Psychological stress and ensuing modulation of the immune and nervous systems can have a significant impact on itch. Stress can exacerbate itch and vice versa, resulting in a vicious cycle that can greatly impair a patient's quality of life. This review summarizes the association between stress and itch, elucidates the mechanism by which these two phenomena influence one another, and explores treatment modalities that aim to reduce stress-induced itch. Methods: A complete search of the PubMed and Google Scholar databases was completed and literature pertinent to this review was compiled. Findings: Both acute and chronic stress can significantly affect itch in healthy individuals and in those diagnosed with itchy skin diseases as well as systemic diseases, thus resulting in a vicious cycle in which stress exacerbates itch and vice versa. The mechanisms by which stress induces or aggravates itch include both central and peripheral activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system. Activation of these systems, in turn, affects the mast cells, keratinocytes, and nerves that secrete neuropeptides, such as substance P, nerve growth factor, acetylcholine, histamine, and itchy cytokines. A dysfunctional parasympathetic response is thought to be involved in the chronic stress/itch response. Brain structures associated with emotion, such as the limbic system and periaqueductal gray, which work on the descending facilitation of itch, play a significant role in stress-induced itch. Implications: As specific brain structures are associated with stress, drug treatments targeting these areas (ie, g-aminobutyric acideergic drugs, serotonin and norepinephrine reuptake inhibitors) may help to modulate itch. Stress can also be combatted using nonpharmacologic treatments such as cognitiveebehavioral therapies and stress-relieving holistic approaches (eg, yoga, acupuncture).

Chronic itch is a common condition that affects the quality of life of many patients and can often be difficult to treat. When managing a patient with itch, the first step requires identification of the underlying cause, which may be dermatologic or nondermatologic in nature. The process begins with a thorough history and physical examination, which may or may not be followed by laboratory tests and imaging. The appropriate treatment for each patient should be considered based on the diagnosis, severity of itch, and individual patient preference. Treatment options range from topical treatments, which may be indicated for more mild types of itch, to systemic treatments, which may be indicated for itch that is more ubiquitous and debilitating in nature. Within the last decade, developments in our understanding of itch pathophysiology has led to new treatment options on the horizon that consist of more targeted medications, including monoclonal antibodies and opioid modulators.

Although psoriasis and psoriatic arthritis (PsA) have been classically considered to be diseases of the skin and joints, respectively, emerging evidence suggests that a combination of innate and environmental factors creates widespread immune dysfunction, affecting multiple organ systems. A greater understanding of the pathogenesis of psoriasis and the systemic effects of psoriatic inflammation has allowed for the development of new, more effective treatments. The second portion of this two-part review series examines the comorbidities associated with psoriasis and PsA as well as the most recent advances in targeted systemic therapies for these conditions.

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Atopic dermatitis (AD) is a chronic inflammatory condition that affects 5–10% of adults and 9–18% of children and its pathology is rooted in the Th-2-mediated immune response. Dupilumab is a fully human IgG4 monoclonal antibody that targets the IL-4 receptor alpha subunit that is endogenously bound by the Th-2 cytokines IL-4 and IL-13. Successful clinical trials of dupilumab showing marked improvements in clinical signs of AD, patient reported symptoms and quality of life measures led to its approval for clinical use for moderate-to-severe AD in 2017. This review details the current body of evidence on the drug’s mechanism of action, pharmacology, clinical efficacy and safety as well as post market and real world use.

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There is a need for new topical antipruritics that are effective on many types of itch. This study examined the antipruritic efficacy of a new formulation of topical acetaminophen. In vitro skin permeability studies showed that 2.5% and 5% formulations are able to rapidly deliver an adequate amount of the drug into the skin. In a double-blind, vehicle-controlled, randomized study in 17 healthy volunteers, 1%, 2.5% and 5% acetaminophen gels and a vehicle gel were applied to the skin prior to histaminergic and non-histaminergic itch induction and assessment of thermal pain thresholds. The 2.5% and 5% gel formulations significantly reduced the itch intensity time course and the area under the curve for both histamine and cowhage itch. No effect was noted on heat pain thresholds and no adverse effects were observed. These results suggest that topical acetaminophen would be a safe and effective over-the-counter medication for itch.

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