Porphyria Cutanea Tarda and Hemochromatosis in Spain

Abstract

To the Editor: We present the case of a 31-year-old woman with no relevant medical history, who consulted because of lesions on the backs of the hands related to minor traumas; the lesions worsened in the summer leaving residual hyperpigmentation (Figure). The patient had phototype III skin and displayed discrete hypertrichosis in the zygomatic areas. Photosensitive dermatosis was suspected and a battery of tests was requested to measure liver function, serum iron, transferrin and ferritin levels, blood and urine porphyrins, and photosensitivity. High levels of porphyrins were found in the 24-hour urine collection: 2104 µg/L (normal values: <200 µg/L), 85 % of which were uroporphyrins. Levels of porphyrins in the plasma were 25 µg/L, exceeding the normal range (< 10 µg/L). Levels for serum iron were 2104 µg/L (normal values: 92-155 µg/ dL); transferrin: 310 mg/dL (normal values: 205-365 mg/dL); and ferritin: 175 µg/mL (normal values: 13-160 µg/mL); all of which were high or at the upper limit of the accepted normal range. Liver ultrasound showed no abnormalities. A diagnosis of porphyria cutanea tarda (PCT) was reached on the basis of the symptoms, clinical indicators, and test results. The patient reported no family history of skin lesions or liver disease. Oral contraceptives (OC) taken by the patient for 6 months prior to consultation were initially considered a possible trigger for the PCT, but the lesions continued to appear after this medication was suspended. There were no other apparent triggers as the patient was not a habitual drinker and tests for hepatitis were negative. Genetic studies for the most common hemochromatosis mutations (C282Y, H63D) showed the patient to be heterozygous for C282Y. This could explain the discreet abnormalities seen in the iron metabolism and, in conjunction with the use of OC, could have contributed to her developing PCT. In view of the patient’s wish to start a family, her husband was tested for hemochromatosis. He was found to be heterozygous for the H63D mutation. Treatment consisted of phlebotomies at 2 week intervals and this led to remission of the skin lesions and a return to normal porphyrin levels in both plasma and urine. We were unable to determine the enzymatic activity of erythrocyte uroporphyrinogen decarboxylase (URO-D) as follow-up of the patient was incomplete. PCT is the outcome of a deficit in or inactivation of the URO-D enzyme, resulting in the accumulation of photosensitive metabolites that are excreted in the urine and feces. 1 There are three main types of PCT: I, II, and III. 2 Type I—the sporadic variety—is most common, with inactivation limited exclusively to the liver in patients with no previous family history. Type 2—the familial variant— is characterized by the inactivation or deficiency of the URO-D enzyme in all tissues. Type III is characterized by inactivation in the liver where there has been some previous family history of the condition. Onset tends to occur in adulthood, and there are several known triggers: viral hepatitis, alcohol, OC and hormone replacement therapy, polychlorinated hydrocarbons, hemodialysis, and situations leading to iron overload like hemochromatosis. 3,4 The most common trigger varies according to age, sex, and geographical location. In men, alcohol abuse and chronic viral hepatitis are the most common triggers, while in women, hormone therapy is the single factor implicated in a large percentage of cases. Exposure to hydrocarbons has been identified as a trigger in developing nations, while infection by the hepatitis C virus is a more common element in the Mediterranean and Latin American countries. 2 Hemochromatosis is a autosomal recessive genetic condition with a prevalence of 1/200. 5 It is characterized