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Brooks SG, Yosipovitch G. Prurigo nodularis in 2025: Current and emerging treatments. Clin Dermatol 2025:S0738-081X(25)00096-3. [PMID: 40107392 DOI: 10.1016/j.clindermatol.2025.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Abstract
Prurigo nodularis (PN) is a chronic inflammatory dermatologic condition that is often incredibly itchy and imposes a debilitating burden on patient quality of life. Patients have historically faced the hurdles of limited knowledge regarding the mechanisms underlying PN, physician awareness, and effective therapies. Many of the conventional treatments offer minimal benefit or are accompanied by adverse effects. Over the last several years, striking advancements in the understanding of the pathogenesis contributing to PN have allowed for the development of novel treatments. The first and only medication approved by the US Food and Drug Administration is dupilumab, a biological agent targeting interleukins 4 and 13, has revolutionized management for patients with moderate-to-severe PN. Several other drugs are on the horizon that have the potential to become widely available. This contribution aims to review the current and emerging therapies for PN and address the challenges that may hinder effective treatment.
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Affiliation(s)
- Sarah G Brooks
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miami Itch Center, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Gil Yosipovitch
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miami Itch Center, University of Miami Miller School of Medicine, Miami, Florida, USA.
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2
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Kwatra SG, Ständer S, Yosipovitch G, Kim BS, Levit NA, O'Malley JT. Pathophysiology of Prurigo Nodularis: Neuroimmune Dysregulation and the Role of Type 2 Inflammation. J Invest Dermatol 2025; 145:249-256. [PMID: 39217537 DOI: 10.1016/j.jid.2024.06.1276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 06/18/2024] [Indexed: 09/04/2024]
Abstract
Prurigo nodularis (PN) is a chronic, inflammatory skin condition characterized by multiple, intensely pruritic, distinctive nodular lesions. Subsequent scratching can further intensify the pruritus, culminating in a self-reinforcing itch-scratch cycle, which drives lesion development. The latest data indicate dysregulation of the neuroimmune axis in PN pathogenesis, including the involvement of sensory neurons, key effector immune cells, proinflammatory cytokines, dermal fibroblasts, and pruritogens. In this review, we highlight evidence supporting the role of type 2 immune axis dysregulation in driving the clinical presentation of PN and discuss how related signaling pathways may offer effective therapeutic targets to control PN signs and symptoms.
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Affiliation(s)
- Shawn G Kwatra
- Department of Dermatology, University of Maryland School of Medicine, Baltimore, Maryland, USA; Maryland Itch Center, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Sonja Ständer
- Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Münster, Germany
| | - Gil Yosipovitch
- Miami Itch Center, Dr. Philip Frost Department of Dermatology & Cutaneous Surgery, University of Miami, Miami, Florida, USA
| | - Brian S Kim
- Mark Lebwohl Center for Neuroinflammation and Sensation, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Noah A Levit
- Dermatology Physicians of Connecticut, Fairfield, Connecticut, USA
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Yan SH, Chen Y, Huang ZQ, Zhong WX, Wang XT, Tang YC, Zhao XY, Wu YS, Zhou C, Zhu W, Xiao W, Li X, Zhang DS. Acupoint Autohemotherapy Attenuates DNCB-Induced Atopic Dermatitis and Activates Regulatory T Cells in BALB/c Mice. J Inflamm Res 2024; 17:2839-2850. [PMID: 38751687 PMCID: PMC11094283 DOI: 10.2147/jir.s454325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 04/16/2024] [Indexed: 05/18/2024] Open
Abstract
Purpose Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown. Methods This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10+, IFN-γ+ and FoxP3+CD4+T cells in murine spleen. Results It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3+, IL-10+ and IFN-γ+ CD4+T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation. Conclusion These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.
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Affiliation(s)
- Shi-Hua Yan
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China
- Department of Traditional Chinese Medicine, The Tenth affiliated Hospital, Southern Medical University (Dongguan People’s Hospital), Dongguan, Guangdong, 523058, People’s Republic of China
| | - Yong Chen
- Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China
| | - Zhi-Qian Huang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China
| | - Wen-Xi Zhong
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China
| | - Xiao-Tian Wang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China
| | - Yang-Can Tang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China
| | - Xu-Yi Zhao
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China
| | - Yu-Shan Wu
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China
| | - Chun Zhou
- School of Pharmaceutical Sciences; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China
| | - Wei Zhu
- Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, People’s Republic of China
| | - Wei Xiao
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China
- Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of China
| | - Xuan Li
- Department of Traditional Chinese Medicine, The Tenth affiliated Hospital, Southern Medical University (Dongguan People’s Hospital), Dongguan, Guangdong, 523058, People’s Republic of China
| | - Dong-Shu Zhang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China
- Department of Traditional Chinese Medicine, The Tenth affiliated Hospital, Southern Medical University (Dongguan People’s Hospital), Dongguan, Guangdong, 523058, People’s Republic of China
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Wei L, Yin M, Yang X, Chen J, Wu R, Yang H, Dou X. Effectiveness of Dupilumab for Chronic Prurigo in Chinese Patients: A Real-World Case Series Study. Clin Drug Investig 2023; 43:799-805. [PMID: 37717240 DOI: 10.1007/s40261-023-01307-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/05/2023] [Indexed: 09/19/2023]
Abstract
BACKGROUND Treatment of chronic prurigo (CPG) is challenging. As an antagonist of IL-4R, dupilumab has shown effectiveness in treating CPG in several clinical studies. Recently, the US Food and Drug Administration (FDA) approved dupilumab for the treatment of prurigo nodularis (PN). OBJECTIVES The purpose of this study was to examine the efficacy of dupilumab in Chinese patients with CPG, and to analyze the difference in response between subtypes of CPG. METHODS This retrospective study included 18 patients with CPG who were treated with dupilumab for at least 16 weeks from March 2022 to October 2022. Disease severity and patient self-assessment questionnaires were assessed at baseline and each visit, including the peak Pruritus Visual Analogue Scale (PP-VAS), Prurigo Activity and Severity Score (PAS), Investigator Global Assessment (IGA), Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS) and Itchy-specific Quality of Life questionnaire (ItchyQoL). RESULTS After 2 weeks of dupilumab treatment, pruritus scores were significantly reduced as measured by PP-VAS scores. Prurigo Activity and Severity scores decreased significantly at Week 2, whereas IGA improved significantly at Week 8. The DLQI, HADS, and ItchyQoL scores at Week 16 also showed significant improvement from baseline. Patients in all subtypes showed improvement in pruritus and lesion severity. CONCLUSIONS Dupilumab was effective in improving pruritus and lesions in patients with various subtypes of CPG.
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Affiliation(s)
- Lu Wei
- Department of Dermatology, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Shenzhen, 518036, Guangdong, People's Republic of China
- Shenzhen University Medical School, Shenzhen, 518061, People's Republic of China
| | - Mengting Yin
- Department of Dermatology, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Shenzhen, 518036, Guangdong, People's Republic of China
| | - Xu Yang
- Department of Dermatology, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Shenzhen, 518036, Guangdong, People's Republic of China
| | - Jiaying Chen
- Department of Dermatology, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Shenzhen, 518036, Guangdong, People's Republic of China
| | - Ruimiao Wu
- Department of Dermatology, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Shenzhen, 518036, Guangdong, People's Republic of China
| | - Heng Yang
- Department of Dermatology, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Shenzhen, 518036, Guangdong, People's Republic of China
| | - Xia Dou
- Department of Dermatology, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Shenzhen, 518036, Guangdong, People's Republic of China.
- Anhui Medical University, Hefei, 230032, Anhui, People's Republic of China.
