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- Presentation
Targeted Therapies for Itch in Autoimmune Disease
Description
The talk reviews itch as a major, often underappreciated symptom in autoimmune disease, emphasizing that it can be more distressing than other disease features and may serve as a biomarker of severity. Itch phenotypes differ by condition: dermatomyositis often causes prominent scalp itch driven by type I interferon/JAK signaling; lupus itch may be burning and can precede flares; systemic sclerosis and Sjogren’s have mixed inflammatory and neuropathic itch; chronic spontaneous urticaria is defined by severe itch; and primary biliary cholangitis produces non-histaminergic itch linked to bile acids and bilirubin. The speaker outlines neuroimmune mechanisms involving IL-4/IL-13, IL-31, interferons, TSLP, MRG receptors, TRP channels, and mast-cell pathways, noting that a single pathway does not explain all patients. Traditional treatments such as immunosuppressants, hydroxychloroquine, IVIG, gabapentinoids, TCAs/SNRIs, and low-dose naltrexone can help but are often slow, limited, or nonspecific. Emerging targeted therapies are highlighted: brepacitinib for dermatomyositis, showing rapid itch improvement via JAK1/TYK2 inhibition; remibrutinib for chronic spontaneous urticaria, with fast and strong responses by targeting BTK; and bile-acid-directed therapies such as linerixibat and seladelpar for PBC, which reduce itch by modifying bile acid signaling and liver inflammation. The main take-home is that understanding the underlying immune and neural drivers enables more precise, condition-specific itch treatment.
View moreConclusions
- Itch in autoimmune disease is a common and underrecognized symptom that often drives patient distress more than other disease manifestations.
- Autoimmune itch is frequently non-histaminergic and requires understanding the specific neuro-immune pathway driving each condition.
- Itch severity often tracks underlying disease activity, making itch a useful biomarker, especially in dermatomyositis and lupus.
- Dermatomyositis itch appears strongly type I interferon-driven and responds best to targeted JAK/TYK2-pathway inhibition such as brepocitinib.
- Type IIb chronic spontaneous urticaria is driven by autoantibody-mediated mast cell activation and appears especially responsive to BTK inhibition with remibrutinib.
- Direct mast-cell depletion with KIT blockade, such as barzolvolimab, is a promising future strategy for severe CSU.
- Cholestatic itch in primary biliary cholangitis is mediated by bile acids and bilirubin acting on sensory receptors such as MRGPRX4 and TGR5.
- Linerixibat and seladelpar represent major advances for PBC by improving both cholestasis-related itch and underlying disease biology.
- Traditional broad therapies like DMARDs, IVIG, gabapentinoids, and low-dose naltrexone can help but are limited by slow onset, incomplete efficacy, and side effects.
- The field is moving toward mechanism-based treatment selection, using the dominant inflammatory, neuropathic, or cholestatic pathway to guide therapy choice.
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