A 68-year-old woman presented with worsening dyspnea. She had presented to her local community hospital 10 days earlier with similar symptoms. She was diagnosed with a right-sided pleural effusion, which was attributed to pneumonia and treated with antibiotics. She underwent two thoracenteses within a week, with relief of dyspnea after each procedure. Two days after hospital discharge, she developed recurrence of dyspnea and presented to our hospital. She denied any cough, fever, chills, or night sweats. She denied leg swelling, orthopnea, or paroxysmal nocturnal dyspnea. She did not have any recent surgeries or trauma. She had a medical history notable for Hodgkin lymphoma treated with radiation 40 years ago, renal cancer treated with nephrectomy, COPD on chronic 2 L oxygen nasal cannula, and pulmonary embolism on chronic anticoagulation. She also had a chronic left-sided chest port, which had been placed for a long-standing history of difficult IV access.

An 80-year-old man with no history of substance addiction presented with complaints of cough and breathlessness for 4 months. His cough was nonproductive, waxing and waning in nature with high symptom load during daytime, but not associated with chest pain or wheezing. He gives no history of nasal or sinus symptoms, aspiration, or reflux symptoms. Breathlessness was nonparoxysmal, independent of cough and progressing from modified medical research council Grade-I to Grade II. It was not accompanied by wheezing or stridor. He denied specific triggers and seasonal, diurnal, or postural variation of symptoms. His medical history was largely unremarkable, apart from hypertension diagnosed 2 decades earlier. Despite 6 months of treatment with dual antihypertensive medications, his BP remained uncontrolled. He did not receive angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for the treatment of hypertension as per his old medical records. He denies history of atopy, occupational or environmental dust exposure. He refused history of fever, significant loss of weight or appetite. He had been treated for asthma with a combination of a long-acting beta-2 agonist and an inhaled corticosteroid inhaler, which provided no relief.

A 36-year-old man with severe Crohn disease complicated by urethral strictures and enterocutaneous and enterovesicular fistulas presented for several weeks of poor appetite, weight loss, failure to thrive, and newly worsening altered mentation. Further history revealed he chronically did not urinate through his urethra, but rather "leaked" through multiple enterocutaneous fistulas in his abdomen and perineum. Medications included ustekinumab (anti-IL12/IL23 monoclonal antibody) for Crohn disease, methadone, and hydrocodone. He had had multiple surgeries because of fistulas related to his Crohn disease, which included subtotal colectomy with ileostomy creation, proctectomy, and ischiorectal flap creation. He drank 10-15 ounces of liquor per week, smoked 10 cigarettes daily, and smoked marijuana weekly.

Zanubrutinib is an orally administered second-generation covalent inhibitor of Bruton tyrosine kinase that was recently approved by the US Food and Drug Administration for the treatment of chronic lymphocytic leukemia and small lymphocytic leukemia. It has been associated with significant major and minor bleeding events, including intracranial and GI hemorrhage and hematuria, with or without concurrent antiplatelet or anticoagulation therapy. We report a case of a 65-year-old man with relapsing chronic lymphocytic leukemia. He presented to us with repeated episodes of worsening dyspnea secondary to hemorrhagic pleural effusion 2 months after the initiation of zanubrutinib with concomitant apixaban use. On discontinuation of zanubrutinib after the second episode, he remained asymptomatic on further follow-up examination. Previously only described with the first-generation Bruton tyrosine kinase inhibitor, our case focuses attention on a rare adverse event and a first reported incidence, to our knowledge, of recurrent hemorrhagic pleural effusion associated with zanubrutinib in a patient with relapsing chronic lymphocytic leukemia.