Diagnosis and management of porphyria

British Medical Journal, June 17, 2000 by Helen Thadani, Allan Deacon, Timothy Peters

Acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria are differentiated by analysis of faecal porphyrins (table). The diagnosis of acute intermittent porphyria can be further confirmed by the demonstration of reduced red cell hydroxymethylbilane synthase activity,[2] although it is important to check that routine haematological indices are normal. DNA analysis is not yet of routine diagnostic value.

Management of acute attacks

About 1% of acute attacks of porphyria may be fatal. Most patients with an acute attack will require admission to hospital. Only drugs known to be safe in porphyria should be prescribed. For severe pain, opiates are safe--that is, non-porphyrogenic. Pethidine, morphine, or diamorphine can be given. Chlorpromazine may be helpful to promote relaxation and sleep. Sympathetic overactivity causing tachycardia and hypertension can be alleviated with propranolol.

Convulsions may occur during an acute attack. Their onset may be precipitated by hyponatraemia, so plasma osmolality and electrolyte values should always be checked.[2] Treatment is by fluid restriction, and the convulsions usually resolve as the attack subsides. Rarely, epilepsy may be the presenting symptom in acute intermittent porphyria. Treatment should be aimed at the underlying disease. Seizures are notoriously hard to manage in porphyria as all commonly used anticonvulsant agents are porphyrogenic and may therefore lead to further exacerbation of the disease.[18 19]

Historically, bromides have been the drug of choice for seizure control in most patients with acute porphyria.[18 20] However, in the mid to late 1990s several new antiepileptic drugs were introduced, and, of these, gabapentin[21-23] and vigabatrin[21] were shown to be successful in seizure control without inducing porphyric crises. These drugs are now the treatment of choice for these patients.

Oral and intravenous glucose (for maintaining a high energy intake) and haem arginate are the mainstay of treatment. They reduce synthesis of aminolaevulinic acid, resulting in a clinical and biochemical remission, with urinary excretion of aminolaevulinic acid and porphobilinogen falling towards normal values. Glucose (10% intravenously) should be given for mild attacks and pending administration of haem arginate.

Haem arginate (Normosang, Leiras Medica, Finland) should be given at an early stage in an attack[24] as it cannot reverse an established neuropathy. It is given at a dose of 3 mg/kg/day for 4 days over 15 minutes by slow intravenous infusion. It is highly irritant so should be given by a central venous line. It acts rapidly and has a dramatic effect within one week. It is expensive and is available on an urgent need basis from the company (Orphan Europe, Henley-on-Thames, Oxfordshire) or from the two supraregional assay service centres. Recently tin protoporphyrin, an inhibitor of haem oxygenase, has been shown to prolong remission when given with haem arginate.[25] Its side effects of cutaneous photosensitivity and potential toxicity limit its use, however, and further evaluation is continuing. A small proportion of patients--mainly females--have recurrent attacks with no apparent precipitants. Prophylactic haem arginate may be necessary on a regular basis for such patients. Induction of a chemical menopause with luteinising hormone releasing hormone agonists has been successfully used in this situation.