Porphyria: Primary Care Overview

Porphyrias are a rare, heterogeneous group of inherited or acquired metabolic disorders caused by defects in the enzymes of the haem biosynthesis pathway. These defects result in the accumulation of porphyrins or their precursors, which are toxic to the nervous system and skin.

The condition is classically divided into:

Acute hepatic porphyrias (AHPs): Present with episodic abdominal pain, neuropsychiatric symptoms, autonomic dysfunction, and potentially life-threatening neuropathy.
Cutaneous porphyrias: Present with photosensitivity, blistering, and skin fragility.

Although porphyria is rare, its presentations may mimic common conditions in primary care (e.g. recurrent abdominal pain, anxiety, neuropathy, or skin rashes), leading to diagnostic delay.

T-2: Porphyria – Primary Care Overview
Aspect	Key Information
What is Porphyria?	A group of rare inherited metabolic disorders affecting heme biosynthesis due to enzyme deficiencies. Accumulation of toxic porphyrin precursors causes either acute neurovisceral attacks or chronic skin photosensitivity.
Types & Prevalence	Acute hepatic: Acute Intermittent Porphyria (AIP, 1:10,000–20,000), Variegate Porphyria (VP), Hereditary Coproporphyria (HCP). Cutaneous: Porphyria Cutanea Tarda (PCT, most common, 1:10,000), Erythropoietic Protoporphyria (EPP, 2.3:100,000). Extremely rare: Congenital Erythropoietic Porphyria (CEP), ALA Dehydratase Deficiency Porphyria (ADP, <10 cases reported).
Inheritance	Most are autosomal dominant with low penetrance (~12.7% in families, 0.5–1% general population). PCT is mostly acquired (75–80% type I sporadic). EPP and CEP are autosomal recessive.
Clinical Presentation	Acute attacks: Severe abdominal pain, vomiting, constipation, dark urine, tachycardia, hypertension, neuropsychiatric symptoms. Cutaneous types: Blistering/fragility (PCT) or acute phototoxic pain/swelling (EPP) on sun-exposed areas.
Triggers	Acute types: Drugs (barbiturates, sulfonamides, hormones), alcohol, fasting, stress, infection. PCT: Alcohol, hepatitis C, iron overload, estrogens. EPP: Visible light exposure.
Diagnosis	Acute attack: Elevated urinary porphobilinogen (PBG) and δ-aminolevulinic acid (ALA). Between attacks: Often normal biochemistry → requires genetic testing. Cutaneous: Plasma/urine/fecal porphyrins, plasma fluorescence.
Emergency Management	Acute attack: IV hemin (Panhematin 3–4 mg/kg for 4 days), high-dose glucose, morphine for pain, avoid unsafe drugs. Monitor: Sodium levels (risk of SIADH), respiratory function, motor weakness.
Routine Management	Acute types: Avoid triggers, educate on safe drugs, genetic counseling. PCT: Phlebotomy, low-dose hydroxychloroquine, treat underlying liver disease. EPP: Photoprotection, beta-carotene, afamelanotide.
Drug Safety	Critical: Many drugs unsafe in acute porphyria – always check UK Porphyria Medicines Information Service (029 2003 2011). Safe: Most antibiotics, paracetamol, morphine, vaccines. Unsafe: Barbiturates, sulfonamides, hormones.
Prognosis	Acute types: Excellent if triggers avoided, but can be fatal during severe attacks. PCT: Excellent with treatment, skin lesions heal completely. EPP: Good overall, but 5% risk of severe liver disease.
Primary Care Role	Maintain high index of suspicion for unexplained recurrent abdominal pain. Ensure drug safety checking, coordinate emergency care, and support trigger avoidance strategies.
Specialist Services	UK: National Acute Porphyria Service (NAPS) – 24/7 emergency support for acute attacks. Drug advice: UK Porphyria Medicines Information Service.

The role of the primary care clinician includes:

Recognising potential porphyria attacks (e.g. severe unexplained abdominal pain, neurological features, or photosensitive skin lesions).
Avoiding precipitating drugs and factors (alcohol, hormonal changes, certain medications).
Ensuring prompt referral to specialist centres for biochemical and genetic testing when suspected.
Supporting patients with known porphyria by coordinating care, reviewing safe medication lists, and reinforcing lifestyle advice.

With timely diagnosis, avoidance of triggers, and specialist management, most patients can live well, though acute attacks require urgent hospital care.

Porphyria – Key AKT Takeaways

Acute attacks present with unexplained severe abdominal pain + neuropsychiatric or neurological symptoms (e.g. anxiety, seizures, peripheral neuropathy) → always think porphyria if “abdominal pain out of proportion to findings” with hyponatraemia.
Drug safety is crucial – many commonly used drugs (barbiturates, certain anti-epileptics, sulfonamides, oestrogens) can precipitate attacks. Knowing to check the safe drug list (via BNF or UK Porphyria Medicines Information Service) is exam-relevant.
Management – acute attacks require hospital admission for IV glucose/haem arginate; long-term care involves avoiding triggers and specialist follow-up.

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[32](https://pmc.ncbi.nlm.nih.gov/articles/PMC11295309/)

[33](https://porphyriafoundation.org/drugdatabase/)