Acute Intermittent Porphyria: Trigger

Acute Intermittent Porphyria (AIP) is a genetic syndrome resulting in impaired synthesis of heme (best known as an important component of hemoglobin which carries oxygen in the blood). Specifically, there is a mutation of porphobilinogen deaminase resulting in decreased activity and an accumulation of porphobilinogen. Although not well defined, the build-up of porphobilinogen is thought to be toxic to neurons, which explains the clinical presentation of effects on the peripheral and autonomic nervous systems. Classic signs and symptoms include abdominal pain, nausea/vomiting and constipation, tachycardia, dark red urine, and sometimes schizophrenic-like psychiatric effects as well as back and leg pain that may progress to paresis.

Attacks are episodic and typically triggered by inciting factors such as medications, drastic diets/fasting, or stress such as an infection or surgery.

Most notably in the practice of anesthesia, barbiturates and other CYP inducers can trigger AIP attacks. Barbiturates lead to increased levels of porphyrin by stimulating aminolevulinic acid (ALA) synthetase. These intermediaries in the heme synthesis pathway then build-up and precipitate an attack. Glucose acts to suppress ALA synthetase and thus is useful in prevention and treatment. Other known triggers include diazepam, sulfonamides, griseofulvin, sex hormones e.g. in contraceptives, glucocorticoids, phenytoin, cigarette smoke, and anti-retrovirals used to treat HIV.

Other common anesthetic agents such as propofol and fentanyl appear to be safe in this population, as do etomidate and ketamine although the latter are potential triggers in animal studies.

Although autosomal dominant, most patients have no family history of the disease as acute attacks only occur in about 10% of carriers, most commonly affecting young adult women.