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Dealing With Recurrent Attacks of Porphyria

DEALING WITH RECURRENT ATTACKS OF PORPHYRIA

With the exception of porphyria cutanea tarda, which is treatable, all porphyrias are by definition chronic illnesses since the underlying inherited abnormality cannot be corrected. Yet despite this, chronic ill health as a result of porphyria is very rare indeed. Most patients, with care and an understanding of their illness, live fulfilling and healthy lives. This is particularly true in the case of variegate porphyria, where chronic ill effects are usually limited merely to skin disease. In most cases, effective diagnostic testing in the patient with variegate porphyria who is said to have chronic abdominal or neuropsychiatric symptoms symptoms will indicate that the porphyria is not responsible for the symptoms. By contrast, some female patients with acute intermittent porphyria have a problem of recurrent acute attacks (usually interspersed with asymptomatic periods of weeks or months). Very occasionally, the attacks are frequent enough to result in chronic, debilitating ill health.


PATTERNS OF CHRONIC OR RECURRENT PORPHYRIA

Typically patients subject to chronic or recurrent porphyria have repeated, stereotyped, discreet episodes typical of the acute attack. These are bouts of severe abdominal pain with reddening of the urine lasting several days at a time, with intervening periods (usually weeks to months) of complete freedom from symptoms in between. Such patients are usually female and have acute intermittent porphyria. Some of these may show a typical periodicity suggesting a correlation with the menstrual cycle. In menstrual-related porphyria, symptoms classically begin 1 to 2 days before the onset of the menstrual period. Recurrent acute attacks are rare in males, and frequently an obvious precipitating cause is present, such as habitual use of porphyrinogenic drugs including alcohol and cannabis.


CONFIRMATION OF PORPHYRIA AS THE SOURCE OF SYMPTOMS

Prove the presence of recurrent acute attacks and of the acute attack

Not infrequently patients are mistakenly diagnosed as having porphyria on the basis of repeated presentations with non-specific symptoms such as chronic abdominal pain, constipation, drug tolerance and psychiatric symptoms. This mistaken diagnosis may have been aggravated by suboptimal laboratory testing. The first step therefore is to perform proper laboratory testing for porphyria as described in Diagnosing porphyria: patients with suggestive symptoms. Even where porphyria is unequivocally proven, this alone is not enough to prove that recurrent symptoms are porphyria-related. This must the confirmed in the laboratory by demonstrating elevated urine ALA, PBG and porphyrins during periods of symptoms, with remission in between.


MANAGEMENT

Remove any obvious precipitating cause. Any unsafe drug the patient is taking must be stopped. Particularly important in the case of males are drugs of abuse such as alcohol and cannabis.

Patients with an established pattern of proven, recurrent attacks

The most important step is to establish a routine whereby the patient is admitted immediately symptoms begin and receives haem arginate without delay (and before serious complications can supervene): such patients can then be guaranteed discharge, well in 3-4 days. Such a routine is absolutely essential in the case of the severe patient with a tendency to develop neuropathy. Provided they receive early treatment, the pre-existing neuropathy will continue to improve over months. If early treatment is not received, the neuropathy will relapse with each episode and continued improvement is impossible.

Females with menstrual-related attacks

If attacks are infrequent (3-4 times per year) it may not be necessary to do any more than establish a system whereby the patient is admitted and the attack promptly terminated with haem arginate. If attacks are more frequent, it is worth considering menstrual suppression with gonadotrophin releasing hormone agonists. (Read Use of GnRH agonists in the acute porphyrias). We prefer not to prescribe menstrual suppression for patients with a"manageable" frequency of menstrually-induced attacks, because of the inevitable development of osteoporosis and other effects of a functional premature menopause.

Severe recurrent acute attacks

A tiny minority of all patients develop severe acute attacks at such frequent intervals that they are more or less permanently hospitalised. An option, which has been undertaken in extreme cases, is liver transplantation, which appears to cure AIP. We presume that the donor PBG deaminase in the transplanted organ is able to correct the metabolic disturbance of the porphyria.

Very rarely, haem arginate appears to become progressively less effective when administered at frequent intervals, probably as a result of tolerance. Experimental treatments such as the use of tin protoporphyrin may be considered in these patients. Read Use of tin protoporphyrin to suppress severe, recurrent acute attacks of porphyria.