Molecular and cellular mechanisms of itch and pain in atopic dermatitis and implications for novel therapeutics

Kwatra, Shawn G.; Miséry, Laurent; Clibborn, Claire; Steinhoff, Martin

doi:10.1002/cti2.1390

Cited by 29 publications

(22 citation statements)

References 146 publications

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“…The pain inflicted by AD can cause sleep disturbances and decrease quality of life. Evidence supports that the underlying mechanism for the pain response in AD is inflammation induced by proinflammatory cytokines and neuropathic pain of the peripheral nervous system ( 76 ). Cytokines involved in the JAK–STAT pathway also contribute to pain modulation.…”

Section: Role Of the Jak–stat Pathway In The Pathogenesis Of Admentioning

confidence: 90%

JAK–STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review

Huang

Hung

et al. 2022

Front. Immunol.

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Atopic dermatitis (AD) is a chronic, inflammatory, pruritic form of dermatosis with heterogeneous manifestations that can substantially affect patients' quality of life. AD has a complex pathogenesis, making treatment challenging for dermatologists. The Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway plays a central role in modulating multiple immune axes involved in the immunopathogenesis of AD. In particular, Th2 cytokines, including interleukin (IL)-4, IL-5, IL-13, IL-31, and thymic stromal lymphopoietin, which contribute to the symptoms of chronic inflammation and pruritus in AD, are mediated by JAK–STAT signal transduction. Furthermore, JAK–STAT is involved in the regulation of the epidermal barrier and the modulation of peripheral nerves related to the transduction of pruritus. Targeting the JAK–STAT pathway may attenuate these signals and show clinical efficacy through the suppression of various immune pathways associated with AD. Topical and oral JAK inhibitors with variable selectivity have emerged as promising therapeutic options for AD. Notably, topical ruxolitinib, oral upadacitinib, and oral abrocitinib were approved by the U.S. Food and Drug Administration for treating patients with AD. Accordingly, the present study reviewed the role of JAK–STAT pathways in the pathogenesis of AD and explored updated applications of JAK inhibitors in treating AD.

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Section: Role Of the Jak–stat Pathway In The Pathogenesis Of Admentioning

confidence: 90%

JAK–STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review

Huang

Hung

et al. 2022

Front. Immunol.

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“…Se pueden mencionar la IL-4, IL-13 e IL-31, entre otras 24 . También la TSLP, derivada de los queratinocitos y algunas células inflamatorias, puede estimular los pruriceptores fijándose a su receptor TSLPR, un heterodímero señalizando mediante JAK1-2 25 . La activación directa por TSLP de los canales iónicos modula esta sensación 26 .…”

Section: Mecanismos Del Pruritounclassified

“…Últimamente se confirma cada vez más la importancia de los queratinocitos en todo el proceso inflamatorio, al igual que en la generación de la señal para el prurito. Se reconoce el importante papel que juega la linfopoietina estromal del timo (TSLP por sus siglas en inglés de Thymic Stromal Lymphopoietin), sustancia que libera el queratinocito al encontrarse con señales de daño o al ser expuesto a sustancias de microorganismos 25 . La TSLP depende de los canales iónicos como TRPA1 y TRPV4 para su señalización del prurito; probablemente tiene también su receptor en los axones de NP2 y NP3 26 .…”

Section: Mecanismos Del Pruritounclassified

Guía de dermatitis atópica para México (GUIDAMEX): lineamientos usando metodología ADAPTE

Larenas‐Linnemann¹,

Rincón-Pérez²,

Luna-Pech³

et al. 2023

GMM

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“…In addition, topical delgocitinib, another pan-JAK inhibitor, entered clinical trials (NCT03826901, NCT03683719) for chronic hand eczema in both pediatric and adult patients [ 30 , 31 ]. Furthermore, similar to AD, the pathogenesis of prurigo nodularis (PN) involves Th2- and Th17/Th22-mediated inflammation, which can both be attenuated through JAK inhibition [ 32 – 34 ]. Other phase 2 studies (NCT05038982, NCT05061693) are examining the role of abrocitinib and INCB054707 in the treatment of prurigo nodularis (PN) and chronic pruritus of unknown origin [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

A Review on the Safety of Using JAK Inhibitors in Dermatology: Clinical and Laboratory Monitoring

Samuel

Cornman

Kambala

et al. 2023

Dermatol Ther (Heidelb)

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Janus kinase (JAK) inhibitors are disease-modifying agents with efficacy in treating a spectrum of burdensome dermatologic conditions. The US Food and Drug Administration (FDA) recently placed a black box warning on this class of medications due to safety concerns based on data from studies investigating tofacitinib in patients with rheumatoid arthritis. Here we provide an overview of the timeline of FDA approval of JAK inhibitors in dermatology. We also discuss the available safety profiles of approved oral JAK1 inhibitors, namely abrocitinib and upadacitinib, oral baricitinib, a JAK1/2 inhibitor, deucravacitinib, a Tyk2 inhibitor, and the topical JAK1/2 inhibitor ruxolitinib in dermatology patients. Additionally, we offer suggestions for initial screening and laboratory monitoring for patients receiving JAK inhibitors. We found that the rates of venous thromboembolism reported in trials ranged from no events to 0.1–0.5% in dermatology-specific phase 3 clinical trials compared with no events in the placebo. The rates of cardiovascular events ranged from no events to 0.4–1.2% compared with no events to 0.5–1.2% in the placebo. The rates of serious infections were 0.4–4.8% compared with no events to 0.5–1.3% in the placebo. The rates of nonmelanoma skin cancer (NMSC) ranged from no event to 0.6–0.9% compared with no events in the placebo. The rates of non-NMSC ranged from no event to 0.2–0.7% compared with no event to 0.6% in the placebo. Most patients who developed these adverse events had risk factors for the specific event. The most common adverse events of oral JAK inhibitors included upper respiratory infections, nasopharyngitis, nausea, headache, and acne. Dermatologists should consider patients’ baseline risk factors for developing serious complications when prescribing oral JAK inhibitors.

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Molecular and cellular mechanisms of itch and pain in atopic dermatitis and implications for novel therapeutics

Cited by 29 publications

References 146 publications

JAK–STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review

JAK–STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review

Guía de dermatitis atópica para México (GUIDAMEX): lineamientos usando metodología ADAPTE

A Review on the Safety of Using JAK Inhibitors in Dermatology: Clinical and Laboratory Monitoring

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