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Richter C, Hafner J, Schuermann M, Tanadini M, Trisconi N, Schmid-Grendelmeier P, Kündig T, Nägeli M, Brüggen MC, Guillet C. Dupilumab for Chronic Prurigo: Case Series on Effectiveness, Safety, and Quality of Life. Dermatology 2023; 239:811-817. [PMID: 37369187 PMCID: PMC10614240 DOI: 10.1159/000531708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 05/28/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Chronic prurigo (CPG) is a pruritic skin disease, characterized by an itch-scratch cycle and scarring. It reduces patients' quality of life (QoL). Dupilumab is a monoclonal human IgG antibody that inhibits signaling of the interleukin 4 (IL-4) and interleukin 13 (IL-13) pathways through blockade of the IL-4 receptor. Patients with CPG who receive dupilumab often report great improvement in itch and overall QoL. We therefore reviewed our experience in order to follow up on QoL, safety, and treatment response in patients with CPG who received dupilumab. METHODS We conducted a real-world retrospective single-center case series. Outcomes were assessed by phone interviews and photographs using validated questionnaires and scores. Demographic data were obtained from the hospital files. Follow-up was up to 2 years. We assessed QoL with the Dermatology Life Quality Index (DLQI) and the Itchy quality of life questionnaire (ItchyQoL). Numerical Rating Scale (NRS) was used to assess itch. Prurigo lesions were documented with the Prurigo activity and severity score (PAS). RESULTS Ten patients were included in this study. Results were reported up to 2 years after treatment with dupilumab. The response variables for DLQI, ItchyQoL, NRS, and PAS analyses showed a statistically significant decrease over time (DLQI: p ≤ 0.0001 [-0.84; -1.27], ItchyQoL: p ≤ 0.0001 [-9.89; -18.69], NRS maximum and average: p ≤ 0.0001 [-0.52; -0.86] and p ≤ 0.0001 [-0.55; -0.94], and PAS number of lesions: p = 0.0005 [-1.70; -5.28]). The percent decrease after 1 year of treatment (this estimate is based on model estimates) ranges from -42% to -82%. Four (40%) patients reported mild side effects. No serious side effects were reported. CONCLUSION Dupilumab treatment of CGP for up to 2 years is associated with improved QoL and less itching.
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Affiliation(s)
- Clara Richter
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Jürg Hafner
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Manuel Schuermann
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | | | | | - Peter Schmid-Grendelmeier
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
- Christine Kühne Center for Allergy Research and Education CK-CARE, Davos, Switzerland
| | - Thomas Kündig
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Mirjam Nägeli
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Marie-Charlotte Brüggen
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Carole Guillet
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
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Yosipovitch G, Mollanazar N, Ständer S, Kwatra SG, Kim BS, Laws E, Mannent LP, Amin N, Akinlade B, Staudinger HW, Patel N, Yancopoulos GD, Weinreich DM, Wang S, Shi G, Bansal A, O'Malley JT. Dupilumab in patients with prurigo nodularis: two randomized, double-blind, placebo-controlled phase 3 trials. Nat Med 2023; 29:1180-1190. [PMID: 37142763 DOI: 10.1038/s41591-023-02320-9] [Citation(s) in RCA: 99] [Impact Index Per Article: 49.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 03/24/2023] [Indexed: 05/06/2023]
Abstract
Prurigo nodularis (PN) is a chronic inflammatory skin disease with intensely pruritic nodules. The LIBERTY-PN PRIME and PRIME2 phase 3 trials enrolled adults with PN with ≥20 nodules and severe itch uncontrolled with topical therapies. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13. Patients were randomized 1:1 to 300 mg dupilumab or placebo subcutaneously every 2 weeks for 24 weeks. The primary endpoint was pruritus improvement, measured by proportion of patients with a ≥4-point reduction in Worst Itch Numeric Rating Scale (WI-NRS) from baseline at week 24 (PRIME) or week 12 (PRIME2). Key secondary endpoints included nodule number reduction to ≤5 at week 24. PRIME and PRIME2 enrolled 151 and 160 patients, respectively. Both trials met all the pre-specified primary and key secondary endpoints. A ≥4-point WI-NRS reduction at week 24 in the dupilumab and placebo arms was achieved by 60.0% and 18.4% of patients, respectively, in PRIME (95% confidence interval (CI), 27.8-57.7 for the difference, P < 0.001) and at week 12 by 37.2% and 22.0% of patients, respectively, in PRIME2 (95% CI, 2.3-31.2; P = 0.022). Dupilumab demonstrated clinically meaningful and statistically significant improvements in itch and skin lesions versus placebo in PN. Safety was consistent with the known dupilumab safety profile.ClinicalTrials.gov identifiers: NCT04183335 and NCT04202679 .
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Affiliation(s)
| | - Nicholas Mollanazar
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | | | - Shawn G Kwatra
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Brian S Kim
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | | | - Nikhil Amin
- Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA
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7
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Olbrich H, Sadik CD, Ludwig RJ, Thaçi D, Boch K. Dupilumab in Inflammatory Skin Diseases: A Systematic Review. Biomolecules 2023; 13:biom13040634. [PMID: 37189381 DOI: 10.3390/biom13040634] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 03/20/2023] [Accepted: 03/29/2023] [Indexed: 04/03/2023] Open
Abstract
Dupilumab was first approved for the treatment of atopic dermatitis (AD) and blocks the signaling of interleukin (IL)-4 and -13. Several other chronic skin conditions share mechanistic overlaps with AD in their pathophysiology, i.e., are linked to type 2 inflammation. Most recently, dupilumab was approved by the U.S. Food and Drug Administration for prurigo nodularis (PN). Given its relatively good safety profile, effective off-label use of dupilumab has been reported for a multitude of dermatologic diseases and several clinical trials for dermatologic skin conditions are currently ongoing. We conducted a systematic review of applications of dupilumab in dermatology other than AD and PN by searching the databases PubMed/Medline, Scopus, Web of Science and Cochrane Library as well as the clinical trial registry ClinicalTrials.gov. We found several reports for effective treatment of bullous autoimmune diseases, eczema, prurigo, alopecia areata, chronic spontaneous urticaria, Netherton syndrome and a variety of other chronic inflammatory skin diseases.
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Affiliation(s)
- Henning Olbrich
- Department of Dermatology, University of Lübeck, 23566 Lübeck, Germany
| | | | - Ralf J. Ludwig
- Department of Dermatology, University of Lübeck, 23566 Lübeck, Germany
- Lübeck Institute of Experimental Dermatology, University of Lübeck, 23566 Lübeck, Germany
| | - Diamant Thaçi
- Department of Dermatology, University of Lübeck, 23566 Lübeck, Germany
- Institute and Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein, 23566 Lübeck, Germany
| | - Katharina Boch
- Department of Dermatology, University of Lübeck, 23566 Lübeck, Germany
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8
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Boyvadoglu C, Inaloz HS. Generalized prurigo nodularis with dramatic response to dupilumab treatment: A case report. World J Dermatol 2023; 11:1-6. [DOI: 10.5314/wjd.v11.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/10/2022] [Accepted: 12/21/2022] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Prurigo nodularis (PN) is a chronic condition characterized by a papulonodular pruriginous eruption of unknown aetiology. Currently, there are no medications for PN that the United States Food and Drug Administration has approved, which leads to very variable practices in the prescription of off-label treatments. Treatment of PN is based on clinical experience rather than controlled trials. We present our case of generalized PN, in which we had a dramatic response with dupilumab.
CASE SUMMARY A 58-year-old female patient was admitted to our clinic with severe itchy, erythematous nodular lesions that were widespread all over her body, especially on the legs and back. It was learned that the patient's complaints started 4 years ago, and there was a significant increase in the lesions in the last period. Dermatological examination revealed diffuse firm erythematous excoriated nodular lesions all over the body. In the blood tests of the patient, serum Immunoglobulin E (IgE) was measured at 9330 IU/mL. The patient was diagnosed with generalized prurigo nodularis together with clinical and histopathological findings. Due to severe clinical findings and the presence of comorbidities, dupilumab treatment was planned for the patient. In the follow-up 4 mo later, it was observed that all nodular lesions healed with postinflammatory hypopigmentation. The IgE value decreased to 1500 IU/mL after 4 mo of dupilumab treatment.
CONCLUSION Dupilumab treatment stands out as an effective and safe systemic treatment agent among existing systemic treatments.
