Case Presentation: A 26-year-old otherwise healthy female was prescribed trimethoprim-sulfamethoxazole (TMP-SMX) for a recurring, spontaneously draining vaginal mass below her urethra with inguinal adenopathy. 5 days after starting TMP-SMX, she developed a full-body rash, fever, myalgia, nausea, and a depressed WBC of 2.4 K/mcL. Possible drug fever was suspected and TMP-SMX was discontinued and covered with levofloxacin, which resolved her vaginal symptoms. TMP-SMX history includes one prior prescription due to penicillin allergies at age 21 or an oral infection with no reported issues. She presented to the ED 5 days later with progressive dyspnea, chest pain, diarrhea, fatigue, and a fever of 103. Community-acquired pneumonia was suspected given negative COVID-19 testing and left basilar infiltrates on CXR. She was prescribed doxycycline, an inhaler, and discharged. Her dyspnea worsened and she returned to the ED less than 2 days later with hypoxia (mid-80s on room air). A CT scan showed diffuse ground glass opacities primarily in the lower lobes posteriorly and parenchymal interstitial emphysema. She was started on IV vancomycin and moxifloxacin and continued doxycycline for broad-spectrum antibiotic coverage. She continued to worsen and was transferred to a tertiary ICU and required intubation (day 9). Repeat CT post-intubation showed diffuse ground glass opacities, moderate right-sided pleural effusion, and segmental and subsegmental pulmonary embolisms. Despite relatively low work of breathing, after being unable to improve saturations to above 85%, she was placed on venovenous ECMO (day 10). Extensive infectious and rheumatological disease workup over the course of admission was negative. No etiology for her respiratory failure could be identified and TMP-SMX triggered ARDS is suspected based on the timing of her exposure, clinical course, and lack of alternative explanation despite extensive evaluation. Due to her high ventilatory support requirement and hypoxia after decannulation, she received a bilateral lung transplant (day 59) and remains admitted for further care.
Discussion: TMP-SMX induced lung injury is scantly documented and there are no reports of TMP-SMX exposure associated with severe ARDS requiring prolonged hospitalization, ECMO support, and bilateral lung transplantation in adults. This is a single case report but it adds to the growing evidence of pulmonary toxicity, as severe as acute respiratory failure, related to TMP-SMX use. Given that TMP-SMX is widely used in both outpatient and inpatient settings, this case illustrates the importance of raising awareness and clinical recognition of rare adverse drug reactions as low prevalence of this case in literature may contribute to under recognition.
Conclusions: In instances of severe acute respiratory failure of unclear etiology in otherwise healthy patients, clinicians should obtain a detailed drug-exposure history, including TMP-SMX exposure. There is need for more research to understand the pathology of this adverse reaction and a need for guidelines to treat this condition.