Should hydroxychloroquine (HCQ) be stopped in a patient with a chronic condition such as rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) who develops an acute infection?

Management of Hydroxychloroquine During Acute Infection

Hydroxychloroquine should generally be continued during acute infections in patients with rheumatoid arthritis or systemic lupus erythematosus, with the specific exception of documented or presumptive COVID-19, where it may be continued but other immunosuppressants should be stopped. 1

General Approach to Acute Infections

Continue HCQ for Most Acute Infections

• For patients with SLE or RA who develop routine acute infections (bacterial, viral, or fungal), hydroxychloroquine should be maintained without interruption. 1, 2
• The rationale is that HCQ actually reduces infection rates in SLE patients despite being used for immune disease, and stopping it risks disease flares that can be more harmful than the infection itself. 2
• Discontinuing hydroxychloroquine in SLE patients is associated with disease exacerbation and increased flare rates (hazard ratio 2.50,95% CI: 1.08–5.58). 1

COVID-19 Specific Guidance

The American College of Rheumatology provides distinct recommendations for SARS-CoV-2 exposure and active COVID-19:

Following known SARS-CoV-2 exposure (but no symptoms):

• HCQ may be continued while awaiting test results or during 2 weeks of symptom-free observation. 1
• Other immunosuppressants (tacrolimus, cyclosporine, mycophenolate, azathioprine, non-IL-6 biologics, JAK inhibitors) should be temporarily stopped. 1

With documented or presumptive COVID-19:

• HCQ may be continued regardless of COVID-19 severity. 1
• However, other DMARDs including sulfasalazine, methotrexate, leflunomide, and traditional immunosuppressants should be stopped or withheld. 1

Critical Considerations for Vital Organ-Threatening Disease

For patients with a history of vital organ-threatening rheumatic disease (such as lupus nephritis or CNS lupus), the decision becomes more nuanced:

• The guidelines state that immunosuppressants should not be dose-reduced in these high-risk patients. 1
• This creates a clinical tension where the risk of disease flare must be weighed against infection severity through shared decision-making. 1

Special Populations

Pregnant Women with SLE

• Hydroxychloroquine should be continued at the same dose during pregnancy, even with acute infections. 1
• HCQ use in pregnancy decreases lupus activity with a satisfactory safety profile for both mother and fetus. 1

Newly Diagnosed Disease

• For patients with newly diagnosed SLE or active disease, HCQ should be started at full dose even during the pandemic or infection concerns. 1

Practical Algorithm

Step 1: Identify the type of infection

• Routine bacterial/viral infection → Continue HCQ
• Known COVID-19 exposure without symptoms → Continue HCQ, stop other immunosuppressants
• Active COVID-19 → Continue HCQ, stop other DMARDs

Step 2: Assess disease severity

• Vital organ-threatening disease history → Strongly favor continuing all medications including HCQ
• Well-controlled disease → More flexibility to temporarily hold other agents (but not HCQ)

Step 3: Monitor for disease flare

• If HCQ is continued (as recommended), monitor closely for infection progression
• If infection worsens significantly, reassess through shared decision-making

Common Pitfalls to Avoid

• Do not reflexively stop HCQ when patients develop infections – this is the most common error, as HCQ has immunomodulatory rather than purely immunosuppressive effects. 2
• Do not confuse HCQ management with other immunosuppressants – the guidance differs significantly, with HCQ having a more favorable continuation profile. 1
• Do not forget that stopping HCQ increases flare risk substantially – the mortality benefit of HCQ in SLE (hazard ratio 0.46 for death) outweighs most infection concerns. 2

Reinitiating Treatment Post-Infection

For patients with uncomplicated infections treated in the ambulatory setting:

• Consideration may be given to restarting other rheumatic disease treatments within 7-14 days of symptom resolution. 1
• HCQ, if continued throughout, requires no reinitiation. 1