What is the management approach for a patient with suspected Acute Intermittent Porphyria (AIP)?

From the Guidelines

Management of a patient with possible acute intermittent porphyria (AIP) requires prompt diagnosis and treatment to prevent complications, with the most recent and highest quality study 1 guiding the approach. The diagnosis of AIP should be confirmed through urine porphobilinogen (PBG) testing during an acute attack, as levels are significantly elevated.

• Initial management focuses on removing triggering factors such as medications (barbiturates, sulfonamides, estrogens), alcohol, fasting, and stress.
• For acute attacks, administer intravenous hemin (Panhematin) at 3-4 mg/kg daily for 3-4 days, which suppresses heme synthesis by inhibiting ALA synthase, as recommended by 1.
• Provide adequate carbohydrate intake (300-400g daily) through IV glucose (10% dextrose) to downregulate ALA synthase.
• Pain management is crucial; use opioids like morphine as needed, avoiding porphyrinogenic medications such as phenytoin or carbamazepine, as suggested by 1.
• Treat nausea with ondansetron 4-8mg IV/PO every 8 hours.
• Monitor for hyponatremia, hypomagnesemia, and autonomic dysfunction, correcting electrolyte imbalances as needed.
• For seizures, use gabapentin or levetiracetam, which are considered safe. Long-term management includes patient education about trigger avoidance, genetic counseling, and consideration of prophylactic hemin for recurrent attacks, as outlined in 1. These interventions are essential because AIP results from deficiency of porphobilinogen deaminase, leading to accumulation of neurotoxic porphyrin precursors that cause the characteristic neurovisceral symptoms, as explained in 1 and 1.

From the FDA Drug Label

Heme acts to limit the hepatic and/or marrow synthesis of porphyrin. This action is likely due to the inhibition of δ-aminolevulinic acid synthetase, the enzyme which limits the rate of the porphyrin/heme biosynthetic pathway. The effectiveness of PANHEMATIN for the amelioration of recurrent attacks of acute intermittent porphyria was evaluated in five open-label studies, one compassionate-use study, case reports, and an observational study investigating patient reported outcomes in patients with acute porphyrias In the initial 5 open-label studies,1-5 99 patients with acute porphyrias (72 with AIP) were treated with 3-4 mg/kg/day of hemin once or twice daily.

To manage a patient with possible Acute Intermittent Porphyria (AIP), the following steps can be taken:

• Administer hemin at a dose of 3-4 mg/kg/day once or twice daily.
• Monitor the patient's symptoms and urinary aminolevulinic acid (ALA) and porphobilinogen (PBG) levels for improvement.
• Consider maintaining the patient on a high carbohydrate diet (250-300 g/24H) during treatment.
• Be aware that PANHEMATIN therapy for the acute porphyrias is not curative, and symptoms may return after discontinuation of treatment 2.

From the Research

Management of Acute Intermittent Porphyria

To manage a patient with possible Acute Intermittent Porphyria (AIP), the following strategies can be employed:

• During an acute attack:
  • Treatment with heme preparations, if the attack is severe or moderate 3
  • Symptomatic treatment of autonomic dysfunctions, polyneuropathy, and encephalopathy 3, 4
  • Exclusion of precipitating factors 3, 4
  • Adequate nutrition and fluid therapy 3, 4
• During remission:
  • Exclusion of precipitating factors (education of patients and family doctors) 3
  • Information about online drug lists 3
  • Mutation screening for family members and education about precipitating factors in mutation-positive family members 3
• Management of patients with recurrent attacks:
  • Evaluation of the lifestyle 3
  • Evaluation of hormonal therapy in women 3
  • Prophylactic heme therapy 3
  • Liver transplantation in patients with severe recurrent attacks 3, 5
• Follow-up of AIP patients for long-term complications:
  • Chronic hypertension 3
  • Chronic kidney insufficiency 3
  • Chronic pain syndrome 3
  • Hepatocellular carcinoma 3

Diagnostic Criteria

The clinical criteria for an acute attack of AIP include:

• Paroxysmal nature and various combinations of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms, in the absence of other obvious causes 3
• More than fivefold elevation of urinary porphobilinogen excretion together with typical symptoms of an acute attack is sufficient to start treatment 3
• Intensive abdominal pain without peritoneal signs, acute peripheral neuropathy, and encephalopathy usually with seizures or psychosis are key symptoms indicating possible acute porphyria 3, 4, 6

Treatment Options

Treatment options for AIP include:

• Heme preparations 3, 4, 6, 5
• Symptomatic treatment of autonomic dysfunctions, polyneuropathy, and encephalopathy 3, 4
• Discontinuation of porphyrogenic agents 6, 5
• Adequate caloric support 3, 4, 5
• Emerging treatments such as enzyme replacement therapy, ALAS1 gene inhibition, and liver gene therapy 5