PREVENTION OF ATTACKS

Patients, who have experienced a clinical attack of porphyria, should be carefully counselled concerning the avoidance of precipitating factors. They should be encouraged to maintain a regular diet and to abstain completely from alcohol and to stop smoking. In addition, they should be warned about the dangers of certain drugs and given a Reference Booklet, showing which drugs are safe and which are unsafe to take (see Tables 1 and 2). It is also important to ensure that the patient's General Practitioner is fully informed about the disease and given advice about management. Patients should be reminded to tell any Medical Attendant that they suffer from porphyria. As an added precaution, they should wear a bracelet or necklace, indicating that they have porphyria, to prevent the administration of dangerous drugs or anaesthetics if an accident or other emergency.

Menstruation:

Some women experience regular attacks in the week prior to the onset of menstruation. These are assumed to be initiated by the hormonal fluctuations, and various attempts have been made to prevent them. Sometimes, merely increasing the carbohydrate intake at the appropriate time of the month is found to be helpful. Interfering with the hormonal fluctuations has produced varying results. Some patients have been reported to benefit from the suppression of ovulation, using various oral contraceptive hormone preparations. However, in our own experience, also that of several other Centres, the contraceptive pill has usually precipitated attacks. Attacks have been successfully prevented by administering haematin, prophylactically, just prior to the time in the month when the attack usually starts and through the long term use of synthetic LHRH analogues.

Pregnancy and Acute Porphyria:

Pregnancy may precipitate acute porphyria, with attacks being most common in early pregnancy and during the puerperium. The first attack often occurs during pregnancy. In patients with the genetic trait, who have normal porphyrin excretion, who have never experienced a clinical attack, pregnancy is, usually, uneventful. If vomiting is a problem in early pregnancy, the patient should be admitted to the hospital at an early stage and dextrose administered, intravenously, to prevent the reduced dietary intake from inducing an attack. Dextrose should also be administered, intravenously, during labour. Patients who have had clinical attacks of porphyria, and have increased urinary excretion of porphyrins and precursors are likely to experience attacks during pregnancy. We advise such patients not to consider pregnancy until they have been free of symptomatic attacks for at least 18 months.

When attacks do occur during pregnancy, they should be treated as already described. But, as there is insufficient information about the effect of Haematin on the foetus, this therapy should be avoided unless the condition of the mother demands it. Most attacks of porphyria during pregnancy settle with adequate supportive therapy, resulting in a successful outcome for both mother and child. We only, rarely, consider therapeutic termination of pregnancy in patients with acute porphyria and then, only in very severe attacks, occurring in early pregnancy. Besides the possible risks of pregnancy, many patients question the advisability of bearing children likely to inherit a genetic disorder. It should be explained to the patient that, although each child will have a 50 per cent chance of inheriting the trait, the majority of porphyrics remain clinically latent throughout life. When affected individuals decide to delay or avoid pregnancy, they should be warned about the dangers of oral contraceptives, and advised about other forms of contraception.

Anaesthetics:

Provided appropriate precautions are taken, most patients with acute porphyria can tolerate surgery and general anaesthesia. However, patients experiencing frequent attacks of porphyria will be at risk of developing complications, and the indications for surgery should be carefully examined. Care must always be taken in selecting safe anaesthetic agents. Atropine and morphine may be used as premedication. Intravenous propofol and ketamine have been found to be safe alternatives to thiopentone as anaesthetic-inducing agents. Cyclopropane and ether are safe inhalation agents with respect to the porphyrias, but they suffer the disadvantages of being potentially explosive and inducing post-operative vomiting. Nitrous oxide, used with intravenous narcotics, and muscle relaxants, may be a more acceptable alternative. Suxamethonium and D-tubocurarine can be used as muscle relaxants and diamorphine, morphine, pethidine or fentanyl are suitable narcotics for controlling post-operative pain. In some situations, epidural anaesthesia may be preferable to general anaesthesia, in which case bupivacaine is the local anaesthetic of choice. To prevent an attack being induced by fasting, an intravenous infusion of dextrose should be commenced prior to surgery, and continued until the patient can eat properly.

Photosensitivity:

Photosensitivity may be found in Variegate porphyria and Hereditary Coproporphyria. The occurrence of skin lesions depends on the degree of porphyrin overproduction and the amount of exposure to sunlight. Skin lesions should be treated by removing any inducing factors, such as drugs, alcohol, or inadequate diet, that may increase the porphyrin overproduction.

There is no specific treatment for the skin photosensitivity occurring in Variegate porphyria and Hereditary coproporphyria, although Beta-carotene treatment has been suggested of benefit. Barrier creams may be used. Avoidance of excess sunlight is advised. The dermatological features often subside after the acute attack, as the amount of circulating porphyrin is reduced.

Prophylaxis and Treatment of Malaria:

The steady encroachment of chloroquine-resistant malaria and increased travel to malarious regions has resulted in a pressing need to re-evaluate the prophylactic strategy for people visiting or residing in areas known to harbour the disease.

Many commonly used antimalarials are known to be porphyrinogenic. Chloroquine has been the most widely used prophylactic and therapeutic agent for decades, however most authorities describe its use in porphyrics as 'contentious'. Added to this is the problem of widespread chloroquine resistance, so that chloroquine per se should not be regarded as adequately protective against malaria. The other agents commonly prescribed for prophylaxis, dapsone and sulphadoxine, are definitely contraindicated in porphyrics. Combined preparations as 'Maloprim' and 'Fansidar' should not be used, as they contain one or other of these agents.

Pyrimethamine is probably safe, but it should have little place in the prophylaxis of malaria because of relative inefficiency. 'Daraclor', contains both chloroquine and pyrimethamine which are suspect not only for safety in porphyrics, but also for their efficacy in resistant malaria. Finally, there are three remaining drugs primaquine, mefloquine and proguanil. These are thought to be safe, mefloquine and proguanil on cell culture tests and primaquine on human experience.

What then, should the porphyric person contemplating a visit to a malarial area be advised to do? An alternative to the use of chloroquine is to consider the prophylactic use of quinine, which is of proven safety in porphyrics. Though widely used as a prophylactic in the past it has the disadvantages of requiring a twice daily administration (compared with once weekly for chloroquine) and of hazardous side-effects, when taken long-term. Yet, it retains efficacy against chloroquine-resistant Falciparum malaria.

A third strategy, the one that is probably safest to suggest now, is to avoid chemoprophylaxis altogether and adopt the following steps:-