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Article ; Online: Safety of Oral Janus Kinase Inhibitors in the Treatment of Moderate-to-Severe Atopic Dermatitis.

Narla, Shanthi / Silverberg, Jonathan I

Dermatitis : contact, atopic, occupational, drug

2023 Volume 34, Issue 5, Page(s) 366–386

Abstract: Multiple Janus Kinase (JAK) inhibitors were developed as potential treatments for moderate-to-severe atopic dermatitis (AD). There is a substantial amount of safety data from recent trials of oral JAK inhibitors in patients with AD. However, the vast ... ...

Abstract	Multiple Janus Kinase (JAK) inhibitors were developed as potential treatments for moderate-to-severe atopic dermatitis (AD). There is a substantial amount of safety data from recent trials of oral JAK inhibitors in patients with AD. However, the vast majority of safety data for oral JAK inhibitors is derived from patients with rheumatoid arthritis and other immune-mediated disorders, and is primarily derived from tofacitinib, a pan-selective JAK inhibitor. This narrative review examines safety data for oral JAK inhibitors from studies in AD and other indications. The available data do demonstrate that rare but serious and life-threatening adverse events can occur with oral JAK inhibitor treatment and should be carefully considered in therapeutic shared decision making.
MeSH term(s)	Humans ; Janus Kinase Inhibitors/adverse effects ; Dermatitis, Atopic/drug therapy ; Dermatitis, Atopic/chemically induced ; Administration, Oral ; Arthritis, Rheumatoid
Chemical Substances	Janus Kinase Inhibitors
Language	English
Publishing date	2023-02-17
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2144723-8
ISSN	2162-5220 ; 1532-8163 ; 1710-3568
ISSN (online)	2162-5220 ; 1532-8163
ISSN	1710-3568
DOI	10.1089/derm.2022.29004.sna
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Article ; Online: Efficacy and Risk Stratification of Janus Kinase Inhibitors in the Treatment of Moderate-to-Severe Atopic Dermatitis.

Narla, Shanthi / Silverberg, Jonathan I

Dermatitis : contact, atopic, occupational, drug

2023 Volume 35, Issue S1, Page(s) S24–S38

Abstract: Recently, 3 oral Janus kinase (JAK) inhibitors-abrocitinib, baricitinib, and upadacitinib-were approved in many regions around the world for the treatment of moderate-severe atopic dermatitis (AD). These JAK inhibitors generally have rapid onset of ... ...

Abstract	Recently, 3 oral Janus kinase (JAK) inhibitors-abrocitinib, baricitinib, and upadacitinib-were approved in many regions around the world for the treatment of moderate-severe atopic dermatitis (AD). These JAK inhibitors generally have rapid onset of action and short half-life. Higher doses of abrocitinib and upadactinib even demonstrated superior efficacy to dupilumab. However, JAK inhibitors can be associated with rare serious and potentially life-threatening adverse events. Heterogeneity in study designs and lack of head-to-head studies make safety comparison between JAK inhibitors difficult. Dose reduction and patient selection are the most important considerations for risk mitigation. This narrative review examines the efficacy data for abrocitinib, baricitinib, and upadacitinib from large phase III double-blinded randomized controlled trials in AD and discusses risk stratification for oral JAK inhibitors in AD patients.
MeSH term(s)	Humans ; Dermatitis, Atopic/drug therapy ; Janus Kinase Inhibitors/adverse effects ; Risk Assessment ; Purines ; Sulfonamides ; Pyrazoles ; Pyrimidines ; Azetidines
Chemical Substances	abrocitinib (73SM5SF3OR) ; baricitinib (ISP4442I3Y) ; Janus Kinase Inhibitors ; Purines ; Sulfonamides ; Pyrazoles ; Pyrimidines ; Azetidines
Language	English
Publishing date	2023-08-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2144723-8
ISSN	2162-5220 ; 1532-8163 ; 1710-3568
ISSN (online)	2162-5220 ; 1532-8163
ISSN	1710-3568
DOI	10.1089/derm.2023.0058
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Article ; Online: Which Clinical Measurement Tools for Atopic Dermatitis Severity Make the Most Sense in Clinical Practice?

Narla, Shanthi / Silverberg, Jonathan I

Dermatitis : contact, atopic, occupational, drug

2023 Volume 35, Issue S1, Page(s) S13–S23

Abstract: Assessment of atopic dermatitis (AD) severity is essential for therapeutic decision making and monitoring treatment progress. However, there are a myriad of clinical measurement tools available, some of which are impractical for routine clinical use ... ...

