The Rapid Review series is designed to briefly review the key emergency medicine points from a single clinical review paper. This post’s topic: Acute Intermittent Porphyria
The paper: Bissell DM, Anderson KE, Bonkovsky HL. Porphyria. The New England journal of medicine. 2017; 377(9):862-872. PMID: 28854095
What is porphyria?
Porphyria is a group of disorders characterized by enzymatic defects in the heme biosynthetic pathway. There are eight forms of porphyria, each type representing a defect in a step to heme formation. This defect leads to an accumulation of heme pathway precursors that enter circulation. The accumulation of metabolic byproducts manifests itself as neurological and/or cutaneous symptoms depending on the defective enzyme.
Porphyrias are generally classified as acute versus cutaneous with acute porphyrias manifesting with predominately neurovisceral symptoms and cutaneous porphyrias characterized by skin photosensitivity.
Which subtype is the most important to know for emergency practice?
Acute Intermittent Porphyria (AIP) is an inherited condition and the most common type of acute porphyria encountered in the emergency department (ED).
How does AIP present?
Typically, patients tend to be young healthy females presenting with several days of non-specific neurovisceral symptoms including abdominal pain, nausea, vomiting, extremity pain, muscle weakness, altered mental affect, and even seizures in 20% of cases. These patients may have a history of previous visits to the ED with similar symptoms and a non-diagnostic evaluation. Abdominal examination and imaging tend to be unremarkable and blood work is generally insignificant other than a minimal elevation in liver enzymes and reduced serum sodium. A triad of seizures, hyponatremia and non-specific abdominal pain in a young female is suggestive of acute intermittent porphyria.
How is AIP triggered?
Acute attacks can be triggered by premenstrual surge in progesterone, caloric deprivation, or certain medications including oral contraceptives.
How is AIP diagnosed?
Diagnosis is established with an elevated random urine or plasma porphobilinogen level. Given its inherited nature, diagnosed patients should inform family members and encourage them to complete genetic screening in order to prevent potential attacks.
How is AIP treated?
Emergency department management is going to be focused on making this rare diagnosis, supportive care, and symptom control. Pain and nausea can be particularly severe. Seizures are common in AIP, and many anti-epileptic medications can exacerbate the condition. Benzodiazepines are safe, however, and should be the focus of management. Definitive treatment is IV heme (panhematin), and should be started as soon as a diagnosis is established.
What is the prognosis?
Several decades ago the mortality rate for AIP attacks was upwards of 25%. Prognosis is improved today with rapid diagnosis and specific treatment, however if patients present with motor neuron disease involvement this may prolong recovery up to 1 year.
Trivia: What is vampire disease?
The photosensitivity associated with cutaneous porphyria is thought to be a possible origin of vampire legends. Patients present with blistering, fragile, and pigmented skin changes, often following sun exposure. Centuries ago, the brown/red appearance of their urine would have suggested possible ingestion of human blood, although we know today that this colored appearance is a result of excess circulating uroporphyrin.