Acute intermittent porphyria (AIP): attacks, triggers, testing and treatment

The porphyrias are a group of relatively rare genetic disorders. The BPA explains that they are named after chemicals called porphyrins, or the simpler chemicals the body uses to make them. Most of the porphyrias are inherited and result from a faulty gene, which leads to difficulty making a chemical called haem, a constituent of many important proteins in the body, including haemoglobin.

Making haem involves a series of steps carried out by enzymes. If an enzyme is faulty, the process may not work properly and precursor chemicals can accumulate, which can cause severe medical problems. In the acute porphyrias, which include AIP, the BPA says acute attacks are caused by a build-up of the precursors ALA and PBG (aminolevulinic acid and porphobilinogen), which results in damage to nerves.

AIP is one of four porphyrias that may present with acute attacks. The BPA says that these attacks are uncommon and often difficult to diagnose, and that about 1 in 75,000 people suffer from the acute porphyrias as a group. Because it is rare and the symptoms are non-specific, AIP is often not suspected at first.

The BPA lists the typical features of acute attacks. They vary from person to person and from attack to attack, and a single attack may involve only some of them.

• Severe pain in the abdomen, back, arms or legs.

• Nausea, vomiting and constipation.

• Low sodium (salt) levels in the blood.

• A rise in pulse rate and blood pressure.

• Confusion.

• Convulsions and muscular weakness.

The BPA says the condition cannot be cured, and that symptoms and their severity vary from patient to patient. Most people have only one or a few acute attacks, whereas a minority suffer repeated attacks, sometimes over several years. The most common age for an attack is from the late teens to the early forties, and attacks are extremely rare in children before puberty.

NICE, describing acute hepatic porphyria more broadly, says people can have acute attacks with extreme pain, nausea and fatigue, which sometimes lead to seizures and paralysis, and can also have chronic pain and fatigue. It describes the condition as rare, progressive and potentially life-threatening, which is why prompt recognition matters.

Because AIP is autosomal dominant, a person who carries the gene may never have symptoms, and the condition can appear to skip a generation. The BPA says the 50% chance of being affected is the same even if the affected parent has never had any symptoms.

The BPA lists commonly prescribed drugs, illegal drugs, alcohol, dieting, stress, infections, viruses and hormonal fluctuations as typical triggers. Everyone with AIP is at risk of acute attacks, so it recommends a few simple precautions.

The most important is medicine safety. If you have an acute porphyria, attacks can be caused by certain medicines, so it is vital to ensure that medicines are safe; the BPA publishes a SAFE drug list for this purpose. Anyone with a diagnosis should tell every prescriber, pharmacist and dentist, and carry information about the condition. People with a skin porphyria, by contrast, do not need to follow the same drug list.

The BPA also points to diet and sleep advice, and to extra thought about contraception and pregnancy for those with an acute porphyria, since hormonal changes can be involved. Dieting is listed among triggers, so any weight loss plan is worth discussing with a specialist first.

The BPA says that once a doctor has thought to investigate porphyria it is relatively easy to eliminate or confirm a diagnosis. If symptoms could potentially be caused by an acute porphyria, the first test is a urine porphobilinogen (PBG) test, and in some cases urinary ALA too. PBG can drop quite quickly after an attack subsides, within about a week, so the test needs to be done during the attack to be reliable.

If the PBG level is raised, further biochemical testing follows to confirm which porphyria is present. Biochemical testing involves checking porphyrin and precursor levels in urine, blood and faeces, because each type has a distinctive pattern. Genetic testing on blood or saliva is used alongside this, not alone: once a porphyria is known, a genetic test can often find the gene fault, and relatives can then be checked relatively quickly.

Diagnostic testing is best done by a specialist porphyria laboratory, because porphyrin levels may be normal in people with porphyria who have no current symptoms and may be raised in people with other conditions. The BPA also notes that sample containers should be wrapped in foil or black plastic quickly after collection because porphyrins degrade in light.

Importantly, the BPA warns that people with porphyria should not assume that all their illnesses are porphyria, as common but potentially serious conditions, such as appendicitis causing abdominal pain, could be overlooked. A PBG test can help to show whether new pain is an attack.

NICE says that the standard NHS treatment for people with recurrent severe attacks is prophylactic haem arginate, offered to most people with recurrent severe attacks, although this use is outside its marketing authorisation.

NICE guidance HST16 recommends givosiran (Givlaari) as an option for acute hepatic porphyria in adults and young people aged 12 and older, only if they have clinically confirmed severe recurrent attacks (4 attacks or more within 12 months) and the company provides it according to the commercial arrangement. NICE states there is no trial directly comparing givosiran with prophylactic haem arginate, but that results suggest givosiran reduces the number of acute attacks and improves chronic symptoms and quality of life.

The BPA reports that a 36-month plain language summary of the ENVISION study found symptom improvements seen in the first 6 months were sustained through the extension period with no new safety concerns. Treatment decisions sit with a specialist porphyria service; the BPA lists UK centres of expertise.

The BPA emphasises that a patient who is knowledgeable about their condition is more likely to stay well. It offers practical guidance on drug safety, diet and sleep, mental health, contraception and pregnancy, help with health costs and insurance. Many people with a porphyria gene live without attacks by avoiding known triggers and keeping a record of safe medicines.

Living with a rare disorder can affect mental wellbeing, and the BPA signposts support for this. If you have a diagnosis, consider carrying a card or note that names the condition and refers to the safe drug list, so that staff in an emergency department can act quickly.

Severe abdominal, back or limb pain with vomiting, constipation, confusion, muscle weakness or seizures needs urgent assessment. If you have a known diagnosis, go to A&E or call 999 and tell staff you have acute porphyria, ask for a urine PBG test and avoid unsafe medicines. If you have not been diagnosed but have repeated unexplained attacks of this kind, ask your GP whether porphyria testing is appropriate.

Do not delay while waiting for a specialist appointment if you feel seriously unwell.