Disorders In-Depth
Cutaneous Porphyrias
Cutaneous porphyrias primarily affect the skin. Areas of skin exposed to the sun become fragile and blistered, which can lead to infection, scarring, changes in skin coloring (pigmentation), and increased hair growth. Cutaneous porphyrias include congenital erythropoietic porphyria, erythropoietic protoporphyria and X-linked protoporphyria, porphyria cutanea tarda, and hepatoerythropoietic porphyria.
Porphyria Cutanea Tarda (PCT)
Porphyria cutanea tarda (PCT) is the most common type of porphyria, with a prevalence of approximately 1 in 10,000. PCT develops when the activity of the enzyme uroporphyrinogen decarboxylase (URO-decarboxylase) becomes severely deficient (less than 20% of normal) in the liver. In most cases these patients do not have URO-decarboxylase gene mutations and are said to have sporadic (or Type I) PCT (sPCT), About 20 percent of cases have familial (or Type II) PCT (fPCT). Such individuals have inherited a URO-decarboxylase gene mutation from one parent, which has reduced the amount of URO-decarboxylase in all tissues to 50% of normal from birth. However, to develop symptoms, other factors must be present to reduce URO-decarboxylase level in the liver to less than 20% of normal. Such fPCT patients may develop blisters at an early age or have relatives with the disease. Excess iron and multiple other susceptibility factors contribute to the development of PCT. These include use of alcohol or estrogens, smoking, chronic hepatitis C, HIV (human immunodeficiency virus), and mutations of the HFE gene which is associated with the disease hemochromatosis. Other factors remain to be identified. A URO-decarboxylase inhibitor generated only in the liver accounts for the severely deficient enzyme activity in PCT.
Symptoms
In PCT the cutaneous blisters develop on sun-exposed areas of the skin, such as the hands and face. The skin in these areas may blister or peel after minor trauma. Increased hair growth, as well as darkening and thickening, of the skin may also occur. Neurological and abdominal symptoms are not characteristic of PCT.
Liver function abnormalities are common, but are usually mild. PCT is often associated with hepatitis C infection, which also can cause these liver complications. However, liver tests are generally abnormal even in PCT patients without hepatitis C infection. Progression to cirrhosis and even liver cancer occurs in some patients.
Diagnosis
The diagnosis of PCT is made by demonstrating a substantial elevation of porphyrins in urine or plasma, with a predominance of uroporphyrin and heptacarboxylporphyrin. PBG is normal and ALA may be slightly elevated. Fecal porphyrins may be normal or somewhat increased, with a predominance of isocoproporphyrins. Patients with f-PCT usually have no family history of the disease, but can be recognized by finding half-normal URO-decarboxylase activity in red blood cells, or preferably by DNA studies. In all patients, it is important to look for all known susceptibility factors, as this affects management.
Treatment and Prognosis
PCT is the most treatable of the porphyrias. Treatment seems to be equally effective in f-PCT and s-PCT. Factors that tend to activate the disease should be removed. The most widely recommended treatment is a schedule of repeated phlebotomies (removal of blood), with the aim of reducing iron in the liver. The target of this treatment is a serum ferritin near the lower limit of normal. Another treatment approach is a low dose regimen of the drug hydroxychloroquine. This mobilizes porphyrins from the liver with some concurrent hepatotoxicity that is minimal with a low-dose regimen. Recurrences can be treated in the same manner.
PCT is difficult to treat while the patient is also being treated for hepatitis C with interferon and ribavirin. Therefore, PCT is generally treated first. Patients with marked iron overload should be treated by phlebotomy rather than hydroxychloroquine. PCT is often more severe and difficult to treat in patients with end-stage renal disease. Iron supplements should be stopped and erythropoietin administered to support small volume phlebotomies to reduce the serum ferritin level. Hydroxychloroquine is not effective in this setting.
