Notalgia Research Articles

From Compression to Itch: Exploring the Link Between Nerve Compression and Neuropathic Pruritus.

Neuropathic itch is a type of chronic pruritus resulting from neural dysfunction along the afferent pathway. It is often accompanied by abnormal sensations such as paresthesia, hyperesthesia, or hypoesthesia. This condition, which may involve motor or autonomic neural damage, significantly impacts patients' quality of life, causing severe itch and associated comorbidities such as depression, disrupted sleep, and social strain. Neuropathic itch accounts for 8% of chronic pruritus cases, though this may be underestimated. This comprehensive review focuses on nerve impingement as the primary pathophysiological mechanism for various forms of neuropathic itch including brachioradial pruritus (BRP), notalgia paresthetica (NP), and anogenital itch. BRP, often seen in middle-aged white women, manifests as pruritus in the dorsolateral forearms typically exacerbated by ultraviolet (UV) exposure and related to cervical spine pathology. NP, prevalent in middle-aged women, presents as pruritus in the upper back due to thoracic spine nerve compression. Anogenital pruritus, affecting 1-5% of adults, is often linked to lumbosacral spine issues after ruling out dermatologic conditions such as lichen sclerosus or lichen simplex chronicus. The pathophysiology of neuropathic itch involves both peripheral and central mechanisms, with nerve damage being a key factor. Diagnosis requires a thorough history, physical examination, and potentially imaging studies. Topical agents such as menthol, capsaicin, and lidocaine are used for mild cases, while systemic medications such as gabapentin, pregabalin, and antidepressants are prescribed for moderate to severe cases; however, no USFood and Drug Administration (FDA)-approved therapies currently exist specifically for neuropathic itch. Understanding the underlying neural dysfunction and appropriate therapeutic strategies is crucial for managing neuropathic itch effectively.

Notalgia Paresthetica Dermatologist Report of Symptom Burden and Treatment: Results from a Physician Survey.

Notalgia paresthetica (NP) is a sensory neuropathy characterized by chronic pruritus, skin pain, and other pathologic sensations affecting the mid-to-upper back. NP may be under-recognized and under-diagnosed, with limited data available on its symptom presentation and treatment patterns. NP-DERM was an internet-based survey of dermatologists (n = 650) from 8 different countries on their perspectives on NP symptoms and current treatment practices. Dermatologists typically treated a median of 12 patients with NP per month. Dermatologists reported that itch (pruritus) was the most common symptom for their patients with NP, followed by hyperpigmentation and sensitive skin. The most burdensome NP symptom was pruritus, followed by burning or hot sensation, and painful or raw skin. The most prescribed treatments included non-medicated skin care, topical corticosteroids, oral antihistamines, medicated topicals, and gabapentin or pregabalin. Physicians reported low satisfaction with available treatments. The most common reason for physicians to discontinue patients' therapy was lack of response.

Patient perspective on symptoms of Notalgia paresthetica: subpopulation results from the Neuropathic Itch Patient Survey (NIRVE)

Background: Notalgia paresthetica (NP) is a form of neuropathic itch characterized by recurrent itch in the mid back. Much about NP remains unclear, especially the patient experience. Objectives: The Neuropathic Itch Patient Survey (NIRVE) was a global, online survey conducted to better characterize the symptom burden of neuropathic itch from the patient perspective. Patients and methods: This report focuses on the symptom burden of the subpopulation of NIRVE participants with a self-reported diagnosis of NP (N = 91). Respondents reported visiting a median of 2 healthcare providers (HCPs) for their symptoms before receiving an accurate diagnosis of NP. Results: The most common cutaneous symptoms ever experienced were itch/pruritus, sensitive skin, painful or raw skin, numbness, and tingling. The symptoms reported by the most respondents as currently being experienced included itch/pruritus, numbness, painful or raw skin, tingling, and burning or hot sensation. Of patients currently experiencing symptoms, numbness and itch/pruritus were ranked as the most intense, followed by tingling, burning or hot sensation, and then painful or raw skin. Most patients consult multiple healthcare providers (HCPs) before receiving a diagnosis for their condition. Conclusion: Itch is overwhelmingly the most prevalent symptom of the condition, although half of patients also report experiencing sensitive skin, painful or raw skin, numbness, or tingling.

