Hydroxychloroquine-induced Phospholipidosis in a Case of SLE: The Wolf in Zebra Clothing

Abstract

A 30 year old lady patient of SLE on steroid and hydroxychloroquine therapy presented with lupus nephritis and later developed cardiac symptoms. Her renal biopsy revealed features of Class III lupus nephritis. Also seen was typical lamellated myelinoid material in the glomerulus. The alpha-galactosidase A activity was normal. The clinical morphological and biochemical findings were consistent with Lupus nephritis showing changes of hydroxychloroquine induced phopholipidosis. Electron microscopy along with careful clinical examination and follow up status was instrumental in the diagnosis of the latter.

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

“…In contrast, patients with numerous podocyte inclusions can have a slower clinical resolution due to the natural enzymatic difficulty in permeate these cells [18]. …”

Hydroxychloroquine and azithromycin used alone or combined are not effective against SARS-CoV-2 ex vivo and in a hamster model

“…A correlation between the induction of phospholipidosis and antiviral activity has been described for several drugs and demonstrated an in vitro antiviral effect solely due to physicochemical properties and not to a specific targeting of SARS-CoV-2. Hence, the in vitro antiviral activity of HCQ and AZM must be rediscussed since these molecules are known or strongly suspected to induce this biological disorder in various models ( Baronas et al, 2007 ; Tsukimura et al, 2021 ; Tummino et al, 2021 ; Van Bambeke et al, 1996 ) and clinical cases ( Costa et al, 2013 ; Khubchandani and Bichle, 2013 ; Manabe et al, 2021 ; Obeidat et al, 2020 ).…”

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.…”