Upadacitinib Associated Pneumocystis Jirovecii Pneumonia

Introduction:Upadacitinib is a new oral janus kinase (JAK) inhibitor that has been approved to treat rheumatoid arthritis. JAK inhibitors carry a black box warning for their association with severe infections especially when used in combination with other immunosuppressants. Although there is a strong association, there are very few reports of Pneumocystis jirovecii pneumonia (PJP) caused by upadacitinib. We describe a case of PJP due to upadacitinib use in rheumatoid arthritis. Case presentation: A 44-year-old woman with a history of rheumatoid arthritis presented with 2 weeks of dyspnea, dry cough and fever after recently starting upadacitinib. She was noted to be tachypneic, tachycardic and hypoxemic on admission. Initial laboratory tests were within normal limits and lactate dehydrogenase was 304. Respiratory viral panel and reverse transcription-polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 were negative. Computerized tomography of the chest revealed diffuse multi-focal ground glass and consolidative opacities. The patient's respiratory status rapidly deteriorated, requiring admission to medical intensive care unit where she was initiated on invasive mechanical ventilation. A 1,3-beta-D-glucan serology test was positive and PJP polymerase chain reaction in bronchoalveolar lavage was positive. She was started on intravenous trimethoprim-sulfamethoxazole 400mg three times a day and intravenous methylprednisolone 500mg twice a day for three days. Her oxygen requirements rapidly improved and she was extubated on day 4 of admission. The patient was discharged without a supplemental oxygen requirement to complete a course of oral trimethoprim-sulfamethoxazole and prednisone. Discussion:JAK inhibitors are increasingly used for the treatment of rheumatoid arthritis and other autoimmune diseases. Other less selective JAK inhibitors such as tofacitinib and baricitinib have been associated with PJP in rheumatoid arthritis. Upadacitinib is a selective JAK1 inhibitor which is thought to give it an improved side effect profile compared to other less selective JAK inhibitors. This represents one of the first cases of PJP associated with the use of upadacitinib, a selective JAK1 inhibitor. PJP should be included in the differential diagnosis of patients treated with upadacitinib who present with fever, hypoxemia and pulmonary infiltrates. Awareness of this disease and its manifestations are critical to appropriate diagnostic evaluation and timely treatment.