Approach

The aim of treatment is to hasten recovery from acute attacks and prevent future attacks and long-term complications. The application of specific and effective treatment can prevent neurologic damage and death.[6][26]

Acute attacks

Acute attacks are treated with supportive care and specific treatments. Patients usually require admission to the hospital and close monitoring for respiratory depression and other complications.[6][16]​ Admission to an intensive care unit is indicated, especially if respiration is impaired. Factors that may have precipitated the attack are identified and removed whenever possible.

Giving intravenous hemin represses synthesis of hepatic delta-aminolevulinic acid (ALA) synthase (ALAS1) and thereby decreases the overproduction of ALA and porphobilinogen. It should be the initial treatment for most acute attacks.[15][16]​ Hemin is available in the US as lyophilized hematin. At many centers it is reconstituted with human albumin, rather than sterile water, in order to enhance stability and prevent adverse effects of hemin degradation products (e.g., phlebitis at the site of infusion and a transient anticoagulant effect).[27] Heme arginate is a more stable preparation of hemin, and is available in Europe and South Africa. Either product may have regulatory approval in some other countries. Clinical improvement is often within 1 to 2 days if hemin is started early in an attack.[6]

Glucose loading may benefit some patients; however, it is considered to be less effective than hemin, so is used to treat an attack only if it is mild (i.e., mild pain [not requiring opioid analgesics]; absence of vomiting, seizures, hyponatremia, paresis, or other complications).[6] When tolerated, glucose may be given orally as sucrose, glucose polymers, or as carbohydrate rich foods. However, most attacks are accompanied by nausea, vomiting, or abdominal distension, and so giving at least 300 g of dextrose (10% glucose) intravenously is recommended. Large volumes of intravenous glucose increase the risk of hyponatremia. In severe attacks, intravenous hemin is started without an initial trial of carbohydrate loading. It is generally better to treat even mild attacks with hemin, to prevent progression and to shorten illness and hospitalization. Therefore, delay in starting hemin treatment should be avoided.

Intravenous fluid replacement using 0.9% saline or 5% dextrose with normal saline may be required to correct dehydration, hyponatremia, and other electrolyte imbalances. Symptomatic treatment is provided for pain, nausea, vomiting, tachycardia and hypertension, depression, or seizures. Drug prescribing should be under specialist advice, especially to avoid drugs that are harmful in acute porphyrias.

Prevention of recurrent acute attacks

Preventive intervention is needed for the few patients who continue to have frequent attacks after known inciting factors are removed.

Givosiran, a long-acting interfering RNA therapeutic that downregulates hepatic ALAS1, is recommended first line. It has been shown to greatly reduce attack frequency in patients experiencing frequent acute exacerbations.[28]

Hemin infusions once or twice weekly can also prevent frequently recurring noncyclic attacks.[6][29] Serum ferritin levels should be monitored because there is some risk of iron overload. Ferritin levels should be measured as long as possible after the last dose of hemin.

Frequent, cyclic attacks in women can be prevented by long-term administration of a gonadotropin-releasing hormone (GnRH) analog, which should be started during days 1 to 3 of the menstrual cycle.[10][30] If a GnRH analog is effective, bone loss during long-term treatment can be prevented by estrogen add-back using a low-dose skin patch.

Recurrent attacks are expected to become less frequent over time. Therefore, stopping a preventive treatment should be considered at some point to check if it is still needed.

Ongoing symptoms unresponsive to medical therapy

Liver transplant is an option for severe cases that do not respond to established medical therapies, and particularly hemin and givosiran. Marked clinical and biochemical improvement has been reported in several severe cases after liver transplantation.[31][32] An increased incidence of hepatic artery thrombosis has been reported in some patients with acute porphyria undergoing liver transplantation.[33][34]

Use of this content is subject to our disclaimer