Category: Rare Genetic and Metabolic Diseases
Objective: To determine the prevalence of concurrent immune-mediated diseases during copper chelation therapy in Wilson’s disease (WD).
Background: Wilson’s disease is a neurometabolic autosomal recessive disorder caused by ATP7B mutation, resulting in abnormal copper accumulation. Lifelong chelation therapeutics is instituted post-diagnosis with careful monitoring. Development of immune-mediated adverse events is a concern, particularly under Penicillamine therapy.
Method: We conducted an observational retrospective study of 96 patients with Wilson’s Disease (Leipzig score ≥ 4) from a tertiary referral hospital. Data on demographic characteristics, clinical features and therapy were collected from clinical records of Neurology and Hepatic Diseases outpatient clinics.
Results: Among 85 eligible patients, 43 (50.6%) were women, with a mean age of 21.5 ± 12.70 years at the time of diagnosis and a mean follow-up time of 17.7 ± 12.1 years. Approximately 25% of patients were followed for more than 25 years. Overall, 82 patients were treated with Penicillamine, 45 with Trientine, and 24 with Zinc.
Thirteen (15.3%) patients experienced chelator induced immunological adverse events, including hypersensitivity reactions (n=4), glomerulonephritis (n=2), autoimmune hepatitis (n=1), lupus (n=4), and rheumatoid arthritis (n=2)-like syndromes. Ten (76.9%) patients were under Penicillamine therapy and the other 3 under Trientine. The median time between side effects and initiation of chelation therapy was 4.6 years (Interquartile range (IQR) 17.8). Four (33.3%) patients subsequently developed an autoimmune disease, Systemic Lupus Erythematosus (n=2), Rheumatoid Arthritis (n=1) and Ulcerative Colitis (n=1). One patient had died of Lupus nephritis complications.
Two (2.4%) patients had autoimmune diseases before WD diagnosis (Ulcerative Colitis and Psoriatic Spondyloarthritis). Two (2.4%) patients were diagnosed with concurrent Autoimmune Hepatitis.
Conclusion: Lifelong chelation therapy poses clinical challenges, with immunological adverse events being an important limitation to the long-term use of cooper chelators, especially with Penicillamine. Nearly 15% patients developed idiosyncratic immune-mediated syndromes. The mechanism of auto-immune complications remains unknown.
To cite this abstract in AMA style:
C. Guedes Vaz, H. Pessegueiro, J. Castro Ferreira, J. Gandara, V. Dionísio Lopes, E. Silva, S. Ferreira, C. Pereira, D. Valadares, L. Maia, J. Presa, A. Pinto, A. Costa, C. Rolanda, C. Agostinho, I. Gonçalves, P. Peixoto, R. Costa, S. Lopes, M. Magalhães. Prevalence of immune-mediated diseases in long-term chelator therapy in Wilson’s Disease [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/prevalence-of-immune-mediated-diseases-in-long-term-chelator-therapy-in-wilsons-disease/. Accessed October 5, 2024.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/prevalence-of-immune-mediated-diseases-in-long-term-chelator-therapy-in-wilsons-disease/