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Affiliation(s)
- Cagdas Boyvadoglu
- Department of Dermatology, University of Gaziantep Faculty of Medicine, Gaziantep 27270, Turkey
| | - Huseyin Serhat Inaloz
- Department of Dermatology, University of Gaziantep Faculty of Medicine, Gaziantep 27270, Turkey
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9
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Cao P, Xu W, Jiang S, Zhang L. Dupilumab for the treatment of prurigo nodularis: A systematic review. Front Immunol 2023; 14:1092685. [PMID: 36742321 PMCID: PMC9895771 DOI: 10.3389/fimmu.2023.1092685] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 01/09/2023] [Indexed: 01/22/2023] Open
Abstract
Background Conventional treatment techniques have limited efficacy and more side effects in the treatment of prurigo nodularis. The better alternative treatment option for better outcomes of the disease is dupilumab. Objective The objective of this study was to systematically review dupilumab-related treatment outcomes in prurigo nodularis. Methods Several databases like Embase, PubMed, Web of Science, and Cochrane library were searched for data acquisition on October 8, 2022. Based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, 24 publications were included in this study. Results After 4,12,16 and more than 16 weeks of dupilumab treatment, 8.3% (n=5/60), 34.4% (n=11/32), 3.6% (n=2/56), and 45.3% (n=29/64) of patients had complete remission, respectively. In addition, 85.0% (n=51/60), 59.4% (n=19/32), 83.9% (n=47/56), and 43.8% (n=28/64) had partial remission, respectively. Moreover, 6.7% (n=4/60), 6.3% (n=2/32), 12.5% (n=7/56), and 10.9% (n=7/64) showed no remission, respectively, and significant reduction of numeric rating scale itch intensity (from 9.0 to 4.9, 2.1, 2.8, 0.9) was attained. There were no serious adverse events observed during treatment, but the most common event observed was conjunctivitis (12.6%, n=15/119). Conclusions Dupilumab has definite effectiveness and safety in prurigo nodularis treatment. Systematic review registration https://www.crd.york.ac.uk/PROSPERO, identifier (CRD42022365802).
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Affiliation(s)
- Peng Cao
- Graduate School, Tianjin Medical University, Tianjin, China.,Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China
| | - Wenjing Xu
- Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China.,Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Shuyi Jiang
- Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China.,Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Litao Zhang
- Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China
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10
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Wu C, Zhang J, Zhao Y. Hypereosinophilic Dermatitis: Successful Treatment with Dupilumab. Biologics 2023; 17:57-60. [PMID: 37101561 PMCID: PMC10124617 DOI: 10.2147/btt.s400073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 04/04/2023] [Indexed: 04/28/2023]
Abstract
Hypereosinophilic dermatitis (HED) is a subtype of hypereosinophilic syndrome. HED is characterized by eosinophilic granulocytes increased in peripheral blood and bone marrow and infiltrated in skin. The clinical manifestations of HED are diffussed by erythema, papule and maculopapule with severe itching. The etiology of HED is unknown. At present, in addition to HED with FIP1L1-PDGFRA fusion gene positive, whose treatment is tyrosine kinase inhibitor, other types of HED first-line treatment are oral glucocorticoids, supplemented by antihistamines and immunosuppressants. Dupilumab is a human monoclonal antibody, which inhibits the IL-4 and IL-13 signaling by binding to the IL-4R-α and IL-13R-α-1 subunits of the receptor. We report a 76-year-old male patient with HED whose peripheral blood eosinophils decreased from 20.7% to 4.1% after 8 weeks of dupilumab, and his pruritus was completely relieved. Dupilumab was discontinued after 6 months of treatment. It is exciting that the patient has not experienced relapse for 17 months after the discontinuation. No adverse event was reported.
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Affiliation(s)
- Chenyu Wu
- Department of Dermatology, People’s Hospital of Peking University, Beijing, People’s Republic of China
| | - Jianzhong Zhang
- Department of Dermatology, People’s Hospital of Peking University, Beijing, People’s Republic of China
| | - Yan Zhao
- Department of Dermatology, People’s Hospital of Peking University, Beijing, People’s Republic of China
- Correspondence: Yan Zhao, Email
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11
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Greiwe J, Honsinger R, Hvisdas C, Chu DK, Lang DM, Nicklas R, Apter AJ. Boxed Warnings and Off-Label Use of Allergy Medications: Risks, Benefits, and Shared Decision Making. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2022; 10:3057-3063. [PMID: 36064185 DOI: 10.1016/j.jaip.2022.08.033] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 08/26/2022] [Accepted: 08/26/2022] [Indexed: 12/14/2022]
Abstract
The Food and Drug Administration is tasked with evaluating the efficacy and safety of a drug. Despite having a regimented appraisal process in place, safety evidence can emerge during clinical trials as well as from observations and studies conducted after the drug has been on the market, which might require a boxed warning. The boxed warning is the most severe warning that the Food and Drug Administration can give to an approved drug. It is commonly referred to as a Black Box Warning because it is outlined in the package insert by a thick black box to garner the attention of prescribers and patients. There are currently more than 400 medications that have boxed warnings, and the information addressing major risks associated with a particular drug may, appropriately or inappropriately, influence patient and clinician decision making. Health care professionals must use the best evidence and clinical judgment in determining whether to prescribe medications with these warnings. Use of an approved drug at dosages or for indications other than what it was originally licensed for is referred to as "off-label" and is legal, commonplace, and may be evidence-based. All drugs may expose patients to possible harm, so prescribers have an obligation to discuss the best available evidence regarding benefits and harms so that patients can participate in shared decision making.
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Affiliation(s)
- Justin Greiwe
- Bernstein Allergy Group, Inc, Cincinnati, Ohio; Division of Immunology/Allergy Section, Department of Internal Medicine, The University of Cincinnati College of Medicine, Cincinnati, Ohio.
| | - Richard Honsinger
- Los Alamos Medical Care Clinic Ltd, Los Alamos, NM; Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM
| | - Christopher Hvisdas
- Department of Pharmacy Penn Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia, Pa
| | - Derek K Chu
- Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - David M Lang
- Department of Allergy and Clinical Immunology, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio
| | | | - Andrea J Apter
- Division of Pulmonary, Allergy, & Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa
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12
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Kim JW, Kim M, Ahn GS, Na JI. Dupilumab provides rapid improvement for morphologic variants of paediatric atopic dermatitis: A case series. Indian J Dermatol Venereol Leprol 2022; 88:834-839. [PMID: 36331828 DOI: 10.25259/ijdvl_759_2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 08/01/2022] [Indexed: 11/07/2022]
Affiliation(s)
- Jee Woo Kim
- Department of Dermatology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Minjae Kim
- Department of Dermatology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Grace Sora Ahn
- Department of Dermatology, University of California San Diego School of Medicine, La Jolla, California, United States
| | - Jung Im Na
- Department of Dermatology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
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13
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Mießner H, Seidel J, Smith ESJ. In vitro models for investigating itch. Front Mol Neurosci 2022; 15:984126. [PMID: 36385768 PMCID: PMC9644192 DOI: 10.3389/fnmol.2022.984126] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 10/10/2022] [Indexed: 12/04/2022] Open
Abstract
Itch (pruritus) is a sensation that drives a desire to scratch, a behavior observed in many animals. Although generally short-lasting and not causing harm, there are several pathological conditions where chronic itch is a hallmark symptom and in which prolonged scratching can induce damage. Finding medications to counteract the sensation of chronic itch has proven difficult due to the molecular complexity that involves a multitude of triggers, receptors and signaling pathways between skin, immune and nerve cells. While much has been learned about pruritus from in vivo animal models, they have limitations that corroborate the necessity for a transition to more human disease-like models. Also, reducing animal use should be encouraged in research. However, conducting human in vivo experiments can also be ethically challenging. Thus, there is a clear need for surrogate models to be used in pre-clinical investigation of the mechanisms of itch. Most in vitro models used for itch research focus on the use of known pruritogens. For this, sensory neurons and different types of skin and/or immune cells are stimulated in 2D or 3D co-culture, and factors such as neurotransmitter or cytokine release can be measured. There are however limitations of such simplistic in vitro models. For example, not all naturally occurring cell types are present and there is also no connection to the itch-sensing organ, the central nervous system (CNS). Nevertheless, in vitro models offer a chance to investigate otherwise inaccessible specific cell–cell interactions and molecular pathways. In recent years, stem cell-based approaches and human primary cells have emerged as viable alternatives to standard cell lines or animal tissue. As in vitro models have increased in their complexity, further opportunities for more elaborated means of investigating itch have been developed. In this review, we introduce the latest concepts of itch and discuss the advantages and limitations of current in vitro models, which provide valuable contributions to pruritus research and might help to meet the unmet clinical need for more refined anti-pruritic substances.