Abstract	Assessment of atopic dermatitis (AD) severity is essential for therapeutic decision making and monitoring treatment progress. However, there are a myriad of clinical measurement tools available, some of which are impractical for routine clinical use despite being recommended for clinical trials in AD. For measurement tools to be used in clinical practice, they should be valid, reliable, rapidly completed, and scored, and easily incorporated into existing clinic workflows. This narrative review addresses content, validity, and feasibility, and provides a simplified repertoire of assessments for clinical assessment of AD based on prior evidence and expert opinion. Tools that may be feasible for clinical practice include patient-reported outcomes (eg, dermatology life quality index, patient-oriented eczema measure, numerical rating scales for itch, pain, and sleep disturbance, AD Control Tool, and patient-reported global assessment), and clinician-reported outcomes (eg, body surface area and investigator's global assessment). AD is associated with variable clinical signs, symptoms, extent of lesions, longitudinal course, comorbidities, and impacts. Any single domain is insufficient to holistically characterize AD severity, select therapy, or monitor treatment response. A combination of these tools is recommended to balance completeness and feasibility.
MeSH term(s)	Humans ; Dermatitis, Atopic/diagnosis ; Pruritus/diagnosis ; Pruritus/etiology ; Body Surface Area ; Pain ; Patient Reported Outcome Measures ; Severity of Illness Index ; Quality of Life
Language	English
Publishing date	2023-04-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2144723-8
ISSN	2162-5220 ; 1532-8163 ; 1710-3568
ISSN (online)	2162-5220 ; 1532-8163
ISSN	1710-3568
DOI	10.1089/derm.2022.0087
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Article ; Online: The suitability of treating atopic dermatitis with Janus kinase inhibitors.

Narla, Shanthi / Silverberg, Jonathan I

Expert review of clinical immunology

2022 Volume 18, Issue 5, Page(s) 439–459

Abstract: Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease with significant morbidity and reduced quality of life, especially in patients with moderate-severe AD. Recently, topical and oral Janus kinase (JAK)-inhibitors were ... ...

Abstract	Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease with significant morbidity and reduced quality of life, especially in patients with moderate-severe AD. Recently, topical and oral Janus kinase (JAK)-inhibitors were investigated as treatments for mild-moderate and moderate-severe AD. However, rare serious adverse-events observed with JAK-inhibitor therapy in AD, rheumatoid arthritis, and other immune-mediated disorders warrant careful consideration. Areas covered: This review examines the efficacy and safety of topical and oral JAK-inhibitors for treatments in AD, and reviews potential applications in AD. Expert opinion: JAK-inhibitors have rapid-onset and robust and durable efficacy, which give them considerable versatility for treating the gamut of AD patients. While the U.S. Food and Drug Administration has only approved upadacitinib and abrocitinib to treat moderate-severe AD refractory to treatment with other systemic medications including biologics, or when use of those therapies is not recommended, oral JAK-inhibitors have the potential to be used both as first-line or second-line systemic therapies in moderate-severe AD. However, oral JAK-inhibitors can lead to laboratory anomalies and rare serious adverse events. All of these important characteristics should be addressed in shared-decision-making conversations, patient counseling, choosing appropriate therapies for patients, and monitoring patients in clinical practice.
MeSH term(s)	Dermatitis, Atopic/chemically induced ; Dermatitis, Atopic/drug therapy ; Humans ; Janus Kinase 1 ; Janus Kinase Inhibitors/therapeutic use ; Quality of Life ; Skin
Chemical Substances	Janus Kinase Inhibitors ; Janus Kinase 1 (EC 2.7.10.2)
Language	English
Publishing date	2022-05-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2274260-8
ISSN	1744-8409 ; 1744-666X
ISSN (online)	1744-8409
ISSN	1744-666X
DOI	10.1080/1744666X.2022.2060822
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Article ; Online: Dermatology for the internist: optimal diagnosis and management of atopic dermatitis.

Narla, Shanthi / Silverberg, Jonathan I

Annals of medicine

2021 Volume 53, Issue 1, Page(s) 2165–2177

Abstract: Internists are front-line health care providers that commonly provide the first encounter to patients for dermatological conditions, especially atopic dermatitis (AD). Internists need to be comfortable with managing mild-moderate AD in their practices. ... ...

