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Pathogenesis and Treatment of Chronic Pruritus
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Pathogenesis and Treatment of Chronic Pruritus

A special issue of Medicines (ISSN 2305-6320).

Deadline for manuscript submissions: closed (31 January 2020) | Viewed by 80894

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Shawn G. Kwatra

E-Mail Website
Guest Editor
Johns Hopkins University School of Medicine, Department of Dermatology, Baltimore, MD 21287, USA
Interests: chronic pruritus; prurigo nodularis; atopic dermatitis; dermatology for ethnic skin

Special Issue Information

Dear Colleagues,

Chronic pruritus, defined as an itch persisting for more than six weeks, dramatically reduces quality of life. Chronic itch is associated with a variety of dermatologic, systemic, neurological, and psychological underlying etiologies. This Special Issue will compile original research and review articles on the pathogenesis and treatment of chronic pruritus. Manuscripts should deal with but are not limited to the list of keywords below:

  • Chronic pruritus
  • Itch 
  • Refractory pruritus
  • Prurigo nodularis
  • Atopic dermatitis 
  • Idiopathic chronic pruritus

Dr. Shawn G. Kwatra
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Medicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • chronic pruritus
  • itch 
  • refractory pruritus
  • prurigo nodularis
  • atopic dermatitis 
  • idiopathic chronic pruritus

Published Papers (14 papers)

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Editorial

Jump to: Research, Review, Other

5 pages, 234 KiB  
Editorial
Emerging Research in Chronic Pruritus: From Bedside to Bench and Back Again
by Kyle A. Williams and Shawn G. Kwatra
Medicines 2020, 7(5), 24; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines7050024 - 29 Apr 2020
Cited by 2 | Viewed by 3100
Abstract
This Medicines 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. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Chronic Pruritus)

