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MMW Fortschritte Der Medizin Sep 2023
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Philosophical Transactions of the Royal... Nov 2023Peptidylarginine deiminases (PADs) transform a protein arginine residue into the non-standard amino acid citrulline. This calcium-dependent post-translational... (Review)
Review
Peptidylarginine deiminases (PADs) transform a protein arginine residue into the non-standard amino acid citrulline. This calcium-dependent post-translational modification of proteins is called citrullination or deimination. As described in this special issue, PADs play a role in various physiological processes, and PAD deregulations are involved in many human diseases. Three PADs are expressed in the epidermis, where their roles begin to be deciphered. PAD1 and PAD3 are involved in keratinocyte differentiation, particularly in the epidermal barrier function, keratins, filaggrin and filaggrin-related proteins being the most abundant deiminated epidermal proteins. Reduced amounts of deiminated proteins and PAD1 expression may be involved in the pathogenesis of psoriasis and atopic dermatitis, two very frequent and chronic skin inflammatory diseases. The trichohyalin/PAD3/transglutaminase three pathway is important for hair shaft formation. Mutations of the gene, leading to a decreased activity or abnormal localization of the corresponding isotype, are the cause of a rare hair disorder called uncombable hair syndrome, and are associated with the central centrifugal cicatricial alopecia, a frequent alopecia mainly affecting women of African ancestry. This article is part of the Theo Murphy meeting issue 'The virtues and vices of protein citrullination'.
Topics: Female; Humans; Alopecia; Epidermis; Filaggrin Proteins; Hair; Hydrolases; Protein Processing, Post-Translational; Protein-Arginine Deiminases
PubMed: 37778378
DOI: 10.1098/rstb.2022.0245 -
JAMA Dermatology Nov 2023Alopecia areata (AA) is characterized by hair loss ranging from patches of hair loss to more extensive forms, including alopecia totalis (AT) and alopecia universalis...
IMPORTANCE
Alopecia areata (AA) is characterized by hair loss ranging from patches of hair loss to more extensive forms, including alopecia totalis (AT) and alopecia universalis (AU). There is a lack of consensus for treatment. Understanding current practice patterns could help the identification of treatment needs and development of standards of care.
OBJECTIVE
To review treatment patterns for adults with AA in the US between 2015 and 2020.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study used medicine and pharmacy claims for commercially insured individuals from the IBM MarketScan Research Database to assess adults (≥18 years) newly treated for AA between October 15, 2015, and February 28, 2020. Alopecia areata was identified based on having at least 1 diagnosis of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code L63.x. Patients were required to have at least 365 days of continuous health plan enrollment before and after the cohort entry date. Patients were required to be free of AA diagnosis codes 365 days before the cohort entry date. Statistical analyses were conducted between 2019 and 2023.
MAIN OUTCOMES AND MEASURES
Main outcomes were treatment patterns for all patients with AA and subgroups of (1) patients with AT or AU and (2) those cared for by a dermatologist on the cohort entry date. Longitudinal therapy course during the first year after the diagnosis was also examined.
RESULTS
The study cohort consisted of 45 483 individuals (mean [SD] age, 43.8 [14.2] years; 29 903 [65.7%] female). During the year of follow-up, 30 217 patients (66.4%) received at least 1 AA treatment. The most common treatments were intralesional (19 014 [41.8%]), topical (18 604 [40.9%]), intramuscular (17 328 [38.1%]), and oral (9378 [20.6%]) corticosteroids. Compared with patients without AT or AU, patients with AT or AU a lower frequency of intralesional steroid (359 [11.1%] vs 18 655 [44.1%], P < .001) and higher frequency of topical corticosteroid (817 [25.4%] vs 17 787 [42.1%], P < .001) use. Almost half of patients (21 489 [47.2%]) received no treatment on the day of diagnosis. By 12 months, 32 659 (71.8%) were not receiving any treatment, making no treatment the largest study group.
