Willingness to Pay and QOL in Alopecia Areata.

Innate lymphoid cells type 1 suffice to induce hallmarks of alopecia areata phenotype in organ-cultured human scalp hair follicles ex vivo and in human scalp skin xenotransplants in vivo, suggesting that these cells play a role in early AA pathogenesis.

Innate lymphoid cells type 1 suffice to induce hallmarks of alopecia areata phenotype in organ-cultured human scalp hair follicles ex vivo and in human scalp skin xenotransplants in vivo, suggesting that these cells play a role in early AA pathogenesis.

Mechanism leading to an abrupt hair loss in diffuse alopecia areata (AA) remains unclear. To explore the characteristics of diffuse AA and possible factors involved in its pathogenesis. Clinical and laboratory data of 17 diffuse AA patients and 37 patchy AA patients were analyzed retrospectively. Serum IgE level was evaluated in all diffuse and patchy AA patients, as well as 27 healthy subjects without hair loss to serve as normal control. Univariate analysis was performed using Fisher's exact test and Wilcoxon rank-sum test. Associations between inflammatory cell infiltration and laboratory values were analyzed using Spearman rank correlation test. The mean age of patients with diffuse AA was 27 years with a mean disease duration of 1.77 months. All of them presented in spring or summer with an acute onset of diffuse hair loss preceded by higher incidence of scalp pruritus. Although no statistically significant difference on the incidence of atopic disease among three groups has been found, serum IgE level in diffuse AA was higher than that in healthy controls, but was comparable to that in patchy AA group. Histopathology of lesional scalp biopsies showed more intense infiltration comprising of mononuclear cells, eosinophils, CD3 + , and CD8 + T cells around hair bulbs in diffuse AA group than in patchy AA group. Moreover, IgE level in diffuse AA patients positively correlated with intensity of infiltration by mononuclear cells, eosinophils, and CD8 + T cells. Hypersensitivity may be involved in pathogenesis of diffuse AA. The acute onset of diffuse AA may be related to intense local inflammatory infiltration of hair loss region and an increase in serum IgE level.

Concordance rate of alopecia areata in identical twins supports both genetic and environmental factors

