Dupilumab improves both histaminergic and touch‐evoked itch sensitization (hyperknesis) in atopic dermatitis: a pilot study

Hashimoto, Takashi; Okuno, Satoshi; Okuzawa, Manami; Satoh, Takahiro

doi:10.1111/jdv.18356

Cited by 6 publications

(8 citation statements)

References 11 publications

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“…Although we did not investigate other factors that could be involved in hyperknesis (e.g. dysfunction of neural circuits in the spine 12 and immune status 13 ) and did not evaluate alloknesis in the cases, this case series suggests that hyperknesis does occur in PHI and seems to be associated with reduced IENFs.…”

Section: Discussionmentioning

confidence: 93%

Increased touch‐evoked itch (punctate hyperknesis) in postherpetic itch: Implications of reduced intraepidermal nerve fibers representing small fiber neuropathy

Hashimoto

Okuzawa

Yamamoto

et al. 2022

The Journal of Dermatology

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Chronic itch conditions are often accompanied by neural itch sensitization, known as hyperknesis (excessive itch induced by stimuli that would normally induce only mild itching or pain) and alloknesis (considerable itch evoked by light tactile stimuli). Herpes zoster (shingles) can cause neuropathic itch (postherpetic itch), although it is unknown whether hyperknesis accompanies postherpetic itch. The authors report five patients with postherpetic itch who showed increased touch‐evoked itch (punctate hyperknesis) in the affected skin areas compared with the contralateral site. Collected skin biopsy specimens from two patients showed histopathologically detected reduced intraepidermal nerve fibers in the affected skin areas, reflective of small C/Aδ fiber neuropathy. In one case, improvement in itching and comparable levels of touch‐evoked itch on the affected and contralateral sites were noted after 6 months without any medication, accompanied by restored intraepidermal nerve fibers proven through rebiopsy of the affected site. Reduced intraepidermal nerve fibers could be one of the precipitating factors for postherpetic itch and its associated punctate hyperknesis.

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Section: Discussionmentioning

confidence: 93%

Increased touch‐evoked itch (punctate hyperknesis) in postherpetic itch: Implications of reduced intraepidermal nerve fibers representing small fiber neuropathy

Hashimoto

Okuzawa

Yamamoto

et al. 2022

The Journal of Dermatology

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“…The monoclonal antibody Dupilumab targets the alpha-subunit of the IL-4 receptor, reducing type 2 cytokines IL-4 and IL-13. A recent small-scale study found Dupilumab to not only reduce itch, but also reduce histaminergic and mechanical hyperknesis in AD patients ( Hashimoto et al, 2022 ). The anti-IL-31 receptor alpha monoclonal antibody, Nemolizumab, may reduce IL-31 induced sensory nerve stimulation, thereby reducing peripheral sensitization ( Ständer et al, 2022 ).…”

Section: Treatments For Neural Sensitization Of Itchmentioning

confidence: 99%

Itch: from the skin to the brain – peripheral and central neural sensitization in chronic itch

Mahmoud,

Oladipo,

Mahmoud

et al. 2023

Front. Mol. Neurosci.

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Similar to chronic pain, chronic itch is frequently linked to neural sensitization, a phenomenon wherein the nervous system becomes hypersensitive to stimuli. This process of neural sensitization of chronic itch is orchestrated by various signaling pathways and mediators in both the peripheral and central nervous systems. At the level of the peripheral nervous system, inflammation and neuroimmune interactions induce plastic changes to peripheral nerve fibers, thereby amplifying the transmission of itch signaling. Neural sensitization in the central nervous system occurs at both the spinal cord and brain levels. At the level of the spinal cord, it involves hyperactivity of itch-activating spinal pathways, dysfunction of spinal inhibitory circuits, and attenuation of descending supraspinal inhibitory pathways. In the brain, neural sensitization manifests as structural and functional changes to itch-associated brain areas and networks. Currently, we have a diverse array of neuroimmune-modulating therapies targeting itch neural sensitization mechanisms to help with providing relief to patients with chronic itch. Itch research is a dynamic and continually evolving field, and as we grow in our understanding of chronic itch mechanisms, so will our therapeutic toolbox. Further studies exploring the peripheral and central neural sensitization mechanisms in the context of chronic itch are needed.

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“…One study showed that dupilumab resulted in a significant improvement in the baseline itch in patients with AD, while the control group which was treated with topical cortical steroids alone experienced increased histaminergic and mechanical hyperknesis. 22 Another report on dupilumab for the treatment of pruritus of unknown origin also demonstrates that the anti-pruritic effects of dupilumab are not simply a sequelae of the reduction in inflammation. 23…”

Section: Il-4 and Il-13 Blockade Has A Direct Effect On The Neurologi...mentioning

confidence: 99%

Unexpected Clinical Lessons Learned From IL-4 and IL-13 Blockade

Bury,

Zirwas

2023

JDD

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Dupilumab improves both histaminergic and touch‐evoked itch sensitization (hyperknesis) in atopic dermatitis: a pilot study

Cited by 6 publications

References 11 publications

Increased touch‐evoked itch (punctate hyperknesis) in postherpetic itch: Implications of reduced intraepidermal nerve fibers representing small fiber neuropathy

Increased touch‐evoked itch (punctate hyperknesis) in postherpetic itch: Implications of reduced intraepidermal nerve fibers representing small fiber neuropathy

Itch: from the skin to the brain – peripheral and central neural sensitization in chronic itch

Unexpected Clinical Lessons Learned From IL-4 and IL-13 Blockade

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