Abstract	Internists are front-line health care providers that commonly provide the first encounter to patients for dermatological conditions, especially atopic dermatitis (AD). Internists need to be comfortable with managing mild-moderate AD in their practices. Criteria and guidelines established in dermatology literature are available to help the general practitioner diagnose and treat AD. AD is a systemic disease associated with multiple cutaneous and extra-cutaneous comorbidities that warrant screening by internists, especially mental health conditions. Environmental factors may play a role in the development or worsening of AD; however, there is currently no strong evidence to guide specific population- or clinic-based interventions for their avoidance. While food allergies are common in AD patients, the role of food allergens as an exacerbating factor for AD is controversial. Before starting any dietary modifications, careful evaluation should be performed by an allergist. If the patient is not well-controlled despite adequate topical therapies or is experiencing severe/worsening disease, early referral to dermatology is warranted to rule out confounding diagnoses and/or escalation to systemic therapies. Finally, it is important to recognise the racial disparities present in AD and address these when formulating treatment plans.Key messages:Confounding dermatoses, either instead of or in addition to AD, should be considered in treatment-refractory AD, and the appropriate workup may be initiated while awaiting dermatology referral.AD patients have multiple cutaneous and extra-cutaneous comorbidities that warrant screening by internists, especially mental health conditions.
MeSH term(s)	Depression ; Dermatitis, Atopic/diagnosis ; Dermatitis, Atopic/epidemiology ; Dermatitis, Atopic/therapy ; Dermatology/standards ; Disease Management ; Food Hypersensitivity ; Humans ; Mental Health ; Sleep
Language	English
Publishing date	2021-11-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1004226-x
ISSN	1365-2060 ; 1651-2219 ; 0785-3890 ; 1743-1387
ISSN (online)	1365-2060 ; 1651-2219
ISSN	0785-3890 ; 1743-1387
DOI	10.1080/07853890.2021.2004322
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Article ; Online: The inpatient burden of pyoderma gangrenosum and associated comorbidities in children in the United States.

Narla, Shanthi / Silverberg, Jonathan I

Archives of dermatological research

2021 Volume 314, Issue 6, Page(s) 613–617

Abstract: Pyoderma gangrenosum is an ulcerating inflammatory condition defined pathologically by an abundance of neutrophils in the absence of infection. Often, hospital admission is necessary for rapidly progressing PG for wound care and adequate pain control. ... ...

Abstract	Pyoderma gangrenosum is an ulcerating inflammatory condition defined pathologically by an abundance of neutrophils in the absence of infection. Often, hospital admission is necessary for rapidly progressing PG for wound care and adequate pain control. However, few large-scaled controlled studies exist examining hospitalizations for PG in the pediatric populations and the associated comorbidities. We sought to determine the prevalence, length of stay (LOS), cost of care, and any risk factors for admission and associated comorbidities in children hospitalized for PG in the U.S. Data were analyzed from the 2002 to 2012 National Inpatient Sample, including a 20% representative sample of all hospitalizations in the United States. The prevalence of hospitalization between 2002 and 2012 ranged from 2 to 11 per million hospitalized children. Hospitalization for PG was associated with older age, female gender, black race/ethnicity, the third quartile for household income, having 2-5 chronic conditions, being admitted to a micropolitan or a non-metro/micropolitan hospital and to a teaching hospital. Hospitalization with vs. without a primary diagnosis of PG was associated with significantly prolonged LOS. The total inflation-adjusted cost of care for hospitalization with a primary diagnosis of PG was $2,202,576; $200,234 per year). The geometric-mean cost of hospitalization was significantly higher in children with vs. without a primary diagnosis of PG. Children hospitalized for PG were found to have higher odds of thyroid disease, inflammatory bowel disease, hematologic malignancy, and other autoimmune disorders. While children are rarely hospitalized for PG, they have prolonged hospitalization, and clinical interventions need to be developed to prevent hospitalization for PG. Further, concomitant workup for other systemic comorbidities is also warranted at the time of diagnosis and throughout disease course.
MeSH term(s)	Child ; Comorbidity ; Female ; Hospitalization ; Humans ; Inpatients ; Length of Stay ; Pyoderma Gangrenosum/diagnosis ; Pyoderma Gangrenosum/epidemiology ; United States/epidemiology
Language	English
Publishing date	2021-01-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	130131-7
ISSN	1432-069X ; 0340-3696
ISSN (online)	1432-069X
ISSN	0340-3696
DOI	10.1007/s00403-021-02189-z
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Article ; Online: Comparing Follicular Extension Between Low-Grade and High-Grade Dysplastic Nevi.

