Porphyria cutanea tarda

Porphyria cutanea porphyria is the most common type of porphyria in the United States and Europe. Onset is usually during the fourth or fifth decade of life, and the disorder is manifested mainly as cutaneous symptoms and hepatopathy. Characteristic skin lesions are blistering and erosions on sun-exposed areas, mainly on the backs of the hands. Porphyria cutanea tarda is usually associated with chronic liver disease. Many patients consume excessive amounts of alcohol, and there is a high prevalence of hepatitis C infection among patients with porphyria cutanea tarda. In susceptible persons, hepatic siderosis is a common histopathologic finding, and accumulation of iron plays a pathogenetic role, probably by inhibiting uroporphyrinogen decarboxylase. In many countries, patients with porphyria cutanea tarda have an increased prevalence of genetic hemochromatosis, some 35 to 45% being heterozygous and 10 to 15% homozygous for major hemochromatosis mutations.

The main biochemical feature in porphyria cutanea tarda is massive overproduction of uroporphyrin. Urinary excretion of uroporphyrin in symptomatic patients is usually more than 2000 nmol per 24 hours (the normal value is less than 100 nmol). Other diagnostic characteristics are increased urinary 7-COOH porphyrin excretion, increased fecal isocoproporphyrin content, and a typical pattern in the plasma fluorescence spectrum.

Treatment

Predisposing factors such as alcohol, iron supplements, and estrogen preparations should be eliminated. In some cases this may result in clinical and biochemical remission.
Two specific and effective treatments for porphyria cutanea tarda are known, namely, iron removal by phlebotomy and low-dose chloroquine therapy. There is no general agreement on which is preferable; the use of chloroquine is more frequent in many European countries than in the United States, where chloroquine is recommended only if phlebotomy is contraindicated. In patients with significant iron overload, phlebotomy is the preferred therapy; in other cases, either treatment may be efficacious. Combination therapy with chloroquine and phlebotomy has also been reported to be useful.
In phlebotomy, 400 to 500 mL of blood is removed at weekly or biweekly intervals until the blood hemoglobin concentration falls to 100 to 110 grams per liter. Usually, 4 to 10 liters of blood must be removed before therapeutic effects are seen. Measurement of urinary excretion of uroporphyrin or total porphyrins is useful for monitoring the therapeutic effect, and phlebotomies can be discontinued when uroporphyrin excretion falls below 500 nmol per 24 hours. Clinical remission occurs usually within 6 months and biochemical remission within 12 months.

In low-dose chloroquine therapy, chloroquine (Aralen) or hydroxychloroquine (Plaquenil) is administered orally 125 mg twice a week. The time needed for clinical and biochemical remission is usually the same as with phlebotomies.
After remission induced by phlebotomy or chloroquine, a relapse usually occurs within 1 to 2 years. Clinical relapse can be predicted by monitoring urinary excretion of porphyrins at intervals of 3 to 6 months. Treatment can be started if porphyrin levels are increasing (e.g., with uroporphyrin levels of 500 to 1000 nmol per 24 hours), which will prevent the occurrence of clinical manifestations.

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