When You Hear Hoofbeats: An Interesting Presentation of Zebra Bodies Associated with Hydroxychloroquine Use

Introduction: The presence of zebra bodies in kidney biopsy is a distinctive characteristic of Fabry disease. However, certain medications such as hydroxychloroquine may also induce zebra body formation by mimicking the phospholipidosis of Fabry disease. First developed as antimalarial drugs, chloroquine and hydroxychloroquine are widely used today in management of autoimmune disorders. While both medications have been generally regarded as safe, serious side effects such as retinopathy, myopathy, and cardiomyopathy have been reported. Hydroxychloroquine in particular has been associated with the presence of zebra bodies in the kidney but the clinical significance of this finding is not well-known. We present a case illustrating zebra bodies in a patient with long-term hydroxychloroquine use. Case Description: A 75 year-old female with history of rheumatoid arthritis was evaluated for proteinuric Stage 3 CKD. Serum electrophoresis revealed a monoclonal band and biopsy was performed. Histologic examination revealed C3 dominant mesangioproliferative glomerulonephritis, but also ultrastructural evidence of podocyte lipid accumulation consistent with Fabry disease. Medication history confirmed that the patient had been on the amphiphilic drug hydroxychloroquine for many years. Discussion: The prevalence of zebra bodies attributable to hydroxychloroquine has been low and the clinical significance remains unclear. While there is an association of zebra bodies and increased phospholipidosis, the histological difference between drug-induced zebra bodies and those observed in Fabry disease requires further clarification. Understanding these differences will allow for further assessment regarding the implications of long-term usage of drugs such as hydroxychloroquine. Our patient was referred to hematology for bone biopsy due to her C3 disease but hydroxychloroquine was not thought to be causative of her kidney disease and was continued.