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Psychiatric Disorders and Suicidal Behavior in Patients with Acne Prescribed Oral Antibiotics versus Isotretinoin: Analysis of a Large Commercial Insurance Claims Database

Ugonabo, Nkemjika; Love, Elyse; Wong, Priscilla W; Rieder, Evan A; Orlow, Seth J; Kim, Randie H; Nagler, Arielle R
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.
PMID: 33727021
ISSN: 1097-6787
CID: 4817712

Topical corticosteroid use for atopic dermatitis in the pediatric emergency department

Wang, Jason F; Young, Trevor K; Melnick, Laura E; Orlow, Seth J; Oza, Vikash S
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.
PMID: 33870556
ISSN: 1525-1470
CID: 4846692

The Alopecia Areata Consensus of Experts (ACE) Study PART II: Results of an International Expert Opinion on Diagnosis and Laboratory Evaluation for Alopecia Areata

Meah, Nekma; Wall, Dmitri; York, Katherine; Bhoyrul, Bevin; Bokhari, Laita; Sigall, Daniel Asz; Bergfeld, Wilma F; Betz, Regina C; Blume-Peytavi, Ulrike; Callender, Valerie; Chitreddy, Vijaya; Combalia, Andrea; Cotsarelis, George; Craiglow, Brittany; Donovan, Jeff; Eisman, Samantha; Farrant, Paul; Green, Jack; Grimalt, Ramon; Harries, Matthew; Hordinsky, Maria; Irvine, Alan D; Itami, Satoshi; Jolliffe, Victoria; King, Brett; Lee, Won-Soo; McMichael, Amy; Messenger, Andrew; Mirmirani, Paradi; Olsen, Elise; Orlow, Seth J; Piraccini, Bianca Maria; Rakowska, Adriana; Reygagne, Pascal; Roberts, Janet L; Rudnicka, Lidia; Shapiro, Jerry; Sharma, Pooja; Tosti, Antonella; Vogt, Annika; Wade, Martin; Yip, Leona; Zlotogorski, Abraham; Sinclair, Rodney D
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.
PMID: 32926985
ISSN: 1097-6787
CID: 4592662

A Global eDelphi Exercise to Identify Core Domains and Domain Items for the Development of a Global Registry of Alopecia Areata Disease Severity and Treatment Safety (GRASS)

Wall, Dmitri; Meah, Nekma; York, Katherine; Bhoyrul, Bevin; Bokhari, Laita; Abraham, Leonardo Spagnol; Adams, Roisín; Bergfeld, Wilma; Betz, Regina C; Blume-Peytavi, Ulrike; Callender, Valerie; Campbell, Chel; Chambers, Jen; Chen, Gang; Chitreddy, Vijaya; Cotsarelis, George; Craiglow, Brittany; Dhurat, Rachita; Dlova, Ncoza; Donovan, Jeff; Duque-Estrada, Bruna; Eisman, Samantha; Ellison, Abby; Farrant, Paul; Barberá, Juan Ferrando; Gadzhigoroeva, Aida; Grimalt, Ramon; Harries, Matthew; Hordinsky, Maria; Irvine, Alan D; Jolliffe, Victoria; Jones, Leslie; King, Brett; Lee, Won-Soo; Lortkipanidze, Nino; McMichael, Amy; Messenger, Andrew; Mirmirani, Paradi; Olsen, Elise; Orlow, Seth J; Ovcharenko, Yuliya; Piraccini, Bianca Maria; Pirmez, Rodrigo; Rakowska, Adriana; Reygagne, Pascal; Riley, Melissa; Rudnicka, Lidia; Saceda Corralo, David; Shapiro, Jerry; Sharma, Pooja; Silyuk, Tatiana; Kaiumov, Spartak; Tobin, Desmond J; Tosti, Antonella; Vañó-Galván, Sergio; Vogt, Annika; Wade, Martin; Yip, Leona; Zlotogorski, Abraham; Zhou, Cheng; Sinclair, Rodney
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.
PMID: 33656556
ISSN: 2168-6084
CID: 4801512

Melanocyte stress response pathways in the onset of vitiligo [Meeting Abstract]

Manga, P; Vega, M; Orlow, S J
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
ISSN: 1755-148x
CID: 4828112

Mucocutaneous Manifestations of Multisystem Inflammatory Syndrome in Children During the COVID-19 Pandemic

