Multiple drugs

Abstract

Various toxicities: case report A man in his 60s’ [exact age not stated] developed relapse of the IgM nephropathy, acute pancreatitis and interstitial pneumonia during treatment with pembrolizumab for metastatic pulmonary adenocarcinoma. Additionally, he exhibited lack of efficacy to methylprednisolone and prednisolone during treatment of relapsed nephrotic syndrome, and furosemide during treatment of hypoxia [not all dosages and routes stated]. The man was admitted with relapse of IgM nephropathy. His medical history was significant for lung aspergillosis, right pyothorax and emphysema 8 years prior to the current hospitalisation. Additionally, he also had deep venous thrombosis, nephrotic syndrome, and IgM nephropathy, which was initially treated with prednisolone and then with low-density lipoprotein adsorption treatment. Two years later, he was diagnosed with metastatic pulmonary adenocarcinoma. Sixty three weeks prior to this admission, he started receiving pembrolizumab [Keytruda] 200mg injection every 3 weeks (for a total of 21 injections), with a significant improvement. One week earlier (62 weeks after initiation of the pembrolizumab therapy), peripheral oedema reappeared, and 2 days earlier, an elevation in the urinary protein-creatinine ratio was noted. He was thus hospitalised and based on symptoms and findings, he was diagnosed with relapse of the nephrotic syndrome (the current presentation). The man’s pembrolizumab therapy was therefore discontinued. In view of the relapsed nephrotic syndrome, he was treated with methylprednisolone 250mg for 3 days, followed by prednisolone 40mg/day. Warfarin was also initiated as a thrombosis prophylaxis. Despite the steroid treatment, his urinary proteinuria remain unchanged (lack of efficacy). Therefore, ciclosporin was initiated. On day 15, he complained about abdominal pain, and a CT scan revealed mesenteric haematoma (haemorrhagic pseudocyst). Prothrombin complex concentrate was thus administered, and his warfarin and ciclosporin were stopped. Eventually, an improvement in his condition was noted. Subsequently, his prednisolone dose was tapered to 30mg/day, and ciclosporin was restarted, along with cotrimoxazole [sulfamethoxazole/trimethoprim]. He eventually developed thrombocytopenia [aetiology not stated]. Therefore, ciclosporin and cotrimoxazole were discontinued on day 30. On day 40, his abdominal pain recurred. A subsequent imaging showed an enlargement of the mesenteric haematoma, which had turned cystic. Laboratory investigations showed elevated levels of serum amylase, AST and ALT, and a CT scan showed swelling of the pancreas. Based on these findings, he was diagnosed with acute pancreatitis (on day 58). Initially, his pancreatitis was controlled by diet fasting. However, exacerbation of the pancreatitis was noted on day 77, following the resumption of his diet. Shrinkage of the mesenteric cystic lesion was noted, with an increase in the amylase level. On day 93, he developed a fever with enlargement of the mesenteric cyst. His chest imaging indicated interstitial pneumonia. Therefore, an infection of the mesenteric cyst was suspected, and a drainage tube was placed. Due to the increased level of amylase in the cyst fluid, a diagnosis of pancreatitis-associated pseudocyst was made. On day 102, he developed complications of peripheral oedema, hypoxaemia and pleural effusion. Subsequently, he was treated with furosemide injection for hypoxia. Regardless of treatment, his hypoxia progressed (lack of efficacy). However, on day 108, he developed respiratory failure and died of it. Autopsy was performed. The autopsy report suggested the development of relapsed IgM nephropathy, acute pancreatitis and interstitial pneumonia was attributed to the repeated administration of pembrolizumab [durations of treatments to reactions onsets not stated].