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VEXAS Syndrome: Differentiating Flares from Infection in the Critical Care Setting

Authors

Emma Mathers BS, Jennifer Weiss, Paritosh Prasad MD DTM&H, Rodolfo Alpizar-Rivas MD

Introduction

VEXAS (vacuoles, E1 enzyme, X-linked, autoimmune and autoinflammatory, and somatic) is an autoinflammatory condition that was described in 2020 in the New England Journal of Medicine by Beck et al. (1). VEXAS predominantly affects older males and is associated with dermatitis, polychondritis, fevers, and hematologic abnormalities. Our case investigates the diagnostic and treatment processes for a VEXAS patient who presented with a clinical picture concerning for pulmonary VEXAS versus infectious pneumonia. There have been a variety of pulmonary manifestations recorded in VEXAS patients as a result of systemic inflammation, including parenchymal changes with ground glass opacities and pleural effusions (2). Importantly, VEXAS patients are also at increased risk for opportunistic infection because of the immune dysfunction associated with the syndrome and the combination of immunosuppressive medications that are used for treatment. The pulmonary manifestations of VEXAS can be difficult to distinguish from pulmonary infection, and both must be considered on a comprehensive differential in these patients.

Case Presentation

This case describes a 63-year-old male diagnosed with VEXAS syndrome (UBA1 and DNMT3a positive) following months of fatigue, weight loss, and auricular chondritis. He was initiated on prednisone and methotrexate at diagnosis. Six months after diagnosis, he presented to the emergency department (ED) with dyspnea, chest pain, tachycardia, and fever (39.2C). He became somnolent and was transferred to the ICU for hypoxic respiratory failure and sepsis. Chest CT showed multifocal opacities in both lungs, and laboratory testing showed neutrophil-predominant leukocytosis. The patient was treated empirically for bacterial pneumonia with vancomycin, piperacillin/tazobactam, and azithromycin. Though microbiological studies were negative, he improved on antibiotics and was discharged after one week. Two weeks later, the patient returned to the ED with dyspnea. On exam, he was tachypneic, hypoxic, and febrile (39C). Chest CT showed diffuse consolidations concerning for infection. There was interval increase in consolidations when compared to the CT scans from the first hospitalization. A repeat infectious workup, which included respiratory viral panel, sputum & blood cultures, Pneumocystis PCR, Streptococcus and Legionella urine antigens, among others, was negative. The patient was again treated empirically for bacterial pneumonia with vancomycin, piperacillin/tazobactam, and azithromycin. He improved and was discharged after one week.

Discussion

The primary question of differential diagnosis for this patient was distinguishing between pulmonary inflammation associated with his VEXAS syndrome and acute respiratory infection. The patient's rheumatology team felt that his presentation was more consistent with an infectious process rather than a VEXAS flare due to the acute onset of fever, chills, and shortness of breath. Additionally, prior to these hospitalizations, the patient had never experienced any pulmonary manifestations of VEXAS. Thus, it was determined to be unlikely that VEXAS would progress to such severe pulmonary symptoms and hypoxia so acutely. Ultimately, despite the absence of diagnostic microbiological data, the patient improved during broad spectrum antibiotic therapy which points to the presence of an underlying infection. Infectious pneumonia should be considered in VEXAS patients with respiratory presentations given their generalized immune dysfunction due to both VEXAS syndrome and the immunosuppressive medications used to treat it.

References

  1. Beck DB, Bodian DL, Shah V, et al. Estimated prevalence and clinical manifestations of UBA1 variants associated with VEXAS syndrome in a clinical population. JAMA. 2023;329:318-324. [PMID: 36692560] doi:10.1001/jama.2022.24836
  2. Casal Moura M, Baqir M, Tandon YK, et al. Pulmonary manifestations in VEXAS syndrome. Respir Med. 2023;213:107245. [PMID: 37062498] doi:10.1016/j.rmed.2023.107245

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