Porphyria

How porphyria develops

Heme is made in 8 steps, mostly in the bone marrow and liver. Each step needs a specific enzyme. When one enzyme is deficient, the substances made before that step (porphyrin precursors and porphyrins) accumulate:

• porphyrin precursors (ALA and PBG) are toxic to nerves, causing acute attacks
• porphyrins react with sunlight in the skin, causing damage and blistering

Main types

Acute porphyria attacks

Attacks are most common in women aged 15 to 45, and many carriers of the gene never have an attack. Symptoms develop over hours to days:

• severe, diffuse abdominal pain, often with a normal examination
• nausea, vomiting and constipation
• dark, red or brown urine, which darkens on standing in light
• fast heart rate and high blood pressure
• anxiety, confusion, hallucinations, insomnia
• muscle weakness, often starting in the arms and shoulders, which can progress to paralysis and breathing failure
• seizures, often linked to low sodium

Triggers

• medicines: some anti-seizure drugs (barbiturates, phenytoin, carbamazepine), sulfonamide antibiotics, some hormonal treatments, and many others. Always check a porphyria drug database before starting a medicine.
• alcohol and smoking
• fasting, crash dieting or low-carbohydrate diets
• hormonal changes in the menstrual cycle
• infection, surgery and stress

Cutaneous porphyrias

Porphyria cutanea tarda (PCT)

The most common porphyria overall. Usually acquired in adulthood, linked to:

• alcohol, smoking, estrogen
• hepatitis C and HIV
• iron overload and hemochromatosis gene variants

Symptoms are fragile skin, blisters and erosions on the backs of the hands, forearms and face, healing with scars and small white cysts, plus increased facial hair and darkened skin.

Erythropoietic protoporphyria (EPP)

Begins in childhood with burning, stinging pain within minutes of sun exposure, often with swelling and redness but few blisters. Some people develop gallstones and, rarely, liver damage.

Diagnosis

• urine PBG test during symptoms: a markedly raised level confirms an acute porphyria attack
• plasma, urine and stool porphyrins to identify the type
• red blood cell protoporphyrin for EPP
• genetic testing to confirm the type and screen relatives
• liver tests, iron studies, hepatitis C and HIV tests in PCT

Treatment

Acute attacks

• stop trigger medicines, alcohol and smoking
• IV hemin (heme arginate or hematin): the main treatment, which switches off overproduction
• IV glucose (carbohydrate loading) for mild attacks or while hemin is arranged
• pain control with porphyria-safe medicines, anti-nausea medicines, treatment of high blood pressure and low sodium
• hospital monitoring for weakness and breathing problems

Preventing attacks

• givosiran: a monthly injection that reduces recurrent attacks in acute hepatic porphyria
• avoiding triggers and eating regular carbohydrate-containing meals
• hormonal suppression for menstrual attacks in some women
• liver transplant for severe, frequent attacks not controlled otherwise

Cutaneous porphyrias

• PCT: regular phlebotomy (blood removal) to lower iron, or low-dose hydroxychloroquine; stop alcohol, smoking and estrogen; treat hepatitis C
• EPP: strict sun protection and protective clothing; afamelanotide implants increase sun tolerance; dersimelagon and other treatments are in development
• visible-light protection: standard sunscreens do not fully protect, so physical protection is key

Long-term care

People with acute hepatic porphyria have a higher risk of liver cancer and kidney disease and need regular monitoring.

Frequently asked questions

What is porphyria?

Porphyria is a group of rare disorders in which the body cannot properly make heme. Toxic building blocks accumulate, causing either attacks of abdominal pain and nerve symptoms, skin damage with sunlight, or both.

What are the symptoms of acute porphyria?

Acute attacks cause severe abdominal pain, vomiting, constipation, dark or reddish urine, a fast heart rate, high blood pressure, anxiety or confusion, muscle weakness and sometimes seizures. They are often triggered by medicines, alcohol, fasting or hormones.

What triggers porphyria attacks?

Common triggers include certain medicines, alcohol, smoking, fasting or crash dieting, menstrual hormone changes, infections and stress. People with acute porphyria should check every new medicine against a porphyria drug safety database.

Is porphyria inherited?

Most types are inherited, although many people carrying an acute porphyria gene never have symptoms. Porphyria cutanea tarda is often acquired, triggered by alcohol, hepatitis C, iron overload or estrogen. Genetic testing can identify relatives at risk.