Plasmapheresis is NOT a Treatment for Von Hippel-Lindau Disease
Plasmapheresis has no role in the management of Von Hippel-Lindau (VHL) disease and should not be used. VHL is a hereditary tumor syndrome, not a condition involving pathogenic circulating antibodies, immune complexes, or plasma proteins that plasmapheresis targets.
Why Plasmapheresis is Inappropriate for VHL
VHL Disease Pathophysiology
- VHL is caused by germline mutations in the VHL tumor suppressor gene on chromosome 3, leading to dysfunction of the VHL protein-Elongin B,C complex and subsequent failure to ubiquitinate hypoxia-inducible factor 1, 2
- This results in development of highly vascular tumors including CNS hemangioblastomas, retinal hemangioblastomas, renal cell carcinoma, pheochromocytomas, and pancreatic neuroendocrine tumors 3, 2
- The disease mechanism is genetic and cellular, not related to circulating plasma factors 1
Plasmapheresis Mechanism Does Not Address VHL
- Plasmapheresis mechanically removes circulating antibodies, immune complexes, and pathogenic proteins from plasma 4
- The procedure is indicated for conditions like thrombotic thrombocytopenic purpura, ANCA-associated vasculitis, Waldenström's macroglobulinemia with hyperviscosity, and antibody-mediated transplant rejection 5, 4
- None of these mechanisms are relevant to VHL disease pathogenesis 1, 3
Actual Management of VHL Disease
Surveillance-Based Approach
- Initiate surveillance in childhood for VHL mutation carriers, including regular examination of retina, CNS, inner ear, kidneys, neuroendocrine glands, and pancreas 3
- Surveillance should begin early as most VHL lesions are initially asymptomatic, making early diagnosis critical 6
Surgical Management
- Most VHL manifestations are currently treated by surgery when tumors reach specific size thresholds or become symptomatic 3
- Treatment should be planned to optimize cure without unnecessary sequelae 3
Targeted Medical Therapy
- Belzutifan (HIF-2α inhibitor) was recently FDA-approved for adult VHL patients with associated renal cell carcinoma, CNS hemangioblastomas, or pancreatic neuroendocrine tumors not requiring immediate surgery 3
- Drugs targeting vascular endothelial growth factors or its receptor are undergoing clinical trials 2
Multidisciplinary Care Requirements
- Management requires collaboration among specialists in ophthalmology, neurosurgery, urology, endocrinology, and genetics 3, 6
- Genetic counseling and systematic registration are fundamental for continuous improvement of clinical care 3
Critical Pitfall to Avoid
Do not confuse VHL disease with Waldenström's macroglobulinemia (WM), which has a similar acronym but is an entirely different condition. Plasmapheresis IS indicated for WM patients with symptomatic hyperviscosity 5, but this has absolutely no relevance to VHL disease management.