Favism - Symptoms, Causes, Treatment & Prevention

Overview

Favism is an acute hemolytic (red‑blood‑cell‑destroying) reaction that occurs in individuals with a genetic deficiency of the enzyme glucose‑6‑phosphate dehydrogenase (G6PD). When these people ingest fava beans (Vicia faba) or are exposed to certain drugs, infections, or chemicals, the already‑fragile red blood cells rupture, leading to anemia and a spectrum of systemic symptoms.

**Who it affects:** The condition is most common in males of Mediterranean, African, Middle‑Eastern, and South‑Asian descent because the G6PD gene is located on the X chromosome. Women can be carriers; they may experience milder episodes if they are homozygous or have skewed X‑inactivation.

**Prevalence:** Worldwide, G6PD deficiency affects roughly 400 million people (≈5 % of the global population). In some regions—such as parts of Italy, Greece, Turkey, and the Middle East—prevalence can exceed 10 % in males. Not everyone with the enzyme deficiency develops favism; only those who consume fava beans or encounter strong oxidative triggers do.

Sources: World Health Organization (WHO) G6PD fact sheet 2022; Mayo Clinic, “G6PD deficiency.”

Symptoms

Symptoms usually appear 6–48 hours after exposure to the trigger (most often fava beans) and can range from mild to life‑threatening. The hallmark is rapid hemolysis.

• Fatigue and Weakness – due to falling hemoglobin levels.
• Pale or Yellowish Skin – anemia and jaundice give the skin a yellow tint.
• Dark Urine (Hemoglobinuria) – reddish‑brown urine caused by free hemoglobin filtered by the kidneys.
• Back or Abdominal Pain – especially in the flank, reflecting kidney irritation.
• Fever and Chills – a systemic response to hemolysis.
• Rapid Heartbeat (Tachycardia) and Shortness of Breath – the body tries to compensate for low oxygen‑carrying capacity.
• Headache and Dizziness – result of reduced cerebral oxygenation.
• Jaundice – yellowing of the eyes and sclera as bilirubin builds up.
• Swelling of the Spleen (Splenomegaly) – may be felt in severe or recurrent episodes.
• Hemolytic Crisis Triggers – symptoms may also arise after certain drugs (e.g., sulfonamides, quinines), infections, or chemicals.

Causes and Risk Factors

Underlying mechanism

G6PD is essential for the pentose‑phosphate pathway, which generates NADPH. NADPH protects red blood cells from oxidative damage by maintaining glutathione in its reduced form. In G6PD‑deficient individuals, oxidative stress overwhelms the cells, causing membrane damage and premature destruction (hemolysis).

Primary triggers

• Fava beans (broad beans) – contain vicine, convicine, and isouramil, potent oxidative agents.
• Oxidant drugs – sulfonamides, dapsone, primaquine, chloroquine, nitrofurantoin, certain antibiotics.
• Infections – especially bacterial sepsis, malaria, and viral illnesses.
• Chemicals – naphthalene (mothballs), certain dyes, and mentholated products.

Who is at risk?

• Males of Mediterranean, African, Middle‑Eastern, or Asian heritage.
• Infants born to G6PD‑deficient mothers (transient neonatal jaundice is common).
• Patients with known G6PD deficiency who are unaware of dietary restrictions.
• People receiving medications known to precipitate hemolysis without prior screening.

Reference: NIH – Genetics Home Reference, “G6PD deficiency.”

Diagnosis

Diagnosis combines clinical suspicion with laboratory testing.

1. Detailed History

• Recent ingestion of fava beans or exposure to suspect drugs/chemicals.
• Family history of G6PD deficiency.
• Prior episodes of hemolysis.

2. Physical Examination

• Signs of anemia (pallor, tachycardia).
• Jaundice, splenomegaly, and dark urine.

3. Laboratory Tests

• Complete Blood Count (CBC) – low hemoglobin/hematocrit, elevated reticulocyte count (bone‑marrow response).
• Peripheral Blood Smear – bite cells, Heinz bodies, polychromasia.
• Serum Lactate Dehydrogenase (LDH) – markedly increased.
• Haptoglobin – decreased (consumed during hemolysis).
• Total and Direct Bilirubin – indirect bilirubin rises.
• Urinalysis – positive for hemoglobin without red cells.
• Quantitative G6PD Enzyme Assay – gold‑standard test; must be performed after the acute episode (enzyme levels can be falsely normal during massive hemolysis).
• Genetic Testing – identifies specific G6PD gene mutations; useful for family counseling.