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Affiliation(s)
- Hendrik Mießner
- Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom
- Dermatological Skin Care, Beiersdorf AG, Hamburg, Germany
| | - Judith Seidel
- Dermatological Skin Care, Beiersdorf AG, Hamburg, Germany
| | - Ewan St. John Smith
- Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom
- *Correspondence: Ewan St. John Smith,
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Froelunde AS, Vestergaard C. Prurigo nodularis: the epidemiology of an under-recognized disease. Br J Dermatol 2022; 187:e171-e172. [PMID: 36047287 DOI: 10.1111/bjd.21843] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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15
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Gil‐Lianes J, Riquelme‐Mc Loughlin C, Mascaró JM. Reactive perforating collagenosis successfully treated with dupilumab. Australas J Dermatol 2022; 63:398-400. [PMID: 35633371 PMCID: PMC9544964 DOI: 10.1111/ajd.13874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 05/01/2022] [Accepted: 05/09/2022] [Indexed: 11/03/2022]
Affiliation(s)
- Javier Gil‐Lianes
- Dermatology DepartmentHospital Clínic de BarcelonaUniversitat de BarcelonaBarcelonaSpain
| | | | - Jose Manuel Mascaró
- Dermatology DepartmentHospital Clínic de BarcelonaUniversitat de BarcelonaBarcelonaSpain
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16
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Patruno C, Potestio L, Napolitano M. Clinical phenotypes of adult atopic dermatitis and related therapies. Curr Opin Allergy Clin Immunol 2022; 22:242-249. [PMID: 35786802 DOI: 10.1097/aci.0000000000000837] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW To report current knowledge on the different clinical phenotypes of adult atopic dermatitis. Possible therapeutic intervention in relation to phenotype is also evaluated. RECENT FINDINGS Atopic dermatitis is a chronic inflammatory disease affecting up to 10% of adults. It can manifest with different clinical phenotypes, causing diagnostic difficulties. Long-term is often required and systemic drugs are needed for moderate-to-severe forms. However, few drugs are registered for atopic dermatitis in many countries. Furthermore, limited data exist regarding the treatment in relation to individual clinical phenotypes. SUMMARY Currently, the most relevant data are those for cyclosporine, alitretinoin, and dupilumab. Cyclosporine and dupilumab showed to be effective in the treatment of atopic dermatitis, although in trials and real-life experiences the different phenotypes treated are usually not reported. However, cyclosporine appears to be effective in prurigo nodularis. Alitretinoin is reported to be particularly efficacious for atopic dermatitis of the hands, while it is ineffective for other locations of the disease. Dupilumab demonstrated its efficacy in prurigo nodularis and nummular eczema phenotypes of atopic dermatitis; moreover, especially in elderly patients, its effectiveness seems to be faster if the folds of the limbs are involved.
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Affiliation(s)
- Cataldo Patruno
- Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro
| | - Luca Potestio
- Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples
| | - Maddalena Napolitano
- Department of Medicine and Health Sciences Vincenzo Tiberio, University of Molise, Campobasso, Italy
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17
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Prurigo crónico: actualización. ACTAS DERMO-SIFILIOGRAFICAS 2022; 113:563-574. [DOI: 10.1016/j.ad.2021.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 06/29/2021] [Accepted: 11/01/2021] [Indexed: 11/23/2022] Open
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18
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Docampo-Simón A, Sánchez-Pujol M, Silvestre-Salvador J. [Translated article] Update on Chronic Prurigo. ACTAS DERMO-SIFILIOGRAFICAS 2022; 113:T563-T574. [DOI: 10.1016/j.ad.2022.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 11/01/2021] [Indexed: 11/29/2022] Open
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19
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Gael M, Adam T, Mariano-Bourin M, Bursztejn AC. Efficacy of dupilumab in chronic prurigo and chronic idiopathic pruritus: A systematic review of current evidence and analysis of response predictors. J Eur Acad Dermatol Venereol 2022; 36:1541-1551. [PMID: 35569006 DOI: 10.1111/jdv.18221] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Accepted: 04/21/2022] [Indexed: 11/28/2022]
Abstract
Dupilumab has demonstrated a great reduction on chronic pruritus that is the hallmark of atopic dermatitis (AD). Underscoring relevant pathogenesis similarities emerging from AD, chronic idiopathic pruritus (CIP) and chronic prurigo (CP), several authors suggested the beneficial role of dupilumab in these conditions. The evidence on this subject is limited with no precise data available. In this study, we carried out a systematic literature review in order to evaluate the efficacy of dupilumab on both pruritus and skin manifestations in the two largest retrospective cohorts of patients with CP and CIP and tried to identify potential response predictors. Electronic searches were conducted on 4 databases. Our primary outcome was the improvement in pruritus measured by a reduction in patient's reported numerical rating scale of itch (NRSI) by > 4. Secondary outcomes included: proportion of patients with complete response at the end of treatment, reduction in the number of lesions by the Investigator Global Assessment (IGA), improvement in numerical rating scale of sleep (NRSS), improvement in quality of life measured by the Dermatology Life Quality Index (DLQI), time until patient perceived any improvement (Time-First) and time until patient reported absence of pruritus (Time-Final). Descriptive statistics were calculated for each demographic and clinical variable. Univariate logistic regression analyses were conducted to explore association between response to dupilumab and potential predictive factors. We included 25 articles in the analysis, counting a total of 153 patients. Based on CP patients' cohort (n=132), the mean NRSI at baseline was 8.79 ±0.86 and the NRSI final was 2.32 ±1.27. The mean time to first improvement was 5.18 ±3.13 weeks, while the time to complete improvement of pruritus (Time-final) was 13.6 ±12.0 weeks. Ninety patients out of 109 (83%) noticed improvement in pruritus before 4 weeks of dupilumab therapy. At the end of treatment, 18 patients out of 126 (14%) had a complete remission of pruritus and 110 patients out of 123 (89%) had a reduction of NRSI > 4. The reduction in NRSI was significantly greater in patients improving before 4 weeks of treatment (6.57 ±1.71) compared to patients improving in more than 4 weeks (5.49 ±1.39, p<0.001). Patients with history of AD and those who have been previously treated with cyclosporine or methotrexate had a significantly lower reduction in NRSI (e.g. 6.05 ±1.34 vs 7.08 ±1.90 p<0.01 for non-associated AD patients). Based on CIP patient's cohort (n=21), the mean NRSI at baseline was 8.33 ±0.80 and the NRSI final was 0.95 ±0.59. The mean time to first improvement was 2 ±0 weeks, while the time to complete improvement (Time-final) was 14.6 ±10 weeks. At the end of treatment, 3 patients out of 21 (14%) had a complete remission of pruritus and 100% of patients had a reduction of NRSI > 4. No serious treatment-emergent adverse events were reported. The most common adverse event was mild conjunctivitis (13 cases). We highlight the importance of one early sign of improvement as predictor of the future response to dupilumab: the improvement before 4 weeks of treatment that leads significantly to a greater final reduction in NRSI. Furthermore, patients with the presence or history of atopy appear to be less responsive to dupilumab than non-atopic patients and develop more side effects, in particular conjunctivitis.
