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Patient Guide (Easily Printable)
MICHAEL R. MOORE
PORPHYRIA RESEARCH UNIT
 THE UNIVERSITY OF QUEENSLAND, NRCET, DEPARTMENT OF MEDICINE --1998

Complete Text Of This Document Can Be Found At:
http://www.uq.edu.au/porphyria/


WHAT IS PORPHYRIA ?
Porphyria is a fairly uncommon condition. It is not one condition, but a group of several related diseases. Most of these are inherited but some may be acquired. People with porphyria may develop skin problems or a condition known as the acute attack. In all the porphyria, the basic dilemma is that excessive amounts of porphyrins and their precursors accumulate in the body. It is under-diagnosed. Many sufferers are completely asymptomatic. All living things, including healthy people produce porphyrins. In porphyria, there is an atypical accumulation of porphyrins as the result of enzyme defects; this results in illness. Our bodies convert two simple substances, 5-aminolaevulinate (ALA) and porphobilinogen (PBG) known as porphyrin precursors, into more complicated substances called porphyrins. These are then converted from one type of porphyrin to the next to form haem. Haem is a vital substance in our bodies. Protoporphyrin together with Iron are the building blocks necessary to make haem. Each step on the pathway is completed by a special protein known as an enzyme. In each type of porphyria, a specific enzyme is deficient, and this is why porphyrins accumulate.
 
ACUTE INTERMITTENT PORPHYRIA (AIP):
AIP is an inherited condition. It is passed on from generation to generation. This means that it may be passed on from parents to their children. This occurs so that half of an affected parent's children are likely to be affected. For example, if you have six children, the chances are that three of them will have porphyria too. Boys and girls stand an equal chance of being affected. Once the condition has entered a family, there is nothing that anyone can do about it. You cannot be blamed for having porphyria or for passing it on to your children!
People with AIP are at risk of developing the acute attack, and you should now read the section The Acute Attack in this booklet. If you have AIP, your skin will not be affected (unlike the other forms of porphyria) so the section The Skin in Porphyria is not relevant to you.
   

THE ACUTE ATTACK
People with AIP HC or VP are always at risk of an acute attack of porphyria. This may be very dangerous, and they should read this section carefully and make sure they understand how they can prevent such an attack. Those with PCT, EPP and CP are not at risk, and this section does not apply to them.
 
WHAT IS AN ACUTE ATTACT?
The acute attack takes place when the levels of the porphyrin precursors become very much raised for one or other reason. One can think of this as an overloading of the body with porphyrins and their precursors. During such an attack, the affected person may experience abdominal pain, cramps, constipation, nausea or vomiting. They may also show marked anxiety or disturbed behaviour. Such attacks can be bad enough to require admission to hospital, and the most severe cases may go on to weakness and paralysis. People have even died of such an attack. Fortunately, a fatal outcome has become rare as modern hospitals now have the facilities to treat such complications. This emphasises the need for people experiencing an acute attack to be admitted to an experienced hospital. It is more common nowadays for people with AIP or VP to develop milder forms of the acute attack with not much more than a feeling of being unwell, some pain in the stomach and, perhaps, nausea. If you are experiencing such problems, it is important that you immediately stop any medication you may be taking and consult your doctor. Yet everyone has some of these symptoms at one time or another and you cannot blame everything on your porphyria!
 
WHAT MAY BRING ON AN ACUTE ATTACK
Acute attacks may follow the use of many drugs. Porphyric people are unable to handle these drugs in the normal way and their bodies respond to them by overproducing porphyrins. This is the commonest cause of the acute attack. However, attacks can also be precipitated by alcohol, by an infection and even by dieting. Smoking has been shown to worsen attacks.
 
WHAT CAN I DO TO AVOID AN ACUTE ATTACK
You must understand that there are many medicines that can aggravate your porphyria, possibly resulting in an acute attack. Therefore, you must never take any medicine or remedy without checking that it is safe for porphyrics. This includes drugs given to you by a doctor, pharmacist or dentist, as well as those you can buy without prescription. Always consult our list (which you will find in this booklet) before you take the medicine given to you. Note that this includes tonics, herbal remedies and even the contraceptive pill, which has been a major factor in the development of acute attacks. If you ever need an operation, you must tell the surgeon and anaesthetist that you have porphyria, as some anaesthetic drugs in common use are very dangerous for porphyrics. Safer alternatives can be used. It is desirable to wear a Medic-Alert disc or carry a similar form of identification, so that doctors will know you have porphyria in the event of an accident. Finally, it is wise to eat regular meals and not to go without food for long periods, or to embark on 'crash' diets. Other than this, there is no special diet that needs to be followed. If you wish to lose weight, discuss your diet with your doctor beforehand. It is also best to avoid alcoholic drinks and to stop (or never start) smoking.

