Lupus Nephritis and Hydroxychloroquine-Associated Zebra Bodies: Not Just in Fabry Disease

Abstract Zebra bodies in kidney biopsies 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. Here, we report five serial kidney biopsy cases diagnosed as lupus nephritis during hydroxychloroquine administration. All five patients exhibited a few, but varying amounts, of zebra bodies in glomerular intrinsic cells, i.e., 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 lupus nephritis patients in the absence of chloroquine or hydroxychloroquine administration. All lupus nephritis patients who received hydroxychloroquine achieved complete remission during continuous usage 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.