Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells

Bangert, Christine; Alkon, Natalia; Chennareddy, Sumanth; Arnoldner, Tamara; Levine, Jasmine P.; Pilz, Magdalena; Medjimorec, Marco A.; Ruggiero, John; Cohenour, Emry R.; Jonak, Constanze; Damsky, William; Griss, Johannes; Brunner, Patrick M.

doi:10.1038/s41467-024-46540-0

Nat Commun

2024

DOI: 10.1038/s41467-024-46540-0

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Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells

Christine Bangert,

Natalia Alkon,

Sumanth Chennareddy

et al.

Abstract: Dupilumab, an IL4R-blocking antibody, has shown clinical efficacy for atopic dermatitis (AD) treatment. In addition to conjunctivitis/blepharitis, the de novo appearance of head/neck dermatitis is now recognized as a distinct side effect, occurring in up to 10% of patients. Histopathological features distinct from AD suggest a drug effect, but exact underlying mechanisms remain unknown. We profiled punch biopsies from dupilumab-associated head and neck dermatitis (DAHND) by using single-cell RNA sequencing and… Show more

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Cited by 8 publications

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Atopic dermatitis: pathogenesis and therapeutic intervention

Yue,

Zhou,

Wang

et al. 2024

MedComm

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The skin serves as the first protective barrier for nonspecific immunity and encompasses a vast network of skin‐associated immune cells. Atopic dermatitis (AD) is a prevalent inflammatory skin disease that affects individuals of all ages and races, with a complex pathogenesis intricately linked to genetic, environmental factors, skin barrier dysfunction as well as immune dysfunction. Individuals diagnosed with AD frequently exhibit genetic predispositions, characterized by mutations that impact the structural integrity of the skin barrier. This barrier dysfunction leads to the release of alarmins, activating the type 2 immune pathway and recruiting various immune cells to the skin, where they coordinate cutaneous immune responses. In this review, we summarize experimental models of AD and provide an overview of its pathogenesis and the therapeutic interventions. We focus on elucidating the intricate interplay between the immune system of the skin and the complex regulatory mechanisms, as well as commonly used treatments for AD, aiming to systematically understand the cellular and molecular crosstalk in AD‐affected skin. Our overarching objective is to provide novel insights and inform potential clinical interventions to reduce the incidence and impact of AD.

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Atopic dermatitis: pathogenesis and therapeutic intervention

Yue,

Zhou,

Wang

et al. 2024

MedComm

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Durable improvements in atopic dermatitis in the head and neck and across other anatomic regions with rocatinlimab

Guttman-Yassky,

Esfandiari,

Mano

et al. 2024

Arch Dermatol Res

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In a randomized phase 2b trial (NCT03703102) for adult patients with moderate-to-severe atopic dermatitis (AD), treatment with the T cell rebalancing anti-OX40 receptor antibody rocatinlimab (AMG 451/KHK4083) led to significant improvements in clinical measurements versus placebo including whole-body Eczema Area and Severity Index (EASI) score. AD manifestations can impact variable anatomic regions, and involvement of the head and neck, a sensitive, hard-to-treat area, can negatively impact quality of life. In this post hoc analysis, we investigated response to rocatinlimab treatment across anatomic regions, including the head and neck. Least squares mean change from baseline to Week 56 in EASI score was analyzed by anatomic region (head and neck, trunk, upper extremities, or lower extremities) for patients with baseline moderate-to-severe AD in the respective anatomic region, using mixed models for repeated measures. Rocatinlimab groups were compared with placebo at Week 16. The proportion of patients achieving at least 75% reduction from baseline in EASI (EASI-75) was calculated. Probability of relapsing in EASI-75 during the off-treatment follow-up period (Weeks 36–56) was estimated using a Kaplan − Meier approach. At Week 16, decrease from baseline in mean EASI score was greater with all rocatinlimab regimens versus placebo across all anatomic regions for patients with baseline moderate-to-severe AD in the respective region (all P < 0.001). EASI scores continued to improve on treatment after Week 16 and were maintained during the off-treatment period across all regions. Among patients with baseline moderate-to-severe AD in the head and neck (n = 219; rocatinlimab, n = 174; placebo, n = 45), mean difference (rocatinlimab vs placebo) at Week 16 in LS mean percent change in head and neck EASI score ranged from − 30.4% to − 42.6% across treatment regimens. In patients who received rocatinlimab from the start of the trial, 47% − 71% achieved EASI-75 in the head and neck at Week 36. Among EASI-75 responders at Week 36, the probability of relapsing in EASI-75 in any region was low (< 25% in the head and neck) 20 weeks after treatment discontinuation until Week 56. Rocatinlimab treatment led to durable improvements in AD across multiple anatomic regions, including the sensitive head and neck region. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s00403-024-03426-x.

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Fungal Head and Neck Dermatitis: Current Understanding and Management

Chong,

Navarro-Triviño,

et al. 2024

Clinic Rev Allerg Immunol

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Head and neck dermatitis (HND) is a form of atopic dermatitis (AD) that affects the seborrheic areas of the body and causes greater quality of life detriments than other types of AD. HND can be challenging to treat since first-line topical therapies may be ineffective or intolerable for long-term use on areas affected by HND while dupilumab may cause dupilumab-associated HND (DAHND). Current evidence implicates fungi, particularly Malassezia spp., in the pathogenesis of HND. Penetration of fungal antigens through the defective AD skin barrier activates the innate and adaptive immune systems to cause cutaneous inflammation via the T helper (Th)17 and/or Th2 axes. Malassezia sensitization may distinguish HND from other forms of AD. Multiple double-blind, placebo-controlled trials have shown antifungals to benefit HND, yet the persistence of symptom relief with sustained use remains unclear. Oral antifungals appear more effective than topical antifungals but may be harmful with long-term use. DAHND may also be fungal-mediated given improvement with antifungals and evidence of an overactive immune response against Malassezia in these patients. Janus kinase inhibitors are effective for HND, including DAHND, but may cause significant side effects when administered systemically. OX40/OX40L inhibitors and tralokinumab may be promising options for HND on the horizon. Demographic and environmental factors influence the host mycobiome and should be considered in future precision-medicine approaches as microbiome composition and diversity are linked to severity of HND.

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Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells

Cited by 8 publications

References 108 publications

Atopic dermatitis: pathogenesis and therapeutic intervention

Atopic dermatitis: pathogenesis and therapeutic intervention

Durable improvements in atopic dermatitis in the head and neck and across other anatomic regions with rocatinlimab

Fungal Head and Neck Dermatitis: Current Understanding and Management

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