What causes itch in atopic dermatitis?
ABSTRACT Itch, the hallmark of atopic dermatitis, has a significant impact on quality of life for patients with this disease. Various central and peripheral mediators have been suggested to play a role in the pathophysiology of atopic eczema itch. Significant cross-talk occurs among stratum corneum, keratinocytes, immune cells, and nerve fibers, which are in close proximity to one another and induce itch. The impaired barrier function associated with the itch-scratch cycle further augments this vicious cycle. Recent advances in our understanding of itch pathophysiology shed light on peripheral and central neural sensitization of nerve fibers that contribute significantly to itch in atopic dermatitis. Recently, several new mediators have been described as associated with itch in atopic dermatitis, including serine proteases, interleukin 31, and nerve growth factor. This review covers the peripheral and central mechanisms and mediators involved in pathogenesis of itch in atopic dermatitis.
- SourceAvailable from: Rodrigo Valdes Rodriguez[Show abstract] [Hide abstract]
ABSTRACT: Chronic itch in the elderly is a common problem, with a significant impact on quality of life and sleep in elderly patients. Chronic itch may be attributable to several causes, including dry skin, immunosenescence and neural degeneration. Itch may also be caused by skin diseases, such as seborrhoeic dermatitis and stasis dermatitis; systemic conditions, such as end-stage renal disease and diabetes; and psychogenic conditions, such as depression and anxiety. The use of polypharmacy may also cause itch, with or without a rash. Specifically, thiazides and calcium channel blockers have been known to cause itch in elderly patients. Management should be tailored according to the underlying dermatological or systemic aetiology of itch. Topical treatment is the mainstay of therapy, providing special emphasis on skin hydration and barrier repair. In addition, topical and oral medications that target the nervous system and reduce neuronal hypersensitization, such as gabapentin and selective antidepressants, have a role in treating patients with severe chronic itch. Furthermore, management must account for changes in metabolism and pharmacokinetics of drugs in the aging population in order to prevent the occurrence of adverse effects.Drugs & Aging 02/2015; 32(3). DOI:10.1007/s40266-015-0246-0 · 2.50 Impact Factor
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ABSTRACT: For centuries, itch was categorized as a submodality of pain. Recent research over the last decade has led to the realization that itch is in fact a separate and distinct, albeit closely related, sensation. Chronic itch is a common complaint and has numerous etiologies. Various receptors (TRPA1, TRPV1, PAR2, gastrin-releasing peptide receptor (GRPR), Mas-related G proteins), secreted molecules (histamine, nerve growth factor (NGF), substance P (SP), proteases), and cytokines/chemokines (thymic stromal lymphopoietin (TSLP), IL-2, IL-4, IL-13, and IL-31) are implicated as mediators of chronic pruritus. While much remains unknown regarding the mechanisms of chronic itch, this much is certain: there is no singular cause of itch. Rather, itch is caused by a complex interface between skin, keratinocytes, cutaneous nerve fibers, pruritogenic molecules, and the peripheral and central nervous systems. Atopic dermatitis is one of the most itchy skin dermatoses and affects millions worldwide. The sensation of atopic itch is mediated by the interplay between epidermal barrier dysfunction, upregulated immune cascades, and the activation of structures in the central nervous system. Clinicians are in possession of an arsenal of different treatment options ranging from moisturizers, topical immunomodulators, topical anesthetic ion channel inhibitors, systemic immunomodulators, as well as oral drugs capable of reducing neural hypersensitization. Emerging targeted therapies on the horizon, such as dupilumab, promise to usher in a new era of highly specific and efficacious treatments. Alternative medicine, stress reduction techniques, and patient education are also important treatment modalities. This review will focus on the mediators of chronic pruritus mainly associated with atopic dermatitis (atopic itch), as well as numerous different therapeutic options.Clinical Reviews in Allergy & Immunology 05/2015; DOI:10.1007/s12016-015-8488-5 · 4.73 Impact Factor
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ABSTRACT: Central serotonin (5-hydroxytryptophan, 5-HT) modulates somatosensory transduction, but how it achieves sensory modality-specific modulation remains unclear. Here we report that enhancing serotonergic tone via administration of 5-HT potentiates itch sensation, whereas mice lacking 5-HT or serotonergic neurons in the brainstem exhibit markedly reduced scratching behavior. Through pharmacological and behavioral screening, we identified 5-HT1A as a key receptor in facilitating gastrin-releasing peptide (GRP)-dependent scratching behavior. Coactivation of 5-HT1A and GRP receptors (GRPR) greatly potentiates subthreshold, GRP-induced Ca2+ transients, and action potential firing of GRPR+ neurons. Immunostaining, biochemical, and biophysical studies suggest that 5-HT1A and GRPR may function as receptor heteromeric complexes. Furthermore, 5-HT1A blockade significantly attenuates, whereas its activation contributes to, long-lasting itch transmission. Thus, our studies demonstrate that the descending 5-HT system facilitates GRP-GRPR signaling via 5-HT1A to augment itch-specific outputs, and a disruption of crosstalk between 5-HT1A and GRPR may be a useful antipruritic strategy.Neuron 11/2014; 84(4):821-834. DOI:10.1016/j.neuron.2014.10.003 · 15.98 Impact Factor