Young, Trevor K; Shaw, Katharina S; Shah, Jinal K; Noor, Asif; Alperin, Risa A; Ratner, Adam J; Orlow, Seth J; Betensky, Rebecca A; Shust, Gail F; Kahn, Philip J; Oza, Vikash S
Importance/UNASSIGNED:To date, no study has characterized the mucocutaneous features seen in hospitalized children with multisystem inflammatory syndrome in children (MIS-C) or the temporal association of these findings with the onset of systemic symptoms. Objective/UNASSIGNED:To describe the mucocutaneous findings seen in children with MIS-C during the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City in 2020. Design, Setting, and Participants/UNASSIGNED:A retrospective case series was conducted of 35 children admitted to 2 hospitals in New York City between April 1 and July 14, 2020, who met Centers for Disease Control and Prevention and/or epidemiologic criteria for MIS-C. Main Outcomes and Measures/UNASSIGNED:Laboratory and clinical characteristics, with emphasis on mucocutaneous findings, of children who met criteria for MIS-C. The characterization of mucocutaneous features was verified by 2 board-certified pediatric dermatologists. Results/UNASSIGNED:Twenty-five children (11 girls [44%]; median age, 3 years [range, 0.7-17 years]) were identified who met definitional criteria for MIS-C; an additional 10 children (5 girls [50%]; median age, 1.7 years [range, 0.2-15 years]) were included as probable MIS-C cases (patients met all criteria with the exception of laboratory test evidence of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection or known exposure). The results of polymerase chain reaction tests for SARS-CoV-2 were positive for 10 patients (29%), and the results of SARS-CoV-2 immunoglobulin G tests were positive for 19 patients (54%). Of the 35 patients, 29 (83%) exhibited mucocutaneous changes, with conjunctival injection (n = 21), palmoplantar erythema (n = 18), lip hyperemia (n = 17), periorbital erythema and edema (n = 7), strawberry tongue (n = 8), and malar erythema (n = 6) being the most common findings. Recognition of mucocutaneous findings occurred a mean of 2.7 days (range, 1-7 days) after the onset of fever. The duration of mucocutaneous findings varied from hours to days (median duration, 5 days [range, 0-11 days]). Neither the presence nor absence of mucocutaneous findings was significantly associated with overall disease severity. Conclusions and Relevance/UNASSIGNED:In this case series of hospitalized children with suspected MIS-C during the COVID-19 pandemic, a wide spectrum of mucocutaneous findings was identified. Despite their protean and transient nature, these mucocutaneous features serve as important clues in the recognition of MIS-C.
PMID: 33295957
ISSN: 2168-6084
CID: 4708992

The "bumpy" adolescent nose: Acne associated angiofibroma-like nasal papules

Roman, Jorge; Krueger, Loren D; Young, Trevor K; Rieder, Evan A; Rothman, Lisa R; Lakdawala, Nikita; Nagler, Arielle R; Meehan, Shane A; Orlow, Seth J; Oza, Vikash S
BACKGROUND/OBJECTIVE/OBJECTIVE:Papular scars are a recently described clinical phenotype of acne scarring characterized by papules occurring on the nose and chin. We have observed a similar presentation of nasal papules among patients seen in our clinic for acne and sought to further characterize the clinical and histopathological characteristics of this entity. METHODS:In this single-site case series, a retrospective review of electronic medical records of patients with nasal papules in association with acne vulgaris between April 2018 and April 2019 was performed. Clinical and histopathologic findings were recorded. RESULTS:We identified 20 patients who presented with a similar clinical phenotype of predominantly skin-colored, dome-shaped papules concentrated on the nose and chin in association with a history of more classic facial acne vulgaris. Papular lesions were seen predominately in adolescent Hispanic males. Concomitant acne on other areas of the face was identified in 18 patients at presentation while two patients had a history of adolescent acne. Biopsies were performed for five patients. Histopathologic examination demonstrated features of fibrosis and dilated thin-walled blood vessels, typical of angiofibromas. CONCLUSION/CONCLUSIONS:We present a series of adolescent patients with large, flesh-colored to erythematous papules seen predominantly on the nose. These lesions are histologically indistinguishable from angiofibromas and may represent an under-recognized yet disfiguring sequela of acne that may disproportionately affect adolescents with skin of color.
PMID: 32767593
ISSN: 1525-1470
CID: 4555732

Biophysical Compatibility of a Heterotrimeric Tyrosinase-TYRP1-TYRP2 Metalloenzyme Complex

