engleski

Chloroquine toxic effect mimicking a Fabry disease. A case report

Clinical history In February 2013 69-year-old female presented with pain in the lumbal region and swollen joints on hands and feet due to the exacerbation of rheumatoid arthritis (diagnosed in 1990) treated with prednisone and methotrexate. In 2013 methotrexate was discontinued due to haematuria and chloroquine was prescribed instead. The patient also suffered from long-term hypertension, heart arrhythmia and osteoporosis. Urinalysis showed microhaematuria and azotemia (creatinine 109 μmol/L, urea 11.0 mmol/L), and therefore the patient was admitted to Nephrology department and kidney biopsy was performed. Macroscopic features Ultrasound showed decreased size of both kidneys (8.5 cm), bilaterally situated cysts in the cortex and con- crements, without dilatation of tubular tract. Microscopic features Kidney biopsy showed ishaemic changes and periglomerular fibrosis affecting 25% glomeruli. Segmental sclerosis was seen in one glomerulus and all other glomeruli had normal morphology. Interstitial fibrosis and tubular atrophy affected 50% of renal cortex. There was a severe arterial hyalinosis and fibrointimal thicke-ning of arterial walls. On immunofluorescent microscopy glomeruli and arterial intima were granular positive for C3. Glomeruli were negative for IgA, IgG, IgM, C1q, kappa and lambda light chains. Two glomeruli along with adjacent tubules were analyzed by electron microscopy (EM). Zebra- bodies were found in endothelium and podocytes. The foot processes were preserved. Glomerular basement membrane was 200 nm in thickness. There were no deposits. Tubules and peritubular capillaries showed normal ultrastructure. Diagnosis Severe nephroangiosclerosis with secondary focal segmental glomerulosclerosis and thin basement membrane nephropathy. Zebra-bodies were found suggesting Fabry disease or possible chloroquine toxicity. Genetic testing excluded Fabry disease. Comments Chloroquine is a drug used to treat malaria, extraintestinal amebiasis, rheumatoid arthritis and lupus. Among its numerous side effects is a syndrome mimicking Fabry disease, a metabolic disorder arising from a defi-ciency of a lysosomal alpha galactosidase A resulting in the systemic accumulation of neutral glycosphin- golipids in vascular endothelia of the kidneys, heart, brain and skin. Specific microscopic features are laminated lipid deposits, known as zebra-bodies. Here we present a case of chloroquine toxic effect mimicking a Fabry disease. Finding of zebra-bodies on EM of kidney biopsy specimen suggests Fabry disease or chloroquine side effects. This finding may lead to mis-diagnosis, especially if a complete history is not available or the pathologist is not aware of patient's therapy.

Chloroquine toxic effect; Fabry disease

nije evidentirano