Related Subjects:
|Acute Porphyrias
|Variegate Porphyria
|Acute Intermittent Porphyria (AIP)
|Porphyria Cutanea Tarda (PCT)
|Porphyria Testing
🩸 Acute porphyrias are hereditary disorders of haem biosynthesis (prevalence ~1 in 75,000). They can cause severe, potentially life-threatening neurovisceral attacks.
⚠️ The BNF advises: if no safe alternative exists, essential drug treatment should not be withheld even in patients with acute porphyria.
📖 About
- 🔗 Disruption of the haem synthetic pathway.
- ☠️ Accumulation of haem precursors causes neurotoxicity and systemic symptoms.
- 💊 Extreme care required when prescribing — always check safe drug lists.
🌐 National UK Links
🧬 Types of Acute Porphyria
| Type |
Details |
| 🩺 Acute Intermittent Porphyria (AIP) |
Most common. Deficiency of porphobilinogen deaminase. Presents with abdominal pain, neuropsychiatric features, and autonomic dysfunction. |
| ☀️ Hereditary Coproporphyria (HCP) |
Deficiency of coproporphyrinogen oxidase. Similar to AIP but can cause photosensitivity. |
| 🌞 Variegate Porphyria (VP) |
Deficiency of protoporphyrinogen oxidase. Acute neurovisceral attacks + blistering photosensitivity. |
| 🧪 ALAD Deficiency Porphyria (ADP) |
Rare. Deficiency of delta-ALA dehydratase. Mainly neurological symptoms. |
⚠️ Precipitants
- 💊 Unsafe drugs (barbiturates, sulfonamides, hormonal contraceptives).
- 🍷 Alcohol, 🚫 fasting, 🩸 hormonal changes (e.g. menstruation).
- 🦠 Infection, stress, dehydration.
🚫 Drugs to Avoid (check full list in BNF/UKPMIS)
- ❌ Barbiturates
- ❌ Sulfonamides, Co-trimoxazole
- ❌ Tricyclics & MAOIs
- ❌ Hormonal contraceptives, HRT
- ❌ Imidazole & Triazole antifungals (oral/IV)
- ❌ Protease inhibitors, NNRTIs
- ❌ Taxanes, Cytotoxics
- ❌ Diclofenac, Rifampicin, Metronidazole, Chloramphenicol
🩺 Clinical Features
- 🔴 Severe abdominal pain (pain out of proportion to exam).
- 🧠 Neurological: weakness (may involve respiratory muscles), delirium, psychosis, hallucinations, progressive paralysis.
- ❤️ Autonomic: tachycardia, hypertension.
- 😵 Fatigue, constipation, irritability.
- ☀️ VP/HCP: blistering photosensitive skin lesions.
- 🧪 Urine: dark red-brown colour during attacks.
🔍 Investigations
| Test | Use |
|---|
| 🧪 Urine PBG | Most important initial test — elevated in AIP attacks. |
| 🧪 Urine ALA | Also elevated during acute attacks. |
| 💡 Plasma fluorescence | Diagnostic for VP & HCP under UV light. |
| 💩 Stool porphyrins | Helps confirm VP/HCP. |
| 🧬 Genetic testing | Confirms mutation and porphyria subtype. |
| 🧪 Enzyme activity | Useful in AIP (PBG deaminase deficiency). |
| 🩺 LFTs | Assess hepatic involvement and monitor long-term risks (HCC). |
💉 Treatment: In the UK, haem arginate (hemin) is given IV during acute crises (via NAPS at Cardiff or King’s College London). IV dextrose is also used to suppress haem synthesis.
🛠️ Management (UK Practice)
- 🚑 Emergency: ABC, monitoring, admit to quiet darkened room.
- ❌ Stop precipitating drugs/triggers.
- 💉 IV glucose (to suppress ALA synthase).
- 🩸 IV haem arginate via NAPS for severe/prolonged crises.
- 💊 Symptom relief: opioids for pain, antiemetics, beta-blockers for tachycardia.
- 🧾 Long-term: trigger avoidance, liver monitoring (↑ HCC risk), genetic counselling.
🛡️ Prevention
- 🚫 Avoid alcohol, starvation, unsafe drugs.
- ☀️ For VP/HCP: avoid sun exposure, use high-factor sunscreen.
- 🩺 Regular liver surveillance for hepatocellular carcinoma.
📚 References
Clinical cases
- 💊 Case 1 – Age 26: Young woman presented with severe, diffuse abdominal pain, vomiting, and dark-red urine. No peritonism on examination. Neurological review revealed mild limb weakness and anxiety.
Investigations: Urine turned red on standing; raised urinary porphobilinogen confirmed acute intermittent porphyria (AIP).
Management: IV hemin and high-carbohydrate infusion given; precipitating factor identified as oestrogen-containing oral contraceptive, which was discontinued.
Teaching point: Acute intermittent porphyria is precipitated by drugs, hormones, or fasting — neurovisceral symptoms without peritoneal signs are classic clues.
- ⚡ Case 2 – Age 34: Male factory worker developed abdominal pain, tachycardia, and proximal muscle weakness after starting phenobarbital for epilepsy. Mild hyponatraemia and dark urine noted.
Investigations: Elevated urinary ALA and porphobilinogen consistent with an acute porphyric attack.
Management: Immediate withdrawal of phenobarbital, IV glucose, and hemin therapy.
Teaching point: Many enzyme-inducing drugs (barbiturates, sulphonamides) trigger porphyric crises by increasing hepatic haem synthesis.
- 🩸 Case 3 – Age 29: Female with recurrent abdominal pain, vomiting, and mood disturbance. During one episode, she developed flaccid paralysis and respiratory distress requiring ICU care.
Investigations: Porphyrin analysis confirmed variegate porphyria.
Management: Supportive care with ventilatory support, IV hemin, and avoidance of porphyrinogenic medications.
Teaching point: Variegate and hereditary coproporphyria share similar acute neurovisceral attacks but may also cause cutaneous photosensitivity — mixed features should raise suspicion.
