Faculty Bibliography

IMPORTANCE/UNASSIGNED:Current measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact. OBJECTIVE/UNASSIGNED:To explore factors associated with AA severity beyond scalp hair loss, and to support the development of the Alopecia Areata Severity and Morbidity Index (ASAMI). EVIDENCE REVIEW/UNASSIGNED:A total of 74 hair and scalp disorder specialists from multiple continents were invited to participate in an eDelphi project consisting of 3 survey rounds. The first 2 sessions took place via a text-based web application following the Delphi study design. The final round took place virtually among participants via video conferencing software on April 30, 2022. FINDINGS/UNASSIGNED:Of all invited experts, 64 completed the first survey round (global representation: Africa [4.7%], Asia [9.4%], Australia [14.1%], Europe [43.8%], North America [23.4%], and South America [4.7%]; health care setting: public [20.3%], private [28.1%], and both [51.6%]). A total of 58 specialists completed the second round, and 42 participated in the final video conference meeting. Overall, consensus was achieved in 96 of 107 questions. Several factors, independent of the Severity of Alopecia Tool score, were identified as potentially worsening AA severity outcomes. These factors included a disease duration of 12 months or more, 3 or more relapses, inadequate response to topical or systemic treatments, rapid disease progression, difficulty in cosmetically concealing hair loss, facial hair involvement (eyebrows, eyelashes, and/or beard), nail involvement, impaired quality of life, and a history of anxiety, depression, or suicidal ideation due to or exacerbated by AA. Consensus was reached that the Alopecia Areata Investigator Global Assessment scale adequately classified the severity of scalp hair loss. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This eDelphi survey study, with consensus among global experts, identified various determinants of AA severity, encompassing not only scalp hair loss but also other outcomes. These findings are expected to facilitate the development of a multicomponent severity tool that endeavors to competently measure various disease impact. The findings are also anticipated to aid in identifying candidates for current and emerging systemic treatments. Future research must incorporate the perspectives of patients and the public to assign weight to the domains recognized in this project as associated with AA severity.

BACKGROUND:The association between isotretinoin and psychiatric disturbance, including depression and suicidal behavior, is controversial. OBJECTIVE:To investigate whether acne patients prescribed isotretinoin or antibiotics were more likely to have psychiatric disorders and/or engage in suicidal behavior. METHODS:Retrospective cohort study identified acne patients prescribed isotretinoin or oral antibiotics in the IBM® MarketScan® Databases of commercial US insurance claims data from 2011-2017 who were also diagnosed with psychiatric disorders or suicidal behavior. RESULTS:A total of 72,555 patients were included. Compared to acne patients prescribed isotretinoin, patients in the general population were 1.47 times more likely to be diagnosed with suicidal ideation or attempt (adjusted OR 1.47; 1.27, 1.70, p <.0001). However, the general population (adjusted OR 0.87; 0.84, 0.89, p<0.0001) and acne patients prescribed antibiotics (adjusted OR 0.88; 0.85, 0.91, p<0.0001) were less likely to have a psychiatric diagnosis compared to acne patients prescribed isotretinoin. The prevalence of suicidal behavior during isotretinoin treatment was lower (0.10%) (p=0.082), than during the year prior to (0.22%) and during the year after isotretinoin treatment (0.34%), (p = 0.004). LIMITATIONS/CONCLUSIONS:Study excludes individuals with public or no insurance and relies on physician coding accuracy. CONCLUSIONS:Compared to the general population, acne patients prescribed isotretinoin were less likely to engage in suicidal behavior. Further exploration is warranted into the slight increase in suicidal behavior seen in isotretinoin patients one year after therapy.

BACKGROUND/OBJECTIVES/OBJECTIVE:To investigate the evaluation and management of atopic dermatitis (AD) in the pediatric emergency department (PED). METHODS:This retrospective chart review was performed at the PED of a single institution and examined data from 2012 to 2017. Of 335 visits from patients 18 years and younger coded for AD, 167 visits with documented findings that supported a diagnosis of AD according to guidelines from the American Academy of Dermatology were included. RESULTS:The mean age of presentation was 6.3 years (standard deviation [SD]: 5.9). Of 11 patients with multiple visits, the mean between-visit interval was 31 days (SD: 41). Topical corticosteroids (TCSs) were not prescribed or recommended in 63/167 visits. In an additional 46/167 visits, over-the-counter topical hydrocortisone was recommended. Of prescribed TCS, the mean TCS class was 5.5 (SD: 1.9). 61/104 recommended or prescribed TCSs were weak (Class 7), the most likely used class (P < .001). Dermatology consultation was requested in 14/167 visits and was associated with higher rates of TCS prescriptions (13/14 vs 91/153, P = .018), a higher mean class of TCS prescribed (3.1 vs 5.9, P < .001), higher prescription rates of systemic antibiotics (8/14 vs 10/153, P < .001), and higher recommendation rates for emollient usage (10/14 vs 46/153, P = .005). CONCLUSIONS:Most patients presenting to the PED for AD were either not prescribed a TCS or were prescribed a weak TCS, often one that is over-the-counter. While there may be a variety of explanations for these findings, it is possible they reveal a practice gap regarding AD management in the PED.

