How to manage an upper respiratory tract infection (URTI) in a patient with rheumatoid arthritis (RA) who is likely immunosuppressed due to RA medications?

Management of Upper Respiratory Tract Infection in Rheumatoid Arthritis

In RA patients on immunosuppressive therapy who develop a URTI, temporarily withhold conventional DMARDs, biologic DMARDs (except IL-1 and IL-6 inhibitors), and targeted synthetic DMARDs until the infection resolves, while continuing glucocorticoids at the lowest effective dose to prevent adrenal insufficiency. 1

Immediate Assessment and Risk Stratification

The critical first step is excluding serious infection that would contraindicate immunosuppression escalation, as this increases mortality. 2

Identify patients requiring immediate antibiotics or hospital referral based on these high-risk features 3:

• Systemically very unwell appearance
• Age >65 years with acute cough plus ≥2 of: hospitalization in previous year, diabetes, heart failure history, current oral glucocorticoids
• Age >80 years with acute cough plus ≥1 of the above factors
• Pre-existing comorbidities (RA patients commonly have chronic lung disease, which independently increases infection risk) 4, 5

RA patients have a >2-fold increased risk of serious infection due to immune system dysfunction, disease-related comorbidities, and immunosuppressive medications. 4

Medication Management During Active URTI

Continue Without Interruption:

• NSAIDs - may be continued for symptom control 1
• Hydroxychloroquine - has minimal immunosuppressive effect and may be continued 1
• Colchicine - may be continued if used for concurrent conditions 1
• Glucocorticoids - must be continued at the lowest effective dose to control underlying RA and avoid adrenal insufficiency 1

Temporarily Withhold Until URTI Resolves:

• Conventional synthetic DMARDs (methotrexate, leflunomide) - should be temporarily delayed 1
• Biologic DMARDs (TNF inhibitors, abatacept, rituximab) - should be temporarily withheld 1
• Targeted synthetic DMARDs (JAK inhibitors: tofacitinib, baricitinib) - should be temporarily delayed 1

May Continue With Caution:

• IL-1 inhibitors (anakinra) - may be continued if necessary to control underlying RA, as they have been used safely in sepsis trials 1
• IL-6 inhibitors (tocilizumab) - may be continued if necessary, though monitor for secondary infections 1

Specific Considerations for Glucocorticoid Management

Glucocorticoids increase serious infection risk up to 4-fold in a dose-dependent manner. 4 During active URTI:

• Continue current dose to prevent adrenal crisis 1
• Reduce to the lowest effective dose possible 1
• Avoid increasing the dose for RA symptoms during active infection 4

The combination of biologics plus high-dose glucocorticoids substantially increases infection risk and should be avoided when possible. 4

Antibiotic Decision-Making

Most URTIs are viral and self-limiting 3, 6, 7. Consider antibiotics only if:

• Patient meets high-risk criteria listed above 3
• Symptoms persist beyond expected viral course (>10-14 days)
• Clinical deterioration occurs

When antibiotics are indicated for respiratory tract infections in RA patients, macrolides or tetracyclines provide coverage for both typical and atypical pathogens (including Mycoplasma pneumoniae, which causes 10% of lower respiratory infections). 7

Timing of DMARD Resumption

Resume withheld immunosuppressive medications when:

• Fever has resolved for 24-48 hours
• Respiratory symptoms are improving
• Patient has returned to baseline functional status

The median time to symptom resolution with appropriate supportive care is typically 2-5 days for uncomplicated viral URTI. 2

Prevention Strategies

Vaccination (implement when patient is well, not during active infection):

• Influenza vaccination should be strongly considered annually for all RA patients 1
• Pneumococcal vaccination should be strongly considered - both PCV13 and PPSV23 per CDC sequential protocol 1
• Non-live vaccines can be safely administered regardless of immunosuppressive therapy 1
• Live-attenuated vaccines should be avoided during immunosuppression 1

Screening for Latent Infections:

• Screen for latent tuberculosis prior to starting biologic or targeted synthetic DMARDs 1
• Reassess infection risk periodically, especially before treatment escalation 1

Common Pitfalls to Avoid

• Do not empirically escalate immunosuppression for presumed RA flare without confirming absence of infection 2
• Do not abruptly stop glucocorticoids even during active infection - taper to lowest effective dose 1
• Do not withhold sulfasalazine or hydroxychloroquine as they have minimal immunosuppressive effects 1
• Do not restart rituximab or cyclophosphamide without ensuring complete infection resolution, as B-cell depletion significantly impairs immune response 1