OBJECTIVES: This systematic literature review assessed the epidemiological, humanistic and economic burden of facial angiofibroma (FA) associated with tuberous sclerosis complex (TSC), to identify evidence and data gaps.

METHODS: Various academic databases, HTA databases, and conferences were searched (March-May 2022). Methodological quality was assessed using STROBE (observational) and the Joanna Briggs Institute (case-series) checklists. Humanistic outcomes’ risk of bias was assessed using a checklist adopted from Huang et. al. (2021) (for all studies), Cochrane RoB v2.0 (randomized controlled trials [RCTs]), and ROBINS-I checklist (non-RCTs). Economic outcomes were assessed using Consensus Health Economic Criteria checklist. Pooled proportion of cases using Meta-analysis of Observational Studies in Epidemiology guidelines was conducted for epidemiological outcomes. Economic outcomes followed guidelines of Campbell & Cochrane Economic Methods Group.

RESULTS: Of 8657 studies identified, 58 were included; 42 reported epidemiological outcomes (23 cohort, 14 cross-sectional, 5 case-series): 4 community-based, 37 hospital-based, and 1 hospital and residential-based. Community- and hospital-based studies in adults and children reported incidence of 60%-86% and 60%-93%, respectively. Pooled proportion, across all diagnostic criteria was 50% (19%-81%: community studies), 59% (46%-72%: hospital-based), and 54% adults (22%-84%), and 46% pediatric (33%-59%) among hospital-based studies. Majority of cohort studies were of high/moderate quality, and cross-sectional studies were of low quality. None of the case-series’ were of low quality. Among the 14 studies providing humanistic outcomes, study population clearly described (13), random sampling method (4), physician’s diagnosis (12), and outcomes measured using validated instruments (10); 2 RCTs each were of low and moderate risk, respectively. Compared to other tools, SF-36 was found to be most sensitive for assessment of quality-of-life. Economic data from 6 observational studies demonstrated substantial cost burden on FA patients with TSC.

CONCLUSIONS: This first comprehensive burden-of-illness review on FA associated with TSC identified key evidence gaps and will help researchers for future research.