Can hydroxychloroquine cause neutropenia? An In-depth Look

October 12, 2025 •

4 min read

While hydroxychloroquine has a relatively safe profile, with one case report noting a 0.73% incidence, it is indeed associated with a rare risk of causing neutropenia, a serious blood disorder. This potential side effect is rare but requires vigilance and understanding for both patients and clinicians.

Quick Summary

Hydroxychloroquine is a medication that carries a rare but serious risk of causing neutropenia, a low white blood cell count. This drug-induced blood disorder typically resolves after stopping treatment but requires careful patient monitoring, especially of complete blood counts, to ensure early detection and management.

Key Points

Rare Side Effect: HCQ can cause neutropenia, a low white blood cell count, but this is a very rare and serious adverse event, often referred to as an idiosyncratic drug reaction.
Mechanism Unclear: The exact cause is unknown but may involve idiosyncratic immune reactions or high drug concentrations, especially with prolonged use or renal impairment.
Risk Factors: Prolonged use, renal impairment, and co-administration with other myelosuppressive drugs can increase the risk of neutropenia.
Monitoring is Key: Periodic blood cell counts, specifically a CBC, are essential for patients on long-term HCQ therapy to detect any hematological abnormalities early.
Management is Discontinuation: The primary treatment is to stop HCQ, which typically resolves the neutropenia. Severe cases may require additional supportive treatment.
Symptom Awareness: Symptoms often relate to infection risk, such as fever, sore throat, or mouth ulcers, and require immediate medical attention.
Alternatives Exist: For patients who cannot tolerate HCQ, other DMARDs like methotrexate or sulfasalazine may be used, though they have their own risk profiles.

Understanding the Link Between Hydroxychloroquine and Neutropenia

Hydroxychloroquine (HCQ) is a well-established antimalarial and immunomodulatory drug, commonly prescribed for autoimmune conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). While effective, like all medications, it carries potential side effects. One of the less common but more serious adverse events is neutropenia, a condition characterized by an abnormally low number of neutrophils, a critical type of white blood cell that fights infection. A more severe form of this condition, known as agranulocytosis, signifies an extremely low neutrophil count and a heightened risk of infection.

The Mechanism Behind Hydroxychloroquine-Induced Neutropenia

The exact mechanism by which HCQ causes neutropenia is not fully understood, but it is believed to be an idiosyncratic drug reaction rather than a dose-dependent effect for all individuals. Several potential factors and theories exist:

Bone Marrow Suppression: In very rare cases, HCQ has been linked to severe blood dyscrasias, including bone marrow suppression, which disrupts the production of blood cells, including neutrophils.
Immunological Reactions: Some theories suggest that an immune-mediated mechanism may be responsible for the destruction of neutrophils, though this is not fully proven.
Genetic Predisposition: As an idiosyncratic reaction, genetic factors may make certain individuals more susceptible to developing this complication.
Drug Accumulation: Because HCQ has a long half-life, especially with chronic use, excessive tissue concentrations may contribute to toxicity. This risk is compounded by other factors, such as renal impairment, which can delay drug clearance.

Incidence and Risk Factors

Neutropenia resulting from HCQ use is rare. Reported incidence rates are very low, with some case studies citing figures under 1%. However, the rarity can sometimes lead to delayed recognition. Key risk factors that may increase the likelihood of developing this adverse event include:

Pre-existing Hematologic Conditions: Patients with prior blood disorders may be more vulnerable.
Renal Impairment: Since HCQ is cleared through the kidneys, impaired renal function can lead to increased drug accumulation and potentially higher toxicity.
Long-Term Use: Neutropenia has most commonly been observed in patients on HCQ for several months or longer.
Combination Therapies: There is a possibility of synergistic effects when HCQ is taken with other drugs, especially those also known to cause blood dyscrasias, such as rituximab.

Symptoms and Clinical Presentation

Symptoms of neutropenia often relate to the increased risk of infection and can include:

Fever: A persistent or unexplained fever is a common sign of infection in a neutropenic patient and warrants immediate medical attention.
Sore Throat or Oral Ulcers: The mouth and throat are frequent sites for bacterial infections when neutrophil counts are low.
Fatigue and Weakness: Unexplained fatigue can be a general symptom of an underlying blood disorder.
Chills and Sweating: These symptoms may indicate an infection entering the bloodstream, which is particularly dangerous with a low neutrophil count.

