Fatal pulmonary toxicity due to carfilzomib (Kyprolis™).

INTRODUCTION: Carfilzomib (Kyprolis™) is a second-generation proteasome inhibitor for the treatment of relapsing multiple myeloma (MM). In 2012, carfilzomib was approved by Food and Drug Administration for the treatment of patients with relapsed MM who had received at least two prior therapies. We present a case of fatal pulmonary toxicity presumed secondary to carfilzomib. CLINICAL PRESENTATION: A 61-year-old male was initially diagnosed with MM in 2003 for which he received multiple treatments. In 2013, he was started on carfilzomib for relapsing MM. After 24 h, the patient developed an acute respiratory distress syndrome for which he needed mechanical ventilation. One week later, patient developed diffuse alveolar hemorrhage and despite aggressive supportive care, the patient died after three weeks. DISCUSSION: The temporal relationship between the first exposure to carfilzomib and development of symptoms, and the exclusion of other possible etiologies, leads us to believe that our patient's lung toxicity is a possible adverse reaction to carfilzomib. To the best of our knowledge, there are no previous reports of deaths due to carfilzomib-related pulmonary toxicity.

Thinking outside the box: a middle-aged man with new-onset dyspnoea on exertion and pedal oedema.

We describe a diagnostic dilemma in a middle-aged man presenting with dyspnoea and bilateral pedal oedema who had been diagnosed with right heart failure based on clinical evidence. The evaluation for aetiology eventually led to discovery of an unusual extrathoracic cause, a left-to-right communication in the renal vasculature. Renal arteriovenous fistulae are rare and can be congenital, acquired or idiopathic. A left-to-right shunt typically presents with high-output cardiac failure involving the left and right sides of the heart. An atypical feature of this case was the finding of overt right heart failure in the setting of a normal left heart. Such a presentation has only been described in a few isolated case reports. Diagnostic approaches include CT angiography and cardiac catheterisation for haemodynamic measurements. The primary treatment options for arteriovenous fistulae are medical management, arterial embolisation and surgical repair.

A 62-year-old women with persistent severe asthma, skin rash, and eosinophilia.

A 62-year-old white woman was admitted with shortness of breath, wheezing, and cough. While in the hospital a generalized pruritic skin rash developed on her trunk and upper and lower extremities. She did not have any fevers, chills, or night sweats. The patient was known to have chronic, difficult-to-control asthma despite being compliant with a treatment regimen consisting of inhaled albuterol, high-dose inhaled steroids, salmeterol, and montelukast. Her medical history was significant for hypertension and gout. She had no family history of asthma. The patient was a life-long nonsmoker and did not drink alcohol. During this hospitalization, she was started on prednisone 40 mg/d po in addition to her home medications.