Background Hepatoerythropoietic porphyria (HEP) is a rare type of inherited porphyria and results from severe uroporphyrinogen decarboxylase (UROD) deficiency. Patients usually suffer in early childhood with extreme skin fagility, cutaneous lesions with fluid-filled blisters that break and heal slowly, hypertrichosis in periorbital areas, and scarring over the light exposed areas. Repeated sun exposure can lead to scleroderma-like changes that can result in photomutilation. There are no effective treatments for individuals with HEP.

Aims Development of the first therapy based on iterative phlebotomies and concomitant administration of afamelanotide 16 mg every two months.

Methods A therapeutic protocol was set up for a 47 years old male HEP, combining administration of Afamelanotide 16 mg with iterative phlebotomy. In a first phase 200 ml of blood were removed every month until iron depletion. Subsequently, treatment was administrated every two months as for maintenance therapy. Concomitant off label use of afamelanotide was performed as photoprotective measure since it stimulates melanogenesis and reduces severity of cutaneous symptoms in erythropoietic protoporphyria.

Results Therapy reduced porphyrins accumulation. Urine porphyrins decreased from 1303 to 240 µmol/mmol creatinine (ULN, upper limit of normal 35 µmol/mmol creatinine), plasma porphyrins decreased from 1376 to 311 nmol/l (ULN 15 nmol/l ). Chronic epathopathy was ameliorate as shown from liver function analyses (transaminases decreased from 3x ULN to normal values). Ferritin was used as index to monitor iron status obtaining a significant reduction after 2 months from 700 ng/ml to 81 ng/ml (v.n.= 13–400 mg/ml). Patient had an improvement of lesions on the scalp and in photoexposed areas. The clinical tolerance was excellent for patient without any adverse effect to report.

Conclusion This is the first report in the literature applying a successfull protocol in a higly uncommom form of porphyria, hence the importance of the case. Higher tolerance to the sun induced by afamelanotide reduced phototoxic chronic damage. If therapy was established precociously, some irreversibile damages, such as phalanges mutilation, could have been reduced and also palpebral ectropion. It suggests that early diagnosis and treatment might prevent the occurrence of devastating and severe consequences of HEP.