Prurigo Nodularis: Review and Emerging Treatments

Maria Leis, BA; Patrick Fleming, MD, FRCPC; Charles W. Lynde, MD, FRCPC

Skin Therapy Letter. 2021;26(3):5-8.

Abstract and Introduction

Abstract

Prurigo nodularis (PN) is a chronic, recalcitrant inflammatory skin condition characterized by the presence of pruritic nodules. The exact pathogenesis of the disease is unknown, although immune and neural dysregulation are indicated in driving the itch-scratch cycle. Specifically, interleukin-4 and interleukin-31 pathways have been recently implicated in transmission of the pruritic sensation. There are currently no US FDA-approved targeted therapies for the treatment of PN. This article aims to review our present understanding of the disease pathogenesis and treatments, with a focus on emerging therapeutics. Specifically, this article explores the developing use of monoclonal antibodies nemolizumab and dupilumab, opioid receptor modulation and cannabinoids as potential treatments for PN.

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Table 1. Current treatments of prurigo nodularis.
Treatment	Level of Evidence	Side Effects
Topical agents: corticosteroids,calcineurin inhibitors, calcipotriol, andcapsaicin	5/5 studies level 2b or higher	Mild; skin irritation
Phototherapy and photochemotherapy	6/8 studies level 2b or higher	Mild; erythema, hyperpigmentation, vesicles, edema
Thalidomide	2/6 studies level 2b or higher	Severe; poor safety profile, including peripheral neuropathy, sedation, dizziness, rash, depression, nausea, thromboembolism, teratogenicity
Systemic immunomodulatory drugs: methotrexate and cyclosporine	4/4 studies level 4	Mild; nausea, transaminitis, gastrointestinal symptoms, hypertension, hypercholesterolemia, elevated creatinine, gingival hyperplasia
Antiepileptics and antidepressants	3/3 studies level 2b	Moderate; central nervous system effects, gastrointestinal effects, cardiovascular effects

Note: Level of evidence (LOE) ratings were assigned according to an adaptation of the Oxford University Centre for Evidence-Based Medicine LOE by a recent systematic review by Qureshi and colleagues.¹⁷
1a: Systematic review of randomized controlled trials
1b: Individual randomized controlled trials
2a: Systematic review of cohort studies
2b: Individual cohort study
3a: Systematic review of case-control studies
3b: Individual case-control study
4: Case series and poor-quality cohort and case-control studies
5: Case reports or expert opinion

Table 2. Emerging treatments of prurigo nodularis.
Treatment	Level of Evidence	Side Effects
Nemolizumab	1b (ongoing RCT)	Mild; abdominal pain and diarrhea, nonspecific musculoskeletal symptoms
Dupilumab	2b	Mild; dry eyes
Opioid receptor modulation: nalbuphine, butorphanol, naloxone, and naltrexone	1b	Moderate; insomnia, constipation, somnolence, dizziness, vomiting, sensation of heat, nasal congestion
Cannabinoids	3a	Unknown