Porphyria Cutanea Tarda

Porphyria Cutanea Tarda: Description, Types, and Treatment

Porphyria cutanea tarda, the most common form of enzymatic disorders known as porphyrias, afflicts about 1 in 25,000 of the world’s population. Generally, four out of five people are afflicted with due to genetics while one out of five has an “acquired form” of the disease.

Porphyrias are defects, inherited or acquired, found in the heme biosynthetic pathway, or in the process in which the body produces heme, which is a major component of many blood proteins, notably hemoglobin and myoglobin. Porphyria is caused by lack of specific enzymes in the heme biosynthetic pathway. Without these enzymes, the precursors of heme, porphyrins, accumulate at the body until it reaches toxic levels. In porphyria cutanea tarda, the specific enzyme absent is uroporphyrinogen (URO) decarboxylase, the fifth enzyme required in the heme biosynthetic pathway.  URO decarboxylase is necessary to convert uroporphyrinogen, a porphyrin, into coproporphyrinogen III.

In sporadic (type I) porphyria cutanea tarda, the URO carboxylase deficiency is found only in liver cells. There is no URO carboxylase deficiency in the UROD gene. Factors that contribute to this are mutations in the HFE gene, a gene which regulates iron absorption, alcohol consumption, which damages liver cells and Hepatitis C infection.

In familial (type II) porphyria cutanea tarda, a mutation at the gene at the UROD locus is responsible for the synthesis of uroporphyrinogen decarboxylase; the mutation turns the normal gene to a gene capable only of making small amounts of functioning URO carboxylase. The abnormal gene is passed down in an autosomal dominant manner. While it does not totally prohibit the body from making URO carboxylase, it does reduce its production drastically, and while many with type II porphyria cutanea tarda are asymptomatic, symptoms occur upon accumulation of uroporphyrinogen.

The signs and symptoms first manifest as photosensitive blisters in parts of the body which are exposed to the sun. Usually, these blisters are found in the face, hands, lower arms, and lower legs. Other skin symptoms include greater fragility; hyperpigmentation, caused by an accumulation of porphyrin that ‘tans’ the skin; and hypertrichosis, which is abnormal hair growth on various parts of the body. Since the disorder is chronic, symptoms often occur and then recede, then occur and then recede again, depending on whether the patient is exposed to risk factors or not. Liver ailments like cirrhosis, inflammation, and fibrosis occur mainly in persons with Type I porphyria cutanea tarda; they also occur in those with the type II variant, but to a lesser extent.

Diagnosis involves urinalysis and fecalysis to detect high amounts of the uroporphyrinogen. Also, testing is done for Hepatitis C and hemochromatosis, as these two conditions are highly associated with porphyria cutanea tarda, and require treatment as well. Positive skin manifestations with negative laboratory results (no uroporphyrinogen in urine and stool, negative for many risk factors), however, could be an indication of the closely related condition pseudoporphyria.

Treatment consists of avoidance of risk factors, like alcohol, iron supplements, sunlight exposure, and estrogen. Excess iron can be removed through phlebotomy; excess porphyrins can be removed by taking antimalarials like quinine. Also, treatment of the main disease may also entail treatment of other associated conditions, like Hepatitis C.