Dear Editors, Alopecia areata (AA) is one of the most common organ-specific autoimmune conditions, characterized by non-scarring, patchy hair loss due to autoimmune activity targeting the skin. It is a chronic disorder that primarily affects children and young adults and involves both genetic and environmental factors.1 AA may be associated with other inflammatory or autoimmune diseases, such as systemic lupus erythematosus, vitiligo, and thyroid-related disorders (AITD), particularly autoimmune forms such as Hashimoto's thyroiditis and Graves’ disease.2, 3 Several studies have investigated the association between AA and AITD, revealing a significant, though variably reported, link.2, 4-7 Therefore, acquiring new, large-scale data from diverse populations worldwide is essential for a more comprehensive understanding. This study sought to explore the association between AA and autoimmune AITD through a population-based case-control design. We conducted a population-based retrospective case-control cohort study that included all patients diagnosed with AA between 2005 and 2019, as recorded in Maccabi Healthcare Services (MHS), the second-largest state-mandated health fund in Israel, which covers approximately 26% of the national population. The MHS database includes demographic information, AA diagnoses (established by board-certified dermatologists using clinical diagnosis codes), comorbid diseases, and treatment data. Diagnoses of Graves’ disease and Hashimoto's disease were made by general physicians and identified using the ICD-10 coding system. All patients with a diagnosis code of AA – regardless of age, severity, or treatment – were included in the study and matched with healthy controls at a 1:2 ratio based on sex for comparison. The primary outcome was the assessment of the prevalence of autoimmune AITD among individuals with AA compared to the control group. Logistic regression analysis was performed to calculate odds ratios (OR) and 95% confidence intervals (CI) for the association between AA and AITD. Data were analyzed using SPSS version 29. p values < 0.05 were considered statistically significant. A total of 33,401 patients with AA were included in the study, representing 1.3% of the MHS population during the study period. These patients were matched to 66,802 controls. In both groups, 56.5% were male. The mean age at AA onset was 29.9 ± 16.9 years. Out of the total cohort, 5,843 individuals (5.83%) were diagnosed with AITD, among whom 5,165 with Hashimoto's disease (5.15%) and 678 with Graves’ disease (0.68%). Hashimoto's disease was identified in 2,316 individuals with AA (6.93%) and in 2,849 healthy controls (4.26%), demonstrating a significant association with AA (OR = 1.67, 95% CI [1.58–1.77]; p < 0.01). Similarly, Graves’ disease was diagnosed in 309 individuals with AA (0.93%) and in 369 controls (0.55%), also indicating a significant association (OR = 1.68, 95% CI [1.44–1.96]; p < 0.01) (Figure 1). Hashimoto's disease preceded AA diagnosis in 55% of the total cohort, while Graves’ was diagnosed before AA in 75% of the individuals. The diagnosis was simultaneous (during a 3-month period) with AA diagnosis in 3.5% of both AITD. AA was diagnosed before Hashimoto's and Graves’ disease in 41.5% and 24.5% of the total cohort, respectively. Xin et al., in their meta-analysis of 17 articles involving 2,850 cases of AA and 4,667 controls, found that the overall prevalence of AITD in patients with AA was significantly increased compared to controls (OR = 3.66; 95% CI [2.90–4.61]).5 Ly et al., in a systematic review of 102 studies comprising 680,823 patients with AA and 72,011,041 healthy controls, reported an even stronger association with Hashimoto's thyroiditis, with an OR of 4.31 (95% CI [2.51–7.40]).2 Additionally, a Korean nationwide, population-based, cross-sectional study found a significant association between AA and both Graves’ disease (OR = 1.42; 95% CI [1.32–1.52]) and Hashimoto's thyroiditis (OR = 1.16; 95% CI [1.08–1.24]), that was comparable to our findings.6 Notably, these associations were significantly stronger in patients with severe AA. Furthermore, a study by Kinoshita-Ise et al. reported that AA is significantly associated with the presence of thyroid antibodies – specifically TPO-Ab (thyroid peroxidase antibodies) and TG-Ab (thyroglobulin antibodies) – rather than with overt clinical or laboratory-defined thyroid dysfunction.7 A shared genetic susceptibility between AA and AITD has been suggested by Noso et al., who identified the HLA-DQB103 allele and the DRB115:01–DQB1*06:02 haplotype as significantly more frequent in TR-Ab-positive patients with AA compared to controls.8 In conclusion, although our study has several limitations related to its retrospective design and the limitation to assess all potential confounding factors, it confirms the significant association between AA and autoimmune AITD. Yet further research is needed to evaluate the clinical usefulness of routine thyroid screening in individuals with AA. Open access funding enabled and organized by Projekt DEAL. None.

Protein biochips have a great potential in future parallel processing of complex samples as a research tool and in diagnostics. For the generation of protein biochips, highly automated technologies have been developed for cDNA expression library production, high throughput protein expression, large scale analysis of proteins, and protein microarray generation. Using this technology, we present here a strategy to identify potential autoantigens involved in the pathogenesis of alopecia areata, an often chronic disease leading to the rapid loss of scalp hair. Only little is known about the putative autoantigen(s) involved in this process. By combining protein microarray technology with the use of large cDNA expression libraries, we profiled the autoantibody repertoire of sera from alopecia areata patients against a human protein array consisting of 37,200 redundant, recombinant human proteins. The data sets obtained from incubations with patient sera were compared with control sera from clinically healthy persons and to background incubations with anti-human IgG antibodies. From these results, a smaller protein subset was generated and subjected to qualitative and quantitative validation on highly sensitive protein microarrays to identify novel alopecia areata-associated autoantigens. Eight autoantigens were identified by protein chip technology and were successfully confirmed by Western blot analysis. These autoantigens were arrayed on protein microarrays to generate a disease-associated protein chip. To confirm the specificity of the results obtained, sera from patients with psoriasis or hand and foot eczema as well as skin allergy were additionally examined on the disease-associated protein chip. By using alopecia areata as a model for an autoimmune disease, our investigations show that the protein microarray technology has potential for the identification and evaluation of autoantigens as well as in diagnosis such as to differentiate alopecia areata from other skin diseases.

