Curvilinear bodies in hydroxychloroquine-induced renal phospholipidosis resembling Fabry disease

Abstract

Inherited and acquired metabolic disorders are responsible for renal intracellular accumulation of phospholipids. Ultrastructural analysis revealing typical myeloid or zebra bodies was previously thought to be exclusive to Fabry disease. However, chloroquine/hydroxychloroquine toxicity can cause similar abnormalities. Recent studies have mentioned curvilinear bodies (CLB) in renal cells in such cases, never described in Fabry nephropathy. We report a 31-year-old patient with systemic lupus erythematosus who was on long-term hydroxychloroquine treatment. The presence of zebra bodies on electron microscopy lead to initial interpretation of Fabry disease, but subsequent genetic analysis did not show a relevant mutation. Further evaluation revealed CLB in renal cells, supporting the diagnosis of hydroxycholoroquine-induced renal phospholipidosis.

Ultrastructural deposits appearing as “zebra bodies” in renal biopsy: Fabry disease?– comparative case reports

“…However, the presence of curvilinear bodies does not seem to be a uniform finding in cases of hydroxychloroquine-induced phospholipidosis [20] in agreement with our findings of no curvilinear bodies in the aforementioned patient. Thus, it is actually just a clue for differential diagnosis between FD and hydroxychloroquine-induced phospholipidosis.…”

The Case | Myeloid bodies in the kidney biopsy of a patient with systemic lupus erythematosus

“…This impairment of lysosomal digestion leads to intracellular accumulation of membrane phospholipids and glycogen, altogether resulting in an increased lysosomal volume, a phenomenon that is frequently seen in storage disorders. 1,2 These findings have also been seen in skeletal myocytes and cardiomyocytes. Remarkably, both drugs may potentially cause neuromuscular and cardiac toxicity.…”

Hydroxychloroquine-induced podocytopathy mimicking Fabry disease

“…Once into lysosome, this weak base is protonated and increases lysosome pH while inhibiting enzyme activities of phospholipase A and C and alphagalactosidase A. Finally, there is an intralysosomal accumulation of phospholipids and debris that appears by electron microscopy as zebra bodies 2–11…”

“…The main side effect of HCQ is retinal toxicity 1. Another less well-known side effect is a drug-induced phospholipidosis: a phospholipid storage disorder characterised by an accumulation of multilamellar bodies (myeloid bodies) in cells and tissues, associated with clinical toxicities (kidney injury, myopathy) that leads to histological abnormalities as cytoplasmic vacuolisation, and ultrastructural changes with intracellular osmiophilic structures called the ‘zebra bodies’ 2–11. These lesions are also specifically observed in Fabry disease (FD), an X-linked inborn deficiency of the lysosomal enzyme alpha-galactosidase A that causes an accumulation of globotriaosylceramide leading to cellular dysfunction 12.…”