Stölzel U1, Richter M1, Schuppan D2, Doss MO3, Wollina U4, Wittekind C5, Tannapfel A5, Köstler E4
1Department of Medicine II, Klinikum Chemnitz, 2Department of Medicine I, University of Erlangen-Nürnberg, 3Division of Clinical Biochemistry, University of Marburg, 4Department of Dermatology, Hospital Dresden-Friedrichstadt, Dresden, 5Institute of Pathology, University of Leipzig, Germany
The role of HFE gene mutations, which are associated with porphyria cutanea tarda (PCT), on the therapeutic response to chloroquine is unknown. We retrospectively analyzed a data base of chloroquine-treated patients with PCT on whether HFE mutations (C282Y and H63D) might have influenced the clinical response, urinary porphyrin excretion, liver enzyme activities and serum iron markers. Sera and corresponding complete sets of data before and after therapy were available in 62 of 207 patients with PCT who were treated exclusively with chloroquine. For treatment low dose chloroquine diphosphate, 125-250 mg twice weekly, was used during a median time of 16 months (range, 12-26). The majority (37/62=61%) of German PCT patients carry HFE mutations. Chloroquine therapy was accompanied by clinical remission and reduced urinary porphyrin excretion (p<0.001) in the 24 (39%) patients with HFE wild type as well as in 34 (55%) HFE heterozygous patients with PCT. Decreases of serum iron markers following chloroquine therapy were limited to patients with PCT and HFE wild-type. All patients homozygous for the C282Y mutation (3/62=5%) had high serum iron, ferritin and transferrin saturation and failed to respond to chloroquine treatment. In conclusion, C282Y heterozygosity and compound heterozygosity of HFE mutations did not compromise the therapeutic response to chloroquine. Since HFE C282Y homozygotes (+/+) did not respond to chloroquine and decrease of serum iron markers was limited to patients with PCT and HFE wild-type, phlebotomy should be first line therapy in patients with PCT and HFE-mutations.