Quantitative sensory testing in notalgia paresthetica reveals small fiber-type-specific differences in non-pruritic sensitivity: a pilot study.

Notalgia paresthetica (NP) is a chronic condition characterized by pruritus and other unpleasant dysesthetic sensations unilaterally on the subscapular back. Its specific underlying mechanisms are largely unknown, though hypothesized to be neuropathic. Determination of possible somatosensory contributors to the condition could pave the way for novel treatments. Given the potential involvement of non-pruritic mechanisms in NP, our objective was to broadly characterize the somatosensory function in NP-affected and unaffected skin using methods that have been standardized in pain-free controls and painful neuropathic disorders. We hypothesized that if NP is caused by neuropathic mechanisms not targeted directly to pruritoceptors in the skin, somatosensory abnormalities would not be itchspecific. Second, given the lack of symptoms on the contralateral side of the back, we hypothesized that this region would be normally sensitive. In this study, quantitative sensory testing (QST) was used to comprehensively assess the somatosensory function in 15 adult patients with NP. Standardized QST metrics were performed in the NP-affected region and compared with the contralateral asymptomatic skin and itch-free individuals using an age, gender, and site-matched reference data set. There were no significant differences in sensitivity between symptomatic and asymptomatic skin, except for increased mechanical-evoked itch on the itchy side. However, reference data set comparisons revealed bilateral hyposensitivity to innocuous cold and noxious pinprick and higher temporal summation of pain in patients with NP. In addition, compared with reference data, patients with NP demonstrated decreased sensitivity to cold and pinprick, presence of paradoxical heat sensations, and increased wind-up of pain. These results suggest a role for Aδ fiber pathways and central sensitization in NP-associated itch. More research is needed to determine whether sensory differences extend beyond the NP-affected dermatomal level and what might cause neuropathy specifically targeting Aδ fibers.

Evaluation of fibromyalgia frequency and quality of life in Notalgia paresthetica patients

Based on the presence of chronic pain and the potential use of common treatment agents in Notalgia Paresthetica (NP) and Fibromyalgia Syndrome (FMS) for improvement, we aimed to investigate the frequency of FMS symptoms in NP patients and its impact on quality of life. This study is a case control cohort study including 26 patients diagnosed with NP and a total of 26 controls matched for age and gender. The 2016 revised fibromyalgia diagnostic criteria by the American College of Rheumatology (ACR) were used to inquire about FMS diagnosis criteria in the study. According to the 2016 ACR revised FMS diagnostic criteria, the frequency of FMS was significantly higher in the patient group (n = 9, 34.6%) compared to the control group (n = 2, 7.7%) (p = 0.042). The Wide Pain Index (WPI) score in the control group was 2.00 (3.25), while in the patient group, it was 4.00 (8.00), with a statistically significant difference between them (p < 0.035). Furthermore, significant statistical differences were found between the two groups in terms of Symptom Severity Scale (SSS), Fibromyalgia Score (FS), and FIQ (p < 0.035, p < 0.001, p < 0.001, respectively). In NP patients with accompanying FMS, Dermatology Life Quality Index was significantly more affected compared to those without FMS (p = 0.025). In conclusion, we recommend that NP patients be questioned about FMS, which is characterized by generalized pain, as well as regional neuropathic symptoms. Treatment success can be enhanced by using common agents in the treatment choice for accompanying FMS.

Valleix's Sign.