Alopecia areata and myasthenia gravis presenting as paraneoplastic phenomena of breast cancer

Introduction. Following the initial BRAVE-AA1 clinical trial, a study addendum was added in which Black patients with severe alopecia areata (AA) were entered into open label treatment with baricitinib 4 mg for 52 weeks. Photographs were taken at screening to confirm eligibility and were reviewed by a central expert reviewer. These photographs provide an opportunity to examine diagnostic challenges in AA, in Black patients, especially women. Methods. In the BRAVE-AA1 addendum 5 study, photographs of five planes of the scalp (left, right, posterior, frontal, and top of head) were obtained at screening and post-baseline. Camera equipment and a study-specific photography manual was provided to all sites, personnel were trained to conduct photography under similar lighting conditions and magnifications. Images were taken with polarization and cross-polarization lenses and reviewed for compliance with standardization procedures. At screening, all images were reviewed centrally by the external reviewer to determine consistency with AA. For this disclosure, images of both AA and non-AA cases were selected by the authors to illustrate key signs that can aid in differentiating AA, from the other alopecias that were observed in the screened patient population. Results. Of the 36 patients with photographs reviewed by the central expert reviewer, 12 (33%) were diagnosed with CCCA or other scarring alopecia; 11 of these patients were female. Based on photography review, presentations involving the vertex, midscalp and parietal scalp, with sparing of the occipital scalp was suggestive of CCCA. The presence of scalp hypopigmentation and hyperpigmentation reflected the inflammatory processes and scarring associated with CCCA. The presence of “fringe sign” suggested traction alopecia; while AA was characterized by the presence of asymmetrically distributed, circular smooth bald patches. The photographic images portrayed the complexities of hair loss patterns that can occur within a single patient, and some patients had co-occurrence of more than one pattern of alopecia. Scalp biopsies were not performed which is limitation of these data. Conclusions. Misdiagnosis of AA can occur in some patient populations with other forms of hair loss that mimic the disease. More than one type of hair loss can co-occur in a single patient, thereby limiting the maximal potential improvement a patient may experience with treatment. While photographic evidence alone may not conclusively determine the diagnosis, the present disclosure provides visual examples of helpful signs that can assist dermatologists to diagnose and to support an appropriately tailored treatment plan.

Gut instinct: Using tofacitinib to treat alopecia areata in the context of comorbid inflammatory bowel disease

Introduction/Background Studies have shown that patients with vs without alopecia areata (AA) have a higher risk of developing atopic dermatitis (AD). However, the real-world prevalence and incidence of moderate-to-severe AD in patients with AA are not well characterized. Objectives To assess the real-world prevalence and incidence of comorbid AD among patients with AA using data from a US administrative claims database. Methods This retrospective analysis evaluated claims from the Merative Marketscan Commercial Claims and Encounters database. Eligible patients were aged ≥12 years at index date (first AA diagnosis), received an AA diagnosis (≥1 inpatient encounter or ≥2 outpatient encounters/claims based on International Classification of Diseases, Clinical Modification, 10th Revision [ICD-10-CM]: L63.x or 9th Revision [ICD-9-CM]: 704.01) between 01/01/2017–07/31/2023, and had continuous plan enrollment for 5 years prior to index. AA disease severity was evaluated during the 6-month follow-up period post-index date. Patients were considered to have moderate-to-severe AA if they were diagnosed with alopecia universalis (ICD-10-CM: L63.1) or alopecia totalis (ICD-10-CM: L63.0) or if they received prescriptions for any systemic immunomodulators, oral corticosteroids, nonsteroidal systemic agents, or phototherapy within 6 months post-index date. Very severe AA (subset of moderate-to-severe AA) was defined by a diagnosis of alopecia universalis (ICD-10-CM: L63.1) or alopecia totalis (ICD-10-CM: L63.0). AD was defined as ≥1 inpatient or ≥2 outpatient claims with diagnosis codes for AD (ICD-10-CM L20.x) or other AD-related conditions (ICD-9-CM 691.8). Moderate-to-severe AD was defined per the AD criteria plus claims indicating 1 of the following: ≥1 dispensing of dupilumab; ≥2 dispensing of high-potency topical corticosteroids or systemic immunosuppressants; or ≥3 dispensing of medium potency topical corticosteroids, topical tacrolimus, phototherapy, or oral/parenteral corticosteroids. AD prevalence was assessed during the 5 years pre-index period; prevalence was also assessed over a longer duration and included those with ≥1 AD diagnosis from 01/01/2007–index. AD incidence was assessed from the 7th month after the AA index date through the time of AD diagnosis or end of continuous enrollment. Relative risk for developing AD comorbidity among patients with AA was evaluated using Cox proportional hazards model, controlling for age, sex, obesity, Charlson Comorbidity Index (CCI), and geographic region. Results Of 429,903 patients identified with AA in the database, 10,863 met eligibility criteria and 9507 completed ≥6 months of follow-up post-index date (mild AA, n=7087; moderate-to-severe AA, n=2420; very severe AA, n=491). The 1-year period prevalence of AA in the US was 0.16% in 2022. Among the 10,863 eligible patients, 63.0% were female, the mean (SD) age was 40.4 (15.1) years, and the mean (SD) CCI was 0.7 (1.2). Among all eligible patients with AA (n=10,863), the prevalence (within 5 years pre-index date) was 3.1% for any AD and 2.3% for moderate-to-severe AD. Among patients with moderate-to-severe AA (n=2420), the prevalence was 4.8% for any AD and 4.2% for moderate-to-severe AD. The prevalence of any AD any time prior to index among all eligible patients with AA and moderate-to-severe AA was 11.9% and 14.6%, respectively. AD incidence at follow-up was 4 per 1000 person-years in patients with mild AA, 7 per 1000 person-years for moderate-to-severe AA, and 6 per 1000 person-years for very severe AA. Mean (SD) time to AD diagnosis after AA index date was 2.1 (1.7) years for patients with mild AA, 2.0 (1.7) years for moderate-to-severe AA, and 2.0 (1.7) years for very severe AA. Risk of developing AD was greater in patients with moderate-to-severe vs mild AA (adjusted hazard ratio 1.63 [95% CI 1.01, 2.64]). Conclusions Patients with moderate-to-severe vs mild AA had higher prevalence and incidence of AD comorbidity and higher prevalence of moderate-to-severe AD.

