Does hydroxychloroquine mask leucocytosis (elevated white blood cell count)?

Hydroxychloroquine Does Not Mask Leukocytosis

Hydroxychloroquine does not mask leukocytosis (elevated white blood cell count) based on the available evidence. While hydroxychloroquine has various immunomodulatory effects, there is no evidence suggesting it conceals or suppresses an elevated white blood cell count.

Immunomodulatory Effects of Hydroxychloroquine

Hydroxychloroquine (HCQ) is an antimalarial medication with well-established immunomodulatory properties that is commonly used in the treatment of systemic lupus erythematosus (SLE) and other autoimmune conditions. Its effects on the immune system include:

• Inhibition of cytokine production including IL-1, IL-2, IL-6, IL-17, IL-22, IFN-α, IFN-γ, and TNF-α 1
• Blocking prostaglandin production by inhibiting arachidonic acid accessibility 1
• Affecting T-helper cell balance by augmenting IL-10 production 1
• Blocking B-cell differentiation into plasmablasts and inhibiting cytokine generation from B-cell subsets 1

Relationship Between HCQ and White Blood Cell Counts

Despite these immunomodulatory effects, there is no evidence in the provided literature that hydroxychloroquine masks or suppresses leukocytosis. In fact:

1. The 2024 KDIGO clinical practice guideline for lupus nephritis mentions various side effects of hydroxychloroquine but does not include masking of leukocytosis among them 2

2. The guidelines discuss monitoring for various adverse effects of hydroxychloroquine (such as retinal toxicity, G6PD deficiency, and cardiotoxicity) but do not mention any effect on white blood cell counts that would require monitoring 2

3. In contrast to masking leukocytosis, there is a documented case of hydroxychloroquine-induced thrombocytopenia in an SLE patient, suggesting that HCQ can actually affect blood cell counts in some cases, but this effect is visible rather than masked 3

Blood Levels and Disease Activity

Research on hydroxychloroquine blood levels shows:

• Low blood concentrations of hydroxychloroquine are associated with SLE disease activity and can predict disease exacerbations 4
• Patients with active SLE disease have significantly lower blood HCQ concentrations compared to those with inactive disease 4
• Monitoring blood levels can help improve treatment adherence and efficacy 5

These findings suggest that if hydroxychloroquine were masking signs of inflammation such as leukocytosis, patients with lower blood levels would be more likely to show these signs. However, the research indicates that lower blood levels are actually associated with increased disease activity, which would typically include inflammatory markers like leukocytosis.

Comparison with Other Medications

It's worth noting that some medications can mask signs of inflammation. For example, there is documentation of quinidine (an antiarrhythmic medication) causing fever with leukocytosis and left shift in white blood cell count that resolved after discontinuation of the drug 6. However, no similar effect has been documented with hydroxychloroquine.

Clinical Implications

For clinicians monitoring patients on hydroxychloroquine:

• An elevated white blood cell count in a patient taking hydroxychloroquine should be taken seriously and not dismissed as a medication effect
• Leukocytosis may indicate:
  • Disease flare in patients with autoimmune conditions
  • Infection, which is an important consideration especially in immunocompromised patients
  • Other inflammatory processes unrelated to the primary condition

Conclusion

Based on the available evidence, hydroxychloroquine does not mask leukocytosis. Clinicians should interpret an elevated white blood cell count in patients taking hydroxychloroquine as a potentially significant finding warranting appropriate investigation, rather than attributing it to medication effect.