Can hydroxyurea cause immunodeficiency?

Hydroxyurea and Immunodeficiency

Yes, hydroxyurea can cause immunodeficiency through its myelosuppressive effects, particularly neutropenia, which increases infection risk and requires regular monitoring of complete blood counts.

Mechanism of Immunosuppression

Hydroxyurea works by inhibiting ribonucleotide reductase, which affects DNA synthesis and cell replication. This mechanism leads to several immunosuppressive effects:

• Myelosuppression: Primarily causes neutropenia, which is dose-dependent and a known adverse effect requiring monitoring 1
• T-cell function impairment: Decreases Th1 cell-mediated immunity by reducing lymphocyte proliferation and gamma interferon production 2
• Cellular immunity reduction: Affects rapidly dividing cells, including immune effector cells 2

Clinical Evidence of Immunosuppression

Research has demonstrated that hydroxyurea has significant effects on immune function:

• In vitro studies show hydroxyurea decreases lymphocyte proliferation and cytokine production in response to microbial antigens 2
• The inhibitory effect requires continuous exposure to the drug but can be reversed when the drug is removed from the environment 2
• Hydroxyurea has been studied as an anti-HIV drug precisely because of its ability to inhibit cellular processes needed for viral replication 3, 4

Monitoring Recommendations

Due to its immunosuppressive effects, regular monitoring is essential:

• Complete blood count (CBC):

  • For sickle cell disease: Monitor every 1-3 months depending on stability of dose 1
  • For polycythemia vera: Monthly intervals after stable dose is achieved 1
  • Initial monitoring should be weekly until stable dose is achieved 1

• Special attention to:

  • Absolute neutrophil count < 1.0 × 10^9/L
  • Platelet count < 100 × 10^9/L
  • Hemoglobin < 100 g/L 1

Clinical Applications and Cautions

Hydroxyurea is used in several conditions despite its immunosuppressive effects:

• Sickle cell disease: Recommended for children with HbSS or Sβ0-thalassemia starting at 9 months of age 1
• Polycythemia vera: First-line cytoreductive therapy for high-risk patients 1
• Psoriasis: Not FDA-approved but used off-label 1

Important Precautions

• Infection risk: Patients should be monitored for signs of infection due to neutropenia
• Drug interactions: Concurrent use with other myelosuppressive agents increases bone marrow depression risk 1
• Pregnancy: Category D; pregnancy and breastfeeding should be avoided during treatment 1
• Vaccination: Live vaccines should be avoided during treatment due to immunosuppression

Common Pitfalls

• Inadequate monitoring: Failure to perform regular CBC monitoring can lead to undetected severe myelosuppression
• Missed drug interactions: Not recognizing that combining hydroxyurea with other myelosuppressive agents increases immunosuppression risk
• Delayed recognition of infections: Immunosuppressed patients may present with atypical or muted infection symptoms
• Failure to adjust dosing: Not reducing dose when early signs of myelosuppression appear

Hydroxyurea's immunosuppressive effects are significant enough to warrant careful monitoring but generally manageable with appropriate surveillance and dose adjustments when used for approved indications.