CONCLUSIONS AND RELEVANCE
In this large cohort study of commercially insured individuals, corticosteroids were the most commonly used treatment for adults with AA between 2015 and 2020. At 365 days after diagnosis, more than two-thirds of patients were no longer receiving any AA treatment. Further studies are needed to understand the reasons for the absence of treatment.
Topics: Adult; Humans; Female; Male; Alopecia Areata; Retrospective Studies; Cohort Studies; Alopecia; Adrenal Cortex Hormones
PubMed: 37728940
DOI: 10.1001/jamadermatol.2023.3109 -
Journal of the European Academy of... Mar 2024Efficacy of the Janus kinase (JAK) inhibitor baricitinib for severe alopecia areata (AA) continuously increased over 52 weeks in two Phase 3 trials. There are limited...
BACKGROUND
Efficacy of the Janus kinase (JAK) inhibitor baricitinib for severe alopecia areata (AA) continuously increased over 52 weeks in two Phase 3 trials. There are limited long-term data on JAK inhibitors in AA.
OBJECTIVES
To evaluate efficacy and safety of baricitinib for severe AA through 104 weeks of continuous therapy.
METHODS
Integrated data from the BRAVE-AA1 and BRAVE-AA2 Phase 3 trials included adults with Severity of Alopecia Tool (SALT) scores ≥50 (≥50% scalp hair loss) randomized to and continuously treated with 2-mg or 4-mg baricitinib through Week 104. Patients who qualified to remain on continuous treatment included subjects who achieved SALT score ≤20 at Week 52 (Week-52 responders; 2-mg: N = 65; 4-mg: N = 129) and baricitinib 4-mg-treated patients who had SALT score >20 at Week 52 but achieved SALT score ≤20 at prior visit(s) and/or had significant improvement in eyebrow or eyelash hair growth relative to baseline by Week 52 (Week-52 mixed responders; N = 110). Week-104 outcomes included the proportion of patients achieving SALT score ≤20 (≤20% scalp hair loss). Data were censored after treatment discontinuation.
RESULTS
Among baricitinib 4-mg-treated and baricitinib 2-mg-treated Week-52 responders, 90.7% and 89.2%, respectively, maintained SALT score ≤20 at Week 104. Among Week-52 mixed responders, 39.1% reached SALT score ≤20 by Week 104. Continued improvement in eyebrow and eyelash regrowth was observed across groups. The most frequent treatment-emergent adverse events were COVID-19, upper respiratory tract infection, headache, nasopharyngitis, acne, urinary tract infection and creatine phosphokinase increase.
CONCLUSIONS
Baricitinib demonstrated a high level of maintenance of efficacy over 104 weeks in patients with severe AA. Efficacy increased in Week-52 mixed responders, illustrating that long-term treatment is necessary to observe maximum benefit in some patients. No new safety signals were observed.
Topics: Adult; Humans; Alopecia; Alopecia Areata; Azetidines; Janus Kinase Inhibitors; Purines; Pyrazoles; Sulfonamides; Randomized Controlled Trials as Topic; Clinical Trials, Phase III as Topic
PubMed: 38391212
DOI: 10.1111/jdv.19665 -
Journal of the American Academy of... Aug 2023Effective hair loss counseling requires an understanding of patients' experiences and how they are impacted by race, ethnicity, culture, resource accessibility, and... (Review)
Review
Effective hair loss counseling requires an understanding of patients' experiences and how they are impacted by race, ethnicity, culture, resource accessibility, and mental health. Clear communication and expectation management are critical. Physicians can empower patients through validating patient attitudes and engaging in shared decision-making to offer treatment, support, or camouflage.
