PracticalDermatology

Article: A 2023 study by Kwatra et al. Through the collaboration of a distinguished panel of experts from the United States, it aims to achieve consensus on uniform nomenclature and diagnosis for neuropathic pruritus. 

Summary: In this qualitative study by Kwatra et al., a virtual roundtable convened ten experts specializing in pruritus and its management in the United States. This assembly aimed to comprehensively address various aspects of neuropathic pruritus, including disease definition, core symptoms, additional disease features, subtypes, treatment modalities, and diagnostic evaluation protocols. The panel conducted a detailed systematic review of prior literature on neuropathic pruritus, utilizing the findings to inform their discussions. Subsequently, a collaborative effort ensued, with all participants revising and endorsing a draft of evidence, helping to ensure a robust and consensus-driven outcome.¹

BACKGROUND AND STUDY RESULTS: 

Neuropathic pruritus, a distressing form of chronic itch, has been largely overlooked in research endeavors thus far.2 Broadly defined, it encompasses any disruption or injury along the afferent itch pathway, driving individuals to incessantly scratch. Alarmingly, neuropathic itch affects a substantial percentage (8% to 19%) of individuals grappling with chronic pruritus.³ Despite notable advancements in understanding itch-specific pathways at the cellular and molecular levels in recent years, their precise role in the pathophysiology of neuropathic itch remains elusive. Additionally, the lack of a dedicated International Classification of Diseases, 10th Revision code, coupled with the absence of U.S. Food and Drug Administration-approved treatments for neuropathic pruritus, further compounds the scarcity of data on its incidence, prevalence, and detailed case studies.^1,4 

To address these limitations and improve care for patients afflicted by neuropathic pruritus, Kwatra et al. undertook a qualitative study aimed at establishing uniform nomenclature and providing guidance on diagnosis and workup. On November 3, 2021, ten experts specializing in pruritic and inflammatory dermatological conditions were convened for discussion via the Internet. Ahead of the meeting, a systematic review of neuropathic pruritus literature from 1991 to 2021 was conducted. During discussions, consensus levels were defined: near-consensus ranged from 70% to 85% agreement, while full consensus required over 85% agreement.¹ 

All participants unanimously reached full consensus on every aspect, including definition, diagnostic workup, and treatment. The definition of neuropathic pruritus centers around itchiness primarily induced by lesions or diseases impacting the somatosensory nervous system. Core features include the presence of normal skin or skin exhibiting only secondary changes, such as excoriation. Neuropathic pruritus typically presents with a localized distribution, occasionally involving dermatomes, and may extend to multiple sites or become generalized due to central sensitization. Several types of neuropathic pruritus were also recognized, such as brachioradial pruritus, notalgia paresthetica, multilevel symmetric pruritus, scalp pruritus, postherpetic neuralgia, small fiber neuropathy, pruritus resulting from central nervous system syndromes, and peripheral nerve damage with mixed causes.¹ 

The diagnostic workup of neuropathic pruritus was also discussed and came to consensus. For diffuse neuropathic pruritus, it’s essential to consider systemic factors that may contribute to itch. Therefore, a comprehensive workup is necessary, which should include renal and liver function testing, thyroid function tests, an iron panel, and fasting glucose or hemoglobin A1C assessment. Age-appropriate cancer screening and evaluation for infectious causes such as HIV, hepatitis B, and hepatitis C should also be considered upon clinical suspicion. Since the pathogenesis of neuropathic pruritus typically does not involve type 2 inflammation or immunologic causes, screening for elevated type 2 markers such as eosinophils and serum IgE may aid in confirming the diagnosis, particularly in cases of atopic disease. In cases of localized neuropathic pruritus, it’s crucial to explore targeted radiological studies to pinpoint conditions like brachioradial pruritus and notalgia paresthetica. For diagnosing brachioradial pruritus, the ice pack test is a valuable diagnostic tool: assessing whether there’s notable relief from pruritus after applying an ice pack to the affected area. Furthermore, if warranted, a skin biopsy is advisable for both diffuse and localized neuropathic pruritus when clinical indicators suggest it.¹ 

Consensus was reached on the treatment options for neuropathic pruritus as well. While the options remain largely anecdotal due to limited reports, identifying the underlying cause typically serves as the initial step. Topical medications may provide short-term relief and are particularly effective for localized neuropathic pruritus like brachioradial pruritus. These include lidocaine and pramoxine for anesthesia, capsaicin cream/patch, cooling agents such as menthol and camphor, as well as topical ketamine and amitriptyline. Tricyclic antidepressants such as doxepin are also recommended. For systemic chronic neuropathic pruritus, treatment options encompass gabapentinoids, antidepressants, kappa/mu opioid axis modulators, and cannabinoids. Procedural therapies, while less understood, may include physical therapy, intralesional botulinum toxin, and transcutaneous electrical nerve stimulation.¹ 

COMMENTS/CLINICAL IMPLICATIONS 

Kwatra et al.’s study sheds light on various diagnostic and management aspects of neuropathic pruritus, offering crucial insights in a field lacking comprehensive clinical studies and guidelines. While it provides a valuable temporary reference for physicians navigating this challenging condition, it also has limitations. The absence of randomized controlled studies and the reliance on expert consensus for recommendations underscore the need for further support through evidence-based outcomes research. Therefore, the development of additional studies and clinical trials exploring various facets of neuropathic pruritus is essential to aid clinicians and scientists in effectively managing this complex condition. 

Aileen Park is a medical student at the University of Colorado School of Medicine. Leo Wan is a medical student at the West Virginia School of Osteopathic Medicine. Peter Lio, MD, is a clinical professor of dermatology and pediatrics at Northwestern University School of Medicine and a partner at Medical Dermatology Associates of Chicago. 

1. Kwatra SG, Elmariah S, Chisolm S, et al. United States expert panel consensus on uniform nomenclature and diagnosis for neuropathic pruritus. Itch. 2024;9(1). Doi: 10.1097/itx.0000000000000073 

2. Kwatra SG, Kambala A, Dong X. Neuropathic pruritus. J Allergy Clin Immunol. 2023;152(1):36-38. Doi:10.1016/j.jaci.2023.04.006 

3. Rosen JD, Fostini AC, Yosipovitch G. Diagnosis and Management of Neuropathic Itch. Dermatol Clin. 2018;36(3):213-224. Doi:10.1016/j.det.2018.02.005 

4. Steinhoff M, Oaklander AL, Szabó IL, Ständer S, Schmelz M. Neuropathic itch. Pain. 2019;160 Suppl 1:S11-S16. Doi:10.1097/j. pain.0000000000001551