Only once in a great while an article makes me want to break into my happy dance – the report of 3 pediatric cases of erythropoietic protoporhyria (EPP) by Tu et al had that effect. Recently, I ran a post on EPP where I discussed the new findings of EPP presenting in adults with acquired ferrochelatase mutations in secondary to myelodysplasia (published April 19th, 2016). Tu’s paper trumps that (undoubtedly, you’ll be hearing that term at least until 2020).
Three girls, aged 13, 10, and 4 years, respectively, all had painful photosensitivity; the oldest had associated cholelithiasis; the other girls had elevated transaminases. All three were given cimetidine at a dose of 30 to 40 mg/kg divided twice daily. Within two weeks, all were able to tolerate sun exposure and demonstrated improvement of their systemic symptoms.
Current therapies for EPP, notably sun protection and beta-carotene are not very effective. Afamelanotide (Scenesse), an a-melanocyte-stimulating hormone, is not yet available in the United States that may help the cutaneous features of EPP. Neither has any effect on the systemic associations.
Cimetidine inhibits delta-aminolevulinic acid synthetase, the first enzyme in the heme biosynthetic pathway. Cimetidine has been reported to dramatically improve acute intermittent porphyria and patients with porphyria cutanea tarda (PCT). The drug is very well tolerated (1). The report of a 78 year old man with PCT responding to cimetidine within two weeks is dramatic (2). It is certainly worthy of consideration with or without phlebotomy and/or hydroxychloroquine. According to Epocrates, there is no drug interaction between cimetidine and hydroxychloroquine.
In addition to it’s immunomodulatory activity in (occasionally) helping clear verrucae and the H-2 blocking that may contribute in treating urticaria, cimetidine may alter hepatic enzymes in the heme biosynthetic pathway thereby improving several forms of porphyria. That offers these long-suffering patients a ray of sunshine and hope. While three cases cannot provide for a definitive recommendation for treating EPP, it certainly shines a brighter light for these patients.
- Tu JH, et al. Novel treatment using cimetidine for erythropoietic porphyria in children. JAMA Dermatology 2016; 152: 1258-61.
- Fujita Y, Sato-Matsumura KC. Effective treatment for porphyria cutanea tarda with oral cimetidine. J Dermatol 2010; 37: 677-9.