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Various toxicities: case report An 17-year-old girl developed neutralising antibodies to metreleptin following treatment with metreleptin for atypical partial lipodystrophy. Thereafter, she developed skin discolouration (tanning) and hypoglycaemia following off-label treatment with setmelanotide for atypical partial lipodystrophy. She also developed antibodies against insulin following treatment with insulin for hyperglycaemia [not all routes, dosages, time to reaction onsets and outcomes stated]. The girl, who had atypical partial lipodystrophy, nonalcoholic steatohepatitis, type 1 diabetes and severe hypertriglyceridemia, started receiving metreleptin injection as a part of clinical trial (NCT01679197). During the initial 12 months, improvement was observed. She continued metreleptin as part of a longer treatment protocol (NCT02654977). However, approximately 18 months after initiation of metreleptin, she presented with concurrent acute hyperglycaemia and hypertriglyceridaemia. Laboratory investigation revealed elevated level of β-hydroxybutyrate and anti-GAD titres. C-peptide level was < 0.01 ng/mL. She was diagnosed with concurrent clinical type 1 diabetes. Investigation revealed undetectable leptin level which persisted 1h after an administered dose of metreleptin. Presence of neutralising antibodies to metreleptin (Nab-leptin) was suspected. Subsequent assays confirmed the presence of Nab-leptin. The level of in vitro neutralisation was reported to be Category E, the highest possible activity. The girl discontinued metreleptin. Her clinical course was further complicated with symptoms indicating concurrent autoimmune hepatitis. Subsequently, her glucose and lipid control substantially worsened. She required multiple hospitalisations due to concurrent hyperglycaemia, diabetic ketoacidosis, and pancreatitis. During these episodes, she was treated with aggressive hydration, IV insulin infusions at high rate, limit on food intake and a reduction in carbohydrate substrate. She also developed antibodies against insulin which were detected a few years after she started insulin treatment. However, the titers were low. She developed progressive hepatic steatosis. Thereafter, she started receiving treatment with off-label setmelanotide under compassionate use program (NCT03262610). Setmelanotide therapy was intiated at a dose of 1 mg/day and the dose was titrated up to a maximum dose of 3 mg/day. Setmelanotide therapy did not result in convincing improvement. She developed skin discoloration (tanning) and mild hypoglycaemia secondary to setmelanotide therapy. Her hypoglycaemia was treated with insulin dose titrations. Category E Nab-leptin persisted throughout the time-course after its first detection. She was diagnosed with colonisation with group B streptococci in the urinary tract [aetiology not stated] and development of a pseudocyst in the abdomen after recurrent pancreatitis episodes. Akinci B, et al. The complicated clinical course in a case of atypical lipodystrophy after development of neutralizing antibo