Is there a relationship between malaria and Rheumatoid Arthritis (RA)?

Relationship Between Malaria and Rheumatoid Arthritis

Antimalarial medications, particularly hydroxychloroquine and chloroquine, have therapeutic benefits in rheumatoid arthritis, but there is no direct causative relationship between malaria infection and RA development.

Antimalarial Drugs in RA Treatment

Therapeutic Benefits

• Hydroxychloroquine (HCQ) and chloroquine are effective treatments for rheumatoid arthritis with a superior benefit-to-risk ratio 1
• These medications show moderate efficacy in approximately 70% of RA patients, with high-grade suppression in 15% and partial suppression in 55% 1
• The American College of Rheumatology guidelines recognize antimalarials as important disease-modifying antirheumatic drugs (DMARDs) for RA management 2

Mechanism of Action

• Antimalarials have immunomodulatory rather than immunosuppressive effects 2
• They work through:
  • Inhibition of lysosomal activity
  • Interference with antigen presentation
  • Inhibition of Toll-like receptors
  • Reduction of pro-inflammatory cytokines including TNF-alpha and IL-6 2

Cardiovascular Benefits

• Hydroxychloroquine use in RA patients may reduce cardiovascular disease risk 3
• This is particularly important as RA patients have a 50% increase in cardiovascular morbidity and mortality 3

Potential Protective Effects

• A retrospective cohort study found that antimalarial use in patients with palindromic rheumatism (a condition that can progress to RA) was associated with significant reduction in the risk of developing RA (hazard ratio = 0.19; 95% CI 0.07-0.57) 4
• The estimated median time to development of RA was 162 months in antimalarial-treated patients versus 56 months in untreated patients 4

Emerging Research on Malaria Treatments and RA

• Artesunate, another antimalarial agent, has shown promising results in animal models of RA by:
  • Attenuating inflammation symptoms
  • Preventing cartilage and bone destruction
  • Decreasing expression of pro-inflammatory cytokines
  • Inhibiting metalloproteinase-9 activity 5

Potential Risks in RA Patients

• Patients receiving TNF inhibitors (like infliximab) for RA treatment may be at increased risk of severe malarial infections if exposed to the parasite 6
• A case report described a 45-year-old woman on infliximab therapy who developed overwhelming Plasmodium falciparum infection with cerebral malaria 6

COVID-19 Connection

• During the COVID-19 pandemic, antimalarials (HCQ/chloroquine) were investigated as potential treatments 2
• Some evidence suggests people predisposed to RA may carry a higher risk of COVID-19 infection 7
• The American College of Rheumatology recommends temporarily withholding HCQ/CQ following SARS-CoV-2 exposure or infection due to potential cardiac toxicity concerns 2

Clinical Implications

• For RA patients traveling to malaria-endemic regions:

  • Continue antimalarial medications as prescribed for RA
  • Be aware that standard RA doses may not provide adequate malaria prophylaxis
  • Patients on biologics should take extra precautions against malaria exposure
  • Consult with rheumatologist and travel medicine specialist before travel

• For patients with history of malaria developing joint symptoms:

  • Consider antimalarial therapy if RA is diagnosed
  • Evaluate for other mimicking diseases as recommended by EULAR 2

In summary, while there is no evidence that malaria infection causes RA, the medications developed to treat malaria have proven highly beneficial in RA management. The relationship is primarily pharmacological rather than pathophysiological.