A Case-Based Review of Iron Overload With an Emphasis on Porphyria Cutanea Tarda, Hepatitis C, C282Y Heterozygosity, and Coronary Artery Disease
Sporadic porphyria cutanea tarda (PCT) is the most common cause of porphyria worldwide.1,2 Unlike other forms of porphyria, PCT usually is an acquired disease precipitated by extrinsic risk factors that commonly include excessive alcohol consumption, smoking, and chronic hepatitis C virus (HCV) infection. Additional risk factors include myeloproliferative disorders, exposure to polyhalogenated compounds, estrogen therapy, diseases of iron overload like hereditary hemochromatosis (HH), and potentially, HIV infection.1-3
In this case report, we present a patient with an iron overload (due in part to an HFE gene mutation) and concomitant PCT,
Case Presentation
Mr. M is a 59-year-old white male of Irish background with a medical history that includes coronary artery disease. He is status post ST-elevation myocardial infarction and percutaneous coronary intervention with placement of 2 drug-eluting stents. Additional medical issues include PCT and HCV infection with cirrhosis. He is an active smoker.
The patient has a long history of developing blisters with minor trauma, such as rubbing against his mattress/bed sheets or bumping into doors. These blisters primarily occur on his upper extremities, but also can occur on his face after shaving. Mr. M was diagnosed with HCV infection in 1979 while on active military duty. At that time, he had an acute HCV infection and jaundice that required a prolonged hospitalization. He reported no IV drug use and that many others on his military base had similar manifestations. He drinks 1 to 2 beers daily, but reports no binge drinking.
His laboratory studies were notable for ferritin, 2,069 ng/mL; serum iron, 317 mcg/dL; total iron binding capacity, 320 mcg/dL; transferrin, 239 mg/dl; liver function test alanine aminotransferase, 151 U/L; aspartate aminotransferase, 159 U/L; total bilirubin, 1.73 mg/dL; albumin, 3.6 g/dL; alkaline phosphatase, 119 U/L; INR, 1.1; and transferrin saturation, 99%. Mr. M’s HCV viral load was 28,700 IU/L with genotype 1b. Hemochromatosis genetic studies were notable for a heterozygous C282Y gene mutation and negative for H63D and S65C mutations. He repeatedly declined completing a 24-hour urine study of porphyrins. Ultrasonography was consistent with cirrhosis and splenomegaly. The patient was treatment naïve for HCV. He declined multiple offers for treatment of his HCV, citing financial considerations.
Porphyria Cutanea Tarda
The pathogenesis of PCT is related to the intrahepatic deficiency of uroporphyrinogen decarboxylase (UROD), an enzyme in the heme biosynthetic pathway (Figure 1). Decreased activity of UROD leads to accumulation of uroporphyrinogen and its derivatives, which most likely are oxidized in presence of cytochrome P450 1A2. Up to 80% of PCT cases are sporadic, in which the deficiency of UROD is acquired by exogenous risk factors as mentioned above. However, the remaining 20% of PCT cases are due to an autosomal dominant mutation of UROD that causes the partial deficiency (up to 50%) of UROD. In these cases, additional risk factors are needed to decrease UROD activity to < 75% for symptoms to occur.