Alopecia Areata Is Associated with Atopic Diathesis: Results from a Population-Based Study of 51,561 Patients

Successful treatment of corticosteroid-resistant ophiasis-type alopecia areata (AA) with platelet-rich plasma (PRP)

Alopecia areata after CoronaVac vaccination.

Alopecia areata describes nonscarring, generally patchy, hair loss which can affect the entire scalp (alopecia totalis) and body (alopecia universalis).1, 2 Although the exact pathogenesis is not yet understood, alopecia areata is considered an acquired autoimmune condition.1, 2 Prevalence of alopecia areata peaks between ages 10 and 30, and younger age at presentation is generally considered a poor prognostic factor.1 However, cases of congenital alopecia areata have been reported.1, 3 Diagnosing congenital alopecia areata is difficult, as many other conditions should be ruled out including, but not limited to, tinea capitis, neonatal telogen effluvium, triangular alopecia, atrichia congenita, Marie-Unna hypotrichosis, and traction alopecia.1, 3 However, proper diagnosis of congenital alopecia areata is important, as treatment is possible.1-3 Therefore, this study aimed to analyze data from existing congenital alopecia areata reports. Following PRISMA guidelines,4 Web of Science and PubMed were searched, and cases of alopecia areata present at birth were included (Figure 1). Twelve congenital alopecia areata patients were identified, with a female predominance (7/12; 58.3%). Three were premature (25.0%). Alopecic pattern at birth was alopecia areata in eight cases (66.7%), alopecia totalis in two (16.7%), and alopecia universalis in two (16.7%). Positive family history of alopecia areata was reported in five cases (42.7%). Nail changes were noted in three patients (25.0%). Congenital alopecia areata diagnosis was clinical in eight cases (66.7%) and biopsy-proven in four (33.3%). Nine patients received/reported treatment (75.0%). Of those treated with topical corticosteroid alone (3/9; 33.3%), two demonstrated total hair regrowth (66.7%), while one progressed to alopecia totalis (33.3%). Two patients were treated with topical corticosteroid and a topical vasodilator, minoxidil (22.2%). One experienced total hair regrowth, while the other demonstrated partial hair regrowth, until the topical corticosteroid was discontinued (i.e. minoxidil was used alone), and alopecia totalis resulted. One patient was treated with topical corticosteroid and oral antihistamine (11.1%), and one was treated with placebo lotion (11.1%). Both experienced partial hair regrowth. Two patients were treated with oral pulse steroid, topical immunomodulator, and minoxidil, but no follow-up was provided (22.2%). Results are summarized in Table 1. Limitations of this review include small sample sizes and the possibility of missed cases due to lack of well-established terminology and underreporting. Additionally, biopsy is not necessary for alopecia areata diagnosis1 but is helpful in confirming unique (e.g. congenital) presentations of the condition. Given that alopecia areata is typically considered an acquired autoimmune condition, congenital cases call our understanding of alopecia areata into question and may provide additional insight into the underlying pathophysiology. Acquired alopecia areata and congenital alopecia areata seem to have many clinical/epidemiological similarities. Positive family history of alopecia areata in five cases suggests genetic factors are involved in the development of congenital alopecia areata. The female predominance of congenital alopecia areata is also in keeping with acquired alopecia areata.1, 3 Additionally, nail changes in 25.0% of congenital alopecia areata cases is similar to rates of nail changes typically seen in acquired alopecia areata.5 Finally, given that topical corticosteroids yielded partial or total hair regrowth in five of six patients who received them (83.3%), topical corticosteroids are a reasonable first-line treatment for congenital alopecia areata, as with acquired alopecia areata.1 In conclusion, congenital cases of alopecia areata may provide insight into the pathophysiology of the condition and should be considered on the differential diagnosis of alopecia in the newborn, thereby ensuring proper treatment of those affected.

