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. 2020 Jan 21;15(1):23.
doi: 10.1186/s13023-019-1258-3.

A systematic review on the burden of illness in individuals with tuberous sclerosis complex (TSC)

Johann Philipp Zöllner  1   2 , David Neal Franz  3 , Christoph Hertzberg  4 , Rima Nabbout  5 , Felix Rosenow  1   2 , Matthias Sauter  6 , Susanne Schubert-Bast  1   2   7 , Adelheid Wiemer-Kruel  8 , Adam Strzelczyk  9   10   11   12
Affiliations

A systematic review on the burden of illness in individuals with tuberous sclerosis complex (TSC)

Johann Philipp Zöllner et al. Orphanet J Rare Dis. .

Abstract

Objective: This review will summarize current knowledge on the burden of illness (BOI) in tuberous sclerosis complex (TSC), a multisystem genetic disorder manifesting with hamartomas throughout the body, including mainly the kidneys, brain, skin, eyes, heart, and lungs.

Methods: We performed a systematic analysis of the available literature on BOI in TSC according to the PRISMA guidelines. All studies irrespective of participant age that reported on individual and societal measures of disease burden (e.g. health care resource use, costs, quality of life) were included.

Results: We identified 33 studies reporting BOI in TSC patients. Most studies (21) reported health care resource use, while 14 studies reported quality of life and 10 studies mentioned costs associated with TSC. Only eight research papers reported caregiver BOI. Substantial BOI occurs from most manifestations of the disorder, particularly from pharmacoresistant epilepsy, neuropsychiatric, renal and skin manifestations. While less frequent, pulmonary complications also lead to a high individual BOI. The range for the mean annual direct costs varied widely between 424 and 98,008 International Dollar purchasing power parities (PPP-$). Brain surgery, end-stage renal disease with dialysis, and pulmonary complications all incur particularly high costs. There is a dearth of information regarding indirect costs in TSC. Mortality overall is increased compared to general population; and most TSC related deaths occur as a result of complications from seizures as well as renal complications. Long term studies report mortality between 4.8 and 8.3% for a follow-up of 8 to 17.4 years.

Conclusions: TSC patients and their caregivers have a high burden of illness, and TSC patients incur high costs in health care systems. At the same time, the provision of inadequate treatment that does not adhere to published guidelines is common and centralized TSC care is received by no more than half of individuals who need it, especially adults. Further studies focusing on the cost effectiveness and BOI outcomes of coordinated TSC care as well as of new treatment options such as mTOR inhibitors are necessary.

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Conflict of interest statement

JPZ reports a speaker’s honorarium from Eisai.

DNF reports travel support and honoraria from Novartis. His employer has also received support for clinical trials and consulting work from Novartis.

RN reports speakers and board fees from GW Pharma, Biocodex, Novartis, Eisai, Nutricia, Zogenix, UCB, Advicenne, Biogene, Stoke and unrestricted educational grants from UCB, Eisai and GW Pharma.

FR reports personal fees from Eisai, GW-Pharma and Desitin Pharma, personal fees and others from Novartis, personal fees from Medtronic, personal fees from Cerbomed, personal fees from Shire, grants from the European Union, the German Minister for Education and Research (BMBF) the LOEWE Programm of the state of Hesse and grants from the Deutsche Forschungsgemeinschaft (DFG) and the Detlev-Wrobel-Fonds for Epilepsy Research .

MS reports personal fees and grants from Novartis.

SSB reports personal fees from UCB, Desitin Arzneimittel, Novartis, Zogenix, LivaNova, and Eisai.

AWK reports grants and personal fees from Novartis and Nutricia, and only personal fees from Desitin Arzneimittel, Dr. Schär, Vitaflo, UCB Pharma.

AS reports personal fees and grants from Desitin Arzneimittel, Eisai, GW pharmaceuticals, LivaNova, Marinus pharmaceuticals, Medtronic, Sage Therapeutics, UCB Pharma, and Zogenix.

CH declares that he has no competing interests.

Figures

Fig. 1
Fig. 1
Results from the systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines
Fig. 2
Fig. 2
Graphical overview of clinical organ manifestations in Tuberous Sclerosis Complex (TSC). Prevalences are given in parentheses after each manifestation. *Prevalence of LAM is given for female patients as there is a high gender-dependency. Prevalences for the majority of manifestations change with age. For sources of the prevalences, please refer to section 3.1 of the manuscript. ADHD = attention deficit hyperactivity disorder, AML = angiomyolipoma, LAM = lymphangioleiomyomatosis, PNET = pancreatic neuroendocrine tumor, SEGA = subependymal giant astrocytoma, SEN = subependymal nodules. Graphic adapted from “Female_shadow_template.svg” and “Girl_diagram_template.svg”, available in the public domain and accessible at https://commons.wikimedia.org/wiki/Human_body_diagrams (original author: Mikael Häggström)
See this image and copyright information in PMC

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