes encoding desmosome proteins. Ventricular arrhythmias are the cardinal and typically early...
RATIONALE
Arrhythmogenic cardiomyopathy is caused primarily by mutations in genes encoding desmosome proteins. Ventricular arrhythmias are the cardinal and typically early manifestations, whereas myocardial fibroadiposis is the pathological hallmark. Homozygous (desmoplakin) and (junction protein plakoglobin) mutations are responsible for a subset of patients with arrhythmogenic cardiomyopathy who exhibit cardiac arrhythmias and dysfunction, palmoplanter keratosis, and hair abnormalities (cardiocutaneous syndromes).
OBJECTIVE
To determine phenotypic consequences of deletion of in a subset of cells common to the heart and skin.
METHODS AND RESULTS
Expression of CSPG4 (chondroitin sulfate proteoglycan 4) was detected in epidermal keratinocytes and the cardiac conduction system. CSPG4 cells constituted ≈5.6±3.3% of the nonmyocyte cells in the mouse heart. Inducible postnatal deletion of under the transcriptional control of the locus led to ventricular arrhythmias, atrial fibrillation, atrioventricular conduction defects, and death by 4 months of age. Cardiac arrhythmias occurred early and in the absence of cardiac dysfunction and excess cardiac fibroadipocytes, as in human arrhythmogenic cardiomyopathy. The mice exhibited palmoplantar keratosis and progressive alopecia, leading to alopecia totalis, associated with accelerated proliferation and impaired terminal differentiation of keratinocytes. The phenotype is similar to human cardiocutaneous syndromes caused by homozygous mutations in .
CONCLUSIONS
Deletion of under the transcriptional regulation of the CSPG4 locus led to lethal cardiac arrhythmias in the absence of cardiac dysfunction or fibroadiposis, palmoplantar keratosis, and alopecia, resembling the human cardiocutaneous syndromes. The findings offer a cellular basis for early cardiac arrhythmias in patients with arrhythmogenic cardiomyopathy and cardiocutaneous syndromes.
Topics: Animals; Antigens; Arrhythmogenic Right Ventricular Dysplasia; Cells, Cultured; Desmoplakins; Humans; Keratinocytes; Keratosis; Mice; Mutation; Myocytes, Cardiac; Phenotype; Proteoglycans; Syndrome
PubMed: 29018034
DOI: 10.1161/CIRCRESAHA.117.311876