Grube, Vanden L / Narla, Shanthi / Mata, Douglas A / Hafeez, Farhaan

The American Journal of dermatopathology

2023 Volume 45, Issue 6, Page(s) 423–424

Abstract: Abstract: Dysplastic nevi are an important subset of melanocytic nevi with atypical clinical, histopathologic, as well as genomic features compared with common acquired nevi. Dysplastic nevi are characterized histologically by both cytologic atypia and ... ...

Abstract	Abstract: Dysplastic nevi are an important subset of melanocytic nevi with atypical clinical, histopathologic, as well as genomic features compared with common acquired nevi. Dysplastic nevi are characterized histologically by both cytologic atypia and architectural disorder. The established criteria for cytologic atypia used to distinguish between low-grade and high-grade dysplastic nevi are often subjective, although there is a dearth of more objective, reproducible features of architectural disorder (eg, pagetoid scatter) that have been validated to differentiate between low-grade and high-grade dysplastic nevi. In this study, we sought to determine whether the presence and degree of follicular extension differ between low-grade and high-grade dysplastic nevi. We retrospectively examined the histopathologic features of 90 dysplastic nevi: 60 cases of low-grade dysplastic nevi (average age of 47.2 ± 18.1 years; 62.7% female) and 30 cases of high-grade dysplastic nevi (average age of 47.4 ± 19.8 years; 60.0% female). After examination, 50% of the cases of dysplastic nevi (n = 45) had hair follicles within the lesion, for which the presence and degree of follicular extension was then determined. Low-grade and high-grade dysplastic nevi do not differ significantly regarding the presence of follicular extension, average depth of follicular extension, and confluence of nevus cells along the follicular epithelium. Both low-grade and high-grade dysplastic nevi in our study demonstrated follicular extension that was superficial, that is, above the level of isthmus of hair follicles (insertion of sebaceous gland into hair follicle). Future studies are warranted to confirm these preliminary findings.
MeSH term(s)	Humans ; Female ; Adult ; Middle Aged ; Aged ; Male ; Dysplastic Nevus Syndrome/pathology ; Skin Neoplasms/pathology ; Retrospective Studies ; Nevus ; Nevus, Pigmented/pathology ; Hyperplasia
Language	English
Publishing date	2023-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	448469-1
ISSN	1533-0311 ; 0193-1091
ISSN (online)	1533-0311
ISSN	0193-1091
DOI	10.1097/DAD.0000000000002438
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Article ; Online: Dermatology for the internist

Shanthi Narla / Jonathan I. Silverberg

Annals of Medicine, Vol 53, Iss 1, Pp 2165-

optimal diagnosis and management of atopic dermatitis

2021 Volume 2177

Abstract: AbstractInternists are front-line health care providers that commonly provide the first encounter to patients for dermatological conditions, especially atopic dermatitis (AD). Internists need to be comfortable with managing mild-moderate AD in their ... ...

Abstract	AbstractInternists are front-line health care providers that commonly provide the first encounter to patients for dermatological conditions, especially atopic dermatitis (AD). Internists need to be comfortable with managing mild-moderate AD in their practices. Criteria and guidelines established in dermatology literature are available to help the general practitioner diagnose and treat AD. AD is a systemic disease associated with multiple cutaneous and extra-cutaneous comorbidities that warrant screening by internists, especially mental health conditions. Environmental factors may play a role in the development or worsening of AD; however, there is currently no strong evidence to guide specific population- or clinic-based interventions for their avoidance. While food allergies are common in AD patients, the role of food allergens as an exacerbating factor for AD is controversial. Before starting any dietary modifications, careful evaluation should be performed by an allergist. If the patient is not well-controlled despite adequate topical therapies or is experiencing severe/worsening disease, early referral to dermatology is warranted to rule out confounding diagnoses and/or escalation to systemic therapies. Finally, it is important to recognise the racial disparities present in AD and address these when formulating treatment plans.Key messages:Confounding dermatoses, either instead of or in addition to AD, should be considered in treatment-refractory AD, and the appropriate workup may be initiated while awaiting dermatology referral.AD patients have multiple cutaneous and extra-cutaneous comorbidities that warrant screening by internists, especially mental health conditions.
Keywords	Atopic dermatitis ; internist ; comorbidities ; screening ; mental health ; depression ; Medicine ; R
Subject code	360
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Taylor & Francis Group
Document type	Article ; Online
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Article ; Online: The inpatient burden and comorbidities of pyoderma gangrenosum in adults in the United States.