WHAT ELSE CAN BE DONE FOR PORPHYRIA?
Unfortunately, there now is no cure for porphyria. Still, there is a lot that you and your doctor can do to make it less severe. With a little care, your symptoms probably will be mild and you can live a normal life, as many porphyrics do. First, you must get an accurate diagnosis so that you can be absolutely certain you have porphyria and if so, what type. Speak to your doctor in this regard. Patients with PCT can be helped by avoiding alcohol or any other known cause of the condition. If the skin remains bad, relief can be obtained by venesection. This means having 500 ml. of blood removed at regular intervals - usually fortnightly - for about eight weeks. Your doctor will arrange this if necessary. People with EPP also must ensure that they have regular medical check-ups as their condition can eventually affect the liver. Regular examinations and blood tests will detect this at an early stage.
 

WHAT ABOUT MY CHILDREN?
If you have AIP, HC, VP or EPP, each child has a 50:50 chance of being affected. If they are affected, this is not a terrible thing! They will probably not be any more seriously affected than you - they may be milder. In fact, more than 50% of porphyrics do not show signs of the condition at all, though they may be positive on testing - these are known as latent cases. With sensible precautions, your children can live to a normal age, marry and have children themselves. Young children tend not to show signs of their porphyria till after puberty - that is, till after they reach sexual maturity. Laboratory tests usually do not even pick it up till then. An acute attack has developed on only very rare occasions in childhood - even before the tests are positive. Therefore, it is wise to make your children take all the same precautions you do, to minimise this risk.
 
 

  • DON'T ALLOW THEM TO HAVE ANY MEDICINES THAT ARE NOT SAFE IN PORPHYRIA AND DO WARN THE DOCTORS BEFORE THEY HAVE ANY ANAESTHETICS.

  • We suggest having your children tested every two years from the age of 12 until they turn 20 years. If the tests are still negative, then they will very likely be free of symptoms of porphyria after that. Unfortunately, a few people are silent cases - though their tests are negative, they carry the defective gene, and porphyria can be precipitated in them if they are exposed to the 'dangerous' medicines on our list. Therefore, the wisest suggestion is that no member of a porphyric family should take any such drug unless essential.
    It must be emphasised that it is essential to have your children adequately tested in a specialist laboratory.
     

    THE PORPHYRIAS:
    A MEDICAL GUIDE

    The Porphyrias are a heterogeneous group of either inherited or acquired disorders of haem biosynthesis. In these diseases, specific abnormalities of enzymes in the biosynthetic pathway cause generalised clinical abnormalities. They are classified, as shown below, into acute and non-acute porphyria.
     
    The effects of drugs are most important in the acute porphyria, which are examples of 'Toxico-genetic diseases'. Patients with the acute form of these disorders are at risk of developing life-threatening attacks of porphyria on exposure to certain commonly prescribed drugs. 'Toxico-genetic diseases' - are diseases, genetically acquired, which show an idiosyncratic reaction to drugs. All the acute porphyria are inherited as mendelian autosomal dominants, and each may be linked to lowered activity of one of the enzymes of the haem biosynthetic pathway: in Acute Intermittent Porphyria - a decrease in porphobilinogen deaminase: in Variegate Porphyria - a decrease in protoporphyrinogen oxidase, and in Hereditary Coproporphyria - a decrease in coproporphyrinogen oxidase.
     
    Features of the Acute Attack.
    Attacks of Acute porphyria vary in their clinical presentation. Severe abdominal pain, vomiting and constipation, with tachycardia and hypertension, are the commonest presenting features. Peripheral neuropathy may develop and lead to fatal respiratory paralysis. Tachycardia and hypertension are usually present, and hypertensive encephalopathy may develop. Besides hypertension, severe postural hypotension, resulting in syncope may occur. Hypertension may persist to some extent between attacks. Other manifestations of autonomic dysfunction, such as profuse sweating, pallor and pyrexia may also occur.
    Severe hyponatraemia, due to inappropriate secretion of antidiuretic hormone, complicates some attacks and sometimes presents as convulsions or deterioration in the conscious level. Another feature of involvement of the Central Nervous System is mental disturbance including agitation, mania, depression, auditory and visual hallucinations, and schizophrenic-like behaviour. Grand-mal convulsions are not uncommon at the height of an attack and may persist between attacks.
    In Variegate Porphyria, and in Hereditary Coproporphyria, there may also be skin involvement, with development of solar photosensitivity.
     
