A prospective study examining the expression of STAT 1, 3, 6 in prurigo nodularis lesions with its immunopathogenic and therapeutic implications

Agrawal, Diksha; Sardana, Kabir; Mathachan, Sinu Rose; Bhardwaj, Minakshi; Ahuja, Arvind; Jain, Swasti

doi:10.1111/jocd.14709

Cited by 21 publications

(26 citation statements)

References 40 publications

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“…One study evaluated the JAK STAT pathway in prurigo nodules to determine if this inflammatory pathway may be prevalent in the disease. 90 The results reported that STAT 2 and 3 were upregulated in PN lesions, as well as corresponding cytokines of Th2, Th17, and Th22. STATs are intracellular transcription factors that propagate extracellular signals from JAK receptors to the nucleus.…”

Section: Current Immunotherapeutics Used For Pnmentioning

confidence: 94%

“…STATs are intracellular transcription factors that propagate extracellular signals from JAK receptors to the nucleus. 90 Numerous cytokines activate the JAK response. Th1, Th2/Th17/Th22, and Th2 cellular pathways are mediated by STAT 1, 3, and 6, respectively.…”

Section: Current Immunotherapeutics Used For Pnmentioning

confidence: 99%

“…Th1, Th2/Th17/Th22, and Th2 cellular pathways are mediated by STAT 1, 3, and 6, respectively. 90 Therefore, the use of JAK inhibitors may be effective at decreasing disease progression. One case report demonstrates the efficacy of oral tofacitinib, a JAK 1 and JAK 3 inhibitor, in minimizing skin lesions by 50% and completely diminishing pruritus in a patient with intractable PN.…”

Section: Current Immunotherapeutics Used For Pnmentioning

confidence: 99%

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Immunotargets and Therapy for Prurigo Nodularis

Labib¹,

Ju²,

Does³

et al. 2022

ITT

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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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Section: Current Immunotherapeutics Used For Pnmentioning

confidence: 94%

Section: Current Immunotherapeutics Used For Pnmentioning

confidence: 99%

Section: Current Immunotherapeutics Used For Pnmentioning

confidence: 99%

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Immunotargets and Therapy for Prurigo Nodularis

Labib¹,

Ju²,

Does³

et al. 2022

ITT

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“…The recalcitrant itch of this disease is not relieved by conventional anti-pruritic therapies. Although the pathogenesis is not fully understood, 1 study reported that STAT 2 and 3 were upregulated in pruritic nodules, as well as the corresponding cytokines Th2, Th17, and Th22 ( 33 ). Two clinical trials have been conducted to evaluate the efficacy of JAK inhibitors in prurigo nodularis ( 32 , 34 ).…”

Section: Resultsmentioning

confidence: 99%

Itch and Janus Kinase Inhibitors

et al. 2023

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Itch is a common skin symptom, with complex aetiology and pathogenesis. It is mediated by 2 pathways, the histaminergic and non-histaminergic pathways. Chronic itch is understood to be processed by the latter and is difficult to treat with traditional pruritus therapies. The Janus kinase and signal transducer and activator of transcription pathway is a signalling mechanism that regulates gene expression through various cytokines. Janus kinase inhibitors, which have been tested and used for several autoimmune diseases, have also been shown to be effective for itch through clinical trials and case reports. Janus kinase inhibitors could be a good choice for pruritus in atopic dermatitis, psoriasis, and other diseases, such as prurigo nodularis and lichen planus, with rapid itch relief compared with conventional treatments. The most common adverse effects reported include nasopharyngitis, acne, and elevated blood creatine phosphokinase levels. Janus kinase inhibitors are currently prescribed with warnings about a potential increase in malignancies and cardiovascular diseases and usage in people of older ages. This review aims to provide knowledge about itch and the Janus kinase and signal transducer and activator of transcription pathway and to analyse the current evidence for itch relief by Janus kinase inhibitors.

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“…These cytokines (IL-4, IL-13, and IL-31) have been found to induce local pruritus in human or in somatic animal models with subcutaneous injections [28,29,30] . Recent studies have revealed that IL-4 and IL-13 can exert intercellular inflammatory transduction by binding to IL-4RA, and that IL4-RA can further induce chronic inflammatory and pruritic responses by further activating the JAK1 signalling pathway [31,32,33] . The mechanism of dupilumab is primarily targeted to antagonize IL-4/13R.…”

Section: Discussion and Literature Reviewmentioning

confidence: 99%

Dupilumab for Recurrent Prurigo Nodularis: A Case Report and Review of the Literature

2023

medsc

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Prurigo nodularis (PN) is a chronic inflammatory skin disease that affects the quality of life of patients and is classified in the ICD-10 as a group of chronic lichen simplex and itchy skin diseases (ICD-10/L28) with an incidence of approximately 36.7-148.53 per 100,000 people. The pathogenesis of PN is closely related to type 2 inflammatory response. There are no standardized treatment guidelines for this disease, and traditional anti-pruritic treatment regimens often fail to control the vicious pruritic-scratch cycle in PN and have a poor safety profile. Traditional treatment options for PN include oral antihistamines, thalidomide, and topical hormones, calcium phosphatase inhibitors, and other treatments. However, traditional treatment options often suffer from poor pruritus control and high side effects. A patient with prurigo nodularis was admitted to our hospital who responded poorly to routine topical glucocorticoids and other drug therapies and relapsed after discharge from treatment. After readmission, the patient was successfully treated with dupilumab, a biological agent targeting interleukin-4/13. The patient's rash was significantly flattened, and the pruritus NRS score was significantly decreased. In this case, successful treatment of refractory PN with dupilumab could provide new ideas for treatment.

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A prospective study examining the expression of STAT 1, 3, 6 in prurigo nodularis lesions with its immunopathogenic and therapeutic implications

Cited by 21 publications

References 40 publications

Immunotargets and Therapy for Prurigo Nodularis

Immunotargets and Therapy for Prurigo Nodularis

Itch and Janus Kinase Inhibitors

Dupilumab for Recurrent Prurigo Nodularis: A Case Report and Review of the Literature

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