BACKGROUND:We previously reported The Alopecia Areata Consensus of Experts (ACE) Study: Results of an International Expert Opinion on Treatments for Alopecia Areata (AA). OBJECTIVE:To report the results of the ACE international expert opinion on diagnosis and laboratory evaluation for AA. METHODS:Fifty hair experts from 5 continents were invited to participate in a 3 round Delphi process. Consensus threshold was set at >66%. RESULTS:Of 148 questions, expert consensus was achieved in 82 (55%) questions. Following round 1 consensus was achieved in 10 of 148 (7%) questions. Round 2 achieved consensus in 47 of 77 questions (61%). The final face-to-face achieved consensus in 25 of 32 (78%) questions. Consensus was greatest for laboratory evaluation (12 of 14 (86%) questions), followed by diagnosis (11 of 14 (79%) questions) of AA. Overall, etiopathogenesis achieved the least category consensus (31 of 68 (46%) questions). LIMITATIONS/CONCLUSIONS:The study had low representation from Africa, South America and Asia. CONCLUSION/CONCLUSIONS:There is expert consensus on aspects of epidemiology, etiopathogenesis, clinical features, diagnosis, laboratory evaluation and prognostic indicators of AA. The study also highlights areas where future clinical research could be directed to address unresolved hypotheses in AA patient care.

Importance/UNASSIGNED:A recent expert consensus exercise emphasized the importance of developing a global network of patient registries for alopecia areata to redress the paucity of comparable, real-world data regarding the effectiveness and safety of existing and emerging therapies for alopecia areata. Objective/UNASSIGNED:To generate core domains and domain items for a global network of alopecia areata patient registries. Evidence Review/UNASSIGNED:Sixty-six participants, representing physicians, patient organizations, scientists, the pharmaceutical industry, and pharmacoeconomic experts, participated in a 3-round eDelphi process, culminating in a face-to-face meeting at the World Congress of Dermatology, Milan, Italy, June 14, 2019. Findings/UNASSIGNED:Ninety-two core data items, across 25 domains, achieved consensus agreement. Twenty further noncore items were retained to facilitate data harmonization in centers that wish to record them. Broad representation across multiple stakeholder groups was sought; however, the opinion of physicians was overrepresented. Conclusions and Relevance/UNASSIGNED:This study identifies the domains and domain items required to develop a global network of alopecia areata registries. These domains will facilitate a standardized approach that will enable the recording of a comprehensive, comparable data set required to oversee the introduction of new therapies and harness real-world evidence from existing therapies at a time when the alopecia areata treatment paradigm is being radically and positively disrupted. Reuse of similar, existing frameworks in atopic dermatitis, produced by the Treatment of Atopic Eczema (TREAT) Registry Taskforce, increases the potential to reuse existing resources, creates opportunities for comparison of data across dermatology subspecialty disease areas, and supports the concept of data harmonization.

Vitiligo is an acquired condition that affects about 1% of the world's population and is defined by macular depigmentation of the skin that develops following melanocyte death. Vitiligo has a significant impact on both the physical and mental health of patients. While autoimmune-mediated destruction of melanocytes ultimately leads to depigmentation, the mechanisms that promote vitiligo onset remain poorly defined. We have been investigating the hypothesis that melanocytes from individuals genetically prone to develop vitiligo are less efficient in protecting against cellular traumas such as chemical exposure, which triggers an immune response against them. We delineated the response of melanocytes from normally pigmented individuals (NMs) to challenge with the topical agent monobenzone (monobenzyl ether of hydroquinone or MBEH). Three key stress response pathways were activated by MBEH exposure: the unfolded protein stress response (UPR), the NRF2-regulated antioxidant response and the nuclear factor-kappa B (NFkappaB) pathway. We established a key role for the UPR and NRF2 pathways in determining melanocyte viability and demonstrated disruption of their activity in melanocytes from individuals who developed vitiligo (VMs). We further showed that the NFkappaB pathway contributes to an increase in expression of IL6 and IL8 following NM exposure to MBEH and that expression of these chemokines is higher in VMs compared to NMs. These chemokines can promote an autoimmune response. We have now used transcriptome analysis to identify additional stress response pathways that are dysfunctional in vitiligo. Our data suggest that multiple signaling pathways that protect cells against trauma and facilitate a return to homeostasis are disrupted in VMs and may cause these cells to be targeted by the immune system