Erythropoietic Protoporphyria and Acute Porphyrias
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Direct answer
Erythropoietic protoporphyria and acute porphyrias are disorders of haem biosynthesis, and they present either with painful photosensitivity or with neurovisceral attacks. EPP, caused by ferrochelatase deficiency, produces burning pain within minutes of sun exposure, usually without blistering. Variegate porphyria and hereditary coproporphyria cause both blistering skin lesions and acute attacks, and attacks are confirmed by raised urinary porphobilinogen and treated with intravenous haem.
What you must remember
- EPP enzyme: ferrochelatase deficiency, with protoporphyrin IX accumulating in erythrocytes, plasma and skin.
- EPP symptoms: pain, burning and itching within minutes of sunlight, with little or no blistering, often starting in childhood.
- Acute porphyrias: acute intermittent porphyria (HMBS), variegate porphyria (PPOX) and hereditary coproporphyria (CPOX).
- Attack features: abdominal pain, peripheral neuropathy, hyponatraemia, tachycardia and psychiatric change.
- Key test in an attack: raised urinary porphobilinogen, the screening test for acute porphyria in a symptomatic patient.
- Skin in acute disease: variegate porphyria and hereditary coproporphyria cause blistering on sun-exposed skin, whereas acute intermittent porphyria does not.
- Complications of EPP: protoporphyrin pigment gallstones and liver dysfunction, so liver function needs checking.
- Treatment: strict sun protection for EPP, with afamelanotide as a melanogenic option; intravenous haem for acute attacks, plus removal of precipitating drugs such as barbiturates.
Matching the porphyria to the clinical picture
All these disorders share the same haem pathway, but the enzyme defect decides whether the patient has skin disease, acute attacks or both. The table compares the three commonest types.
| Feature | EPP | Variegate porphyria | Acute intermittent porphyria |
|---|---|---|---|
| Enzyme defect | Ferrochelatase | Protoporphyrinogen oxidase | Porphobilinogen deaminase |
| Skin | Burning pain, little blistering | Blistering on sun-exposed skin | No skin lesions |
| Acute attacks | None | Abdominal pain, neuropathy | Abdominal pain, neuropathy |
| Key test | Red cell protoporphyrin | Faecal and urinary porphyrins | Urinary porphobilinogen |
Hereditary coproporphyria resembles variegate porphyria clinically, which is why faecal porphyrin profiling is used to tell them apart. A patient with blistering on sunlit skin and abdominal pain sits in the variegate or coproporphyria group, while one with pain but no blisters points to acute intermittent porphyria or EPP.
In EPP, sun avoidance remains the core advice because no therapy reliably removes photosensitivity, and specialist hepatology review is needed once liver involvement is suspected.
Where the exam tries to catch you
Stems test whether you can separate pain without blisters from blisters with attacks, and then act on an attack.
- Trap: assuming any photosensitive blistering porphyria is EPP. Correct: EPP causes pain without blistering, so blisters suggest variegate porphyria or coproporphyria and call for faecal porphyrins.
- Trap: labelling recurrent abdominal pain as functional without a urine test. Correct: a raised urinary porphobilinogen during an attack points to acute porphyria, which then needs intravenous haem.
- Trap: giving barbiturates or other enzyme-inducing drugs during an attack. Correct: these precipitate attacks, so choose safe analgesia and stop the offending drug.
Frequently asked questions
Which porphyria causes painful photosensitivity without blistering?
Erythropoietic protoporphyria causes painful, burning photosensitivity within minutes of sun exposure, usually without blistering. The defect is in ferrochelatase, and red cell protoporphyrin measurement confirms the diagnosis.
What is the first-line treatment for an acute porphyric attack?
Intravenous haem, given as haem arginate, is the first-line treatment for an acute attack of acute porphyria. It is given with carbohydrate loading, removal of precipitating drugs and supportive care for pain, electrolytes and autonomic symptoms.
Why does acute intermittent porphyria not cause skin lesions?
Acute intermittent porphyria does not cause skin lesions because its defect in porphobilinogen deaminase does not generate the photoactive porphyrins that damage sun-exposed skin. It presents with neurovisceral attacks rather than photosensitivity.
Which test screens for acute porphyria during an attack?
Urinary porphobilinogen is the screening test for acute porphyria during an attack. A raised level in a patient with unexplained abdominal pain and neuropathy points to acute porphyria, and faecal and urinary porphyrin profiles then identify the specific type.