Abstract
Zebra bodies in kidney biopsy specimens are widely accepted as a specific feature of Fabry disease but they can also be present in a drug-induced mimic of Fabry disease, phospholipidosis. Chloroquine and hydroxychloroquine may both induce zebra body formation and kidney phospholipidosis. However, the frequency and clinical significance of such changes remain unknown. We report 5 serial kidney biopsy cases diagnosed as lupus nephritis during hydroxychloroquine administration. All 5 patients exhibited a few, but varying amounts, of zebra bodies in glomerular intrinsic cells, that is, podocytes, parietal epithelial cells, mesangial cells, and endothelial cells. Most of the zebra bodies detected were subtle, though certainly recognizable; these zebra bodies were much smaller than those observed in Fabry disease. Zebra bodies were not observed in patients with lupus nephritis in the absence of chloroquine or hydroxychloroquine administration. All patients with lupus nephritis who received hydroxychloroquine achieved complete remission during continuous use of hydroxychloroquine, though kidney toxicity of drug-induced phospholipidosis might be masked by immunosuppression. Based on this small series of cases, we speculate that the hydroxychloroquine-associated manifestation of zebra bodies and phospholipidosis in the kidney may be frequent phenomena and may have only a subclinical influence on kidney function, at least in the short term.
Highlights
We report 5 serial kidney biopsy cases diagnosed as lupus nephritis during hydroxychloroquine treatment
We report 5 serial kidney biopsies of patients with lupus nephritis during hydroxychloroquine treatment
The number and size of zebra bodies formed during hydroxychloroquine treatment were far smaller than those in patients with Fabry disease
Summary
Chloroquine and hydroxychloroquine, which were first developed as antimalarial agents, are used widely for treating systemic lupus erythematosus because of their numerous immunomodulatory functions.[1,2] Chloroquine and hydroxychloroquine ameliorate systemic lupus erythematosus by suppressing the activation of Toll-like receptors that are expressed on the surface of endosomes.[1,2] At the same time, chloroquine and hydroxychloroquine accumulate in lysosomes, resulting in inhibition of the endosome-lysosome pathway and autophagic flux.[2,3] Chloroquine and hydroxychloroquine are effective for systemic lupus erythematosus treatment; some serious adverse effects, such as retinopathy, myopathy, and cardiomyopathy, have been reported.[1,2,4,5] The mechanism underlying the adverse effects of chloroquine and hydroxychloroquine is associated with their accumulation in lysosomes, which increases their intravesicular pH, resulting in lysosomal enzyme dysfunction and metabolite accumulation, namely phospholipids.[1,2,3,6] Experiments investigating chloroquine-associated phospholipidosis have demonstrated the accumulation of zebra bodies and phospholipids in systemic organs.[4]. We report 5 serial kidney biopsy cases diagnosed as lupus nephritis during hydroxychloroquine treatment. These results suggested that zebra body formation and kidney phospholipidosis may be frequently associated with hydroxychloroquine administration.
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