Can Rinvoq (upadacitinib) cause painful axillary lymphadenopathy in patients, particularly those with a history of autoimmune or inflammatory conditions?

Can Rinvoq Cause Painful Axillary Lymphadenopathy?

Rinvoq (upadacitinib) is not specifically documented to cause painful axillary lymphadenopathy in the available clinical trial data or FDA-approved prescribing information, though general lymphadenopathy and infections that could secondarily cause lymph node inflammation are recognized adverse events.

Evidence from Clinical Trials and Safety Data

The most comprehensive safety analysis of upadacitinib across multiple indications (over 27,000 patient-years of exposure) does not list painful axillary lymphadenopathy as a distinct adverse event 1. The most frequently reported adverse events include:

• Infections: COVID-19, upper respiratory tract infections, nasopharyngitis, urinary tract infections 1
• Herpes zoster: Rates ranging from 2.4-6.6 per 100 patient-years across indications, with higher rates (4.0% at 15 mg and 7.2% at 30 mg maintenance doses) reported in Crohn's disease trials 2, 1
• Dermatologic events: Acne, particularly in atopic dermatitis patients 1
• Serious infections: Rates ranging from 1.3-4.6 per 100 patient-years 1

Mechanism and Theoretical Considerations

As a selective JAK1 inhibitor, upadacitinib suppresses cytokine signaling pathways involved in immune responses 3. This immunosuppressive mechanism theoretically increases susceptibility to infections that could cause reactive lymphadenopathy, but direct drug-induced lymph node inflammation is not documented 4, 3.

Clinical Approach to Painful Axillary Lymphadenopathy in Patients on Upadacitinib

Immediate Assessment

Evaluate for infectious causes first, as upadacitinib increases infection risk:

• Herpes zoster: Check for vesicular rash in dermatomal distribution, as this is the most common infection associated with upadacitinib 4, 1
• Bacterial lymphadenitis: Assess for rapid onset, fever, erythema, and warmth over the lymph node 5
• Cellulitis: Particularly relevant if there is surrounding skin involvement 5

Diagnostic Workup

• Complete blood count with differential: To assess for leukocytosis, lymphocytosis, or cytopenias 6
• Inflammatory markers: ESR and CRP to quantify systemic inflammation 7
• Blood cultures: If fever is present or acute onset of symptoms 7
• Imaging: Ultrasound of the axilla to characterize lymph node size, architecture, and vascularity 2

Key Distinguishing Features

Lymph nodes >1 cm are generally considered abnormal, and nodes >1.5 cm increase concern for malignancy or chronic infection 5. Important characteristics include:

• Painful, tender nodes with fever and erythema: Suggest acute bacterial infection requiring antibiotics 5
• Painless, hard, or persistent nodes >4 weeks: Require imaging and possible biopsy to exclude malignancy 5
• Non-tender lymphadenopathy: May indicate non-tuberculous mycobacteria, lymphoma, or other chronic processes 5

Critical Safety Monitoring

Baseline and ongoing monitoring requirements for upadacitinib include 6:

• Tuberculosis screening (baseline)
• Hepatitis B and C screening (baseline)
• Complete blood count with differential (baseline and regular intervals)
• Liver enzymes (baseline and regular intervals)
• Lipid panel (baseline and regular intervals)
• Signs of venous thromboembolism: chest pain, leg swelling, shortness of breath 6

When to Consider Alternative Diagnoses

If lymphadenopathy persists despite treatment of identified infections or occurs without clear infectious etiology, consider:

• Underlying autoimmune disease activity: Particularly relevant in patients with inflammatory bowel disease or rheumatologic conditions 2
• Malignancy: Especially if nodes are painless, hard, and progressive 2, 5
• Paradoxical immune reactions: Though not specifically documented with upadacitinib, other biologics have been associated with paradoxical inflammatory responses 2

Management Algorithm

1. Assess for infection immediately: Examine for herpes zoster rash, signs of bacterial infection, and systemic symptoms 4, 1
2. Obtain laboratory studies: CBC, ESR, CRP, blood cultures if febrile 6, 7
3. Perform imaging: Ultrasound of axilla to characterize lymph nodes 2
4. Treat identified infections appropriately: Antibiotics for bacterial infections, antivirals for herpes zoster 5
5. If no infection identified and nodes persist >4 weeks: Proceed to core needle biopsy to exclude malignancy 2
6. Continue upadacitinib monitoring: Do not automatically discontinue unless serious infection or malignancy is confirmed 6, 1

Common Pitfalls to Avoid

• Do not dismiss new lymphadenopathy as benign without proper workup, especially given the increased infection risk with JAK inhibitors 4, 1
• Do not overlook herpes zoster, which can present with lymphadenopathy before or concurrent with rash development 1
• Do not delay biopsy if lymph nodes are painless, hard, and persistent, as malignancy risk exists with chronic immunosuppression 2, 5