Research

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9 pages, 899 KiB  
Article
Association between Prurigo Nodularis and Etiologies of Peripheral Neuropathy: Suggesting a Role for Neural Dysregulation in Pathogenesis
by John-Douglas Matthew Hughes, Taylor E. Woo, Micah Belzberg, Raveena Khanna, Kyle A. Williams, Madan M. Kwatra, Shahzeb Hassan and Shawn G. Kwatra
Medicines 2020, 7(1), 4; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines7010004 - 08 Jan 2020
Cited by 14 | Viewed by 3985
Abstract
Background: Prurigo nodularis (PN) is an intensely pruritic skin condition of considerable morbidity. However, the pathogenesis of PN and its association with underlying neuropathy is unclear. Objective: We sought to investigate the association between PN and etiologies of peripheral neuropathy. Methods [...] Read more.
Background: Prurigo nodularis (PN) is an intensely pruritic skin condition of considerable morbidity. However, the pathogenesis of PN and its association with underlying neuropathy is unclear. Objective: We sought to investigate the association between PN and etiologies of peripheral neuropathy. Methods: A cross-sectional analysis of adult patients (≥18-year-old) with PN, AD, and Psoriasis at the Johns Hopkins Health System over a six-year period (January 2013–January 2019) was performed. The strength of association with etiologies of peripheral neuropathy were compared to a control cohort of individuals without PN, as well as those with AD or psoriasis. Results: A total of 1122 patients with PN were compared to 10,390 AD patients, 15,056 patients with psoriasis, and a control cohort of 4,949,017 individuals without PN, with respect to 25 comorbidities associated with peripheral neuropathies. Limitations: Comparisons between peripheral neuropathies and PN represent associations but are not causal relationships. Conclusion: Prurigo nodularis is strongly associated with peripheral neuropathies, suggesting a role for neural dysregulation in pathogenesis. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Chronic Pruritus)
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12 pages, 901 KiB  
Article
Comorbidities in Mycosis Fungoides and Racial Differences in Co-Existent Lymphomatoid Papulosis: A Cross-Sectional Study of 580 Patients in an Urban Tertiary Care Center
by Subuhi Kaul, Micah Belzberg, John-Douglas Matthew Hughes, Varun Mahadevan, Raveena Khanna, Pegah R. Bakhshi, Michael S. Hong, Kyle A. Williams, Annie L. Grossberg, Shawn G. Kwatra and Ronald J. Sweren
Medicines 2020, 7(1), 1; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines7010001 - 26 Dec 2019
Cited by 8 | Viewed by 3175
Abstract
Background: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma. Previous reports have suggested MF is associated with inflammatory conditions such as psoriasis, increased cardiovascular risk factors as well as secondary neoplasms. Methods: A cross-sectional study of MF patients seen from 2013 to 2019 [...] Read more.
Background: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma. Previous reports have suggested MF is associated with inflammatory conditions such as psoriasis, increased cardiovascular risk factors as well as secondary neoplasms. Methods: A cross-sectional study of MF patients seen from 2013 to 2019 was performed. Comorbidities were selected based on the 2015 Medicare report highlighting the most common chronic medical illnesses in the United States. Lifetime comorbidity occurrence in patients with MF were compared with that in patients with atopic dermatitis, psoriasis and patients without MF. Additional analyses were performed with patients sub-stratified by race. Results: Compared to control groups, MF was strongly associated with lymphomatoid papulosis and Hodgkin’s disease, but not significantly associated with lung, breast or colon cancer. Interestingly, the association with lymphomatoid papulosis was observed in Caucasians (CI 1062-4338; p < 0.001) and not African Americans (p = 0.9). Patients with MF had a greater association with congestive heart failure, hypertension (HT) and hyperlipidemia (HLD) compared with the general population. However, they were significantly less likely to have HT and HLD when compared with psoriasis patients (HT CI: 0.6–0.9; p < 0.001, and HLD CI: 0.05–0.07; p < 0.001). MF patients were also significantly less likely to have concomitant vitamin D deficiency compared with atopic dermatitis (AD) and psoriasis (p < 0.001). Conclusions: Our results suggest that the association of MF with lymphomatoid papulosis varies by race. Compared to the general population, hypertension and hyperlipidemia were positively associated with MF, however, these were significantly less likely on comparison to psoriasis. Unlike previously described, vitamin D deficiency was found to be significantly less in patients with MF. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Chronic Pruritus)
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8 pages, 1239 KiB  
Article
Proteomic and Phosphoproteomic Analysis Reveals that Neurokinin-1 Receptor (NK1R) Blockade with Aprepitant in Human Keratinocytes Activates a Distinct Subdomain of EGFR Signaling: Implications for the Anti-Pruritic Activity of NK1R Antagonists
by Shawn G. Kwatra, Emily Boozalis, Amy H. Huang, Cory Nanni, Raveena Khanna, Kyle A. Williams, Yevgeniy R. Semenov, Callie M. Roberts, Robert F. Burns, Madison Krischak and Madan M. Kwatra
