What is the management and treatment of acute intermittent porphyria?

Management and Treatment of Acute Intermittent Porphyria

Immediately discontinue all porphyrinogenic drugs and initiate intravenous hemin therapy (3-4 mg/kg/day) along with IV dextrose as first-line treatment for acute attacks, with hospitalization required for patients presenting with severe abdominal pain, vomiting, or hypertension. 1, 2

Acute Attack Management

Immediate Interventions

• Stop all porphyrinogenic drugs and chemicals immediately upon suspicion of an acute attack, even before biochemical confirmation is obtained. 2
• Administer intravenous hemin (PANHEMATIN) at 3-4 mg/kg/day as the definitive treatment, which inhibits hepatic δ-aminolevulinic acid synthase and suppresses porphyrin synthesis. 1, 3
• Provide IV dextrose (glucose) concurrently to suppress hepatic heme synthesis through carbohydrate loading. 1, 2
• Hospitalize patients with severe abdominal pain, vomiting, and hypertension, as they can deteriorate rapidly with potential respiratory failure requiring ventilator support. 1, 4

Symptomatic Management

• Provide aggressive analgesic therapy for severe abdominal pain, which occurs in 90% of patients. 1, 4
• Administer antiemetics for nausea and vomiting. 1
• Monitor and correct hyponatremia, which occurs in 25-60% of acute attacks. 2
• For seizures, use gabapentin or propofol rather than conventional antiepileptics, as many standard agents are porphyrinogenic. 4

Clinical Response Expectations

• Clinical response (improvement of symptoms and pain reduction) occurs in 85.5% of treatment courses with hemin therapy. 3
• Chemical response (normalization of urinary ALA and PBG) occurs in all treated patients. 3
• Most patients experience rapid clinical improvement after hemin infusion, though PANHEMATIN is not curative and symptoms may return after discontinuation. 3

Prevention of Recurrent Attacks

Prophylactic Hemin Therapy

• Patients experiencing 4 or more attacks per year are candidates for prophylactic hemin infusions administered weekly, bimonthly, or monthly. 1, 2
• For menstrual cycle-related attacks, administer prophylactic hemin once or twice during the luteal phase. 5, 2
• Less frequent than weekly dosing may not be effective since heme is metabolized rapidly by heme oxygenase. 1

Avoidance of Triggering Factors

• All patients must avoid porphyrinogenic drugs, fasting, alcohol, and smoking, which can precipitate attacks. 1, 5
• Maintain adequate caloric intake and avoid fasting to prevent attacks. 5
• Patients should consult publicly available drug databases before starting any new medications. 1
• Women should carefully select contraceptives, as progestin-containing contraceptives may trigger attacks and should be avoided. 5, 2
• Provide patients with special identification cards and up-to-date lists of safe drugs. 6

Monitoring and Surveillance

Iron Overload Monitoring

• Measure serum ferritin every 3-6 months or after every ~12 doses in patients receiving prophylactic or frequent hemin treatment, as hemin contains 9% iron by weight. 1
• Begin therapeutic phlebotomy when ferritin levels exceed 1000 ng/mL, with a goal of reducing serum ferritin to ~150 ng/mL. 1

Annual Monitoring Requirements

• Obtain liver function tests (aminotransferases are elevated in ~13% during attacks). 2
• Complete blood count and ferritin levels. 2
• Metabolic panel including estimated glomerular filtration rate (eGFR) for renal function assessment. 2
• Screen for iron deficiency, which is common in young women and should be treated. 2

Long-Term Complication Screening

• Screen for hepatocellular carcinoma in all patients with confirmed acute intermittent porphyria, as they carry increased risk. 1, 2
• Monitor for chronic kidney disease, typically chronic tubulointerstitial nephropathy or focal cortical atrophy. 2
• Aggressively monitor and treat hypertension, which may help prevent renal damage. 2

Patient Classification System

The American Association for the Study of Liver Diseases classifies patients into four subgroups that determine follow-up frequency and management intensity: 1, 5

• Latent genetic mutation carriers: Annual follow-up with avoidance counseling
• Asymptomatic high excretors (ASHE): Annual monitoring with biochemical surveillance
• Sporadic attack patients: Annual follow-up with trigger avoidance education
• Recurrent attack patients: More frequent monitoring and consideration for prophylactic therapy

Special Populations

Perioperative Management

• Administer IV fluids containing dextrose routinely to all patients who are fasting, including latent cases. 1
• Review current medications pre-procedure and plan anesthesia using agents that are safe in acute intermittent porphyria. 1

Pregnancy and Reproductive Considerations

• Provide pre-conception evaluation for all women planning pregnancy. 5, 2
• Arrange high-risk obstetrical care during pregnancy, as hormonal changes increase attack risk. 2

Definitive Treatment Options

Liver Transplantation

• Orthotopic liver transplantation is curative and should be considered for patients with severe, disabling attacks or attacks refractory to hemin therapy. 1, 2
• Combined liver-kidney transplantation may benefit patients with both recurrent attacks and end-stage renal disease. 1, 5

Genetic Counseling

• All heterozygotes, whether symptomatic, asymptomatic high excretors, or latent, should receive appropriate genetic counseling about inheritance patterns. 1
• Screen family members to detect genetic carriers, which permits precautionary measures and prevention of attacks. 7

Critical Pitfalls to Avoid

• Never delay hemin therapy while waiting for biochemical confirmation—stop porphyrinogenic drugs and initiate treatment based on clinical suspicion alone. 2
• Do not assume the disease is truly "intermittent"—95% of patients with frequent attacks experience both acute exacerbations and chronic day-to-day symptoms including pain, nausea, fatigue, and neuropathy. 8
• Avoid conventional antiepileptics for seizure management, as most are porphyrinogenic. 4
• Do not overlook the need for iron overload monitoring in patients receiving chronic hemin therapy. 1