    Precipitating Factors
    It should be emphasised that most subjects who have inherited one of these diseases will enjoy normal health and go through life without any knowledge of his or her disorder or ever experiencing an acute attack. Such, is the latent phase of the disease. All porphyrics, however, are at risk of developing an attack if exposed to various precipitating factors. Drugs are the most common precipitating agents. Other factors that may trigger attacks, include alcohol ingestion, reduced caloric intake, due to fasting or dieting, and infection. We have also noted that smoking can cause more frequent attacks. Hormones are also important. Attacks are more common in females and, rarely, occur before puberty or after the menopause. Pregnancy and oral contraceptives may also precipitate attacks. Some women experience regular attacks, commencing in the week prior to the onset of menstruation. Although most of the drugs incriminated as porphyrinogenic are lipophilic and inducers of the hepatic mixed function oxidase system, it is impossible to reliably predict from chemical structure whether a drug will be safe for use in the porphyric patient.

    ACUTE PORPHYRIA -DIAGNOSIS:
    Acute porphyria should be considered in any patient presenting with unexplained abdominal pain, mental dysfunction or peripheral neuropathy. A further clue to the diagnosis is discolouration of the urine. During an attack, the urine is a dark reddish brown and this becomes more pronounced if it is left standing. A simple bedside test can confirm the diagnosis. Quantitative studies of the different porphyrins and precursors in the urine and faeces should be performed later by a specialist laboratory to identify the particular type of acute porphyria.
    Successful treatment of an acute attack of Porphyria depends largely on, early diagnosis, removal of precipitating factors, and provision of intensive supportive therapy. On first diagnosing an attack, a careful search should be made for any precipitating factors, and if possible, these should be removed. The patient's current drug therapy should be scrutinised and a search made for any underlying infection. When appropriate, a pregnancy test should be performed.
     
    Screening of Families
    Latent cases in affected families may be diagnosed, either by measurement of porphyrins and their precursors in urine, faeces and blood, or by measurement of the activities of the enzymes of the Haem biosynthetic pathway. Where such screening is required, most Analytical Laboratories, such as our own, prefer to receive samples of urine, stool and heparinized blood. Prophylaxis is extremely important. In particular, Drugs listed in the 'Unsafe Groupings' in Tables 1 and 2, should be avoided. Patients should also be counselled on the dangers of alcohol, smoking and dieting.
     
    A Preliminary Test for The Presence of Porphobilinogen in the Urine
    Equal volumes of Urine and Ehrlich's reagent (An acidic solution of p-dimethyl aminobenzaldehyde) are mixed in a tube. If the solution takes a pink colouration, this indicates the presence of porphobilinogen or urobilinogen. The presence of porphobilinogen may be confirmed by the addition of about 2 volumes of chloroform to the solution and shaking thoroughly. When the mixture is allowed to stand and separate the pink colouration should have remained in the upper aqueous layer. If it moves to the lower chloroform layer the colouration is due to urobilinogen and not porphobilinogen. When urobilinogen concentrations are high it may be necessary to repeat the extraction.
     
    MANAGEMENT OF THE ACUTE ATTACK:
    Specific therapies are few: these include the use of high carbohydrate intake and haematin infusion. Initially, steps should be taken to ensure an adequate carbohydrate intake. Most patients suffer from nausea and vomiting during an attack and their poor carbohydrate intake aggravates the disease process. This cycle must be broken. In mild attacks, this is achieved by ensuring an adequate oral intake of Glucose Polymer drinks, such as Caloreen (Roussel) or Hycal (Beecham Products). In patients experiencing more severe attacks, the constant slow infusion of Carbohydrate solution via a fine bore Teflon nasogastric tube, is helpful. If the symptoms are not controlled, an infusion of Haem Arginate should be considered.(See below). This treatment is still on trial and may be obtained from the appropriate drug company on a named patient basis.
     
