Page 587 - Hematology_ Basic Principles and Practice ( PDFDrive )

502 Part V Red Blood Cells

Precipitating Factors in Acute Porphyria TABLE Precipitating Factors in Acute Porphyria
38.4
Most patients who have inherited acute porphyria enjoy normal health
and go through life without any knowledge of their disorder or ever Drugs Other Stimuli
experiencing an acute attack. All porphyric patients, however, are Alcohol Fasting or dieting
at risk for developing an attack if exposed to various precipitating
factors. Drugs are the most common precipitating agents. Other factors Barbiturates Hormones, stress
that may trigger attacks include alcohol ingestion, reduced caloric Angiotensin-converting enzyme (ACE) inhibitors Smoking
intake (from fasting or dieting), and infection. Smoking can cause Anticonvulsants
more frequent attacks.
Hormonal status is also important. Attacks are more common in Antidepressants
females, and they rarely occur before puberty or after menopause. Calcium channel blockers
Although generally uncomplicated, pregnancy in addition to oral con-
traceptives may precipitate attacks. Some women experience regular Cephalosporins
60
attacks, commencing in the week before the onset of menstruation. Ergot derivatives
These may require luteinizing hormone–releasing hormone (LH-RH)
antagonists for control (Table 38.4). Erythromycin
Drugs for Porphyria Steroids or anabolic steroids
Before prescribing any medication to a porphyric patient, advice must Contraceptives, hormone replacement therapy
be sought from an appropriate specialist. Full drug lists are avail- Sulfonamides
able on the Internet at www.porphyriafoundation.com (in the United
States) and www.porphyria-europe.com (in European Union countries, Sulfonylureas
South Africa, and Canada), and a guide for drug prescription at
www.drugs-porphyria.org. It should be borne in mind that such lists are
far from encyclopedic, that new drugs are constantly being introduced
to the pharmacopeia, and that any form of combined preparation must
be viewed with suspicion, because little is known about metabolic
61
interactions in these diseases. More details of such use and side
effects of drugs can be sought from the literature. 62

Acute Intermittent Porphyria
Clinical and Laboratory Manifestations

Acute intermittent porphyria is the most severe of the acute porphyr-
ias. During an attack, patients display abdominal and neuropsychiatric
or neurovisceral disturbances. Onset occurs in puberty; female
patients exhibit a fourfold greater incidence of attacks than males.
Attacks occur mainly in young adults and become less frequent after
57
menopause. It is uncommon to see attacks in children. Crises may
vary in duration from several days to months. They are most com-
monly followed by complete remission, although deaths are still Fig. 38.4 BILATERAL WRISTDROP CAUSED BY PERIPHERAL NEU-
58
reported, especially with AIP (see box on Precipitating Factors in ROPATHY IN A PATIENT WITH ACUTE INTERMITTENT
Acute Porphyria). Late complications of AIP include renal impair- PORPHYRIA.
ment, hypertension, and hepatocellular carcinoma, and patients
should be monitored for these complications. 59
Gastrointestinal symptoms occur in 95% of cases; most patients Severe anxiety, depression, and frank psychosis are the main psy-
present with acute colicky central abdominal pain. Examination chiatric manifestations of porphyric attacks. These psychiatric mani-
reveals tenderness but little rigidity, and patients may also experience festations may result in a patient being misdiagnosed as suffering
limb pain or generalized muscular aches. Severe vomiting may occur, from a primary psychiatric disorder. Agitation, mania, depression,
and constipation is usual. Hyponatremia occurs in severe attacks. hallucinations, and schizophrenic-like behavior may occur. Psychiat-
63
Motor neuropathy complicates two-thirds of porphyric attacks ric manifestations may persist between attacks. Quality of life is
and may be the presenting feature. Motor involvement is most severely affected in those suffering from repeated attacks of acute
common, but paresthesias may also occur. Paralysis usually starts porphyria. 64
peripherally and then spreads proximally; however, in some patients, The cardiovascular system is involved in approximately 70% of
shoulder girdle involvement may be the first manifestation. The attacks. Sinus tachycardia (to 160 beats/min) and hypertension can
neuropathy may progress rapidly, resulting in respiratory insufficiency. occur; these elevations usually revert to normal after an attack. There
Weakness, usually symmetric, involves proximal and distal limb is evidence that hypertension may occasionally be permanent, even
muscles more often than those of the trunk. Upper limbs and proxi- in latent cases of AIP (see box on Differential Diagnosis of Acute
mal muscles are often affected. Involvement of the wrists, ankles, and Intermittent Porphyria).
small muscles of the hand may lead to a permanent deformity (Fig.
38.4), and trunk muscle weakness can lead to respiratory embarrass-
ment. Death is usually caused by respiratory paralysis. Progressive Other Acute Porphyrias
weakening of the voice may suggest this; treatment requires trache-
otomy and intermittent positive pressure ventilation. Paresthesias, Hereditary Coproporphyria
numbness, and objective evidence of sensory impairment may occur
with loss of pinprick sensation, which is most marked around the Hereditary coproporphyria combines the clinical features of acute
shoulder and hip areas; generalized tonic-clonic seizures occasionally porphyria with photosensitive skin manifestations. It results from
occur. various mutations in the gene encoding coproporphyrinogen oxidase,