Medicines 2019, 6(4), 114; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines6040114 - 09 Dec 2019
Cited by 2 | Viewed by 3250
Abstract
Background: Epidermal growth factor receptor (EGFR) inhibitors can cause serious cutaneous toxicities, including pruritus and papulopustular acneiform skin eruptions. Increasingly, the neurokinin-1 receptor (NK1R) antagonist aprepitant is being utilized as an anti-pruritic agent in the treatment of EGFR-inhibitor induced pruritus. Aprepitant is [...] Read more.
Background: Epidermal growth factor receptor (EGFR) inhibitors can cause serious cutaneous toxicities, including pruritus and papulopustular acneiform skin eruptions. Increasingly, the neurokinin-1 receptor (NK1R) antagonist aprepitant is being utilized as an anti-pruritic agent in the treatment of EGFR-inhibitor induced pruritus. Aprepitant is believed to reduce itching by blocking NK1R on the surface of dermal mast cells. However, the effects of aprepitant on human keratinocytes remains unexplored. Methods: Herein, we examine the effects of aprepitant on EGFR stimulation in HaCaT cells using a phosphoproteomic approach including reverse phase protein arrays and Ingenuity Pathway Analysis. Changes in EGFR phosphorylation were visualized using Western blotting and the effect of EGF and aprepitant on the growth of HaCaT cells was determined using the WST-1 Cell Proliferation Assay System. Results: We found that aprepitant increased the phosphorylation of EGFR, as well as 10 of the 23 intracellular proteins phosphorylated by EGF. Analysis of phosphoproteomic data using Ingenuity Pathway Analysis software revealed that 5 of the top 10 pathways activated by EGF and aprepitant are shared. Conclusions: We propose that aprepitant produces its antipruritic effects by partially activating EGFR. Activation of EGFR by aprepitant was also seen in primary human keratinocytes. In addition to itch reduction through partial activation of shared EGFR pathways, aprepitant exerts a dose-dependent cytotoxicity to epithelial cells, which may contribute to its antitumor effects. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Chronic Pruritus)
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8 pages, 257 KiB  
Article
Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus
by Akishi Momose, Micihihiro Yabe, Shigetoshi Chiba, Kenjirou Kumakawa, Yasuo Shiraiwa and Hiroki Mizukami
Medicines 2019, 6(4), 110; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines6040110 - 13 Nov 2019
Cited by 6 | Viewed by 4535
Abstract
Background: We investigated ion channels at the skin, including peripheral nerve endings, which serve as output machines and molecular integrators of many pruritic inputs mainly received by multiple G protein-coupled receptors (GPCRs). Methods: Based on the level of chronic kidney disease–associated pruritus (CKD-aP), [...] Read more.
Background: We investigated ion channels at the skin, including peripheral nerve endings, which serve as output machines and molecular integrators of many pruritic inputs mainly received by multiple G protein-coupled receptors (GPCRs). Methods: Based on the level of chronic kidney disease–associated pruritus (CKD-aP), subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 12) and CKD-aP (mild, moderate, or severe pruritus; n = 11). Skin samples were obtained from the forearm or elbow during operations on arteriovenous fistulas. We measured ion channels expressed at the skin, including peripheral nerve endings by RT-PCR: Nav1.8, Kv1.4, Cav2.2, Cav3.2, BKCa, Anoctamin1, TRPV1, TRPA1, and ASIC. Results: Expression of Cav3.2, BKCa, and anoctamin1 was significantly elevated in patients with CKD-aP. On the other hand, expression of TRPV1 was significantly reduced in these patients. We observed no significant difference in the levels of Cav2.2 or ASIC between subjects with and without CKD-aP. TRPA1, Nav1.8, and Kv1.4 were not expressed. Conclusions: It was concluded that this greater difference in the expression of ion channels in the skin tissue including, specially cutaneous peripheral nerve endings in CKD patients with CKD-aP may increase generator potential related to itching. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Chronic Pruritus)
9 pages, 1919 KiB  
Article
Association between Itch and Cancer in 3836 Pediatric Pruritus Patients at a Tertiary Care Center
by Micah Belzberg, Valerie A. Larson, Raveena Khanna, Kyle A. Williams, Yevgeniy Semenov, Sonja Ständer, Anna L. Grossberg and Shawn G. Kwatra
Medicines 2019, 6(4), 99; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines6040099 - 05 Oct 2019
Cited by 6 | Viewed by 3057
Abstract
Background: Pruritus is a well-recognized paraneoplastic phenomenon. Previous studies have examined the association of itch with a variety of malignancies in adults. However, no large study has examined this association in a pediatric population. Methods: A retrospective study was conducted of [...] Read more.