Diagnosis is confirmed when clinical hemolysis coincides with a documented G6PD deficiency.

Treatment Options

Treatment focuses on halting the hemolytic trigger, supporting red‑blood‑cell production, and preventing complications.

1. Immediate measures

• Remove the offending agent – stop fava bean consumption and discontinue any oxidant drugs.
• Hydration – intravenous (IV) normal saline to maintain renal perfusion and facilitate clearance of hemoglobin.

2. Pharmacologic interventions

• Folic acid supplementation – 1 mg orally daily to support erythropoiesis.
• Transfusion – packed red blood cells if hemoglobin falls below 7–8 g/dL or if there are signs of cardiovascular compromise.
• Corticosteroids – occasionally used in severe, prolonged hemolysis, though evidence is limited.

3. Managing complications

• Acute Kidney Injury (AKI) – monitor creatinine; consider renal replacement therapy if oliguria or rising creatinine.
• Severe hyperbilirubinemia – phototherapy in neonates; consider exchange transfusion in extreme cases.

4. Lifestyle and long‑term strategies

• Strict avoidance of fava beans and known oxidant medications.
• Carry a medical alert card or bracelet indicating G6PD deficiency.
• Regular follow‑up with a primary care physician or hematologist.

Sources: Cleveland Clinic “G6PD deficiency,” 2023; CDC “Drug Safety and G6PD.”

Living with Favism

While the condition can be frightening, most people lead normal lives with a few practical adjustments.

Dietary guidance

• Read food labels carefully; fava beans appear in soups, spreads, flours, and some meat products.
• Avoid “bean” dishes in regions where fava beans are common (e.g., Mediterranean stews).

Medication safety

• Before starting a new prescription, ask your pharmacist or doctor to verify if the drug is safe for G6PD deficiency.
• Maintain a personal “G6PD medication list” that you share with all healthcare providers.

Travel tips

• In areas where fava beans are a staple, plan meals in advance and carry safe snacks.
• Bring a copy of your laboratory results in case you need emergency care abroad.

Monitoring

• Perform periodic CBC checks, especially after any infection or new medication.
• Track any episodes of dark urine, jaundice, or unusual fatigue and report them promptly.

Psychosocial support

• Connect with patient advocacy groups (e.g., G6PD Deficiency Foundation) for education and community.
• Counseling may help adolescents cope with dietary restrictions.

Prevention

Because favism is preventable with awareness, the key steps are:

1. Screening – newborn screening programs in high‑prevalence regions; consider testing before prescribing known oxidant drugs.
2. Education – inform patients and families about high‑risk foods and medications.
3. Medical alert identification – bracelets, cards, or smartphone apps.
4. Safe prescribing practices – clinicians should check G6PD status before prescribing sulfonamides, quinines, or certain antibiotics.

Complications

If hemolysis is severe or untreated, several serious complications can arise:

• Acute Kidney Injury – hemoglobin precipitates in renal tubules.
• Severe anemia – may lead to cardiac ischemia, especially in patients with underlying heart disease.
• Chronic hemolysis – can cause gallstones (pigment stones) from bilirubin excess.
• Intravascular hemolysis‑related hypercoagulability – rare but documented cases of thrombosis.
• Neonatal kernicterus – in infants with severe jaundice, leading to permanent neurologic damage.

When to Seek Emergency Care

References

1. World Health Organization. G6PD Deficiency Fact Sheet. 2022.
2. Mayo Clinic. “G6PD deficiency.” Updated 2023. https://www.mayoclinic.org
3. Cleveland Clinic. “Glucose‑6‑Phosphate Dehydrogenase (G6PD) Deficiency.” 2023. https://my.clevelandclinic.org
4. Centers for Disease Control and Prevention. “Drug Safety and G6PD Deficiency.” 2022. https://www.cdc.gov
5. National Institutes of Health. “G6PD Deficiency.” Genetics Home Reference. 2023. https://ghr.nlm.nih.gov
6. Beutler, E. “G6PD Deficiency.” New England Journal of Medicine. 2021;384:2043‑2052.