Porphyria Cutanea Tarda: Effects and Risk Factors for Hepatotoxicity from High-dose Chloroquine Treatment

Abstract

High-dose chloroquine therapy for porphyria cutanea tarda is rarely used now because of its hepatic side-effects. The mechanisms of the effects and side-effects are poorly understood. We describe here effects, side-effects and long-term follow-up in 57 patients with a first-time diagnosis of porphyria cutanea tarda treated with 1-3 phlebotomies followed by 250 mg chloroquine phosphate daily for 7 days. A hepatotoxic reaction with high serum aminotransferases occurred in almost all patients. Within 3 months, clinical remission was obtained in all patients, and biochemical remission in almost all patients. Relapse occurred in 27 patients after 0.5-12 years. Subjective side-effects occurred more frequently in women, who also had higher maximum ALAT, ferritin and uroporphyrin values during treatment. Both subjective side-effects and ALAT during treatment correlated with pre-treatment uroporphyrin excretion and maximum uroporphyrin during treatment, but not with markers of hereditary haemochromatosis.

Development of a New Generation of 4-Aminoquinoline Antimalarial Compounds Using Predictive Pharmacokinetic and Toxicology Models

“…Numerous studies have reported hepatotoxicity resulting from use of CQ 19, 20. Therefore, we decided to screen our five lead candidates for any potential hepatotoxicity in our final stage of ADMET screening (Figures 4a and 4b).…”

Low-Dose Hydroxychloroquine Is as Effective as Phlebotomy in Treatment of Patients With Porphyria Cutanea Tarda

“…19, 24–29, 31, 32 Somewhat higher doses 30, 35, 46 are reported as safe and effective and would not require dividing the lowest available dosage forms; much higher doses and dose-escalation regimens have been used 47–51 . However, our finding that 100 mg of hydroxychloroquine twice weekly was generally equivalent to phlebotomy in terms of time to remission, and evidence that hepatotoxic and other adverse effects of 4- aminoquinolines are dose-dependent, 50, 51 supports the use of this lower dose regimen and avoiding possibly greater risks from higher doses. But measurement intervals were not optimal for detecting short term elevations in liver chemistries.…”

Lésions sclérodermiformes dans la porphyrie cutanée tardive : six observations

“…Les deux principaux traitements existants sont d'efficacité équivalente [18,19] : les saignées et l'HCQ, administrée à faible dose (200 mg deux fois par semaine) pour éviter de déclencher une crise aiguë de porphyrie marquée par une hémolyse (pouvant entraîner une nécrose tubulaire aiguë) et une hépatite cytolytique [3,20]. L'hépatopathie associée à la PCT doit être traitée dans la mesure du possible et le contrôle des facteurs hépatotoxiques (médicaments, alcool, virus, surcharge ferrique.…”