Upadacitinib-Associated Lymphadenopathy

Clinical Presentation and Diagnosis

• The American College of Physicians recommends evaluating for infectious causes first in patients on upadacitinib, as the drug increases infection risk, with herpes zoster being the most common infection associated with upadacitinib 2
• The National Comprehensive Cancer Network suggests that lymph nodes greater than 1 cm are generally considered abnormal, and nodes greater than 1.5 cm increase concern for malignancy or chronic infection 2
• A complete blood count with differential is recommended to assess for leukocytosis, lymphocytosis, or cytopenias in patients on upadacitinib 3
• Inflammatory markers such as ESR and CRP should be quantified to assess systemic inflammation in patients on upadacitinib 4

Imaging and Monitoring

• The National Comprehensive Cancer Network recommends ultrasound of the axilla to characterize lymph node size, architecture, and vascularity in patients with lymphadenopathy 5
• Baseline and ongoing monitoring requirements for upadacitinib include tuberculosis screening, hepatitis B and C screening, complete blood count with differential, liver enzymes, lipid panel, and signs of venous thromboembolism 3

Management and Treatment

• The American Academy of Family Physicians suggests treating identified infections appropriately, with antibiotics for bacterial infections and antivirals for herpes zoster 2
• If no infection is identified and nodes persist for more than 4 weeks, a core needle biopsy should be performed to exclude malignancy 5
• The European League Against Rheumatism recommends continuing upadacitinib monitoring and not automatically discontinuing unless serious infection or malignancy is confirmed 3