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Affiliation(s)
- M Gael
- Department of Dermatology, CHRU de Nancy, 6 rue du Morvan, 54500 Vandœuvre lès, Nancy, France
| | - T Adam
- Department of Allergology, CHRU de Nancy, 6 rue du Morvan, 54500 Vandœuvre lès, Nancy, France
| | - M Mariano-Bourin
- Department of Dermatology, CHRU de Nancy, 6 rue du Morvan, 54500 Vandœuvre lès, Nancy, France
| | - A C Bursztejn
- Department of Dermatology, CHRU de Nancy, 6 rue du Morvan, 54500 Vandœuvre lès, Nancy, France
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20
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Sammarra I, Bennardo L, Provenzano E, Patruno C, Nisticò SP. Post-Stroke Asymmetric Prurigo Nodularis Responding to Dupilumab Treatment: A Case Report. Brain Sci 2022; 12:605. [PMID: 35624992 PMCID: PMC9139789 DOI: 10.3390/brainsci12050605] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Revised: 04/24/2022] [Accepted: 05/04/2022] [Indexed: 11/16/2022] Open
Abstract
Prurigo nodularis (PN) is a dermatological condition characterized by nodular hyperkeratotic lesions mainly on the legs and arms. Asymmetrical PN is a rare dermatological condition often associated with paralysis and stroke. In this paper, we present the case of a 77-year-old woman who developed post-ictal PN which responded to dupilumab, an anti-interleukin-4/13 drug approved for the management of AD, with an extreme reduction in itch sensation. Dupilumab and other therapies reducing Th2 inflammation may, in the future, become an alternative treatment for post-ictal pruritus/PN nonresponding to traditional therapies. Of course, larger studies will be necessary to confirm our case's findings.
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Affiliation(s)
- Ilaria Sammarra
- Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy;
| | - Luigi Bennardo
- Department of Health Sciences, Magna Graecia University, 88100 Catanzaro, Italy; (L.B.); (C.P.); (S.P.N.)
- Unit of Dermatology, Mariano Santo Hospital, 87100 Cosenza, Italy
| | | | - Cataldo Patruno
- Department of Health Sciences, Magna Graecia University, 88100 Catanzaro, Italy; (L.B.); (C.P.); (S.P.N.)
| | - Steven Paul Nisticò
- Department of Health Sciences, Magna Graecia University, 88100 Catanzaro, Italy; (L.B.); (C.P.); (S.P.N.)
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21
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Cunha IM, Valadão I, Gomes E, Marinho A. Dupilumab: A Safe and Successful Treatment in Refractory Prurigo Nodularis. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2022; 10:1365-1366. [PMID: 35331683 DOI: 10.1016/j.jaip.2022.02.029] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 02/09/2022] [Accepted: 02/10/2022] [Indexed: 06/14/2023]
Affiliation(s)
- Inês Machado Cunha
- Immunoallergology Department, Centro Hospitalar Universitário do Porto, Porto, Portugal.
| | - Ivone Valadão
- Internal Medicine Department, Hospital de Santo Espírito da Ilha Terceira, Açores, Portugal
| | - Eva Gomes
- Immunoallergology Department, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - António Marinho
- Internal Medicine Department, Centro Hospitalar Universitário do Porto, Porto, Portugal; Clinical Immunology Unity, Centro Hospitalar Universitário do Porto, Porto, Portugal
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22
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Frølunde AS, Wiis MAK, Ben Abdallah H, Elsgaard S, Danielsen AK, Deleuran M, Vestergaard C. Non-Atopic Chronic Nodular Prurigo (Prurigo Nodularis Hyde): A Systematic Review of Best-Evidenced Treatment Options. Dermatology 2022; 238:950-960. [PMID: 35417906 DOI: 10.1159/000523700] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 02/06/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Chronic nodular prurigo (CNPG) is a chronic, inflammatory skin disease, characterized by intense and debilitating pruritus. The pathophysiology is not fully understood, and the condition is difficult to treat with no targeted therapies. The aim of this systematic review was to review the evidence of therapies for non-atopic CNPG and conduct a meta-analysis of the results. SUMMARY We conducted a systematic review of the literature concerning effect of treatment for non-atopic CNPG. Due to few randomized controlled trials (RCTs) and case series, the literature was unfortunately too sparse to conduct a meta-analysis of the results. Instead, we thoroughly report important data from the three existing RCTs and 6 case studies with more than 15 patients. Evaluated therapies include nemolizumab, aprepitant, topical therapy with hydrocortisone and pimecrolimus, thalidomide, UVA phototherapy, pregabalin, and naltrexone. Included RCTs and case studies all had a heterogeneous methodology making direct comparison almost impossible. KEY MESSAGES There is sparse evidence for the currently used therapies for non-atopic CNPG. Several RCTs on new therapies are running or in the pipeline, hopefully providing new, effective, and targeted treatment possibilities for CNPG patients both with and without an atopic predisposition.
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Affiliation(s)
- Anne Sofie Frølunde
- Department of Dermatology and Venerology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Hakim Ben Abdallah
- Department of Dermatology and Venerology, Aarhus University Hospital, Aarhus, Denmark
| | - Stine Elsgaard
- Department of Dermatology and Venerology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Mette Deleuran
- Department of Dermatology and Venerology, Aarhus University Hospital, Aarhus, Denmark
| | - Christian Vestergaard
- Department of Dermatology and Venerology, Aarhus University Hospital, Aarhus, Denmark
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23
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Labib A, Ju T, Vander Does A, Yosipovitch G. Immunotargets and Therapy for Prurigo Nodularis. Immunotargets Ther 2022; 11:11-21. [PMID: 35502157 PMCID: PMC9056055 DOI: 10.2147/itt.s316602] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Accepted: 04/08/2022] [Indexed: 12/18/2022] Open
Abstract
Prurigo nodularis is a chronic inflammatory skin disease consisting of severely pruritic nodules that can be very debilitating for patients. The basis of this skin condition is immunological dysregulation and neural amplification, driven by T-lymphocytes, mast cells, eosinophilic granulocytes, macrophages, and cytokines mediating itchy processes. Further complicating this already taxing diagnosis is the lack of approved treatment and consensus on management; although there are off-label treatments utilized as therapy. Immunomodulators are the cornerstone of treatment for PN, and additional novel therapies targeting key players in the immunological cascade are currently undergoing investigation. In this review, we will highlight targets of the immune cascade and explore current immunomodulating treatments as well as immunotherapies on the horizon for the management of prurigo nodularis.
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Affiliation(s)
- Angelina Labib
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery and Miami Itch Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Teresa Ju
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery and Miami Itch Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Ashley Vander Does
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery and Miami Itch Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Gil Yosipovitch
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery and Miami Itch Center, University of Miami Miller School of Medicine, Miami, FL, USA
- Correspondence: Gil Yosipovitch, Dr Phillip Frost Department of Dermatology and Cutaneous Surgery and Miami Itch Center, University of Miami Miller School of Medicine, 1600 NW 10th Ave RMSB Building 2067B, Miami, FL, USA, Tel +1 305 213-5824, Email
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24
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Peng C, Li C, Zhou Y, Wang Q, Xie P, Li T, Hao P. Tofacitinib for Prurigo Nodularis: A Case Report. Clin Cosmet Investig Dermatol 2022; 15:503-506. [PMID: 35340735 PMCID: PMC8956247 DOI: 10.2147/ccid.s354025] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 03/01/2022] [Indexed: 11/23/2022]
Abstract
Purpose Despite recent advances in the treatment of prurigo nodularis, conventional treatment suffers from a dilemma of poor efficacy. The clinical use of Janus kinase (JAK) inhibitors in the treatment of Prurigo nodularis has rarely been explored. Patients and Methods We present a case of prurigo nodularis successfully treated with, JAK inhibitor tofacitinib with no adverse effects. Results This case report of successful treatment shows a good clinical efficacy of using JAK inhibitor tofacitinib in the treatment of prurigo nodularis. Cytokines may be an important cause of prurigo nodularis. Conclusion JAK inhibitor tofacitinib may be a new option for the treatment of prurigo nodularis, especially for patients who have failed conventional treatment.
