Porphyria

Introduction

• Metabolic disorders due to altered activity of heme synthesis enzymes
• Three subtypes
  • Neurovisceral (abdo pain, motor/sensory peripheral neuropathy, neuropsychiatric) e.g. Acute intermittent porphyria (AIP)
  • Cutaneous chronic blistering e.g. Porphyria cutanea tarda (PCT)
  • Cutaneous acute non-blistering e.g. Erythropoietic protoporphyria (EPP)
• All inherited EXCEPT porphyria cutanea tarda, which is also the most common
• The three main subtypes equate to three main screening tests

Acute intermittent porphyria

• Inherited autosomal dominant mutation in hydroxymethylbilane (HMBS) enzyme
• Leads to accumulation of toxic porphyrin precursors
• Usually first episodes arise after puberty, more commonly in women
• Requires a trigger for an acute episode
  • Stress
  • Caloric restriction (especially carbohydrates)
  • Alcohol
  • Medications e.g. barbiturates
  • Cyclic hormonal changes

• Most common presenting symptom is neuropathic abdominal pain
• Motor, sensory and autonomic dysfunction
• Physical findings often minimal compared to symptoms
• Always consider in unexplained abdominal pain
  • Typically severe pain with minimal exam findings often combined with CNS symptoms (insomnia, agitation, hallucinations, seizures, hyponatraemia and peripheral neuropathy)
  • Pain may also be in neck, back, chest, limbs or neck
• Classic triad of abdo pain, CNS and PNS findings
• Red or brown urine may suggest severe case
• Screen = Urine porphobilinogen (PBG)  Need low threshold
  • Highly sensitive AND specific
  • Remains elevated for months to years after an acute episode

Acute hepatic porphyria

• Treatment
  • Hemin (synthetic haem)
  • Look for and cease precipitants e.g. infection, drugs
  • Provide carbohydrates and fluids
  • Pain control

Blistering cutaneous porphyrias

• Chronic blistering cutaneous lesions on sun-exposed skin
• Prototype and most common is porphyria cutanea tarda (PCT)
• Especially dorsum of hands, less often face, neck, ears and feet
• Screen = Plasma or urine porphyrins (light sensitive so wrap sample in alfoil)
• Treatment
  • Avoid sunlight
  • Lesions prone to bacterial infection
  • PCT = Phlebotomy and low-dose hydroxychloroquine reduce hepatic iron

Acute non-blistering cutaneous porphyria

• Acute non-blistering photosensitivity
• Most common type is erythropoietic protoporphyria (EPP)
• Immediate photosensitivity with acute pain
• May suffer gallstones also
• Screen = Erythrocyte total protoporphyrin
• Treatment = Sun avoidance + beta-carotene

Last Updated on October 7, 2026 by Andrew Crofton