Case StudiesChloroquine-induced phospholipidosis of the kidney mimicking fabry's disease: Case report and review of the literature☆,☆☆
Section snippets
Case report
A 46-year-old female patient had suffered from Sjögren's syndrome with keratoconjunctivitis, xerostomia, and arthralgias for 13 years before presenting to the clinic. The diagnosis of Sjögren's syndrome was confirmed by positive immunoserologic findings for antinuclear antibodies, rheumatoid factor, and SS-A and SS-B antibodies. The patient had a 10-year history of poorly controlled arterial hypertension (160/100 mm Hg). Renal function was impaired (serum creatinine [CR] 1.9 to 2.1 mg/dL; blood
Light microscopy
Light microscopy of the renal biopsy (1.2 cm) showed 7 glomeruli, 3 of which were completely obliterated. In the remaining glomeruli a slight and focal increase in mesangial cellularity was seen (Fig 1).There was no necrosis of glomerular tufts and no
Discussion
The ultrastructural investigation of the patient's kidney revealed an accumulation of myeline-like bodies consisting of concentric lamellae of dark and clear layers, similar to what is seen in Fabry's disease. The phospholipid material was found mainly in podocytes and to a lesser degree in the glomerular and vascular endothelium, as well as in vascular smooth muscle cells. In Fabry's disease, including oligosymptomatic manifestations restricted to the kidneys, a similar renal storage pattern
Acknowledgements
The authors thank Brigitte Schult and Maria Wittmeier for carefully preparing the manuscript and Sabine Schäfer for valuable technical assistance. This paper is dedicated to G. H. Thoenes on the occasion of his 65th birthday.
References (52)
- et al.
A female heterozygous patient with Fabry's disease with renal accumulation of trihexosylceramide detected with a monoclonal antibody
Am J Kidney Dis
(1995) - et al.
Electron microscopic demonstration of lysosomal inclusion bodies in lung, liver, lymph nodes and blood leukocytes of patients with amiodarone pulmonary toxicity
Am J Med
(1985) - et al.
Histopathologic analysis of suspected amiodarone hepatotoxicity
HUM PATHOL
(1990) - et al.
Endomyocardial biopsy finding in two patients with idiopathic dilated cardiomyopathy receiving long-term treatment with amiodarone
Am J Cardiol
(1991) - et al.
Immunohistochemical evidence for amyloid beta in rat soleus muscle in choloroquine-induced myopathy
Neurosci Lett
(1994) - et al.
Lysosomotropic agents
Biochem Pharmacol
(1974) - et al.
Inhibition of lysosomal function in red and white skeletal muscles by choloroquine
Exp Neurol
(1981) - et al.
Increased autophagy in choloroquine treated tonic and phasic muscles; an alternative view
Tissue Cell
(1981) - et al.
Studies on mechanism of phospholipid storage induced by amantadine and choloroquine in Madin Darby canine kidney cells
Biochem Pharmacol
(1982) - et al.
Effect of choloroquine on the activity of some lysosomal enzymes involved in ganglioside degradation
Biochem Biophys Acta
(1987)
Effects of ethanol on the changes in renal fluid and electrolyte handling and kidney morphology induced by long-term choloroquine administration to rats
Alcohol
Effects of choloroquine treatment on antioxidant enzymes in rat liver and kidney
Free Radic Biol Med
An atypical variant of Fabry's disease with manifestations confined to the myocardium
N Engl J Med
Atypical Fabry's disease: An oligosymptomatic variant
Arch Pathol Lab Med
Fabry's disease: Primary diagnosis by electron microscopy
Am J Surg Pathol
Renal pathological changes in Fabry disease
J Inherit Metab Dis
Drug-induced and naturally occuring myeloid bodies
Lab Invest
Drug-induced lysosomal storage disorders
Drug-induced phospholipidosis
CRC Crit Rev Toxicol
Side effects and possible contraindications of amiodarone use
Am Heart J
Amiodarone toxicity: Functional and ultrastructural evaluation
Thorax
Amiodarone-associated cirrhosis with hepatic and lymph node granulomas
Histopathology
Chloroquine keratopathy as an example of drug-induced phospholipidosis
Klin Monatsbl Augenheilkd
Diagnosis of choloroquine cardiomyopathy by endomyocardial biopsy
N Engl J Med
Choloroquine cardiomyopathy
Arch Pathol Lab Med
Cardiomyopathy after choloroquine treatment
Acta Med Scand
Cited by (64)
Does administration of hydroxychloroquine/amiodarone accelerate accumulation of globotriaosylceramide and globotriaosylsphingosine in Fabry mice?
2021, Molecular Genetics and Metabolism ReportsLupus Nephritis and Hydroxychloroquine-Associated Zebra Bodies: Not Just in Fabry Disease
2021, Kidney MedicineCitation Excerpt :Absence or reduced α-galactosidase activity results in the accumulation of glycosphingolipids, a subtype of glycolipids, which ultrastructurally form zebra bodies.6,8-15 Phospholipases A and C metabolize phospholipids, and their reduced activity results in an accumulation of osmiophilic phospholipids.8,10,13,16 Therefore, inhibition of these enzymes by chloroquine and hydroxychloroquine is presumed to result in the formation of zebra bodies and osmiophilic granules.
Incidental finding of cornea verticillata or lamellar inclusions in kidney biopsy: measurement of lyso-Gb3 in plasma defines between Fabry disease and drug-induced phospholipidosis
2021, Biochimica et Biophysica Acta - Molecular Basis of DiseaseThe endosomal lipid bis(monoacylglycero) phosphate as a potential key player in the mechanism of action of chloroquine against SARS-COV-2 and other enveloped viruses hijacking the endocytic pathway
2020, BiochimieCitation Excerpt :Therefore CQ accumulates where large amounts of BMP are found and where the enzymes presumably involved in its synthesis are found. CQ was also found to induce phospholipidosis in various cell cultures, including 3T3-L1K murine adipocytes [80], primary cultures of rat hepatocytes [81], in mice J774A.1 cells [54] and MDCK kidney cells [82], as well as in renal cells in which a phenotype resembling Fabry’s disease is observed [83,84]. BMP is involved in the inward budding of ILVs into the acidic lumen of late endosomes, a process that leads to the formation of MVB [85].
Fabry Disease
2017, National Kidney Foundation's Primer on Kidney DiseasesDiagnostic Pathology: Kidney Diseases: A volume in Diagnostic Pathology
2015, Diagnostic Pathology: Kidney Diseases
- ☆
Address correspondence and reprint requests to J. Mũller-Hõcker, MD, PhD, Pathologisches Institut der Ludwig-Maximilians Universitãt Mũnchen, Thalkirchner Straβe 36, D - 80337 Munich, Germany.
- ☆☆
0046-8177/03/3403-0014$30.00/0