Background: Pruritus is a well-recognized paraneoplastic phenomenon. Previous studies have examined the association of itch with a variety of malignancies in adults. However, no large study has examined this association in a pediatric population. Methods: A retrospective study was conducted of patients age 18 or less seen at Johns Hopkins Health System between 2012 and 2019. Results: A pediatric hospital population of 1,042,976 patients was reviewed. Pruritus was observed in 3836 pediatric patients of whom 130 also had cancer. Pediatric patients with pruritus were significantly more likely to have concomitant malignancy compared to pediatric patients without pruritus (OR 12.84; 95% CI 10.73–15.35, p < 0.001). Malignancies most strongly associated with pruritus included neoplasms of the blood (OR 14.38; 95% CI 11.30–18.29, p < 0.001), bone (OR 29.02, 95% CI 18.28–46.06, p < 0.001) and skin (OR 22.76, 95% CI 9.14–56.72, p < 0.001. Conclusions: Pruritus is significantly associated with malignancy in the pediatric hospital population. Clinicians should also be aware of the high burden of itch in pediatric malignancies and the variation in pruritus across malignancies. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Chronic Pruritus)
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7 pages, 1188 KiB  
Article
Racial and Gender Differences in the Presentation of Pruritus
by Katherine A. Whang, Raveena Khanna, Jamael Thomas, Crystal Aguh and Shawn G. Kwatra
Medicines 2019, 6(4), 98; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines6040098 - 27 Sep 2019
Cited by 28 | Viewed by 3462
Abstract
Background: Pruritus is a common disease symptom with a variety of etiologies known to reduce patient quality of life. We aimed to characterize the racial and gender differences in the presentation of pruritus for itch-related patient visits both within a single institution and [...] Read more.
Background: Pruritus is a common disease symptom with a variety of etiologies known to reduce patient quality of life. We aimed to characterize the racial and gender differences in the presentation of pruritus for itch-related patient visits both within a single institution and nationally. Methods: Cross sectional study of patients ≥ 18 years old seen at Johns Hopkins Health System between 1/1/12 and 1/1/18. Results were compared to data from 2005–2011 from the National Ambulatory Medical Care Survey (NAMCS) and the National Health Ambulatory Medical Care Survey (NHAMCS). Results: Our findings indicate that itch patients at JHHS (n = 18,753) were more likely to be black compared to white patients (37% vs. 19%, p < 0.01) when compared to patients without itch—a trend also noted nationally based on data from NAMCS/NHAMCS (26% vs. 21%, p = 0.05). Black itch patients are also more likely to be diagnosed with prurigo nodularis (OR 2.37, p < 0.0001), lichen planus (OR 1.22, p < 0.0001), and atopic dermatitis OR 1.51, p < 0.0001). Female itch patients are more likely to be diagnosed with autoimmune (OR 1.66, p < 0.0001) and psychiatric comorbidities (OR 1.2–1.8, p < 0.0001) than male itch patients. When compared to black itch patients nationally, white itch patients were more likely to visit a dermatologist (29% vs. 18%, p = 0.028). Our data can identify associated conditions and demographic differences but are unable to support a causal relationship. Conclusions: Black and female patients are more likely to present with pruritus, a symptom associated with comorbidities such as prurigo nodularis, lichen planus, atopic dermatitis, and psychiatric conditions. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Chronic Pruritus)
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10 pages, 4011 KiB  
Communication
Diagnostic Workup and Evaluation of Patients with Prurigo Nodularis
by Christina D. Kwon, Raveena Khanna, Kyle A. Williams, Madan M. Kwatra and Shawn G. Kwatra
Medicines 2019, 6(4), 97; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines6040097 - 26 Sep 2019
Cited by 32 | Viewed by 18972
Abstract
Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized oftentimes by symmetrically distributed, severely pruritic nodules. Currently, the pathophysiology of PN remains to be fully elucidated, but emerging evidence suggests that neuroimmune alterations play principal roles in the pathogenesis of PN. There [...] Read more.
Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized oftentimes by symmetrically distributed, severely pruritic nodules. Currently, the pathophysiology of PN remains to be fully elucidated, but emerging evidence suggests that neuroimmune alterations play principal roles in the pathogenesis of PN. There are several associated etiologic factors thought to be associated with PN, including dermatoses, systemic, infectious, psychiatric, and neurologic conditions. We conducted a systematic literature review to evaluate the clinical presentation, diagnosis, and etiologic factors of PN. In this review, we discuss common differential diagnoses of PN and recommend an evidence-based, standardized diagnostic evaluation for those with suspected PN. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Chronic Pruritus)
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10 pages, 832 KiB  
Article
Inpatient Burden of Prurigo Nodularis in the United States
by Katherine A. Whang, Sewon Kang and Shawn G. Kwatra
Medicines 2019, 6(3), 88; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines6030088 - 11 Aug 2019
Cited by 34 | Viewed by 6007
Abstract
Background: Although prurigo nodularis (PN) has a significant burden of disease, little is known about its epidemiology and disease burden within the United States. We describe the characteristics of hospitalized patients diagnosed with PN and assess the factors associated with hospitalization. Methods: We [...] Read more.