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Affiliation(s)
- Changlan Peng
- Department of Dermatology, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Chunxiao Li
- Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Yingying Zhou
- Department of Dermatology, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Qiuyue Wang
- Department of Dermatology, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Ping Xie
- Department of Dermatology, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Tianhao Li
- Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Pingsheng Hao
- Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
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25
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Wu D, Daniel BS, Lai AJX, Wong N, Lim DKA, Murrell DF, Lim BXH, Mehta JS, Lim CHL. Dupilumab-associated ocular manifestations: A review of clinical presentations and management. Surv Ophthalmol 2022; 67:1419-1442. [PMID: 35181280 DOI: 10.1016/j.survophthal.2022.02.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 02/07/2022] [Accepted: 02/11/2022] [Indexed: 10/19/2022]
Abstract
Dupilumab is a first-in-class biologic approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (US FDA) for the treatment of multiple atopic diseases, including atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis. Since gaining traction as an effective treatment modality, multiple reports have highlighted the many ocular side effects associated with dupilumab usage. These range from mild diseases such as conjunctivitis, dry eyes, and blepharitis, to more severe manifestations such as intraocular inflammation and cicatrising conjunctivitis. The pathogenesis behind these manifestations remains controversial but are likely multi-factorial. We review the current evidence surrounding ocular manifestations of dupilumab-associated disease and proposed treatments to provide an overview of this unique disease entity. With increasing usage of dupilumab, formal recommendations regarding the treatment of dupilumab-associated ocular disease are warranted to provide standardised clinical guidance. Furthermore, it is important for healthcare practitioners to remain abreast with existing literature to adequately counsel and empower patients with the knowledge surrounding contemporary treatments for atopic diseases and their associated side-effects.
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Affiliation(s)
- Duoduo Wu
- Yong Loo Lin School of Medicine, National University of Singapore
| | - Benjamin S Daniel
- St George Hospital, Kogarah, Sydney, NSW, Australia; St Vincent's Hospital, Melbourne, Victoria, Australia
| | - Andre J X Lai
- Yong Loo Lin School of Medicine, National University of Singapore
| | - Nathan Wong
- Royal Victorian Eye and Ear Hospital, Melbourne, Australia
| | - Dawn K A Lim
- Yong Loo Lin School of Medicine, National University of Singapore; Department of Ophthalmology, National University Health System, Singapore
| | - Dedee F Murrell
- St George Hospital, Kogarah, Sydney, NSW, Australia; School of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Blanche X H Lim
- Yong Loo Lin School of Medicine, National University of Singapore; Department of Ophthalmology, National University Health System, Singapore
| | - Jodhbir S Mehta
- Duke-NUS Graduate Medical School, Singapore; Singapore Eye Research Institute, Singapore; Singapore National Eye Centre, Singapore
| | - Chris H L Lim
- Yong Loo Lin School of Medicine, National University of Singapore; Department of Ophthalmology, National University Health System, Singapore; Singapore Eye Research Institute, Singapore; School of Optometry and Vision Science, University of New South Wales, Sydney, NSW, Australia.
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26
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Agrawal D, Sardana K, Mathachan SR, Bhardwaj M, Ahuja A, Jain S. A prospective study examining the expression of STAT 1, 3, 6 in prurigo nodularis lesions with its immunopathogenic and therapeutic implications. J Cosmet Dermatol 2021; 21:4009-4015. [DOI: 10.1111/jocd.14709] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 12/09/2021] [Accepted: 12/13/2021] [Indexed: 12/29/2022]
Affiliation(s)
- Diksha Agrawal
- Department of Dermatology and STDs Dr RML Hospital and ABVIMS New Delhi India
| | - Kabir Sardana
- Department of Dermatology and STDs Dr RML Hospital and ABVIMS New Delhi India
| | - Sinu Rose Mathachan
- Department of Dermatology and STDs Dr RML Hospital and ABVIMS New Delhi India
| | | | - Arvind Ahuja
- Department of Pathology Dr. RML Hospital and ABVIMS New Delhi India
| | - Swasti Jain
- Department of Pathology Dr. RML Hospital and ABVIMS New Delhi India
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27
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Abstract
INTRODUCTION Prurigo nodularis (PN) or chronic prurigo of nodular type (CNPG) is a subtype of chronic prurigo with severe pruritus and neuroimmune underlying pathophysiology occurring in a plethora of dermatological, systemic, neurologic, and psychiatric conditions. AREAS COVERED We review the increasing repertoire of biologics in the treatment of CNPG focusing on those targeting interleukins 4, 13, 31, oncostatin M and IgE. Presented information is based on a database research on current clinical trials (clinicaltrials.gov, European Clinical Trials Database (EudraCT), US clinical trial registry ICH-GCP) and a PubMed search for latest publications conducted with the combinations of the terms 'chronic prurigo,' 'prurigo nodularis,' 'pathophysiology,' 'treatment,' 'therapy', and 'biologics.' EXPERT OPINION CNPG gets more and more attention as new therapeutic targets have been revealed in recent years, thus allowing the use of targeted approaches. The off-label advent of dupilumab offered advanced insight into the pathogenesis of CNPG and showed an impressive relief of pruritus in the vast majority of patients. New therapies including biologics (e.g. nemolizumab, tralokinumab, lebrikizumab), small molecules (e.g. neurokinin-1 receptor antagonists, janus kinase inhibitors) as well as mu-opioid receptor antagonists and nalbuphine, a μ-antagonist/κ-agonist, are in the pipeline and offer new hope for an improved future patient care.
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Affiliation(s)
- Svenja Müller
- Department of Dermatology and Allergy; Christine Kühne-Center for Allergy Research and Education (CK-CARE), University Hospital Bonn, Bonn, Germany
| | - Thomas Bieber
- Department of Dermatology and Allergy; Christine Kühne-Center for Allergy Research and Education (CK-CARE), University Hospital Bonn, Bonn, Germany
| | - Sonja Ständer
- Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Münster, Germany
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Satoh T, Yokozeki H, Murota H, Tokura Y, Kabashima K, Takamori K, Shiohara T, Morita E, Aiba S, Aoyama Y, Hashimoto T, Katayama I. 2020 guidelines for the diagnosis and treatment of prurigo. J Dermatol 2021; 48:e414-e431. [PMID: 34314056 DOI: 10.1111/1346-8138.16067] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 06/24/2021] [Accepted: 06/25/2021] [Indexed: 11/28/2022]
Abstract
Prurigo is a treatment-resistant skin disease characterized by multiple isolated papules/nodules that cause severe itch. Prurigo papules/nodules occur either as primary lesions or as secondary lesions due to persistent scratching. The fundamental concepts and classifications of prurigo have not been sufficiently established, and considerable confusion remains regarding this topic. Clinical guidelines for chronic prurigo in Japan were published in 2012 in an attempt to reduce confusion regarding the concepts of prurigo and to standardize laboratory tests and treatments. However, the diagnostic terms for prurigo and associated concepts have changed over time, and new forms of treatment are under development. We have, thus, updated and revised the guidelines to classify prurigo based on clinical forms and causes, and disease name classifications based on the clinical form have been further simplified, such as prurigo nodularis, prurigo chronica multiformis, and prurigo (not otherwise specified). Expressions for acute, subacute, and chronic forms are not used. These guidelines outline the current concepts and specify treatments for prurigo.
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Affiliation(s)
- Takahiro Satoh
- Department of Dermatology, National Defense Medical College, Tokorozawa, Japan
| | - Hiroo Yokozeki
- Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hiroyuki Murota
- Department of Dermatology, School of Medical Sciences, Nagasaki University, Nagasaki, Japan
| | - Yoshiki Tokura
- Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Kenji Kabashima
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Kenji Takamori
- Juntendo Itch Research Center, Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Tetsuo Shiohara
- Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Eishin Morita
- Department of Dermatology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Setsuya Aiba
- Department of Dermatology, Tohoku University School of Medicine, Sendai, Japan
| | - Yumi Aoyama
- Department of Dermatology, Kawasaki Medical School, Kurashiki, Japan
| | - Takashi Hashimoto
- Department of Dermatology, National Defense Medical College, Tokorozawa, Japan
| | - Ichiro Katayama
- Department of Dermatology, Course of Integrated Medicine Graduate School of Medicine, Osaka University, Suita, Japan
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29
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Belmesk L, Muntyanu A, Cantin E, AlHalees Z, Jack CS, Le M, Sasseville D, Iannattone L, Ben-Shoshan M, Litvinov IV, Netchiporouk E. Prominent Role of Type 2 Immunity in Skin Diseases-Beyond Atopic Dermatitis. J Cutan Med Surg 2021; 26:33-49. [PMID: 34261335 DOI: 10.1177/12034754211027858] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Type 2 immunity, illustrated by T helper 2 lymphocytes (Th2) and downstream cytokines (IL-4, IL-13, IL-31) as well as group 2 innate lymphoid cells (ILC2), is important in host defense and wound healing.1 The hallmark of type 2 inflammation is eosinophilia and/or high IgE counts and is best recognized in atopic diathesis. Persistent eosinophilia, such as seen in hypereosinophilic syndromes, leads to fibrosis and hence therapeutic Type 2 inhibition in fibrotic diseases is of high interest. Furthermore, as demonstrated in cutaneous T cell lymphoma, advanced disease is characterized by Th1 to Th2 switch allowing cancer progression and immunosuppression. Development of targeted monoclonal antibodies against IL-4Rα (eg, dupilumab) led to a paradigm shift for the treatment of atopic dermatitis (AD) and stimulated research to better understand the role of Type 2 inflammation in other skin conditions. In this review, we summarize up to date knowledge on the role of Type 2 inflammation in skin diseases other than AD and highlight whether the use of Type 2 targeted therapies has been documented or is being investigated in clinical trials. This manuscript reviews the role of Type 2 inflammation in dermatitis, neurodermatitis, IgE-mediated dermatoses (eg, bullous pemphigoid, chronic spontaneous urticaria), sclerodermoid conditions and skin neoplasms.