Narla, Shanthi / Silverberg, Jonathan I

Archives of dermatological research

2020 Volume 313, Issue 4, Page(s) 245–253

Abstract: Hospital admission is often necessary for management of pyoderma gangrenosum (PG), including wound care and pain control. No large-scale controlled studies examined the burden of hospitalization for PG. The objective of this study is to determine the ... ...

Abstract	Hospital admission is often necessary for management of pyoderma gangrenosum (PG), including wound care and pain control. No large-scale controlled studies examined the burden of hospitalization for PG. The objective of this study is to determine the prevalence, predictors, outcomes, and costs of hospitalization for PG in United States adults. Data were analyzed from the 2002 to 2012 National Inpatient Sample, including a 20% representative sample of United States hospitalizations. The prevalence of hospitalization for PG increased between 2002 and 2012. Primary admission for PG was associated with age 40-59 years, female sex, black race/ethnicity, second-quartile household income, public or no insurance, and multiple chronic conditions. PG admissions were more likely at teaching and medium or large hospitals. Geometric-mean length and cost of hospitalization were higher in inpatients with vs. without a primary diagnosis of PG. The majority of inpatients with PG were classified with minor (64.4%) or moderate (25.7%) likelihood of dying, but moderate (52.5%) and major (28.7%) loss of function. PG was associated with numerous other health disorders. The limitation of this study is the lack of data on PG treatment. This study demonstrated a substantial and increasing inpatient burden of PG in the United States, with considerable disability and mortality risk, multiple comorbid health disorders, and costs.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Comorbidity ; Cost of Illness ; Female ; Health Care Costs/statistics & numerical data ; Health Care Costs/trends ; Humans ; Length of Stay/economics ; Length of Stay/statistics & numerical data ; Length of Stay/trends ; Male ; Middle Aged ; Mortality/trends ; Patient Admission/economics ; Patient Admission/statistics & numerical data ; Patient Admission/trends ; Prevalence ; Pyoderma Gangrenosum/economics ; Pyoderma Gangrenosum/epidemiology ; Retrospective Studies ; United States/epidemiology ; Young Adult
Language	English
Publishing date	2020-07-03
Publishing country	Germany
Document type	Journal Article
ZDB-ID	130131-7
ISSN	1432-069X ; 0340-3696
ISSN (online)	1432-069X
ISSN	0340-3696
DOI	10.1007/s00403-020-02098-7
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Article ; Online: The Role of Environmental Exposures in Atopic Dermatitis.

Narla, Shanthi / Silverberg, Jonathan I

Current allergy and asthma reports

2020 Volume 20, Issue 12, Page(s) 74

Abstract: Purpose of review: Although genetic factors clearly play a role in the development of atopic dermatitis (AD), the recent dramatic increase in the prevalence of AD in low- and middle-income countries is not consistent with only a role of genetic factors. ...

Abstract	Purpose of review: Although genetic factors clearly play a role in the development of atopic dermatitis (AD), the recent dramatic increase in the prevalence of AD in low- and middle-income countries is not consistent with only a role of genetic factors. These findings strongly suggest that environmental factors may play an important role in the pathogenesis of AD. Recent findings: We reviewed the role of gene-environment studies; in utero exposures including tobacco smoke, alcohol, maternal stress, various digestive supplements, and gestational diabetes; early-life exposures including diet, gut microbiota, antibiotics, and breastfeeding; climate including temperature, ultraviolet radiation exposure, and air pollution; and household products, indoor allergens, water hardness, pH, and skin microbiota and their effects on AD. Environmental factors definitely play a role in the pathogenesis of AD. However, identifying definitive factors continues to be difficult in the setting of conflicting evidence and the complex interactions between genotypes and the environment resulting in a multitude of AD phenotypes. All of the different environmental interactions discussed highlight the importance of intervening on multiple levels in a patient's environment to improve or even prevent AD symptoms. Further, the importance of modifying environmental factors early on in a person's life is demonstrated. When possible, all of these environmental factors should be considered in treating a patient with AD and the appropriate modifications should be made at population and individual levels.
MeSH term(s)	Adult ; Animals ; Dermatitis, Atopic/etiology ; Dermatitis, Atopic/pathology ; Environmental Exposure/adverse effects ; Female ; Humans ; Male ; Mice ; Risk Factors ; Young Adult
Language	English
Publishing date	2020-10-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057370-4
ISSN	1534-6315 ; 1529-7322
ISSN (online)	1534-6315
ISSN	1529-7322
DOI	10.1007/s11882-020-00971-z
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