    Symptomatic Therapy

    Pain:
    This is a feature of most attacks. When mild, it may be adequately controlled with aspirin, paracetamol or dihydrocodeine. For more severe pain, pethidine (meperidine), morphine or diamorphine may be required. Buprenorphine, which may be administered either sublingually or intramuscularly, is also useful. More constant pain relief may be achieved by the continuous intravenous infusion of analgesics. There is a danger of addiction in patients experiencing frequent attacks, who require large amounts of narcotic analgesics, and every attempt should be made to withdraw all narcotic drugs between attacks.
    In a few unfortunate patients, the pain is refractory to even very large doses of narcotic analgesics, and signs of respiratory and cardiovascular system depression appear before pain relief is obtained. Many of our patients report that the only time the pain goes away is when they are asleep. This observation may be used to advantage by encouraging sleep for several hours by combining chlorpromazine or promazine with the analgesics and leaving the patient undisturbed in a darkened room.
    Some patients continue to complain of chronic abdominal pain, unaccompanied by any other symptoms between attacks. This can be very difficult to manage, and the risk of narcotic addiction in these patients is high. Although, sometimes, a psychological overlay may be a factor - in others, the pain is clearly genuine and presumably a manifestation of residual neurological damage.
     
    Nausea, Vomiting and Constipation:
    These are frequent symptoms and may be controlled with chlorpromazine, promazine or prochlorperazine. As the narcotic analgesics used in controlling the pain often aggravate the nausea and vomiting, it is usually helpful to administer antiemetics with or shortly before the analgesics. Besides their antiemetic effects, chlorpromazine and promazine control the agitation and other psychiatric manifestations of the attack. In our experience, some porphyria patients develop extrapyramidal side-effects with phenothiazines, necessitating substitution with cyclizine hydrochloride. Constipation, where it occurs, may be severe - to the point of obstipation - and Neostigmine is beneficial in these circumstances.
     
    Tachycardia and Hypertension:
    These are present in most attacks. They are thought to be the result of sympathetic overactivity and should be controlled with propranolol. The dose can be titrated against its effect on the Cardiovascular System. Frequently very large doses are required. The pulse and blood pressure should be closely monitored, as they tend to be labile and hypertensive encephalopathy may develop. Postural hypotension, leading to syncope, may occur when a patient sits upright, even when the patient has been hypertensive in the supine position. When postural hypotension does occur, the supine blood pressure should still be adequately controlled with propranolol, taking care when moving the patient. Paroxysmal cardiac arrhythmias, sometimes leading to collapse, may also occur. These may be precipitated by the patient suddenly sitting upright. Whenever there is evidence of cardiovascular instability, continual ECG monitoring should be performed and full resuscitative facilities kept at hand.
     
    Convulsions:
    Convulsions are not infrequent at the peak of an attack. Their onset may be a sign of hyponatraemia, due to inappropriate antidiuretic hormone secretion, and plasma osmolality, and electrolyte values should be checked. If hyponatraemia is the underlying cause, it should be corrected by restricting fluid intake to not more than 700 ml. The onset of convulsions may also be a sign of hypertensive encephalopathy, and the blood pressure should be checked. Convulsions, occurring during the attack, usually disappear as the attack resolves and, therefore, therapy should be aimed at treating the underlying disease process.
    Some patients continue to experience convulsions while in remission. This presents a therapeutic dilemma. Phenobarbitone, primidone, phenytoin and carbamazepine all increase cellular haem utilisation by inducing the synthesis of hepatic monoxygenases, and are contraindicated. The benzodiazepines and sodium valproate are not inducers of the monoxygenases and, although they are porphyrinogenic in experimental models of porphyria, there is limited evidence that they are porphyrinogenic in man. Status epilepticus, in our own experience, has been treated successfully with intravenous diazepam. Seizure prophylaxis can be undertaken as a calculated risk with clonazepam or sodium valproate if this is essential, although sporadic clinical reports of porphyr- inogenicity do exist. Sodium bromide and magnesium sulphate are safe, but generally outmoded anticonvulsants.
     