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Affiliation(s)
| | - Anastasiya Muntyanu
- 544735620507266 Division of Dermatology, McGill University Health Centre, Montreal, QC, Canada
| | | | - Zeinah AlHalees
- 544735620507266 Division of Dermatology, McGill University Health Centre, Montreal, QC, Canada
| | - Carolyn S Jack
- 544735620507266 Division of Dermatology, McGill University Health Centre, Montreal, QC, Canada
| | - Michelle Le
- 544735620507266 Division of Dermatology, McGill University Health Centre, Montreal, QC, Canada
| | - Denis Sasseville
- 544735620507266 Division of Dermatology, McGill University Health Centre, Montreal, QC, Canada
| | - Lisa Iannattone
- 60301 Division of Dermatology, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada
| | - Moshe Ben-Shoshan
- Division of Pediatric Allergy Immunology and Dermatology, Department of Pediatrics, McGill University Health Center, Montreal, QC, Canada
| | - Ivan V Litvinov
- 544735620507266 Division of Dermatology, McGill University Health Centre, Montreal, QC, Canada
| | - Elena Netchiporouk
- 544735620507266 Division of Dermatology, McGill University Health Centre, Montreal, QC, Canada
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Abstract
Dermatitis encompasses a spectrum of inflammatory skin disorders with aberrant immune responses classified as type 1, type 2, and/or type 3. Major advances in the understanding of the pathogenesis of atopic dermatitis (AD) have shed new light on how innate immune responses critically regulate type 2 inflammation and itch. This article highlights the diverse ways by which type 2 immune cells regulate diseases beyond AD. The discovery of human Mas-related G protein-coupled receptor X2 on mast cells has revealed novel T cell-independent and immunoglobulin E-independent mechanisms of allergic contact dermatitis-associated and urticarial itch, respectively.
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Affiliation(s)
- Damien Abreu
- Medical Scientist Training Program, Washington University School of Medicine, Box 8226, 660 South Euclid Avenue, St. Louis, MO 63110-1093, USA; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
| | - Brian S Kim
- Division of Dermatology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St Louis, MO 63110, USA; Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
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31
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Napolitano M, Di Guida A, Nocerino M, Fabbrocini G, Patruno C. The emerging role of dupilumab in dermatological indications. Expert Opin Biol Ther 2021; 21:1461-1471. [PMID: 33769900 DOI: 10.1080/14712598.2021.1907341] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Dupilumab represents a breakthrough in the management of atopic dermatitis (AD), thanks to its powerful T-helper (Th)2-mediated immunity modulating activity. It can reduce the atopic skin molecular signature and induce a significant decrease in the clinical signs and symptoms of AD patients. AREAS COVERED Th2 activation has been confirmed or suspected in skin diseases other than AD, and several reports about the treatment with dupilumab in these conditions have been published. In order to review the new indications of dupilumab in dermatology, we performed a search on PubMed, Embase, Cochrane Skin databases, and clinicaltrials.gov. EXPERT OPINION The analysis of available literature suggests that dupilumab may have a large application in dermatology, besides AD. Clinical trials are underway on some widespread disease (i.e. chronic urticaria, bullous pemphigoid, alopecia areata, or allergic contact dermatitis). The data are still partial, but they seem to indicate that dupilumab is efficacious and safe. On the other hand, the dupilumab use in some rare skin diseases remains only hypothetical or linked to few case reports. Dupilumab could have a prominent position in the therapeutic algorithm of chronic skin diseases that significantly affect the quality of life of patients, require long-term treatment, or lacking effective therapies.
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Affiliation(s)
- Maddalena Napolitano
- Department of Medicine and Health Sciences Vincenzo Tiberio, University of Molise, Campobasso, Italy
| | - Adriana Di Guida
- Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy
| | - Mariateresa Nocerino
- Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy
| | - Gabriella Fabbrocini
- Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy
| | - Cataldo Patruno
- Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
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Takeuchi S, Inoue K, Kuretake K, Kiyomatsu-Oda M, Furue M. Dupilumab shows slow, steady effectiveness for intractable prurigo in patients with atopic dermatitis. J Dermatol 2021; 48:638-644. [PMID: 33742710 DOI: 10.1111/1346-8138.15843] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 02/17/2021] [Accepted: 02/21/2021] [Indexed: 11/27/2022]
Abstract
Prurigo lesions in atopic dermatitis are intractable. This single-center, retrospective study examined dupilumab's clinical effects on intractable prurigo. Twenty adult atopic dermatitis patients (12 with prurigo, eight without) were administrated dupilumab. Its effects on itching and disease severity were examined with Numerical Rating Scale-Itch (NRS-I), Eczema Area and Severity Index (EASI), and Investigator Global Assessment (IGA) scores; body surface areas (BSA); and thymus- and activation-regulated chemokine (TARC), total immunoglobulin (Ig)E, and eosinophil levels. NRS-I scores, EASI scores, TARC levels, and total IgE levels before dupilumab treatment were not statistically different between the prurigo and non-prurigo groups. With dupilumab treatment, NRS-I scores, EASI scores, IGA scores, BSA, TARC levels, and total IgE levels were significantly reduced from baseline in both groups at 1-2 months and onward, but skin symptom improvement in the prurigo group was slower than in the non-prurigo group, as evidenced by significantly higher EASI scores, BSA, and TARC levels at several time points during the 12 months of dupilumab treatment. Prurigo patients were slower in EASI-50 achievement and significantly lower in EASI-90 achievement at 12 months than non-prurigo patients. Adherence to dupilumab was not different, but total equivalent amounts of concomitant therapeutic agents (corticosteroids and tacrolimus) used during dupilumab treatment were significantly higher in the prurigo group (median, 56.2 g/week) than in the non-prurigo group (median, 33.7 g/week). There were 2.2 adverse events per patient on average; ocular complaints were most frequent. Dupilumab was effective in treating intractable prurigo, but despite significantly greater concomitant therapeutic agent use, skin symptom improvement was slower in prurigo patients than in non-prurigo patients.
