Immune checkpoint inhibitor-induced diabetes mellitus with nivolumab.

Immune checkpoint inhibitors (ICIs) have been increasingly used in the treatment of various advanced cancers; however, therapy can be complicated by immune-related adverse events (irAEs). We present the case of a man in his 40s, with metastatic melanoma treated with nivolumab immunotherapy who developed ICI-induced diabetes mellitus (ICI-DM). Hyperglycaemia in the absence of ketoacidosis was incidentally noted when he presented to the emergency department for review of an urticarial rash. Further testing, including haemoglobin A1c and C-peptide level, confirmed his presentation was most consistent with ICI-DM and he was commenced on appropriate diabetes treatment. This report aims to detail an atypical presentation of ICI-DM and to highlight the importance of clinician awareness in identifying this irAE in patients receiving ICIs.

Immune checkpoint inhibitor-induced diabetes mellitus with pembrolizumab.

An 81-year-old woman with a background of metastatic melanoma on pembrolizumab with no history of diabetes was brought into the emergency department with polyuria, polydipsia and weight loss. The initial assessment was consistent with severe diabetic ketoacidosis (DKA) and prerenal acute kidney injury with no clinical evidence of infection. The patient was treated with fluid resuscitation and an insulin infusion and eventually transitioned to a basal-bolus insulin regime, which was continued after discharge. Diabetes autoantibody screen returned negative, and she was diagnosed with immune checkpoint inhibitor-induced diabetes mellitus (ICI-induced DM) due to pembrolizumab. The patient has clinically improved and pembrolizumab was continued. The aim of this report is to highlight the importance of recognising ICI-induced DM as a rare immune-related adverse event in patients receiving programmed cell death protein 1/programmed cell death protein-ligand 1 inhibitor therapy and provide clinicians with insight into immune checkpoint endocrinopathies with an emphasis on diabetes and DKA.

Flucloxacillin and paracetamol induced pyroglutamic acidosis.

A 75-year-old woman was admitted to a regional hospital with an acute kidney injury (AKI) and nausea on a background of recent treatment for Staphylococcus aureus bacteraemia secondary to pneumonia. The treatment thereof resulted in a high anion gap metabolic acidosis (HAGMA). The pneumonia was initially treated with intravenous piperacillin and tazobactam and the patient transferred to a tertiary hospital. There, the diagnosis of S. aureus bacteraemia secondary to a pulmonary source was confirmed and treatment was changed to intravenous flucloxacillin and the patient was discharged to hospital in the home (HITH is a service that allows short-term healthcare at home to be provided to people who would otherwise need to be in hospital) to complete the antibiotic course. Five weeks after commencing flucloxacillin, the patient was referred back to hospital with nausea and worsening kidney function with an associated significant HAGMA. The patient has a background of chronic kidney disease and chronic back pain for which she was taking long-term paracetamol. The HAGMA was determined to be due to a pyroglutamic acidosis (PGA), deemed secondary to the combined use of paracetamol and flucloxacillin. This was subsequently confirmed with a plasma pyroglutamic acid concentration level of 7467 µmol/L (reference range 20-50 µmol/L) and a urinary level of 1700 mmol/mol creatinine (<110 mmol/mol creatinine). To our knowledge, this is the highest plasma and urinary levels published to date. Furthermore, considering the common use of paracetamol and penicillins, it is important to recognise HAGMA as a potential complication of co-administration of paracetamol and iso-oxylopenicillin. The HAGMA resolved after cessation of flucloxacillin despite the continuation of paracetamol and without administration of N-acetylcysteine. PGA-related HAGMA appears to be a unique potential side effect of iso-oxylopenicillin rather than other beta-lactams.

Acquired pyroglutamic acidosis due to long-term dicloxacillin and paracetamol use.

An 85-year-old man with a background of transfusion-dependent chronic myelomonocytic leukaemia and chronic kidney disease stage III presented with symptomatic anaemia, acute kidney injury, sepsis and high anion gap metabolic acidosis (HAGMA). Initial treatment with intravenous antibiotics and blood transfusion was complicated by transfusion-associated circulatory overload, necessitating diuresis and non-invasive ventilation. Despite gradual clinical improvement, the patient's HAGMA persisted, and no cause was identified on urine testing or renal ultrasound. As the patient was on long-term dicloxacillin for infective endocarditis prophylaxis and regular paracetamol, pyroglutamic acidosis (PGA) (5-oxoproline acidosis) was considered. This was later confirmed with elevated serum levels, and the HAGMA resolved following cessation of these medications. Although considered an uncommon cause of HAGMA, PGA is likely also under-recognised, and to our knowledge, this may be the second reported case in the context of dicloxacillin.