Pembrolizumab-induced thrombotic thrombocytopenic purpura.

INTRODUCTION: Pembrolizumab is a humanised monoclonal antibody targeting the receptor programmed cell death protein-1 (PD-1), with anti-tumour activity demonstrated for many malignancies. Such immune checkpoint inhibitors are associated with many immune-related adverse events including rash, colitis, hepatitis, pneumonitis, endocrinopathy and, rarely, haematological adverse events, including immune-related thrombocytopenia. CASE REPORT: We report a 60-year-old female with metastatic non-small cell lung cancer treated with pembrolizumab every three weeks. Following her fifth cycle, she presented to our hospital with community-acquired pneumonia. Thrombocytopenia developed the next day and, after detailed investigations, thrombotic thrombocytopenic purpura was diagnosed. MANAGEMENT AND OUTCOME: Pembrolizumab was immediately ceased and plasma exchange commenced along with IV methylprednisolone 250 mg daily for three days followed by oral prednisolone. After five days of plasma exchange, platelet counts normalised and haemolytic anaemia resolved. DISCUSSION: Acquired thrombotic thrombocytopenic purpura is an autoimmune disorder caused by an inhibitory autoantibody against ADAMTS-13. While most cases of acquired thrombotic thrombocytopenic purpura are idiopathic, certain conditions (e.g. bacterial infection, autoimmune disorders, malignancies) and medications are associated with thrombotic thrombocytopenic purpura. Other potential causes were eliminated in our patient. As acquired thrombotic thrombocytopenic purpura is an autoimmune disorder, pembrolizumab, given its unique mechanism of action and association with immune-related adverse events, is believed to be implicated in the development of thrombotic thrombocytopenic purpura. This case is one of only two linking anti-PD-1 therapy to thrombotic thrombocytopenic purpura development (the other occurring in a patient on nivolumab plus ipilimumab). Thrombotic thrombocytopenic purpura is life-threatening and clinicians are advised to be aware of its possible occurrence in immune checkpoint inhibitor-treated patients.

Optic neuritis induced by 5-fluorouracil chemotherapy: Case report and review of the literature.

Introduction: For over 50 years, 5-Fluorouracil has played a critical role in the treatment of numerous malignancies, including colorectal cancer. Ocular side effects are uncommon and include blurred vision, conjunctivitis, excessive lacrimation and keratitis. Case report: We report a 57-year-old male with metastatic colorectal cancer who had received extensive chemotherapy with 5-Fluorouracil-based regimens for over 12 months. Following his seventh cycle of cetuximab/FOLFIRI, he developed acute onset global headache, nausea and loss of vision in the right eye. After detailed investigations, including ophthalmologic and neurologic consultations, a diagnosis of optic neuritis was made. Management and outcome: Chemotherapy was ceased immediately, and intravenous methylprednisolone (1 g) daily for five days was commenced. His headache resolved and vision started to improve within 24 h. Three weeks after completion of corticosteroids, constriction of the right visual field had fully resolved. Discussion: Atypical optic neuritis is an inflammatory optic neuropathy that can be caused by ischaemia, mechanical compression, nutritional deficiency, toxins and drugs. Drug-induced optic neuritis, while rare, is associated with cytotoxic medications including methotrexate, cisplatin, carboplatin, vincristine and paclitaxel. There have only been five previous case reports implicating 5-Fluorouracil in the development of optic neuropathy. The likelihood of the adverse drug reaction due to 5-Fluorouracil was assessed using the Naranjo algorithm. A score of +7 indicates probable causality. Clinicians should be alert to this potential ocular toxicity in order to initiate prompt cessation of treatment and early ophthalmology referral to prevent visual loss and damage to ocular structures.