BACKGROUND: Alopecia areata (AA) is an autoimmune disease characterized by nonscarring hair loss. AA frequently co-occurs with other inflammatory autoimmune conditions, presenting a significant clinical burden. OBJECTIVE: To compare the burden of illness, direct and indirect costs in adult patients with AA vs atopic dermatitis (AD). METHODS: This retrospective cohort study used US administrative claims data from the Merative MarketScan Commercial Claims and Encounters Database to compare commercially insured adults with AA to those with AD. Patients with an AA diagnosis between January 2017 and September 2019 were propensity score matched to patients with AD. Comorbidity burden, medication use, health care resource utilization, health care costs, and indirect costs during a 12-month follow-up period were compared between cohorts. RESULTS: Overall, 25,446 adult patients with AA were selected for the matched analysis with the AD cohort. Patients with AA generally had lower comorbidity burden than patients with AD; mean Deyo-Charlson Comorbidity Index scores were 0.36 (SD = 0.99) and 0.39 (SD = 0.92), for AA and AD, respectively (P = 0.007). Patients with AA had significantly lower proportions of allergic rhinitis, asthma, pruritus, skin infections, and urticaria, but higher proportions of thyroid disease, when compared with patients with AD (all P < 0.001). A smaller proportion of patients with AA had prescriptions for topical (45.3% vs 64.8%; P < 0.001) and oral (20.3% vs 29.6%; P < 0.001) corticosteroids and antianxiety and/or antidepressants (24.7% vs 29.7%; P < 0.001), but a significantly larger proportion for intralesional corticosteroids (triamcinolone) (49.6% vs 21.7%; P < 0.001), compared with patients with AD. Despite a lower comorbidity burden and generally less medication usage in patients with AA, total all-cause health care costs did not significantly differ between the AA and AD cohorts ($10,705 vs $10,816; P = 0.712), and outpatient costs were higher in patients with AA ($6,297 vs $5,859; P = 0.014). Female patients with AA had significantly greater costs for both outpatient and outpatient pharmacy when compared with female patients with AD. Patients with AA were more likely to have a claim for long-term disability (0.6% vs 0.3%; P = 0.001) and higher long-term disability-associated indirect costs ($73 [SD = $1,442] vs $25 [SD = $774]; P = 0.004) compared with patients with AD. CONCLUSIONS: We found similar total health care costs in patients with AA and AD, despite a lower proportion of comorbidities and prescription use in patients with AA. Outpatient costs were also significantly higher overall in patients with AA. Although often dismissed as a cosmetic condition, AA, an autoimmune disease, has a similar level of medical expenditure as AD. DISCLOSURES: This study was funded by Eli Lilly and Company. Mr Fenske and Drs Ding, Morrow, and Smith are employed by Eli Lilly and Company. Drs Manjelievskaia, Moynihan, and Silver are employed by Merative. Drs Manjelievskaia, Moynihan, and Silver were employed by IBM Watson Health at the time of study completion. IBM Watson Health received funding from Eli Lilly and Company to conduct this study.