Hydroxychloroquine (HCQ) should be avoided in patients with Fabry disease (FD) since its use in these patients can lead to increased toxicity, decreased treatment effectiveness, and accelerated progression of the disease, according to research presented the 17th Annual WORLDSymposium.

The clinical presentation of FD, a lysosomal storage disease caused by a lack of alpha-galactosidase A, varies greatly patient-to-patient. Because of this, a true diagnosis of the disease may be delayed or the condition may be completely misdiagnosed, as it often masquerades as a rheumatological disease. Subsequently, FD patients are initiated on immunomodulators, such as HCQ, which increase lysosomal pH and inactivate lysosomal enzymes. “Thus, both FD and HCQ inactivate lysosomal enzymes resulting in lysosomal lipidosis, the former being inherited-lipidosis and the latter being acquired-lipidosis,” the authors explained. Reports of patients who experienced HCQ toxicity mimicking or worsening FD have been reported.

In this report, the cases of 4 female FD patients (age, 50-77 years old) who tolerated the discontinuation of HCQ without experiencing a recurrence of “rheumatological” symptoms were presented. Three of the patients were receiving either enzyme replacement therapy or oral chaperone therapy. The cumulative lifetime dose of HCQ was reported to be between 1095g and 1374g over approximately 8 to 11 years.

Findings of the analysis revealed that 2 patients had evidence of myopathy with increased levels of creatine phosphokinase. Although these levels decreased upon cessation of HCQ, disease progression still occurred in these patients. “The first patient had biopsy-proven HCQ toxicity and eventually died from a multifactorial neuromyopathy,” the authors reported. For the second patient, the biopsy revealed FD progression only. Although the other 2 patients were asymptomatic and did not have evidence of either HCQ toxicity or disease progression, HCQ was discontinued out of precaution.

“In conclusion, patients with FD are often misdiagnosed and treated with HCQ,” the authors stated. They added, “Due to their similar mechanism of action resulting in a lysosomal storage disorder, the combination of FD and HCQ may increase HCQ toxicity, decrease the effectiveness of FD treatment, and/or accelerate the progression of FD.”


Kapoor S, Ramani R, Ortiz D, Boyd-Shiwarski C. Hydroxychloroquine use and toxicity in patients with Fabry disease: A case series. Presented at: 17th Annual WORLDSymposium; February 8-12, 2020. Poster #112.