Some patients present with clinical symptoms of localized tenderness and pain associated with a specific peripheral nerve, such as the ulnar nerve at the elbow or the sciatic nerve, which has been called, although rarely, "Valleix point" or "Valleix phenomenon". The purpose of this article was to translate and research the 719-page book "Traité des névralgies ou affections douloureuses des nerfs" dated 1841, dedicated solely to nerve pain (neuralgia), written by the French physician François Louis Isidore Valleix (1807-1855). He may have been the first person to observe and describe this phenomenon of localized pain, but he was probably also the first to describe distal nerve radiation, which he called "élancement" or lancinating, or stabbing. He described the phenomenon of a nerve producing pain at points along its course that we now understand to be sites of compression, clearly describing cubital and fibular tunnel syndromes, which he called neuralgias. He also described some rarer sites of compression, such as supraorbital and occipital neuralgia, notalgia paresthetica, and ACNES, but he did not describe the most common site of compression today, the median nerve at the wrist. Valleix's descriptions are clear and precede the classic 1915 reports of Hoffmann's and Tinel's signs by 74 years.

Coexistence of Notalgia Paresthetica and Cervical Discopathy in a Young Girl

Coexistence of Notalgia Paresthetica and Cervical Discopathy in a Young Girl

On the Question of Differential Diagnosis of Skin Hyperpigmentations: The Clinical Case of Notalgia Paresthetica

Introduction. Developmental disorders acquire an extensive group of diseases, including congenital forms in inheritance variants, as well as secondary acquired forms due to skin or systemic manifestations.The purpose of this publication is to demonstrate the features of the differential diagnosis of skin hyperpigmentation to identify the clinical manifestation of notalgia paresthetica.Materials and methods. A review of foreign and domestic literary sources was carried out using the search engines eLibrary.Ru, Scopus, PubMed. On the basis of the patient’s voluntary informed consent, an analysis of medical documentation was carried out, taking into account clinical and anamnestic data and the results of laboratory and instrumental examination. Results. The article presents a review of the literature, as well as a clinical case of notalgia paresthetica in a patient with degenerative-dystrophic changes in the thoracic spine.Discussion. Notalgia paresthetica belongs to a large group of cutaneous dysesthesias and is a sensory neuropathy characterized by localized unilateral itching and hyperpigmentation of the skin of the back in the zone of innervation of the cutaneous branches of the thoracic spinal nerves, affecting more often adult and elderly women. The nonspecificity of skin manifestations of notalgia paresthetica and the low awareness of doctors about this disease can lead to diagnostic and tactical errors. Skin itching of varying intensity is the main symptom of the disease, leading to an accentuation of its disease and a decrease in the quality of life of patients.Conclusion. Given the interdisciplinary nature of the pathology, the article may be of interest to neurologists, neurosurgeons, dermatovenereologists, general practitioners, general practitioners, oncologists, and endocrinologists.

Novel Clinical Applications of Topical Ruxolitinib: A Case Series.

Topical ruxolitinib, a potent Janus kinase (JAK) inhibitor, has shown significant efficacy in treating inflammatory skin conditions. While its use has already been established in atopic dermatitis and vitiligo, recent reports suggest its potential efficacy in treating other dermatoses. Specifically, topical ruxolitinib may be an effective treatment option for refractory dermatological conditions that are inflammation-driven with dysregulated activity of cytokines implicated in the JAK/STAT pathway. In this case series, we present four novel clinical applications of topical ruxolitinib in treatment-resistant dermatological conditions. These cases include pediatric lichen sclerosus et atrophicus, morphea, perioral dermatitis, and notalgia paresthetica. All four patients reported noticeable symptomatic improvement and a significant improvement in the condition of their skin lesions. Our results suggest that ruxolitinib cream can successfully manage these conditions and may serve as supporting evidence for its formal evaluation. &nbsp; J Drugs Dermatol. 2024;23(3): doi:10.36849/JDD.7696.