Monitoring and Management

Early detection is key to managing HCQ-induced neutropenia. Management primarily involves the discontinuation of HCQ, which typically leads to neutrophil recovery. For severe cases, particularly with documented infections, additional supportive care may be necessary. Monitoring and management strategies include:

Regular Blood Tests: Periodic complete blood counts (CBCs) are crucial for patients on prolonged HCQ therapy. The American College of Rheumatology conditionally recommends annual CBC and liver function tests, though more frequent monitoring may be necessary for high-risk patients.
Discontinuation of Drug: If a severe blood disorder is detected and cannot be attributed to the underlying disease, stopping HCQ is the primary intervention.
Use of Hematopoietic Growth Factors: In severe cases of neutropenia, particularly with infectious complications, treatment with granulocyte-colony stimulating factor (G-CSF) may be warranted to stimulate neutrophil production.

Comparison of HCQ vs. Alternative DMARDs

For patients with autoimmune diseases, understanding the hematologic side effects of different disease-modifying antirheumatic drugs (DMARDs) is important. Below is a comparison of HCQ with some common alternatives.


Feature	Hydroxychloroquine (HCQ)	Methotrexate (MTX)	Sulfasalazine (SSZ)
Mechanism of Action	Immunomodulatory; blocks Toll-like receptors.	Folic acid antagonist; suppresses inflammatory cells.	Anti-inflammatory and immunomodulatory.
Risk of Neutropenia	Rare, idiosyncratic; typically resolves upon discontinuation.	Potential for bone marrow suppression, requiring regular monitoring.	Less frequent than MTX, but still a known risk.
Onset of Neutropenia	Usually after several months of therapy.	Can occur at various stages of treatment.	Can occur at various stages of treatment.
Management	Discontinuation; potential G-CSF for severe cases.	Discontinuation; folic acid supplementation.	Discontinuation; supportive care.
Monitoring	Periodic CBC recommended, especially with prolonged use.	Regular CBC and liver function tests are standard.	Regular CBC and liver function tests are standard.

Conclusion

While hydroxychloroquine is a valuable and generally well-tolerated medication for autoimmune diseases, it carries a rare but serious risk of causing neutropenia. Patients and healthcare providers must be aware of this potential side effect, especially with prolonged use. Regular monitoring of complete blood counts is a key preventative strategy. Should neutropenia occur, prompt discontinuation of the drug and, in severe cases, supportive therapy can lead to a full recovery. Awareness and early action are critical to managing this adverse event safely. For more information on side effects, patients should always consult their physician or pharmacist and refer to authoritative resources like the FDA drug label.

Frequently Asked Questions

Neutropenia caused by hydroxychloroquine is considered a very rare side effect. Although specific figures vary, case reports cite incidences of less than 1%. Severe forms, such as agranulocytosis, are even rarer.

Symptoms of neutropenia often arise from infections due to the weakened immune system. These can include fever, sore throat, unexplained fatigue, mouth ulcers, or other signs of infection. Any unexplained fever should be reported to a doctor immediately.

Diagnosis is made through a complete blood count (CBC) test, which measures the number of neutrophils and other blood cells. Regular monitoring with CBCs is recommended for patients on long-term HCQ therapy to catch any issues early.

If neutropenia is detected, the primary course of action is to stop taking hydroxychloroquine. The condition is typically reversible, and neutrophil counts often return to normal within days or weeks after discontinuation.

Yes, certain factors increase risk. Patients with pre-existing kidney disease or other blood disorders may be more susceptible. Long-term use and co-administration with other drugs that can affect blood cell production also increase the risk.

Yes, although it is extremely rare. A case report has documented a severe case in an infant, underscoring the importance of careful monitoring even in pediatric patients.

Alternative DMARDs for autoimmune conditions include methotrexate, sulfasalazine, and leflunomide. The choice of alternative depends on the patient's specific condition and other health factors, and requires careful discussion with a rheumatologist.