Management of Hydroxychloroquine During Acute Infection

General Approach to Acute Infections

The American College of Rheumatology recommends that 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
For patients with SLE or RA who develop routine acute infections, hydroxychloroquine should be maintained without interruption, as discontinuing it is associated with disease exacerbation and increased flare rates (hazard ratio 2.50, 95% CI: 1.08–5.58) 2

The American College of Rheumatology provides distinct recommendations for SARS-CoV-2 exposure and active COVID-19, including that HCQ may be continued while awaiting test results or during 2 weeks of symptom-free observation, and other immunosuppressants should be temporarily stopped 1, 3
With documented or presumptive COVID-19, HCQ may be continued regardless of COVID-19 severity, but other DMARDs including sulfasalazine, methotrexate, leflunomide, and traditional immunosuppressants should be stopped or withheld 1, 3

The American College of Rheumatology recommends that hydroxychloroquine should be continued at the same dose during pregnancy, even with acute infections, as HCQ use in pregnancy decreases lupus activity with a satisfactory safety profile for both mother and fetus 1, 2, 3
For patients with newly diagnosed SLE or active disease, HCQ should be started at full dose even during the pandemic or infection concerns 1, 3

The American College of Rheumatology recommends a step-wise approach to managing hydroxychloroquine during acute infections, including identifying the type of infection, assessing disease severity, and monitoring for disease flare 3
For patients with vital organ-threatening disease history, the guidelines state that immunosuppressants should not be dose-reduced, and the decision to continue or stop HCQ should be made through shared decision-making 1, 3

The American College of Rheumatology recommends that consideration may be given to restarting other rheumatic disease treatments within 7-14 days of symptom resolution, and HCQ, if continued throughout, requires no reinitiation 1

The European League Against Rheumatism (EULAR) recommends Hydroxychloroquine as the backbone treatment for autoimmune diseases, particularly systemic lupus erythematosus, due to its multiple immunomodulatory effects that reduce disease activity, prevent organ damage, decrease infection and thrombosis risk, and improve survival, while maintaining a favorable safety profile compared to traditional immunosuppressants 4, 5

The EULAR 2024 systematic review confirmed that Hydroxychloroquine reduces mortality with a pooled hazard ratio of 0.46 for death in SLE patients 5
Hydroxychloroquine prevents disease flares and reduces organ damage accrual in SLE patients 5
Hydroxychloroquine decreases thrombosis risk and lowers infection rates in SLE patients, despite being used for immune disease 5
The American College of Rheumatology and EULAR suggest that Hydroxychloroquine improves joint inflammation and reduces cardiometabolic risk in rheumatoid arthritis patients when used as part of combination DMARD therapy 5, 6, 7

The EULAR guidelines state that all patients with SLE should receive Hydroxychloroquine unless absolute contraindications exist, as it is considered the foundation of lupus therapy 4, 5
Hydroxychloroquine is commonly used in combination with other immunosuppressants for lupus nephritis remission and to prevent lupus flares during pregnancy, reducing adverse pregnancy outcomes 5

Hydroxychloroquine accumulates in acidic intracellular vesicles, increasing the pH and inhibiting pH-dependent proteases and acidic hydrolases, according to the Mayo Clinic Proceedings 8
The drug inhibits the intracellular processing of secretory proteins, leading to reduced production of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), as reported by the Mayo Clinic Proceedings 8

The American College of Rheumatology recommends hydroxychloroquine as an immunomodulatory agent, which has a favorable safety profile due to its distinction from traditional immunosuppressive agents, as noted in the Journal of Autoimmunity 9