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.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/prevalence-of-immune-mediated-diseases-in-long-term-chelator-therapy-in-wilsons-disease/