Related Subjects:
|Acute Porphyrias
|Variegate Porphyria
|Acute Intermittent Porphyria (AIP)
|Porphyria Cutanea Tarda (PCT)
|Porphyria Testing
🩸 Acute hepatic porphyrias (AHP) are rare inherited disorders of hepatic haem biosynthesis that can cause severe, potentially life-threatening neurovisceral attacks.
⚠️ The BNF advises that if no safe alternative exists, essential drug treatment should not be withheld in a person with acute porphyria.
📖 About
- Acute attacks result from overproduction of hepatic haem precursors, especially ALA and porphobilinogen (PBG).
- These intermediates are associated with neurotoxicity, autonomic disturbance, and systemic symptoms.
- Acute attacks are uncommon, but when they occur they can be medical emergencies.
- Prescribing requires care: always check the current UK porphyria drug safety resource.
🌐 National UK Links
🧬 Types of acute hepatic porphyria
| Type |
Details |
| 🩺 Acute Intermittent Porphyria (AIP) |
The commonest acute hepatic porphyria. Deficiency of porphobilinogen deaminase (hydroxymethylbilane synthase). Typically causes abdominal pain, autonomic disturbance, and neuropsychiatric features. |
| ☀️ Hereditary Coproporphyria (HCP) |
Deficiency of coproporphyrinogen oxidase. Can cause acute attacks and may also cause cutaneous photosensitivity. |
| 🌞 Variegate Porphyria (VP) |
Deficiency of protoporphyrinogen oxidase. Acute neurovisceral attacks plus blistering photosensitivity. |
| 🧪 ALAD Deficiency Porphyria (ADP) |
Very rare. Deficiency of ALA dehydratase. Mainly neurological presentation. |
⚠️ Common precipitants
- 💊 Porphyrinogenic medicines — always verify safety using the current UKPMIS/WMIC resource.
- 🚫 Fasting, crash dieting, low calorie intake.
- 🍷 Alcohol.
- 🩸 Hormonal triggers, especially in some women around menstruation.
- 🦠 Intercurrent infection, stress, dehydration, and other physiological stressors.
🚫 Drug safety
- Do not rely on old static “avoid” lists alone — drug advice changes as evidence evolves.
- Check the current UKPMIS/WMIC safe drug list or specialist advice for each medicine.
- The BNF specifically notes that essential treatment should not be withheld if there is no safer alternative.
🩺 Clinical Features
- 🔴 Severe abdominal pain, often out of proportion to physical findings.
- 🤢 Nausea, vomiting, constipation, abdominal distension.
- ❤️ Autonomic overactivity: tachycardia, hypertension, sweating.
- 🧠 Neuropsychiatric features: anxiety, agitation, insomnia, confusion, hallucinations, seizures.
- 💪 Motor neuropathy: limb weakness that may progress and can involve respiratory muscles.
- 🧂 Hyponatraemia is an important and potentially dangerous complication.
- ☀️ In VP/HCP, blistering photosensitivity may coexist.
- 🧪 Urine may appear dark or reddish-brown during an attack, but colour change is not sufficiently sensitive for diagnosis.
🔍 Investigations
| Test | Use |
|---|
| 🧪 Spot urine PBG | Key first-line test in a suspected acute attack; usually markedly raised in AIP, VP, and HCP during attacks. |
| 🧪 Urine ALA | Supports biochemical diagnosis and may also be elevated. |
| 🧂 U&E / sodium | Essential to detect hyponatraemia. |
| 🩸 FBC, CRP, LFTs | Supportive tests to assess differential diagnoses, complications, and baseline status. |
| 💡 Plasma / faecal porphyrin studies | Help distinguish VP and HCP from AIP. |
| 🧬 Genetic testing | Confirms subtype and supports family screening after biochemical diagnosis. |
💉 Specific treatment: In the UK, haem arginate (Normosang®) is the specific treatment for moderate, severe, or unremitting acute attacks and should be discussed with the National Acute Porphyria Service (NAPS). It is thought to work best when started early after diagnosis is established.
🛠️ Management (UK practice)
- 🚑 Initial management: ABCDE assessment, admit if significant symptoms, and monitor closely.
- ❌ Stop potential triggers, including unsafe medicines where possible.
- 🧪 Send urgent urine PBG in suspected attack.
- 🍬 Ensure adequate carbohydrate intake; IV glucose may help in mild attacks, but this is not a substitute for haem arginate in moderate or severe attacks.
- 🩸 Discuss early with NAPS if the attack is moderate, severe, prolonged, recurrent, or associated with neuropathy.
- 💊 Give symptom relief using porphyria-safe medicines:
- opioids for severe pain,
- safe antiemetics for nausea/vomiting,
- appropriate management of tachycardia/hypertension if needed.
- 🧂 Monitor and treat hyponatraemia carefully; correct slowly according to severity and symptoms.
- 🫁 Watch for progressive weakness and respiratory compromise; ICU support may be needed.
- 🧠 Seizures require urgent treatment with porphyria-safe anticonvulsant choices.
🛡️ Prevention / long-term care
- 🚫 Avoid fasting, unsafe drugs, excess alcohol, and other known triggers.
- 🧾 Provide patients with up-to-date information on drug safety and emergency contacts.
- ☀️ For VP/HCP, advise sun protection if cutaneous symptoms occur.
- 🩺 People with recurrent attacks or established disease need specialist follow-up; some may receive specialist therapies such as givosiran under specialist supervision.
- 🧬 Offer family/genetic counselling where appropriate.
- 🫀 Long-term follow-up may include monitoring for complications such as hypertension, chronic kidney disease, and hepatocellular carcinoma in selected patients.
⚠️ Exam Pearls
- Abdominal pain + normal abdominal exam + tachycardia + hyponatraemia should make you think of an acute porphyric attack.
- Urine PBG is the key first diagnostic test in a suspected acute attack.
- Dark urine is a clue, not a rule.
- Neuropathy and hyponatraemia are major severity markers.
- Drug safety must be checked dynamically using current UK porphyria resources.
📚 References
Clinical cases
- 💊 Case 1 – Age 26: Young woman with severe abdominal pain, vomiting, tachycardia, and limb discomfort but no peritonism.
Investigations: Urgent urine PBG raised, confirming an acute hepatic porphyria attack.
Management: Trigger review, supportive care, carbohydrate support, and early discussion with NAPS about haem arginate; likely hormonal trigger addressed.
Teaching point: Severe visceral pain with minimal abdominal signs is a classic clue.
- ⚡ Case 2 – Age 34: Man develops abdominal pain, tachycardia, weakness, and hyponatraemia after starting a porphyrinogenic medicine.
Investigations: Raised urine PBG and ALA during attack.
Management: Stop trigger, monitor sodium, use only porphyria-safe drugs, and escalate for specific therapy if moderate/severe.
Teaching point: Hyponatraemia is both a clue and a management priority.
- 🩸 Case 3 – Age 29: Recurrent attacks complicated by progressive weakness and respiratory distress.
Management: ICU support, haem arginate, and specialist porphyria follow-up.
Teaching point: Motor neuropathy can progress rapidly and is the major life-threatening complication.
