The neuropathic itch: Don't scratch your head too hard!

Patnaik, Soumya; Imms, John; Váradi, Gábor

doi:10.1002/ccr3.3688

Cited by 4 publications

(7 citation statements)

References 12 publications

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“…For example, in VZV-induced postherpetic itch (PHI), only 5% of epidermal sensory nerve fibers remained (Oaklander, 2011;Oaklander et al, 2002;Steinhoff et al, 2018). In a study of over a hundred adults with shingles, 17% developed PHI (Oaklander et al, 2003), with varying degrees of itch intensity; some described as a "compulsive scratching" of the affected areas leading to severe deep tissue damage (Oaklander et al, 2002;Patnaik et al, 2021). VZV only infects humans but its numerous similarities to PRV in causing neuropathic itch may hint at a role for DDX3X, though this needs to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Pseudorabies virus hijacks DDX3X, initiating an addictive “mad itch” and immune suppression, to facilitate viral spread

Cronin,

Tejada,

Song

et al. 2023

Preprint

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Infections with defined Herpesviruses, such as Pseudorabies virus (PRV) and Varicella zoster virus (VZV) can cause neuropathic itch, referred to as 'mad itch' in multiple species. The underlying mechanisms involved in neuropathic 'mad itch' are poorly understood. Here, we show that PRV infections hijack the RNA helicase DDX3X in sensory neurons to facilitate anterograde transport of the virus along axons. PRV induces re-localization of DDX3X from the cell body to the axons which ultimately leads to death of the infected sensory neurons. Inducible genetic ablation of Ddx3x in sensory neurons results in neuronal death and 'mad itch' in mice. This neuropathic 'mad itch' is propagated through activation of the opioid system making the animals 'addicted to itch'. Moreover, we show that PRV co-opts and diverts T cell development in the thymus via a sensory neuron-IL-6-hypothalamus-corticosterone stress pathway. Our data reveal how PRV, through regulation of DDX3X in sensory neurons, travels along axons and triggers neuropathic itch and immune deviations to initiate pathophysiological programs which facilitate its spread to enhance infectivity.

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Section: Discussionmentioning

confidence: 99%

Pseudorabies virus hijacks DDX3X, initiating an addictive “mad itch” and immune suppression, to facilitate viral spread

Cronin,

Tejada,

Song

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…It is estimated that up to 30% of people with Rare Diseases -Recent Advances postherpetic neuralgia have pruritus [17,18]. Postherpetic pruritus is also a common cause of NP in the dermatomal area affected by the peripheral nerve region damaged by the varicella zoster virus [19][20][21].…”

Section: Clinical Disorders Causing Neuropathic Pruritus 21 Postherpe...mentioning

confidence: 99%

“…The intensive, persistent, and subconscious desire to scratch, which usually occurs during sleep, causes chronic and deep excoriations on the scalp. The resulting wounds can sometimes even reach the bones [20][21][22]. These patients often refer to dermatologists, but neurologists should be consulted to identify and treat the underlying cause [14,16].…”

Section: Trigeminal Trophic Syndrome (Tts)mentioning

confidence: 99%

“…While it is ideal to target the cause of pruritus, such as decompression of the spine or resection of the tumor, these interventions are often incurable and rarely practical. Therefore, treatment is usually directed toward symptomatic therapy to improve quality of life [14,16,20].…”

Section: Treatment and Management Of Neuropathic Pruritusmentioning

confidence: 99%

“…Sevgi Akarsu Faculty of Medicine, Department of Dermatology, Dokuz Eylül University, Izmir, Turkey *Address all correspondence to: sevgi.akarsu@deu.edu.tr the itch-scratch cycle and improve quality of life [20,23]. Again, an exercise regimen consisting of physical rehabilitation and spinal range of motion exercises, mild mobilization, and muscle stretching has been found to be beneficial in patients with scalp dysesthesia [21].…”

Section: Author Detailsmentioning

confidence: 99%

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Neuropathic Pruritus: An Underrecognized and Often Misdiagnosed and Difficult to Treat Medical Condition

Akarsu¹

2023

Rare Diseases - Recent Advances

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It is estimated that approximately 8% of chronic pruritic cases are of neuropathic origin. Common neuropathic pruritic syndromes include different clinical presentations such as postherpetic pruritus, trigeminal trophic syndrome, anogenital pruritus, scalp dysesthesia, nerve compression syndromes (e.g., notalgia paresthetica, brachioradial pruritus), small-fiber neuropathy (secondary to various metabolic, infectious, autoimmune, and genetic diseases), and disorders affecting the central nervous system (occupying lesions, iatrogenic, infectious, neurodegenerative, or demyelinating diseases). Although general practitioners are most likely to see the itchy cases first and consider referring them to further medical advice, it would be a better approach for the physicians to cooperate with dermatologists and neurologists and physiotherapists in particular especially in chronic persistent itchy conditions. Neuropathic pruritus must first be differentiated from other possible etiologies of pruritus by medical history and physical examination, laboratory tests, skin biopsy, and radiological and functional evaluations. It often does not respond to classical antipruritic treatments and different treatment options such as neuroleptics, topical capsaicin, epidural steroid injections, botulinum injections, nerve blocks, and neurostimulation techniques have been tried with variable success responses. This chapter provides a comprehensive overview of the characteristics and clinical presentations of neuropathic pruritus and the diagnostic and therapeutic management used in such patients.

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Aetiology, pathogenesis and management of neuropathic itch: A narrative review with recent updates

Poddar¹,

Mondal

Podder

2023

IJDVL

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Neuropathic itch is a relatively common yet under-reported cause of systemic pruritus. It is a debilitating condition often associated with pain, which impairs the patient’s quality of life. Although much literature exists about renal and hepatic pruritus, there is a dearth of information and awareness about neuropathic itch. The pathogenesis of neuropathic itch is complex and can result from an insult at any point along the itch pathway, ranging from the peripheral receptors and nerves until the brain. There are several causes of neuropathic itch, many of which do not produce any skin lesions and are thus, often missed. A detailed history and clinical examination are necessary for the diagnosis, while laboratory and radiologic investigations may be needed in select cases. Several therapeutic strategies currently exist involving both non-pharmacological and pharmacological measures, the latter including topical, systemic, and invasive options. Further research is ongoing to clarify its pathogenesis and to design newer targeted therapies with minimal adverse effects. This narrative review highlights the current understanding of this condition, focusing on its causes, pathogenesis, diagnosis, and management, along with newer investigational drugs.

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The neuropathic itch: Don't scratch your head too hard!

Abstract: Postherpetic complications can sometimes result in significant debility. A multidisciplinary approach is crucial in deciding the appropriate treatment strategy in these patients.

Cited by 4 publications

References 12 publications

Pseudorabies virus hijacks DDX3X, initiating an addictive “mad itch” and immune suppression, to facilitate viral spread

Pseudorabies virus hijacks DDX3X, initiating an addictive “mad itch” and immune suppression, to facilitate viral spread

Neuropathic Pruritus: An Underrecognized and Often Misdiagnosed and Difficult to Treat Medical Condition

Aetiology, pathogenesis and management of neuropathic itch: A narrative review with recent updates

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