Rapid Reduction and Free or Almost Free of Itch Response With Oral Difelikefalin in Subjects With Notalgia Paresthetica and Moderate-to-Severe Pruritus

Rapid Reduction and Free or Almost Free of Itch Response With Oral Difelikefalin in Subjects With Notalgia Paresthetica and Moderate-to-Severe Pruritus

United States expert panel consensus on uniform nomenclature and diagnosis for neuropathic pruritus

Importance: Neuropathic pruritus is a debilitating condition lacking a uniform approach to nomenclature and diagnosis. Objective: A panel of dermatologist experts in pruritus was convened to develop definitions, diagnostic recommendations, and treatment guidelines for neuropathic pruritus. Evidence review: A roundtable discussion of 10 experts was conducted on November 3, 2021, via the Zoom platform. This study follows the Standards for Reporting Qualitative Research reporting guidelines for qualitative studies. A systematic review of prior literature on the definition, scope, diagnostic, and treatment was performed, looking at sources of treatment from 1991 to 2021. Consensus was defined as &gt;70% agreement for acceptance of a definition or recommendation. A draft of evidence was subjected to revision by all participants and was endorsed by all participants. Findings: The roundtable identified definitions for neuropathic pruritus, which included different forms of the condition based on cause and presentation such as brachioradial pruritus, notalgia paresthetica, and scalp pruritus. Diagnostic and treatment guidelines were also established. Limitations of this process included lack of randomized controlled studies. These recommendations are also based on expert consensus and must be further supported by evidence-based outcomes research. Conclusions: Neuropathic pruritus contains numerous subtypes, causes, diagnostic methods, and treatment modalities. The recommendations developed by this panel are meant to serve as shared nomenclature for future clinical studies.

Dextrose Injection in Treatment of a Patient Who Was Diagnosed with Notalgia Paresthetica: a Case Report

Dextrose Injection in Treatment of a Patient Who Was Diagnosed with Notalgia Paresthetica: a Case Report

43755 Rapid Reduction and Strict Complete Response in Itch With Oral Difelikefalin in Subjects With Notalgia Paresthetica and Moderate-to-Severe Pruritus

43755 Rapid Reduction and Strict Complete Response in Itch With Oral Difelikefalin in Subjects With Notalgia Paresthetica and Moderate-to-Severe Pruritus

New Treatment for Notalgia Paresthetica Shows Modest Efficacy with Side Effects

New Treatment for Notalgia Paresthetica Shows Modest Efficacy with Side Effects

Notalgia Paresthetica Review: Update on Presentation, Pathophysiology, and Treatment

Notalgia paresthetica (NP) is a chronic cutaneous neuropathy primarily characterized by localized pruritus and associated dysesthesias, including sensations of pain, numbness, and tingling. The sensory neuropathy characteristic of NP is thought to result from spinal nerve entrapment caused by degenerative changes in the spine or musculoskeletal compression. This review summarizes the current medical literature with a focus on the past five years regarding NP, its pathophysiology, presentation, and current treatment options. Though treatments exist with varying efficacy, to date, there exists no definitive treatment for NP. Treatment options for NP are varied and range from topical and oral agents to interventional procedures and physical therapy. Of the treatments evaluated, topical capsaicin remains the most efficacious treatment for NP. The lack of established treatment guidelines makes treating NP complicated as it dramatically affects patients' quality of life. Further research with larger sample sizes is needed to evaluate better the most effective treatment and dosing regimen for patients afflicted with NP.

Phase 2 Trial of Difelikefalin in Notalgia Paresthetica

BackgroundNotalgia paresthetica is a neuropathic disorder characterized by pruritus in a circumscribed region of the upper back. Difelikefalin, a selective kappa opioid receptor agonist, has shown efficacy in other chronic pruritic conditions and is being investigated for the treatment of notalgia paresthetica.MethodsIn this phase 2, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, patients with moderate-to-severe pruritus caused by notalgia paresthetica to receive 2 mg of oral difelikefalin or placebo twice daily for 8 weeks. The primary outcome was the change from baseline at week 8 in the weekly mean score on the daily Worst Itch Numeric Rating Scale (WI-NRS; scores range from 0 [no itch] to 10 [worst itch imaginable]). The secondary clinical outcomes were itch-related quality-of-life and itch-related sleep measures.ResultsA total of 126 patients were enrolled; 62 patients were assigned to receive difelikefalin, and 63 were assigned to receive placebo. One patient who had been assigned to receive difelikefalin withdrew consent before the first dose and is not included in the main analyses. The mean baseline WI-NRS score was 7.6 (indicating severe itch) in each group. The change from baseline in the weekly mean WI-NRS score at week 8 was −4.0 points in the difelikefalin group and −2.4 points in the placebo group (difference in change, −1.6 points; 95% confidence interval, −2.6 to −0.6; P=0.001). The results for the secondary outcomes generally did not support those of the primary analysis. Headache, dizziness, constipation, and increased urine output occurred more frequently in the difelikefalin group than in the placebo group.ConclusionsAmong patients with notalgia paresthetica, oral treatment with difelikefalin resulted in modestly greater reductions in itch intensity scores than placebo over a period of 8 weeks but was associated with adverse events. Larger and longer trials are needed to assess the efficacy and safety of difelikefalin treatment in this disorder. (Funded by Cara Therapeutics; KOMFORT ClinicalTrials.gov number, NCT04706975.)

