INDIVIDUAL ARTICLE: Management of Prurigo Nodularis.

BACKGROUND: Prurigo nodularis (PN) is a chronic disease characterized by intense pruritus and nodular lesions associated with reduced quality of life. Until recently, no US Food and Drug Administration (FDA)-approved therapies have been available for the management of PN. Treatment regimens have been highly variable and clinical management guidelines are lacking overall; formal treatment guidelines do not exist within the US. In 2022, dupilumab became the first FDA-approved medication for PN. Multiple novel agents that target the neuroimmune underpinnings of the disease are currently in development and show promise for this challenging disorder. OBJECTIVE: To review current treatments and emerging therapies for effective management of patients with PN. METHODS: We reviewed publications on PN management identified from PubMed, Embase, Web of Science, and the Cochrane Library. We also included publicly available data on clinical trials for PN therapies reported on the US National Library of Medicine ClinicalTrials.gov, the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) Database, and the European Clinical Trials (EudraCT) Database. RESULTS: The recommended management of PN begins with an assessment of disease severity, including disease burden and pruritus intensity, and evaluation of comorbid medical disorders. Treatment goals include resolution of itch, improvement in nodules or cutaneous lesions, and improvement in quality of life. Therapies should be selected based on a patient’s clinical presentation and comorbidities. Treatment should simultaneously address the neural and immunologic components of PN. Combination therapy, particularly with conventional agents, may be beneficial. LIMITATIONS: Data on most conventional PN treatments are limited to anecdotal reports, small clinical trials, or expert consensus recommendations. No head-to-head comparative trials have evaluated the relative efficacy of conventional and/or emerging agents, or combination therapy. CONCLUSION: An effective treatment approach for patients with PN should reduce pruritus, allow nodular lesions to heal, and improve individual quality of life. The treatment landscape for PN is rapidly evolving with one FDA-approved agent and several new promising therapies on the horizon. J Drugs Dermatol. 2023;22:12(Suppl 2):s15-22.

Germline ERBB2/HER2 Coding Variants Are Associated with Increased Risk of Myeloproliferative Neoplasms.

Familial cases of myeloproliferative neoplasms (MPN) are relatively common, yet few inherited risk factors have been identified. Exome sequencing of a kindred with a familial cancer syndrome characterized by both MPN and melanoma produced a germline variant in the ERBB2/HER2 gene that co-segregates with disease. To further investigate whether germline ERBB2 variants contribute to MPN predisposition, the frequency of ERBB2 variants was analyzed in 1604 cases that underwent evaluation for hematologic malignancy, including 236 cases of MPN. MPN cases had a higher frequency of rare germline ERBB2 coding variants compared to non-MPN hematologic malignancies (8.9% vs. 4.1%, OR 2.4, 95% CI: 1.4 to 4.0, p = 0.0028) as well as cases without a blood cancer diagnosis that served as an internal control (8.9% vs. 2.7%, OR 3.5, 95% CI: 1.4 to 8.3, p = 0.0053). This finding was validated via comparison to an independent control cohort of 1587 cases without selection for hematologic malignancy (8.9% in MPN cases vs. 5.2% in controls, p = 0.040). The most frequent variant identified, ERBB2 c.1960A > G; p.I654V, was present in MPN cases at more than twice its expected frequency. These data indicate that rare germline coding variants in ERBB2 are associated with an increased risk for development of MPN. The ERBB2 gene is a novel susceptibility locus which likely contributes to cancer risk in combination with additional risk alleles.