Cimetidine (H2 histamine antagonist), Fexofenadine (H1 histamine antagonist), and Zinc sulphate in the treatment of erythropoietic protoporphyria

Background: Erythropoietic protoporphyria (EPP) patients are deficient in the ferrochelatase enzyme which converts protoporphyrin IX (PpIX) into heme, causing PpIX to accumulate in mature erythrocytes and skin. When skin is exposed to visible light, a phototoxic reaction occurs with clinical symptom...

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Main Authors: Hans Christian Wulf, Peter A. Philipsen, Catharina M. Lerche
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Photodiagnosis and Photodynamic Therapy
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Online Access:http://www.sciencedirect.com/science/article/pii/S1572100025001760
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author Hans Christian Wulf
Peter A. Philipsen
Catharina M. Lerche
author_facet Hans Christian Wulf
Peter A. Philipsen
Catharina M. Lerche
author_sort Hans Christian Wulf
collection DOAJ
description Background: Erythropoietic protoporphyria (EPP) patients are deficient in the ferrochelatase enzyme which converts protoporphyrin IX (PpIX) into heme, causing PpIX to accumulate in mature erythrocytes and skin. When skin is exposed to visible light, a phototoxic reaction occurs with clinical symptoms of erythema, pain, and edema. Cimetidine (H2 histamine antagonist) may inhibit the δ-aminolevulinic acid synthase, reducing the build-up of PpIX. Fexofenadine (H1 histamine antagonist) may reduce histamine release and associated phototoxicity symptoms. Zinc sulphate, by inhibiting the formation of reactive oxygen species, may lessen exposure-related pain. Methods: Thirty-two EPP patients were treated for 68 summer seasons with Cimetidine, Fexofenadine, or Zinc sulphate. Primary outcome was the effect on PpIX levels. Treatment effects were registered in a quality-of-life questionnaire, including hours spent outdoors, time to sun induced skin pain, and maximal seasonal pain compared to a control year without treatment. Sun protection habits were also investigated. Results: Our EPP patients had significant clinical improvement on Cimetidine or Zinc sulphate monotherapy. Fexofenadine had no significant effect. Combining Cimetidine with Zinc sulphate lowered PpIX levels by 5.7 %, and 94 % of patients taking Cimetidine and Zinc sulphate reported an 80 % increase in time spent outdoors. Time to symptom onset was prolonged by 92 %, maximal pain intensity was reduced by 29 %, and quality of life improved by 36 %. Conclusion: Combination therapy with Cimetidine and Zinc sulphate is a safe, well tolerated, effective, low-cost treatment for EPP patients. Quality of life is improved, time to sun induced symptoms is prolonged, and pain is reduced.
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spelling doaj-art-59383ecb9f5142ffb0dbc90b9b613ed12025-08-20T02:37:39ZengElsevierPhotodiagnosis and Photodynamic Therapy1572-10002025-06-015310464410.1016/j.pdpdt.2025.104644Cimetidine (H2 histamine antagonist), Fexofenadine (H1 histamine antagonist), and Zinc sulphate in the treatment of erythropoietic protoporphyriaHans Christian Wulf0Peter A. Philipsen1Catharina M. Lerche2Department of Dermatology, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Denmark; Corresponding author: Department of Dermatology, Copenhagen University Hospital – Bispebjerg, Nielsine Nielsens Vej 9, 2. DK-2400, Copenhagen, NV, Denmark.Department of Dermatology, Copenhagen University Hospital – Bispebjerg and Frederiksberg, DenmarkDepartment of Dermatology, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Denmark; Department of Pharmacy, University of Copenhagen, DenmarkBackground: Erythropoietic protoporphyria (EPP) patients are deficient in the ferrochelatase enzyme which converts protoporphyrin IX (PpIX) into heme, causing PpIX to accumulate in mature erythrocytes and skin. When skin is exposed to visible light, a phototoxic reaction occurs with clinical symptoms of erythema, pain, and edema. Cimetidine (H2 histamine antagonist) may inhibit the δ-aminolevulinic acid synthase, reducing the build-up of PpIX. Fexofenadine (H1 histamine antagonist) may reduce histamine release and associated phototoxicity symptoms. Zinc sulphate, by inhibiting the formation of reactive oxygen species, may lessen exposure-related pain. Methods: Thirty-two EPP patients were treated for 68 summer seasons with Cimetidine, Fexofenadine, or Zinc sulphate. Primary outcome was the effect on PpIX levels. Treatment effects were registered in a quality-of-life questionnaire, including hours spent outdoors, time to sun induced skin pain, and maximal seasonal pain compared to a control year without treatment. Sun protection habits were also investigated. Results: Our EPP patients had significant clinical improvement on Cimetidine or Zinc sulphate monotherapy. Fexofenadine had no significant effect. Combining Cimetidine with Zinc sulphate lowered PpIX levels by 5.7 %, and 94 % of patients taking Cimetidine and Zinc sulphate reported an 80 % increase in time spent outdoors. Time to symptom onset was prolonged by 92 %, maximal pain intensity was reduced by 29 %, and quality of life improved by 36 %. Conclusion: Combination therapy with Cimetidine and Zinc sulphate is a safe, well tolerated, effective, low-cost treatment for EPP patients. Quality of life is improved, time to sun induced symptoms is prolonged, and pain is reduced.http://www.sciencedirect.com/science/article/pii/S1572100025001760AntihistamineCimetidineErythropoietic protoporphyriaProtoporphyrin ixquality of lifeZinc sulphate
spellingShingle Hans Christian Wulf
Peter A. Philipsen
Catharina M. Lerche
Cimetidine (H2 histamine antagonist), Fexofenadine (H1 histamine antagonist), and Zinc sulphate in the treatment of erythropoietic protoporphyria
Photodiagnosis and Photodynamic Therapy
Antihistamine
Cimetidine
Erythropoietic protoporphyria
Protoporphyrin ix
quality of life
Zinc sulphate
title Cimetidine (H2 histamine antagonist), Fexofenadine (H1 histamine antagonist), and Zinc sulphate in the treatment of erythropoietic protoporphyria
title_full Cimetidine (H2 histamine antagonist), Fexofenadine (H1 histamine antagonist), and Zinc sulphate in the treatment of erythropoietic protoporphyria
title_fullStr Cimetidine (H2 histamine antagonist), Fexofenadine (H1 histamine antagonist), and Zinc sulphate in the treatment of erythropoietic protoporphyria
title_full_unstemmed Cimetidine (H2 histamine antagonist), Fexofenadine (H1 histamine antagonist), and Zinc sulphate in the treatment of erythropoietic protoporphyria
title_short Cimetidine (H2 histamine antagonist), Fexofenadine (H1 histamine antagonist), and Zinc sulphate in the treatment of erythropoietic protoporphyria
title_sort cimetidine h2 histamine antagonist fexofenadine h1 histamine antagonist and zinc sulphate in the treatment of erythropoietic protoporphyria
topic Antihistamine
Cimetidine
Erythropoietic protoporphyria
Protoporphyrin ix
quality of life
Zinc sulphate
url http://www.sciencedirect.com/science/article/pii/S1572100025001760
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