Treatment of Notalgia Paresthetica with botulinum toxin A: a review

Treatment of Notalgia Paresthetica with botulinum toxin A: a review

Dermatological Findings in Glaucoma Patients: Comparison Between Pseudoexfoliative and Primary Open-angle Glaucoma.

To compare the frequency of dermatological manifestations between patients with pseudoexfoliative glaucoma and those with primary open-angle glaucoma. A cross-sectional study was done on all consecutive pseudoexfoliative glaucoma (PEXG) and primary open-angle glaucoma (POAG) patients evaluated in a tertiary eye hospital during the study period. Eligible patients were referred to the dermatology department for complete skin, hair, nail, and mucosal examinations. Twenty-one patients in the PEXG group and 26 patients in the POAG group were included in this study. The most common skin manifestations in the study were seborrheic dermatitis, dry skin, and cherry angioma. The frequency of lentigines was significantly higher in the PEXG patients than in the POAG group (P = 0.013). More than half of the study population had seborrheic dermatitis (57.1% and 61.5% in the PEXG and POAG groups, respectively); however, the difference between the groups was not statistically significant (P = 0.775). Similarly, the frequencies of skin dryness, cherry angioma, nevus, psoriasis, contact dermatitis, itching, seborrheic keratoses, notalgia paresthetica, and vitiligo in the two groups were not statistically significantly different (P 0.1 for all comparisons). There was no significant association between the frequency of the investigated skin manifestations and patients' age, visual acuity, intraocular pressure, and cup-to-disc ratio. Integumentary system disorders are pervasive in glaucoma patients, and dermatologic evaluation in glaucoma patients should be considered for diagnostic and therapeutic purposes.

A Phase 2 Study of Oral Difelikefalin for Moderate-to-Severe Pruritus in Subjects With Notalgia Paresthetica (KOMFORT)

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Understanding the patient experience of living with notalgia paresthetica: A qualitative interview study

BackgroundNotalgia paresthetica (NP) is a chronic sensory neuropathy that causes intense pruritus, typically affecting the upper portion of the back and lasting for months to years. The impacts of pruritus and the full symptom experience are not well documented. ObjectiveTo describe patients’ NP symptom experience and the impacts of living with NP-related itch. MethodsSemistructured, one-to-one qualitative telephone interviews were conducted in adults living with NP. The worst itch severity during the previous 24 hours was assessed using an 11-point numerical rating scale. ResultsThirty participants (23 females; aged 41-80 years) completed interviews. Seventeen NP-related symptoms were described, with daily itch being the most common. Participants’ itch ranged from severe to very severe (50%) and was experienced for a median of 2.8 years. Most (73%) participants were not receiving treatment for NP at the time of the study. Other reported symptoms included skin pain or sensitivity and secondary symptoms from itching (skin discoloration, lumps or bumps, bleeding or scabbing). NP-related itch was frequently reported to affect mood, interfere with sleep, and disrupt self-care. LimitationsOnly English-speaking participants living in the United States were included. ConclusionThis study highlights the patient experience of living with NP and findings reveal that there remains an unmet need for effective therapeutic options to address NP-related itch.