Background: Although prurigo nodularis (PN) has a significant burden of disease, little is known about its epidemiology and disease burden within the United States. We describe the characteristics of hospitalized patients diagnosed with PN and assess the factors associated with hospitalization. Methods: We performed a cross-sectional study of the 2016 National Inpatient Sample, a representative sample of 20% of hospital discharges nationally. Results: Patients diagnosed with PN accounted for 3.7 inpatient visits per 100,000 discharges nationally in 2016. Patients with PN were more likely to be black (odds ratio (OR) 4.43, 95% CI (3.33–6.08), p < 0.001) or Asian (OR 3.44, 95% CI (1.39–5.08), p = 0.003) compared with white patients. Patients diagnosed with PN had both a longer length of hospital stay (mean ± SD, 6.51 ± 0.37 days vs. 4.62 ± 0.02 days, p < 0.001) and higher cost of care ($14,772 ± $964 vs. $11,728 ± $106, p < 0.001) compared with patients without PN. Patients with PN were significantly more likely to be admitted for HIV complications (OR 78.2, 95% CI (46.4–131.8), p < 0.001). PN contributes to increased inpatient cost of care and length of hospitalization. Conclusions: There are racial disparities associated with hospital admission of patients diagnosed with PN. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Chronic Pruritus)
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7 pages, 558 KiB  
Article
Pruritus Associated with Commonly Prescribed Medications in a Tertiary Care Center
by Amy H. Huang, Benjamin H. Kaffenberger, Adam Reich, Jacek C. Szepietowski, Sonja Ständer and Shawn G. Kwatra
Medicines 2019, 6(3), 84; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines6030084 - 04 Aug 2019
Cited by 11 | Viewed by 6141
Abstract
Background: Sparse data are available on rates of drug-induced pruritus, a well-recognized adverse reaction. We sought to assess relative rates of pruritus associated with commonly prescribed medications. Methods: Using the electronic medical record system EPIC, retrospective data were collected on patients seen at [...] Read more.
Background: Sparse data are available on rates of drug-induced pruritus, a well-recognized adverse reaction. We sought to assess relative rates of pruritus associated with commonly prescribed medications. Methods: Using the electronic medical record system EPIC, retrospective data were collected on patients seen at Johns Hopkins who received a medication of interest in a five-year period (2013–2018). Sequential criteria were used to identify the subpopulation who presented with a chief complaint of “pruritus” or diagnosis of “itching” within three months of receiving drugs. Results: We identified 9802 patients with pruritus after drug initiation and 1,085,404 patients without. A higher proportion of those with pruritus were female (70%) than those without (58%), p < 0.001. Patients in both groups were most commonly 50 to 79 years old. A higher proportion of patients with pruritus were black (40%) compared to those without (23%), p < 0.001. In this study, the highest rates of pruritus were observed with heparin (1.11%), trimethoprim-sulfamethoxazole (1.06%), and calcium channel blockers (0.92%). Psychiatric/neurologic drugs used to treat pruritus were associated with low rates of itch. Conclusions: Certain cardiovascular and antimicrobial agents are associated with increased frequencies of pruritus. This knowledge may guide providers in clinical selection of commonly used agents to minimize adverse effects associated with reduced compliance. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Chronic Pruritus)
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15 pages, 799 KiB  
Article
Chronic Pruritus Responding to Dupilumab—A Case Series
by Lisa L. Zhai, Kevin T. Savage, Connie C. Qiu, Annie Jin, Rodrigo Valdes-Rodriguez and Nicholas K. Mollanazar
Medicines 2019, 6(3), 72; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines6030072 - 29 Jun 2019
Cited by 47 | Viewed by 7740
Abstract
Background: Chronic pruritus is defined as itch lasting for greater than six weeks. Pruritus is a burdensome manifestation of several internal and external disease states with a significant impact on quality of life. Dupilumab has shown promise in treating a number of conditions [...] Read more.
Background: Chronic pruritus is defined as itch lasting for greater than six weeks. Pruritus is a burdensome manifestation of several internal and external disease states with a significant impact on quality of life. Dupilumab has shown promise in treating a number of conditions including atopic dermatitis (AD) and asthma. Its success in reducing pruritus in AD has generated interest regarding its potential application in other pruritic conditions, such as chronic pruritus of unknown origin, uremic pruritus, and pruigo nodularis. Methods: In this retrospective analysis, we present a series of 20 recalcitrant pruritus patients seen at a tertiary center treated with off-label dupilumab at standard AD dosing. Results: Dupilumab was successful at reducing itch in all treated patients, leading to complete resolution in 12/20 patients and an overall mean NRSi reduction of 7.55. Dupilumab was well tolerated with no significant adverse effects. Conclusions: Our case series suggests dupilumab may be a safe and efficacious therapeutic option in several pruritic conditions and demonstrates the need for further studies to better ascertain its place in the pruritus treatment armamentarium. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Chronic Pruritus)
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Review

