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/ |
