Scabies itch: an update on neuroimmune interactions and novel targets

Frequently described as 'the worst itch' one can ever experience scabies itch is the hallmark of Sarcoptes scabiei mite infestation. Notably, the itchiness often persists for weeks despite scabicides therapy. The mechanism of scabies itch is not yet fully understood, and effective treatment modalities are still missing which can severely affect the quality of life. The aim of this review is to provide an overview of the scope of itch in scabies and highlight candidate mechanisms underlying this itch. We herein discuss scabies itch, with a focus on the nature, candidate underlying mechanisms and treatment options. We also synthesize this information with current understanding of the mechanisms contributing to non-histaminergic itch in other conditions. Itch is a major problem in scabies and can lead to grave consequences. We provide the latest insights on host-mite interaction, secondary microbial infection and neural sensitization with special emphasis on keratinocytes and mast cells to better understand the mechanism of itch in scabies. Also, the most relevant current modalities remaining under investigation that possess promising perspectives for scabies itch (i.e. protease-activated receptor-2 (PAR-2) inhibitor, Mas-related G protein-coupled receptor X2 (MRGPRX2) antagonist) are discussed. Greater understanding of these diverse mechanisms may provide a rational basis for the development of improved and targeted approaches to control itch in individuals with scabies.