Browse by Audience
This special issue highlights emerging research spanning from epidemiology to diagnostic workup, pathogenesis, and therapeutics for patients suffering from chronic pruritus. The special issue contains 13 articles reporting relevant epidemiologic and experimental data on chronic pruritus.
Learn More >Itch is an unpleasant sensation that emanates primarily from the skin. The chemical mediators that drive neuronal activity originate from a complex interaction between keratinocytes, inflammatory cells, nerve endings and the skin microbiota, relaying itch signals to the brain. Stress also exacerbates itch via the skin-brain axis. Recently, the microbiota has surfaced as a major player to regulate this axis, notably during stress settings aroused by actual or perceived homeostatic challenge. The routes of communication between the microbiota and brain are slowly being unraveled and involve neurochemicals (i.e., acetylcholine, histamine, catecholamines, corticotropin) that originate from the microbiota itself. By focusing on itch biology and by referring to the more established field of pain research, this review examines the possible means by which the skin microbiota contributes to itch.
Learn More >Itch is an unpleasant sensation that can be debilitating, especially if it is chronic and of non-histaminergic origin, as treatment options are limited. Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor that also has the ability to induce a burning, non-histaminergic pruritus when exogenously administered, by activating the endothelin A receptor (ETR) on primary afferents. ET-1 is released endogenously by several cell-types found in the skin, including macrophages and keratinocytes. Mast cells express ETRs and can thereby be degranulated by ET-1, and mast cell proteases chymase and carboxypeptidase A3 (CPA3) are known to either generate or degrade ET-1, respectively, suggesting a role for mast cell proteases in the regulation of ET-1-induced itch. The mouse mast cell proteases (mMCPs) mMCP4 (chymase), mMCP6 (tryptase), and CPA3 are found in connective tissue type mast cells and are the closest functional homologs to human mast cell proteases, but little is known about their role in endothelin-induced itch.
Learn More >Most clinical trials assessing systemic immunomodulatory treatments for patients with atopic dermatitis are placebo-controlled.
Learn More >Omiganan is an indolicidin analogue with antimicrobial properties that could be beneficial for patients with atopic dermatitis. This randomized, double-blind, placebo-controlled phase II trial explored efficacy, pharmacodynamics and safety of topical omiganan once daily in 36 patients with mild to moderate AD. Patients were randomized to apply topical omiganan 1%, omiganan 2.5% or vehicle gel to one target lesion once daily for 28 consecutive days. Small but significant improvements of the local oSCORAD index and morning itch were observed in the omiganan 2.5% group compared to the vehicle gel group (-18.5%; 95%CI=-32.9,-1.0; p=0.04 and -8.2; 95%CI=-16.3,-0.2; p=0.05 respectively). A shift from lesional to non-lesional skin microbiota was observed in both omiganan treatment groups, in contrast to the vehicle group. In conclusion, treatment with topical omiganan improved dysbiosis in patients with mild to moderate atopic dermatitis and small but statistically significant improvement of clinical scores were detected. Our findings warrant further exploration in future clinical trials.
Learn More >Research suggests that itch and psychiatric diseases are intimately related. In efforts to examine the prevalence of psychiatric diagnoses in patients with chronic itch not due to psychogenic causes, we conducted a retrospective chart review of 502 adult patients diagnosed with chronic itch in an outpatient dermatology clinic specializing in itch and assessed these patients for a co-existing psychiatric disease. Psychiatric disease was identified and recorded based on ICD-10 codes made at any point in time which were recorded in the patient's electronic medical chart, which includes all medical department visits at the University of Miami. Fifty-five out of 502 (10.9%) of patients were found to have a comorbid psychiatric diagnosis based on ICD-10 codes. The most common psychiatric diagnoses were anxiety disorders (45.5%), followed by major depressive disorder (36.4%). There was no significant association of any specific type of itch to a particular psychiatric disorder. No unique itch characteristics were noted in patients with underlying psychiatric diagnoses.
Learn More >Atopic dermatitis (AD) is a common and relapsing skin disease that is characterized by skin barrier dysfunction, inflammation, and chronic pruritus. While AD was previously thought to occur primarily in children, increasing evidence suggests that AD is more common in adults than previously assumed. Accumulating evidence from experimental, genetic, and clinical studies indicates that AD expression is a precondition for the later development of other atopic diseases, such as asthma, food allergies, and allergic rhinitis. Although the exact mechanisms of the disease pathogenesis remain unclear, it is evident that both cutaneous barrier dysfunction and immune dysregulation are critical etiologies of AD pathology. This review explores recent findings on AD and the possible underlying mechanisms involved in its pathogenesis, which is characterized by dysregulation of immunological and skin barrier integrity and function, supporting the idea that AD is a systemic disease. These findings provide further insights for therapeutic developments aiming to repair the skin barrier and decrease inflammation.
Learn More >Dry skin itch is one of the most common skin diseases and elderly people are believed to be particularly prone to it. The inflammasome has been suggested to play an important role in chronic inflammatory disorders including inflammatory skin diseases such as psoriasis. However, little is known about the role of NLRP1 inflammasome in dry skin-induced chronic itch.
Learn More >Understanding of cortical encoding of itch is limited. Injection of pruritogens and algogens into the skin of the cheek produces distinct behaviors, making the rodent cheek a useful model for understanding mechanisms of itch and pain. We examined responses of neurons in the primary somatosensory cortex by applying of mechanical stimuli (brush, pressure, and pinch) and stimulations by intradermal injections of pruritic and algesic chemical of receptive fields located on the skin of the cheek in urethane-anesthetized rats. Stimuli included chloroquine, serotonin, beta-alanine, histamine, capsaicin, and mustard oil. All 33 neurons studied were excited by noxious mechanical stimuli applied to the cheek. Based on mechanical stimulation most neurons were functionally classified as high threshold. Of 31 neurons tested for response to chemical stimuli, 84% were activated by one or more pruritogens/partial pruritogens. No cells were activated by all five substances. Histamine activated the greatest percentage of neurons and evoked the greatest mean discharge. Importantly, no cells were excited exclusively by pruritogens or partial pruritogens. The recording sites of all neurons that responded to chemical stimuli applied to the cheek were located in the dysgranular zone (DZ) and in deep laminae of the medial border of the vibrissal barrel fields (VBF). Therefore, neurons in the DZ/VBF of rats encode mechanical and chemical pruritogens and algogens. This cortical region appears to contain primarily nociceptive neurons as defined by responses to noxious pinching of the skin. Its role in encoding itch and pain from the cheek of the face needs further study.
Learn More >Self-report measures are needed to better understand the relationships among sleep, itching, scratching, and chronic itch conditions and their associations with disease severity, quality of life, health, and functioning. Two scales related to sleep and/or scratch were recently developed and assessed in 137 patients with chronic itch and atopic dermatitis or psoriasis. The Scratch Intensity and Impact Scale consisted of two factors (Scratching Intensity and Impact of Scratching on Quality of Life) that accounted for 64.59% of the variance with a total of 13 items, an overall Cronbach's alphas of 0.93, and test-retest reliability of 0.66. The Sleep-Related Itch and Scratch Scale consisted of one factor that accounted for 63.01% of the variance with a total of 16 items, an overall Cronbach's alphas of 0.98, and test-retest reliability of 0.66. Both measures demonstrated significant correlations with each other as well as other itch-related measures and non-significant correlations with scales hypothesized to be unrelated. The final measures demonstrated adequate preliminary psychometric characteristics. It is hoped that these scales will be used for future research and clinical purposes to help fill recognized gaps in understanding about sleep, itch, scratching, atopic dermatitis, and psoriasis.
Learn More >