Ultraviolet A phototest positivity is associated with higher free erythrocyte protoporphyrin IX concentration and lower transferrin saturation values in erythropoietic protoporphyria.

Giovanni Genovese,Angelo Valerio Marzano,Giacomo De Luca,Carlo Alberto Maronese,Francesca Granata,Roberta Piccinno,Maria Domenica Cappellini,Dario Antonio Marletta,Giovanna Graziadei,Chiara Moltrasio,Elena Di Pierro

doi:10.1111/phpp.12727

Abstract

BackgroundErythropoietic protoporphyria (EPP) is a rare disorder of heme biosynthesis hallmarked by early‐onset photosensitivity and mainly due to defective ferrochelatase activity leading to increased erythrocyte protoporphyrin IX (PPIX) levels. Evidence regarding the relationship between erythrocyte PPIX concentration and photosensitivity is limited.MethodsTo investigate the relationship between free erythrocyte PPIX (FEP) concentration; routine laboratory tests, particularly iron metabolism biomarkers; and ultraviolet (UV) A/visible light phototesting findings, 20 genetically confirmed EPP and one XLPP treatment‐naive patients were included in our study. They underwent UVA and visible light phototesting. On the same day, blood samples were collected for measurement of FEP, serum iron, transferrin, transferrin saturation, and ferritin, 25‐hydroxyvitamin D, and liver enzyme levels.ResultsMedian FEP concentration at the time of phototesting was 57.50 (IQR: 34.58‐102.70) μg/g of Hb. UVA and visible light phototesting were positive in 9 (42.9%) and 8 (38.1%) patients, respectively. Median FEP concentration was significantly higher in UVA phototest–positive patients than in those negative (64.37 [IQR: 57.45‐121.82] vs 45.35 [IQR: 24.53‐74.61] μg/g of Hb, respectively; P = .04486). Similarly, UVA photosensitive individuals had significantly lower median serum iron levels (61.5 [IQR: 33.5‐84] μg/dL vs 109 [IQR: 63.25‐154] μg/dL, respectively; P = .01862) and transferrin saturation values (15.005 [IQR: 7.0775‐18.41] % vs 29.645 [IQR: 17.8225‐34.3575] %; P = .0109) than those negative.ConclusionsOur study demonstrates that UVA phototest positivity is associated with higher FEP concentration and lower transferrin saturation and serum iron concentration in EPP.

Highlights

Erythropoietic protoporphyria (EPP) is a rare metabolic disease of heme biosynthesis characterized by cutaneous manifestations, including acute photosensitivity associated with painful erythematous- edematous changes, lichenification of chronically sun-exposed areas, and grooving around the lips; occasional microcytic anemia; and potential development of cholestatic hepatopathy.[1]
No statistically significant difference was documented between patients with positive and negative visible light phototesting in terms of free erythrocyte protoporphyrin IX (PPIX) (FEP) concentration (64.99 [interquartile range (IQR): 44.06-107.52]) vs 57.5 [IQR: 25.10-105.14] μg/g of Hb, respectively; P = .6065)
A retrospective observational study including 53 Danish EPP patients aged 0-90 years demonstrated that the intraerythrocyte levels of PPIX increase with age up until adulthood and are higher in men.[13]

Summary

Introduction

Erythropoietic protoporphyria (EPP) is a rare metabolic disease of heme biosynthesis characterized by cutaneous manifestations, including acute photosensitivity associated with painful erythematous- edematous changes, lichenification of chronically sun-exposed areas, and grooving around the lips; occasional microcytic anemia; and potential development of cholestatic hepatopathy.[1]. No statistically significant difference was documented between patients with positive and negative visible light phototesting in terms of FEP concentration (64.99 [IQR: 44.06-107.52]) vs 57.5 [IQR: 25.10-105.14] μg/g of Hb, respectively; P = .6065).

Results

Conclusion