Prevalence of Metabolic Diseases in Patients With Prurigo Nodularis: A Systematic Review and Meta‐Analysis

Prurigo nodularis (PN) is a neuroinflammatory disorder characterized by chronic pruritus and pruriginous nodular lesions [1]. Recent studies suggest that PN patients may have a higher burden of metabolic comorbidities, including endocrine, hepatic, and weight-related disorders; however, this association remains poorly understood [2, 4]. We performed a systematic review and meta-analysis of the published literature to explore this relationship further. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines to systematically search Embase, PubMed, Scopus, CINAHL Complete, and the Cochrane Database for original published studies that involved metabolic comorbidities in PN patients (Figure 1), including metabolic comorbidities such as type 2 diabetes mellitus (T2DM), obesity, metabolic syndrome, hyperlipidemia, and chronic liver disease (CLD) (PROSPERO CRD42024574847). Articles through July 24, 2024, were included using specific search terms. Original studies with ≥ 20 individuals with clinician-diagnosed PN were included. Exclusion criteria included reviews, qualitative analyses, and studies published in languages other than English. Two reviewers (N.C. and M.D.) independently screened titles and/or abstracts. Consensus was reached with discussion, with other authors (C.H.C. and M.T.P.) acting as an additional screener in case of a tie. This process was repeated for the subsequent full-text screening. Of 759 abstracts identified through the search, 595 were deemed eligible for initial screening, 41 full texts were assessed for eligibility, and 11 articles were included for final analysis (pooled n = 15,706) (Table 1). Metabolic comorbidities described in these studies included T2DM, CLD, obesity, hyperlipidemia, gout, and iron deficiency anemia. Meta-analysis was performed using the Jamovi statistical package (version 2.3.28) [5]. Using a standard random effects model (Dersimonian–Laird), we estimated pooled proportions with 95% confidence intervals for T2DM and CLD—other common metabolic disorders such as obesity, metabolic syndrome, and hyperlipidemia were not reported frequently enough for pooled analysis (Table 1). The prevalence of T2DM among PN patients was estimated to be 35.2% [95% CI 18.1%–52.3%] across eight studies (n = 3944) with high heterogeneity (I2 = 97.85%, p < 0.001). CLD was present in 16.1% [95% CI 8.8%–23.3%] of PN patients across three studies (n = 2477), with moderate heterogeneity (I2 = 72.72%, p = 0.02). Most reports were cross-sectional without corresponding reference arms, and thus, an association could not be calculated. TriNetX, a global health records database Hadassah Medical Center, Sheba Medical Center, and Soroka Medical Center, Israel Limitations of the current approach include few published manuscripts to date, a relative lack of both controlled and prospective studies, and, importantly, convenience samples in multiple studies. However, similar metabolic comorbidities were noted among subjects enrolled in the recently published global phase 3 PRIME and PRIME2 clinical trials for dupilumab, including diabetes mellitus, hepatobiliary disorders, and dyslipidemia, though these data were not included in the current analysis given the trial method of comorbidity classification and relatively narrow PN inclusion criteria [6]. These data may suggest that screening PN patients for select comorbid metabolic diseases, including T2DM and CLD, could be warranted, but prospective, well-controlled studies are needed to reveal potential associations between PN and metabolic disease and underlying pathomechanisms. In clinical practice, awareness of these possible comorbidities may assist in comprehensive patient care and highlight the need to better understand targeted interventions from a dermatologic perspective. R.C. has served as an advisor, consultant, speaker, and/or investigator for AbbVie, Amgen, AnaptysBio, Apogee Therapeutics, Arcutis, Argenx, ASLAN Pharmaceuticals, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, CLn Skin Care, Dermavant, Eli Lilly and Company, EMD Serono, FIDE, Formation Bio, Galderma, Genentech, GSK, Incyte, LEO Pharma, L'Oréal, Nektar Therapeutics, Novartis, Opsidio, Pfizer Inc, RAPT, Regeneron, Sanofi, Sitryx, Takeda, TRex Bio, and UCB. N.C., M.D., C.H.C., and M.T.P. have no conflicts of interest to declare. Supporting Information is available upon reasonable request from the corresponding author.