Topics: Humans; Counseling; Alopecia; Hair; Communication; Decision Making, Shared
PubMed: 37591566
DOI: 10.1016/j.jaad.2023.03.059 -
Indian Journal of Dermatology,... 2023The Janus kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathway has been identified as a key player in the pathophysiology of alopecia areata... (Review)
Review
The Janus kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathway has been identified as a key player in the pathophysiology of alopecia areata and a potential target for therapy. Here, we give a narrative review of what is known about Janus kinase inhibitors in alopecia areata. Several clinical trials as well as smaller studies have demonstrated hair regrowth and remission with oral Janus kinase inhibitors therapy, even in patients who failed conventional treatment. Baricitinib is the only US FDA-approved treatment for alopecia areata but data for other oral Janus kinase inhibitors such as tofacitinib, ruxolitinib and ritlecitinib are also promising. Fewer clinical trials have investigated topical Janus kinase inhibitors for alopecia areata, with many of them terminated early due to unfavourable results. Overall, Janus kinase inhibitors are an efficacious addition to the therapeutic arsenal for treatment-refractory alopecia areata. Further work is needed to examine the effects of long-term usage of Janus kinase inhibitors, the efficacy of topical Janus kinase inhibitors, as well as to identify biomarkers that could predict differential therapeutic responses to the various Janus kinase inhibitors.
Topics: Humans; Alopecia Areata; Janus Kinase Inhibitors; Alopecia; Hair; Janus Kinases
PubMed: 37436019
DOI: 10.25259/IJDVL_1093_2022 -
Journal of the American Academy of... Sep 2023
Topics: Humans; Dermatitis, Atopic; Alopecia Areata; Mendelian Randomization Analysis
PubMed: 37207955
DOI: 10.1016/j.jaad.2023.05.023 -
Journal of the American Academy of... Dec 2023Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia seen primarily in women of African descent but rarely reported in men. The etiology of CCCA is...
BACKGROUND
Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia seen primarily in women of African descent but rarely reported in men. The etiology of CCCA is unknown, but genetic variants, type 2 diabetes mellitus, and bacterial infections may play a role.
OBJECTIVES
We aimed to characterize the demographics, medical histories, and clinical findings of male patients with CCCA with the hypothesis that features may differ from women.
METHODS
This was a case series of adult male patients with biopsy-confirmed CCCA seen at an academic dermatology department between 2012 and 2022.
RESULTS
In total, 17 males had a scalp biopsy and clinical findings consistent with CCCA. The average age was 43 years, and 88.2% of cases identified as Black race. Scalp pruritus was the most common symptom, and few patients endorsed high-risk hair care practices. None of the cases had diagnosis of type 2 diabetes mellitus, but 17.6% had history of latent tuberculosis, and 47.1% had a positive family history of alopecia. We observed 8 patients with atypical CCCA, and 29.4% had an overlapping scalp diagnosis.
LIMITATIONS
This study is limited by the single center, retrospective design and small sample size.
CONCLUSIONS
It is important to consider CCCA in the differential diagnosis of alopecia in adult Black males.
Topics: Adult; Humans; Male; Female; Diabetes Mellitus, Type 2; Retrospective Studies; Black or African American; Alopecia; Scalp; Dermatitis; Cicatrix
PubMed: 37495175
DOI: 10.1016/j.jaad.2023.07.1011 -
JAMA Dermatology Feb 2024
Topics: Humans; Alopecia Areata; COVID-19; Risk Factors
PubMed: 38198177
DOI: 10.1001/jamadermatol.2023.5559 -
Stem Cell Reviews and Reports Aug 2023Androgenetic alopecia is the most common cause of hair loss aggravated by increased life pressure, tension, and anxiety. Although androgenetic alopecia (AGA) does not... (Review)
Review
Androgenetic alopecia is the most common cause of hair loss aggravated by increased life pressure, tension, and anxiety. Although androgenetic alopecia (AGA) does not significantly effect physical health, it can have serious negative impact on the mental health and quality of life of the patient. Currently, the effect of medical treatment for AGA is not idealistic, stem cell-based regenerative medicine has shown potential for hair regrowth and follicle repair, but the long-term effect and mechanism of stem cell therapy is not quite explicit. In this review, we summarize the methods, efficacy, mechanism, and clinical progress of stem cell therapies for AGA by now, hope it will present a more comprehensive view in this topic.
Topics: Humans; Quality of Life; Alopecia; Hair; Cell- and Tissue-Based Therapy; Stem Cells
PubMed: 37277541
DOI: 10.1007/s12015-023-10532-2