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Affiliation(s)
- Satoshi Takeuchi
- Department of Dermatology, Federation of National Public Service Personnel Mutual Aid Associations, Hamanomachi Hospital, Fukuoka, Japan.,Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Keiichi Inoue
- Department of Dermatology, Federation of National Public Service Personnel Mutual Aid Associations, Hamanomachi Hospital, Fukuoka, Japan
| | - Keisuke Kuretake
- Department of Dermatology, Federation of National Public Service Personnel Mutual Aid Associations, Hamanomachi Hospital, Fukuoka, Japan
| | - Mari Kiyomatsu-Oda
- Department of Dermatology, Federation of National Public Service Personnel Mutual Aid Associations, Hamanomachi Hospital, Fukuoka, Japan
| | - Masutaka Furue
- Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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33
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Toffoli L, Farinazzo E, Zelin E, Agozzino M, Dianzani C, Di Meo N, Nan K, Zalaudek I, Conforti C. Dupilumab as promising treatment for prurigo nodularis: current evidences. J DERMATOL TREAT 2021; 33:1306-1311. [PMID: 33588666 DOI: 10.1080/09546634.2021.1886232] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Prurigo nodularis (PN) is a debilitating chronic disease characterized by intense itching and excoriated hyperkeratotic nodules distributed on the trunk and extremities, especially the extensor surfaces. The pathophysiology includes complex and not yet well-understood mechanisms involving inflammation and dysregulation of the nervous system. Currently, there are no approved therapies by the Food and Drug Administration (FDA) and the few treatment approaches for this condition are often ineffective and related to severe side effects. An emerging therapeutic option is dupilumab, a monoclonal antibody for adults and adolescents with moderate-to-severe atopic dermatitis, that inhibits interleukin-4 receptor alpha subunit (IL4-Rα) and the signaling pathways activated by interleukin (IL)-4 and IL-13. These cytokines seem to be involved in the development and perpetuation of PN and other type-2 inflammation diseases. Data on this topic are limited, but the emergent positive effects of this drug, reported in the literature and summarized in this review, suggest that it can be a safe and efficient therapy in PN.
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Affiliation(s)
- Ludovica Toffoli
- Dermatology & Venereology Department, Maggiore Hospital, University of Trieste, Trieste, Italy
| | - Eleonora Farinazzo
- Dermatology & Venereology Department, Maggiore Hospital, University of Trieste, Trieste, Italy
| | - Enrico Zelin
- Dermatology & Venereology Department, Maggiore Hospital, University of Trieste, Trieste, Italy
| | - Marina Agozzino
- Dermatology & Venereology Department, Maggiore Hospital, University of Trieste, Trieste, Italy
| | - Caterina Dianzani
- Plastic and Reconstructive Surgery Department, Section of Dermatology, Campus Biomedico University, Rome, Italy
| | - Nicola Di Meo
- Dermatology & Venereology Department, Maggiore Hospital, University of Trieste, Trieste, Italy
| | - Katiuscia Nan
- Dermatology & Venereology Department, Maggiore Hospital, University of Trieste, Trieste, Italy
| | - Iris Zalaudek
- Dermatology & Venereology Department, Maggiore Hospital, University of Trieste, Trieste, Italy
| | - Claudio Conforti
- Dermatology & Venereology Department, Maggiore Hospital, University of Trieste, Trieste, Italy
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Fachler T, Maria Faitataziadou S, Molho-Pessach V. Dupilumab for pediatric prurigo nodularis: A case report. Pediatr Dermatol 2021; 38:334-335. [PMID: 33247435 DOI: 10.1111/pde.14464] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Herein we report on a 9-year-old girl with recalcitrant prurigo nodularis unresponsive to multiple standard treatments. She was started on dupilumab therapy with rapid improvement in pruritus within 2 weeks and near complete regression of lesions at 3 months. Dupilumab should be considered as an off-label treatment for refractory prurigo nodularis in children.
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Affiliation(s)
- Tahel Fachler
- Department of Dermatology, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Sofia Maria Faitataziadou
- Department of Dermatology, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Vered Molho-Pessach
- Department of Dermatology, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
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35
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Husein-ElAhmed H, Steinhoff M. Dupilumab in prurigo nodularis: a systematic review of current evidence and analysis of predictive factors to response. J DERMATOL TREAT 2020; 33:1547-1553. [DOI: 10.1080/09546634.2020.1853024] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Affiliation(s)
- Husein Husein-ElAhmed
- Department of Dermatology and Venereology, Hospital de Baza, Granada, Spain
- Hamad Medical Corporation, Translational Research Institute, Doha, Qatar
| | - Martin Steinhoff
- Hamad Medical Corporation, Translational Research Institute, Doha, Qatar
- Department of Dermatology and Venereology, Hamad Medical Corporation, Doha, Qatar
- Weill Cornell Medicine-Qatar, College of Medicine, Doha, Qatar
- Medical School, Qatar University, Doha, Qatar
- Department of Dermatology, Weill Cornell Medicine, New York, NY, USA
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36
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Abstract
Chronic pruritus, defined as an unpleasant sensation resulting in a need to scratch that lasts more than 6 weeks, is a prevalent and bothersome symptom associated with both cutaneous and systemic conditions. Due to complex pathogenesis and profuse contributing factors, chronic pruritus therapy remains challenging. Regardless of the well-established antipruritic properties of classic pharmacotherapy (topical therapy, phototherapy and systemic therapy), these methods often provide insufficient relief for affected individuals. Owing to the growing interest in the field of pruritic research, further experimental and clinical data have emerged, continuously supporting the possibility of instigating novel therapeutic measures. This review covers the most relevant current modalities remaining under investigation that possess promising perspectives of approval in the near future, especially opioidergic drugs (mu-opioid antagonists and kappa-opioid agonists), neurokinin-1 receptor antagonists, biologic drugs, Janus kinase inhibitors, ileal bile acid transporter inhibitors, aryl hydrocarbon receptor agonists and histamine H4 receptor antagonists.
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Affiliation(s)
- Radomir Reszke
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, 1 Chalubinskiego Street, 50-368, Wrocław, Poland
| | - Piotr Krajewski
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, 1 Chalubinskiego Street, 50-368, Wrocław, Poland
| | - Jacek C Szepietowski
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, 1 Chalubinskiego Street, 50-368, Wrocław, Poland.
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37
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Fourzali K, Golpanian RS, Yosipovitch G. Dupilumab use in atopic dermatitis and beyond in skin diseases. Immunotherapy 2020; 12:1221-1235. [PMID: 32892674 DOI: 10.2217/imt-2020-0175] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
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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Affiliation(s)
- Kayla Fourzali
- Dr Phillip Frost Department of Dermatology & Cutaneous Surgery & Miami Itch Center, University of Miami Miller School of Medicine, 1600 NW 10th Ave, RMSB 2023, Miami, FL 33136, USA
| | - Rachel Shireen Golpanian
- Dr Phillip Frost Department of Dermatology & Cutaneous Surgery & Miami Itch Center, University of Miami Miller School of Medicine, 1600 NW 10 Ave, RMSB 2023, Miami, FL 33136, USA
| | - Gil Yosipovitch
- Dr Phillip Frost Department of Dermatology & Cutaneous Surgery & Miami Itch Center, University of Miami Miller School of Medicine, 1600 NW 10 Ave, RMSB 2023, Miami, FL 33136, USA
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38
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Erickson S, Heul AV, Kim BS. New and emerging treatments for inflammatory itch. Ann Allergy Asthma Immunol 2020; 126:13-20. [PMID: 32497711 DOI: 10.1016/j.anai.2020.05.028] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 05/20/2020] [Accepted: 05/25/2020] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To summarize recent therapeutic developments for chronic pruritus with a focus on allergic and type 2 inflammatory pathways. DATA SOURCES Literature search of PubMed, industry websites, and review of the ClinicalTrials.gov database. STUDY SELECTIONS Peer-reviewed publications and public disclosures by industry relating to chronic pruritus pathophysiology and therapeutics. RESULTS Histamine and immunoglobulin E remain primary targets for the treatment of itch in the setting of chronic urticaria. More recently, blockade of type 2 immune cell-associated cytokines, including interleukin (IL) 4, IL-13, and IL-31, and the epithelial cell-derived cytokines, specifically IL-33 and thymic stromal lymphopoietin, has and is revolutionizing the treatment of chronic pruritic dermatoses, such as atopic dermatitis and prurigo nodularis. Other novel targets include histamine receptor 4, Janus kinases, κ-opioid receptor, neurokinin 1 receptor, and phosphodiesterase 4. CONCLUSION Advances in our understanding of the neuroimmunology of chronic pruritus have led to the identification of new therapeutic targets and the rapid development of cutting-edge clinical trials. Although incredible advances have already been made, chronic itch continues to be an area of great unmet need.
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Affiliation(s)
- Stephen Erickson
- Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
| | - Aaron Ver Heul
- Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, Missouri
| | - Brian S Kim
- Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, Missouri; Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
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