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 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.