INTRODUCTION
Psoriasis is a polygenic, interleukin (IL)-17 and IL-23 driven chronic relapsing inflammatory multisystem disease caused by a complex interplay of endogeneous and environmental factors resulting in accelerated epidermal proliferation.1 According to the World Health Organization (WHO), psoriasis is considered a serious global problem with at least 100 million individuals affected worldwide.2 Itch is not only the most common cutaneous symptom in psoriasis affecting approximately 80% of patients3,4 but also the most bothersome, adding significantly to the burden of disease. In most psoriasis patients, itch is associated with lesional skin, however, at times, it may be generalized.3,5 Itch in non-lesional skin might indicate a subclinical inflammation, wherein normally innocuous stimuli elicit itch.6,7 Hence, itching is important to address, not only to provide symptomatic relief, but also to prevent development of new lesions due to scratching-induced koebnerization.8 Factors aggravating psoriatic itch are emotional stress, dry skin, sweating, and change of ambient temperatures. Itch frequently affects sleep quality, daytime performance, and quality of life, thus contributing to stress and aggravation of psoriasis.9
Pathogenesis of Itch in Psoriasis
The pathogenesis of itch in psoriasis is abundantly complex, multifaceted, and not yet fully elucidated. Various neuropeptides are released from keratinocytes, dermal cells, and dermal nerve endings resulting in neurogenic inflammation.10 These include substance P (SP), calcitonin gene-related peptide (CGRP), β-endorphin, vasoactive intestinal peptide (VIP), somatostatin, and neuropeptide Y.11 Downstream effects are hyperproliferation of keratinocytes, degranulation of dermal mast cells, and stimulation of angiogenesis. Downstream effects are hyperproliferation of keratinocytes, degranulation of dermal mast cells, and stimulation of angiogenesis.8,11,12 It has also been hypothesized that itch in psoriasis arises due to abnormal skin innervation ("nerve sprouting"). Earlier studies have demonstrated elevated expression of nerve growth factor (NGF) and reduced expression of semaphorin-3A in lesional skin. This may act as a trigger for increased innervation of lesional skin by pruriceptive C fibers, resulting in itch.13 The endogenous opioid system has also been postulated to be involved in the itch pathway in psoriasis.14 Lesional skin was found to have more μ-opioid and less κ-opioid receptors, a
Pathogenesis of Itch in Psoriasis
The pathogenesis of itch in psoriasis is abundantly complex, multifaceted, and not yet fully elucidated. Various neuropeptides are released from keratinocytes, dermal cells, and dermal nerve endings resulting in neurogenic inflammation.10 These include substance P (SP), calcitonin gene-related peptide (CGRP), β-endorphin, vasoactive intestinal peptide (VIP), somatostatin, and neuropeptide Y.11 Downstream effects are hyperproliferation of keratinocytes, degranulation of dermal mast cells, and stimulation of angiogenesis. Downstream effects are hyperproliferation of keratinocytes, degranulation of dermal mast cells, and stimulation of angiogenesis.8,11,12 It has also been hypothesized that itch in psoriasis arises due to abnormal skin innervation ("nerve sprouting"). Earlier studies have demonstrated elevated expression of nerve growth factor (NGF) and reduced expression of semaphorin-3A in lesional skin. This may act as a trigger for increased innervation of lesional skin by pruriceptive C fibers, resulting in itch.13 The endogenous opioid system has also been postulated to be involved in the itch pathway in psoriasis.14 Lesional skin was found to have more μ-opioid and less κ-opioid receptors, a
