Understanding the Expert Consensus on AhR Agonists in Inflammatory Skin Disease

In this segment, Christopher Bunick, MD, reviews the recently published expert roundtable consensus on the role of aryl hydrocarbon receptor (AhR) agonists in inflammatory skin disease, distilling the publication's nine consensus statements into four overarching themes that define this emerging therapeutic class and its role in clinical practice, with a particular focus on tapinarof.

Why this consensus was needed

Dr Bunick begins by placing the consensus into the context of recent advances in topical therapy for psoriasis and atopic dermatitis (AD). As awareness of topical steroid stewardship has grown, so too has the need for effective nonsteroidal treatment options that offer novel mechanisms of action, durable efficacy, and favorable long-term safety profiles.

According to Dr Bunick, the goal of the expert consensus was to clearly define the role of AhR agonists as a new therapeutic class, explain their unique mechanism of action, provide practical guidance for clinical use, and outline how these agents can support modern approaches to topical steroid stewardship.

He summarizes the publication by organizing its nine consensus statements into four key clinical themes.

AhR agonists represent a distinct therapeutic class

The first major takeaway is that AhR agonists constitute a unique therapeutic class in dermatology, distinguished by a multimodal mechanism of action.

Dr Bunick explains that AhR agonists such as tapinarof exert their effects through 3 complementary mechanisms:

• Immune modulation: AhR activation influences gene transcription across multiple inflammatory pathways, including TH1, TH2, TH17, and TH22 signaling

• Skin barrier normalization: In addition to modulating inflammation, AhR agonists promote barrier repair by increasing structural proteins such as filaggrin, loricrin, and involucrin while improving tight junction integrity

• Antioxidant activity: Activation of the NRF2 pathway provides antioxidant effects that complement both immune regulation and barrier normalization

Together, these multimodal actions differentiate AhR agonists from both topical corticosteroids and currently available nonsteroidal therapies, supporting their classification as a distinct therapeutic approach.

Safety and tolerability support flexible and long-term use

Dr Bunick next reviews the consensus statements addressing safety and tolerability.

He notes that clinical trial data have demonstrated a favorable safety profile, with mild-to-moderate folliculitis representing the most commonly reported adverse event. In most cases, these events were self-limited and required little or no intervention.

Importantly, AhR agonists are not restricted by treatment duration, body surface area, or application site. Dr Bunick highlights the clinical significance of this flexibility, noting that chronic diseases such as psoriasis and AD require therapies that can be used on sensitive areas, including the face and intertriginous regions, as well as over larger body surface areas and for extended periods when clinically appropriate.

Defining the role of AhR agonists in clinical practice

A central focus of the consensus is clarifying where AhR agonists fit within current treatment algorithms.

Dr Bunick explains that the panel supports their use as a first-line topical treatment option for both psoriasis and AD. Their long-term safety profile also makes them well suited for chronic disease management without the need to routinely cycle between therapies.

He also discusses their role alongside systemic treatment. Many patients receiving biologic or systemic therapy continue to experience residual localized disease, and AhR agonists provide an effective nonsteroidal option for managing these persistent areas.

The consensus also addresses pediatric care. Tapinarof is approved in patients aged 2 years and older with AD, and Dr Bunick emphasizes that its availability expands the range of advanced nonsteroidal options for younger patients with inflammatory skin disease.

Finally, he highlights a practical consideration regarding phototherapy. Because preclinical and in vitro studies have demonstrated some UV instability of tapinarof, the consensus recommends applying the medication after phototherapy sessions to preserve product integrity.

Supporting topical steroid stewardship

The final theme centers on topical steroid stewardship, a concept that Dr Bunick describes as a recurring thread throughout the consensus publication.

As clinicians increasingly seek to minimize long-term corticosteroid exposure when appropriate, advanced nonsteroidal therapies offer additional flexibility in managing chronic inflammatory skin diseases. Dr Bunick positions AhR agonists as an important component of this evolving treatment paradigm, providing clinicians with another effective option that can be incorporated into both initial and long-term management strategies.

He concludes by encouraging clinicians to review the full consensus publication for more practical guidance for integrating AhR agonists into everyday care for patients with psoriasis and AD.