Lavinda, Olga; Manga, Prashiela; Orlow, Seth J; Cardozo, Timothy
Tyrosinase (TYR) is a copper-containing monooxygenase central to the function of melanocytes. Alterations in its expression or activity contribute to variations in skin, hair and eye color, and underlie a variety of pathogenic pigmentary phenotypes, including several forms of oculocutaneous albinism (OCA). Many of these phenotypes are linked to individual missense mutations causing single nucleotide variants and polymorphisms (SNVs) in TYR. We previously showed that two TYR homologues, TYRP1 and TYRP2, modulate TYR activity and stabilize the TYR protein. Accordingly, to investigate whether TYR, TYRP1, and TYRP2 are biophysically compatible with various heterocomplexes, we computationally docked a high-quality 3D model of TYR to the crystal structure of TYRP1 and to a high-quality 3D model of TYRP2. Remarkably, the resulting TYR-TYRP1 heterodimer was complementary in structure and energy with the TYR-TYRP2 heterodimer, with TYRP1 and TYRP2 docking to different adjacent surfaces on TYR that apposed a third realistic protein interface between TYRP1-TYRP2. Hence, the 3D models are compatible with a heterotrimeric TYR-TYRP1-TYRP2 complex. In addition, this heterotrimeric TYR-TYRP1-TYRP2 positioned the C-terminus of each folded enzymatic domain in an ideal position to allow their C-terminal transmembrane helices to form a putative membrane embedded three-helix bundle. Finally, pathogenic TYR mutations causing OCA1A, which also destabilize TYR biochemically, cluster on an unoccupied protein interface at the periphery of the heterotrimeric complex, suggesting that this may be a docking site for OCA2, an anion channel. Pathogenic OCA2 mutations result in similar phenotypes to those produced by OCA1A TYR mutations. While this complex may be difficult to detect in vitro, due to the complex environment of the vertebrate cellular membranous system, our results support the existence of a heterotrimeric complex in melanogenesis.
PMID: 33995009
ISSN: 1663-9812
CID: 4876532

A Review of Vitamin D and Scarring: The Potential for New Therapeutics

Akoh, Christine C; Orlow, Seth J
Introduction: Recent research on vitamin D has shown that the fat-soluble micronutrient has anti-microbial, anti-inflammatory, and anti-proliferative effects in cells and tissues. During wound healing, abnormal scarring may occur and lead to reduced mobility, disfigurement, and psychosocial concerns. The role of vitamin D in the pathogenesis and treatment of scarring has not been reviewed previously. Methods: A literature search was performed on PubMed to identify articles on vitamin D and keloid, hypertrophic, or burn scars. Results: Molecular, epidemiological, and human clinical studies are discussed. Overall, the evidence suggests lower levels of vitamin D precursors, the active metabolite, and receptor, are associated with increased risk of scar development and increased severity. Conclusions: Scars are challenging to treat, and patients are increasingly interested in non-invasive treatment options. Although few human clinical studies have been reported, vitamin D may be beneficial as an adjunct therapy to current treatment options. J Drugs Dermatol. 2020;19(7): doi:10.36849/JDD.2020.4986.
PMID: 32721140
ISSN: 1545-9616
CID: 4540582

The Alopecia Areata Consensus of Experts (ACE) Study: Results of an International Expert Opinion on Treatments for Alopecia Areata

Meah, Nekma; Wall, Dmitri; York, Katherine; Bhoyrul, Bevin; Bokhari, Laita; Sigall, Daniel Asz; Bergfeld, Wilma F; Betz, Regina C; Blume-Peytavi, Ulrike; Callender, Valerie; Chitreddy, Vijaya; Combalia, Andrea; Cotsarelis, George; Craiglow, Brittany; Donovan, Jeff; Eisman, Samantha; Farrant, Paul; Green, Jack; Grimalt, Ramon; Harries, Matthew; Hordinsky, Maria; Irvine, Alan D; Itami, Satoshi; Jolliffe, Victoria; King, Brett; Lee, Won-Soo; McMichael, Amy; Messenger, Andrew; Mirmirani, Paradi; Olsen, Elise; Orlow, Seth J; Piraccini, Bianca Maria; Rakowska, Adriana; Reygagne, Pascal; Roberts, Janet L; Rudnicka, Lidia; Shapiro, Jerry; Sharma, Pooja; Tosti, Antonella; Vogt, Annika; Wade, Martin; Yip, Leona; Zlotogorski, Abraham; Sinclair, Rodney
BACKGROUND:A systematic review failed to identify any systemic therapy used in alopecia areata (AA) where use is supported by robust evidence from high quality randomized controlled trials (RCTs). OBJECTIVE:To produce an international consensus statement on the use and utility of various treatments for AA. METHODS:Fifty hair experts from 5 continents were invited to participate in a 3 round Delphi process. Agreement >66% was considered consensus. RESULTS:In the first round, consensus was achieved in 22 of 423 (5%) questions. Following a face-to-face meeting in round 3, overall, consensus was achieved for only 130 (33%) treatment specific questions. There was greater consensus for intralesional treatment of AA 19 (68%) followed by topical treatment 25 (43%). Consensus was achieved in 45 (36%) questions pertaining to systemic therapies in AA. The categories with the least consensus were phototherapy and non-prescription therapies. LIMITATIONS/CONCLUSIONS:The study included a comprehensive list of systemic treatments for AA, but not all treatments used. CONCLUSION/CONCLUSIONS:Despite divergent opinions amongst experts, consensus was achieved on a number of pertinent questions. The concluding statement also highlights areas where expert consensus is lacking and where an international patient registry could enable further research.
PMID: 32165196
ISSN: 1097-6787
CID: 4349242