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Stigmatization related to cutaneous neurofibromas in neurofibromatosis 1: development, validation and severity strata
Laura Fertitta1,2,3, Kavita Y Sarin4, Carlos G Romo5
1Department of Dermatology, National Referral Center for Neurofibromatoses (CERENEF), Henri-Mondor Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), 94010 Créteil, France.
Background:
Cutaneous neurofibromas (cNFs) are benign skin tumours affecting over 95% of individuals with neurofibromatosis type 1 (NF1). Their visible appearance often leads to altered body image, social isolation and discrimination. Although stigma is a well-recognized burden in NF1 and has been identified by the Response Evaluation in Neurofibromatosis and Schwannomatosis consortium as a key outcome subdomain for future cNF clinical trials, no specific tool has been developed to assess stigma in relation to cNFs.
Objectives:
To adapt, develop and validate a patient-reported outcome measure (PROM) specifically designed to assess stigma in adults with NF1 and cNFs, and to define its severity strata.
Methods:
An expert working group including patients with NF1 modified the existing Patient Unique Stigmatization Holistic tool in Dermatology (PUSH-D) (used in chronic dermatoses) to create the 19-item cNF-PUSH-D. Following a pilot phase, a 13-item version was tested and validated through two cross-sectional studies: one in France (n = 224) via the ComPaRe NF1 cohort, and another in the USA (n = 142) via the NF Genetics Cohort. Psychometric properties were evaluated through exploratory and confirmatory factor analyses, Cronbach's α and intraclass correlation coefficients (ICCs). Convergent validity was assessed against the cNF-Skindex, the Generalized Anxiety Disorder (GAD-7) and the nine-item Patient Health Questionnaire (PHQ-9). Severity strata were defined using responses to a stigma anchor item.
Results:
The cNF-PUSH-D demonstrated excellent reliability (Cronbach's α = 0.941, ICC = 0.939) and strong construct validity. We identified two dimensions: 'felt stigma' and 'enacted stigma'. The score correlated significantly with anxiety, depression and quality-of-life measures (all P < 0.001). Severity strata were defined as low (0-21), moderate (22-32) and high (> 33) stigma (κ = 0.516). A higher number of cNFs (≥ 100) was significantly associated with greater stigma. Scores were comparable between the US and French cohorts, and measurement invariance testing confirmed that the factorial structure remained consistent across countries.
Conclusions:
The cNF-PUSH-D is the first validated PROM to assess stigma specific to cNFs. It demonstrates strong psychometric properties across international populations and fills a critical gap for ongoing and future clinical trials in NF1. By quantifying stigma, the tool enables better understanding, monitoring and management of this key aspect of the cNF disease burden. An author video to accompany this article is available online.
