Ulrich Stölzel, MD (1); Erich Köstler, MD (2); Detlef Schuppan, MD (3); Matthias Richter, MD (1); Manfred O. Doss, MD (4); Uwe Wollina, MD (2)

1 Department of Medicine II, Klinikum Chemnitz, 2 Department of Dermatology, Hospital Dresden-Friedrichstadt, Dresden, 3 Department of Medicine I, University of Erlangen-Nuernberg 4 Division of Clinical Biochemistry, University of Marburg, Germany

Background: Porphyria cutanea tarda (PCT) is caused by decreased activity of the enzyme uroporphyrinogen decarboxylase in the liver. Alcohol, hormones, drugs, iron and viral infections are known trigger factors responsible for the precipitation of PCT and the associated hepatic alterations.

Methods: Over a period of 20 years we studied a cohort of 207 patients with PCT, skin symptoms, liver injury and urinary uro-and heptaporphyrin excess on whether hepatitis B and C, HFE mutations (C282Y and H63D), liver and serum iron, diabetes, autoantibodies, drugs and alcohol consumption might have an influence on the clinical course, urinary porphyrin excretion, liver enzyme activities (ALT, AST), serum collagen peptides (PNIIIP, CVI) and histological abnormalities. Most of the patients were treated with low dose chloroquine diphosphate 125-250 mg twice weekly.

Results: Eight % of the PCT patients tested positive for hepatitis C and 13% for hepatitis B virus antibodies. The majority (61%) carried HFE mutations. The prevalence of diabetes mellitus type II was increased (15%) and autoantibodies (ANA, ASMA) were found significantly less common than in controls.

Serum and liver iron, serum ferritin and collagen peptide (PNIIIP) levels, and liver enzyme activities (ALT, AST) correlated significantly with urinary porphyrins and the clinical stage (overt, remission, relapse). Using multivariate regression analysis urinary porphyrins were found to strongly predict liver damage as reflected by elevated liver enzymes  (p< 0.0001).

Chloroquine therapy was accompanied by clinical remission and reduced urinary porphyrin excretion (p < 0,001) among patients with both HFE wild type as well as in HFE heterozygous patients with PCT. Patients homozygous for the C282Y mutation (5%) failed to respond to chloroquine treatment.

Conclusions: Our findings confirm the multi-factorial pathogenesis of PCT.  Increased urinary porphyrins strongly correlate with serum markers of liver fibrosis and liver damage. Simple or compound heterozygosity of HFE mutations did not affect the therapeutic response to chloroquine in PCT. Since HFE C282Y homozygotes did not respond to chloroquine, phlebotomy should be first-line therapy in patients with PCT and HFE-mutations.