Symptomatic Therapy

Symptomatic Therapy

Patients with acute attacks usually have symptoms that may necessitate medication or other therapies. Pain is typically severe, often requiring opiate analgesics for control; morphine, meperidine, or other opiates in normal doses may be used. For insomnia, chloral hydrate or benzodiazepines can be used. Chlorpromazine (Thorazine), up to 25 mg three or four times a day, can be given for major psychologic symptoms.
Seizures, which may occur during acute attacks, should not be treated with phenytoin or barbiturates because they are porphyric attack-precipitating drugs. Diazepam (Valium) and clonazepam (Klonopin) are probably safe and can be used in appropriate doses. Peripheral motor neuropathy tends to resolve slowly, with improvement to normal over weeks or months. Thus, it should be treated with effective physiotherapy and, if respiratory muscles are involved, with mechanical ventilation.

Prevention of Acute Attacks

After an acute attack the patient must be informed about precipitating factors to prevent future episodes. A list of unsafe drugs should be provided, and avoidance of alcohol consumption should be emphasized. Some authors recommend more strict regulation of dietary intake, e.g., a carbohydrate intake of 55 to 60% of total energy intake, but there is no evidence that this regimen improves the outcome. Our policy is to instruct the patient to avoid fasting or vigorous weight reduction but otherwise not to regulate food intake.
A few female patients with acute porphyria may have frequent symptoms associated with menstrual cycles. The symptoms usually develop during the premenstrual phase. Various hormonal manipulations have been tried for prevention of symptoms. Exogenous estrogens and progestins, e.g., oral contraceptive pills, have been reported to prevent attacks in some patients. These agents must be administered with caution, because female sex hormones are also regarded as precipitating drugs. In some patients, symptoms can be prevented by using gonadotropin-releasing hormone analogues. If there is a good response to one of these agents for several months, low doses of estradiol can be added to control the adverse effects of inadequate endogenous estrogens. Hormonal treatment for cyclical attacks is seldom needed for more than 1 to 3 years, which suggests that such attacks do not occur throughout the reproductive period of life. If hormonal manipulation does not control cyclical attacks, prophylactic heme administration can be used. The dose of heme in the prophylactic use is not established, but most treatment centers administer one infusion of 3 mg per kg weekly or, in milder cases, biweekly. An alternative approach is to administer heme only during the luteal phase of the cycle if the symptoms occur regularly premenstrually.
Management of acute attacks does not require identification of the exact type of acute porphyria, because the treatment and prevention are the same in all three types of acute porphyria. Prevention of attacks also includes evaluation of family members to find asymptomatic individuals with porphyria. In the asymptomatic phase, each of the acute porphyrias (acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria) has characteristic biochemical findings. Thus, choosing appropriate laboratory tests for screening family members calls for precise identification of the type of porphyria. Biochemical tests identify most asymptomatic individuals with porphyria, but normal results do not exclude porphyria. The genes coding for the enzymes of heme biosynthesis are known, and various mutations have been described in patients with all three types of acute porphyria. Because of genetic heterogeneity, no universal DNA tests are available for acute porphyrias, but whenever the mutation is known a DNA analysis is the method of choice to diagnose or exclude porphyria among family members.
Also, asymptomatic family members should be informed about precipitating factors. Susceptibility to precipitating agents varies greatly, and many persons with latent porphyria tolerate them without harm. For that reason, in porphyric individuals who previously have been asymptomatic, strict avoiding of all drugs listed as unsafe is not necessary. Thus, for example, moderate alcohol intake is not necessarily prohibited, and contraceptive pills or postmenopausal hormone preparations can be allowed when appropriate.

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