Jump to: Editorial, Research, Other

14 pages, 1633 KiB  
Review
Breaking the Itch–Scratch Cycle: Topical Options for the Management of Chronic Cutaneous Itch in Atopic Dermatitis
by Ian P. Harrison and Fabrizio Spada
Medicines 2019, 6(3), 76; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines6030076 - 18 Jul 2019
Cited by 18 | Viewed by 8813
Abstract
Chronic itch is an unpleasant sensation that triggers a desire to scratch that lasts for six weeks or more. It is a major diagnostic symptom of myriad diseases, including atopic dermatitis for which it is the most prominent feature. Chronic itch can be [...] Read more.
Chronic itch is an unpleasant sensation that triggers a desire to scratch that lasts for six weeks or more. It is a major diagnostic symptom of myriad diseases, including atopic dermatitis for which it is the most prominent feature. Chronic itch can be hugely debilitating for the sufferer, damaging in terms of both the monetary cost of treatment and its socioeconomic effects, and few treatment options exist that can adequately control it. Corticosteroids remain the first line treatment strategy for atopic dermatitis, but due to the risks associated with long-term use of corticosteroids, and the drawbacks of other topical options such as topical calcineurin inhibitors and capsaicin, topical options for itch management that are efficacious and can be used indefinitely are needed. In this review, we detail the pathophysiology of chronic pruritus, its key features, and the disease most commonly associated with it. We also assess the role of the skin and its components in maintaining a healthy barrier function, thus reducing dryness and the itch sensation. Lastly, we briefly detail examples of topical options for the management of chronic pruritus that can be used indefinitely, overcoming the risk associated with long-term use of corticosteroids. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Chronic Pruritus)
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Other

7 pages, 388 KiB  
Perspective
Itch in Chronic Wounds: Pathophysiology, Impact, and Management
by Michela Iannone, Agata Janowska, Valentina Dini, Giulia Tonini, Teresa Oranges and Marco Romanelli
Medicines 2019, 6(4), 112; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines6040112 - 15 Nov 2019
Cited by 2 | Viewed by 3108
Abstract
Background: The aims of this review are to analyze the current literature regarding the characteristics and pathophysiological mechanisms of itch in chronic wounds, to assess the impact on quality of life and delayed-healing, to focus on the best strategies of prevention and treatment, [...] Read more.
Background: The aims of this review are to analyze the current literature regarding the characteristics and pathophysiological mechanisms of itch in chronic wounds, to assess the impact on quality of life and delayed-healing, to focus on the best strategies of prevention and treatment, to highlight the importance of on-going research in order to fully understand the pathophysiology, and to improve the management of target therapies. Methods: A systematic literature review was performed using MEDLINE, PubMed, Embase, Scopus, ScienceDirect, and the Cochrane Library. We included a total of 11 articles written in English with relevant information on the pathophysiology of itch in chronic wounds and on management strategies. Results: Itch in chronic wounds was found to be correlated with xerosis, larger wound areas, necrotic tissue and amount of exudate, peripheral tissue edema, sclerosis, granulation tissue, contact dermatitis, and bacterial burden, as well as with lower quality of life. Conclusions: Although there are several aspecific pharmacological and non-pharmacological approaches, there appears to be no validated prevention or management strategy for itch in chronic wounds. Further studies are needed to clarify the association and pathophysiology of itch in chronic wounds, to evaluate the safety and efficacy of topical treatments on perilesional skin to reduce itch, to characterize multidimensional sensations of itch in chronic wounds, to identify specific cytokine and chemokine expressions that are correlated to a tailored-based approach, and to develop practical guidelines. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Chronic Pruritus)
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5 pages, 502 KiB  
Letter
Mirtazapine for the Treatment of Chronic Pruritus
by Raveena Khanna, Emily Boozalis, Micah Belzberg, John G. Zampella and Shawn G. Kwatra
Medicines 2019, 6(3), 73; https://0-doi-org.brum.beds.ac.uk/10.3390/medicines6030073 - 06 Jul 2019
Cited by 16 | Viewed by 4544
Abstract
Background: Chronic pruritus is a debilitating condition associated with a wide range of dermatologic, systemic and psychogenic etiologies. In patients with chronic pruritus that is refractory to conventional therapy, symptoms can significantly decrease quality of life by contributing to anxiety, sleep disturbances, and [...] Read more.
Background: Chronic pruritus is a debilitating condition associated with a wide range of dermatologic, systemic and psychogenic etiologies. In patients with chronic pruritus that is refractory to conventional therapy, symptoms can significantly decrease quality of life by contributing to anxiety, sleep disturbances, and in many cases depression. Recent studies have demonstrated the effectiveness of mirtazapine in relieving chronic itch that is refractory to standard first-line therapies. Methods: We searched PubMed for English-language articles containing the words (“pruritus” or “itch”) AND “antidepressant” and then conducted a systematic review of the current literature to summarize the efficacy of mirtazapine in treating chronic itch. Results: All studies reported a reduction in itch intensity following the administration of mirtazapine. Conclusion: Collectively, these studies suggest the potential for mirtazapine to relieve chronic itch attributed to dermatological causes and malignancies. As, such mirtazapine may be an option for patients with chronic pruritus that is refractory to typical first-line treatments. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Chronic Pruritus)
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