    Neuropathy:
    All patients should be examined for evidence of developing peripheral neuropathy. This may progress rapidly, leading to quadriplegia and bulbar and ventilatory paralysis. The latter is heralded by weakening of the voice. When signs of peripheral neuropathy are present, the expiratory peak flow-rate should be monitored. If there is any reduction in this rate, the blood gases should be checked, and the patient nursed in an Intensive Care Unit with facilities for assisted ventilation. Even in patients in whom there is widespread paralysis requiring assisted ventilation for many months, good functional recovery can still be expected. Attention should be given to splinting of the joints and appropriate physiotherapy in the paralysed patient.
     
    Fluid and Electrolyte Balance:
    Various disturbances of fluid and electrolyte balance are seen during the acute attack. Dehydration may occur, owing to persistent vomiting. Hyponatraemia, secondary to inappropriate antidiuretic hormone secretion, may also occur, sometimes first becoming apparent after commencing intravenous fluids. The hyponatraemia can usually be controlled by restricting fluid intake. To maintain adequate carbohydrate intake while restricting fluid intake, it may be necessary to use higher concentrations of glucose, administered via a central venous line.
     
    SPECIFIC THERAPY OF THE ACUTE ATTACK:

    Haematin Therapy: ( Haem Arginate )
    So far we have concentrated on treating the acute attack by correcting any factors that may have precipitated it, and providing adequate supportive therapy while the attack spontaneously resolves. It is also possible to treat the underlying disease process more directly by administering the end product of the deranged pathway as intravenous haematin. In the liver, it is thought to supplement the depleted intracellular 'free haem pool', thus repressing the activity of the initial and rate-controlling enzyme of haem biosynthesis, ALA synthase, and reducing the overproduction of porphyrins and precursors formed prior to the enzyme block. In an acute attack of porphyria, the intravenous administration of haematin consistently reduces both the plasma concentration and the urinary excretion of porphyrin precursors. Its effect may be supplemented with inhibitors of the haem degradative enzyme, Haem oxygenase, such as Tin protoporphyrin.
    The clinical response to the therapy is more difficult to assess. In a disease characterised by spontaneous relapses and remissions, it is difficult to be sure whether improvement is the result of therapy or just the natural course of the disease. Our current impression is that haematin does curtail the clinical attack, and we frequently employ it.
    No major side-effects have been reported with haematin when used in the standard doses. Phlebitis, around the injection site, occurs in a few patients. This can be prevented by injecting the solution into a large peripheral vein or via a central venous line, or by administering the haematin, with human albumin solution, to which it will bind. During haematin therapy, there is a mild disturbance of coagulation, with prolongation of the prothrombin and partial thromboplastin times, and a slight reduction in the platelet count. This reverts to normal on completion of the haematin course, and has only very rarely resulted in haemorrhagic complications. As mentioned above coagulation indices and the platelet count should be monitored during therapy and haematin should not be used with anticoagulant therapy.
    Transient acute renal failure has been reported in one patient who received a bolus intravenous injection of 1000 mg of haematin. Yet, no renal complications have occurred with the standard recommended dosages, and even patients with renal insufficiency appear to tolerate haematin well, although it is probably wise to reduce the dosage slightly as an added precaution.
    A commercially available haematin preparations is:
    NORMOSANG ( Haem Arginate - Leiras)
     

    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:-
     

    • 1. Direct prophylactic measures against the vector instead of the parasite, thus reducing the risk of an infected bite. This has been shown to reduce the risk of contracting malaria considerably and entails: (i) visiting malarial areas in the dry rather than the wet season; (ii) staying in towns rather than the bush; (iii) covering up with long sleeves and trousers at sundown; (iv) liberal use of insect repellants, both on the person and in the environment; (v) the use of mosquito coils; (vi) proper use of mosquito netting.

        2. The visitor should be advised to carry a course of quinine sulphate tablets at all times and be instructed on the possible symptoms of malaria, particularly pyrexia, backache, nausea and headache. A course of quinine should be commenced at the first sign of an illness and medical support sought as quickly as possible.

    Such an approach is favoured by some authorities as a general strategy against chloroquine resistant malaria and hence, if applied to porphyrics, as outlined, does not represent a major departure from current thinking.
    What of treatment of established malaria in porphyric patients? The course here is clear: They should receive quinine sulphate alone; this will be efficacious against chloroquine resistant malaria and is of proven safety in porphyria. Finally, where malaria, other than Falciparum, is suspected, primaquine may safely be employed to eradicate the exo-erythrocytic cycle of these parasites.


    Complete Text Of This Document Can Be Found At:
    http://www.uq.edu.au/porphyria/