What is the management and treatment of acute intermittent porphyria?

Management and Treatment of Acute Intermittent Porphyria

The management of acute intermittent porphyria (AIP) requires immediate hemin therapy (3-4 mg/kg/day) during acute attacks, along with comprehensive avoidance of triggering factors such as certain medications, alcohol, fasting, and stress to prevent recurrent attacks. 1

Diagnosis and Initial Assessment

• Diagnostic confirmation:

  • Quantitative measurement of urinary porphobilinogen (PBG) and aminolevulinic acid (ALA) in a spot urine sample (protected from light) 2
  • Normal urinary PBG excludes AIP as the cause of symptoms 2
  • Genetic testing to identify specific mutation after biochemical confirmation 2

• Baseline laboratory tests:

  • Complete blood count and ferritin (iron deficiency should be treated) 2
  • Metabolic panel including electrolytes (hyponatremia occurs in 25-60% of symptomatic cases) 2
  • Renal function (eGFR) 2
  • Liver function tests 1

Management of Acute Attacks

1. Immediate interventions:

   • Discontinue any potentially triggering medications 1
   • Administer carbohydrate loading (300g/day orally or 10% glucose IV) 1
   • Initiate hemin therapy (3-4 mg/kg/day IV once or twice daily) 3
     • Clinical response occurs in 85.5% of treatment courses 3
     • Hemin reduces urinary ALA and PBG levels by 50-100% 3

2. Supportive care:

   • Aggressive pain management with safe analgesics 1
   • Monitor and correct electrolyte abnormalities, particularly hyponatremia 1
   • Seizure management with levetiracetam or gabapentin if needed 1

Prevention of Recurrent Attacks

1. Avoidance of triggering factors:

   • Medications: Verify all medications through porphyria drug safety databases 1
     • Avoid drugs that induce cytochrome P450 enzymes 1
     • Benzodiazepines are generally considered safer options 1
   • Lifestyle modifications:
     • Avoid alcohol consumption 1
     • Avoid fasting or severe caloric restriction 1
     • Minimize stress 1

2. For patients with recurrent attacks (≥4 per year):

   • Consider prophylactic hemin infusions 1
   • Consider GnRH analogues with low-dose estrogen supplementation for women 1
   • Givosiran (RNAi therapeutic targeting hepatic ALAS1) may be considered 1
   • Liver transplantation may be considered for severe, disabling, intractable attacks refractory to hemin therapy 1

Follow-up and Monitoring

• Frequency based on clinical subgroup:

  • Recurrent attack patients: Every 3-6 months 1
  • Sporadic attack patients: At least annually 1
  • Latent carriers: Every 1-3 years 1

• Monitoring parameters:

  • Urinary ALA and PBG levels 2
  • Renal function 2
  • Quality of life assessment 1

Special Considerations

1. Pregnancy:

   • Pre-conception evaluation recommended 1
   • High-risk obstetrical care during pregnancy 1
   • Hemin can be safely administered during pregnancy if needed 1

2. Contraception:

   • Caution with hormonal contraceptives (progestins may trigger attacks) 1

3. Psychiatric support:

   • Psychiatric evaluation and pain management are essential components of care 1

Clinical Pearls and Pitfalls

• AIP is often misdiagnosed due to nonspecific symptoms, with diagnosis delays exceeding 15 years 1
• A very dilute urine sample may lead to false-negative results if not normalized to urine creatinine 2
• Iron deficiency is not caused by AIP but is common in young women and should be treated 2
• Patients should receive special identification cards and up-to-date lists of safe medications 4