Inflammatory involvement into phototoxic reaction in erythropoietic protoporphyria (EPP) patients

  • Francesca GranataEmail author
  • Lorena Duca
  • Giovanna Graziadei
  • Valentina Brancaleoni
  • Pasquale Missineo
  • Giacomo De Luca
  • Silvia Fustinoni
  • Elena Di Pierro
Original Article


Phototoxic reaction is a known feature of EPP at least in part triggered by the oxidative status, complement system activation, and mast cell response. The aim of this study was to verify some aspects involved in phototoxic reaction during a season. The complement system was evaluated by C3 assay, alternative pathway by factor-B, and classical pathway by C1q; oxidative status was tested with malondialdehyde (MDA) and mast cell by IL-10 assay. The serum samples were collected in winter and summer from 19 EPP patients and 13 controls. The reaction to sun exposure within each group was monitored without any invasive treatment. In summer, C3 and factor B were higher in patients than in controls (p = 0.002 and < 0.0001 respectively), while no change was detected for C1q. The oxidative stress was increased in summer in comparison with the control group (p = 0.04), and IL-10 an assay was normal in both seasons. The correlation between the C3 and factor-B in summer was significant. This study shows that the phototoxic reaction is not limited to the dermis but can also exert a systemic response, which could affect the general health of a patient. The knowledge of the pathophysiology of phototoxic reaction is essential for identifying new disease markers useful for improving clinical studies of known and future drugs.


Erythropoietic protoporphyria Oxidative status Complement system Alternative pathway Phototoxic reaction 



We are indebted to all patients who participated in this research and made it possible and to the DH staff of UOC rare centre diseases at Fondazione IRCCS Ospedale Maggiore Policlinico, who assisted every day the EPP patients, especially during the summer season.

The author would like to acknowledge, with gratitude, Prof. MD Cappellini for her constant support. The RC–2018/ RC–2019 to MDC supported this work.

Author contributions

FG designed the study, performed statistical analysis, and wrote the manuscript. LD performed the ELISA experiments. GG recruited the patients. VB executed the genetic diagnosis of patients. PM determined the PPIX levels. SF critically revised the manuscript. EDP critically revised the results and manuscript.

Funding information

Ministero della salute: RC-2019 to MDC supported this work.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent for the research was obtained from all individual participants included in the study.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Francesca Granata
    • 1
    Email author
  • Lorena Duca
    • 1
  • Giovanna Graziadei
    • 1
  • Valentina Brancaleoni
    • 1
  • Pasquale Missineo
    • 2
  • Giacomo De Luca
    • 1
  • Silvia Fustinoni
    • 3
  • Elena Di Pierro
    • 1
  1. 1.Fondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoU.O.C. Medicina GeneraleMilanItaly
  2. 2.Dipartimento di Scienze Cliniche e di ComunitàUniversità degli Studi di MilanoMilanItaly
  3. 3.EPIGET - Epidemiology, Epigenetics, and Toxicology Lab, Department of Clinical Sciences and Community HealthUniversità degli Studi di Milano, Italy. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, U.O.S TossicologiaMilanItaly

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