Name: Dersimelagon (MT-7117) in Erythropoietic protoporphyria or X-linked protoporphyria: Pathophysiology
Published: 2026-09-21T21:42:40-04:00

Protoporphyrin IX accumulation and photoactivation in dermal vasculature

“Protoporphyrin is believed to be taken up from plasma by vascular endothelial cells in the skin where photoactivation by visible light leads to the formation of reactive oxygen species that cause cellular damage, inflammation, and cutaneous phototoxicity.” (opens the source at this quote in a new tab)

“The accumulated protoporphyrin is activated by sunlight exposure, generating singlet oxygen radical reactions leading to tissue damage and excruciating pain.” (opens the source at this quote in a new tab)

Action spectrum: the Soret band near 400 nm

“The skin of persons with EPP is maximally sensitive to visible blue-violet light near 400 nm, which corresponds to the so-called Soret band (the narrow peak absorption maximum that is characteristic for protoporphyrin and other porphyrins). When porphyrins absorb light they enter an excited energy state.” (opens the source at this quote in a new tab)
“Photosensitivity symptoms are provoked mainly by visible blue-violet light in the Soret band and to a lesser degree in the long-wave UV region.” (opens the source at this quote in a new tab)

Complement activation and mast cell degranulation

“Thunell et al., in 2000, first hypothesized that PPIX excitated at 410 nm leads to singlet oxygen (1O2*) mediated damage of endothelial cells” (opens the source at this quote in a new tab)
“The photodamage leads to the stimulation of an inflammatory response, occurring via complement system (CS) activation and mast cell degranulation, with exocytosis of vasoactive mediators.” (opens the source at this quote in a new tab)

“Photoactivation of the complement system and release of histamine, kinins, and chemotactic factors may mediate skin damage.” (opens the source at this quote in a new tab)

Histologic substrate of the phototoxic reaction

“Histologically, the subpapillary vascular endothelial cells and the basal membranes are most harmed, resulting in an activation of the complement system,” (opens the source at this quote in a new tab)

“Histological examination of acute lesions shows epidermal vacuolization and intercellular edema in addition to endothelial vacuolization and cytolysis in the superficial blood vessels of the skin” (opens the source at this quote in a new tab)

Dissociation between pain and visible skin change

“although the skin typically exhibits no visible alterations within the first few minutes to hours. Instead, these alterations become apparent hours to days after the onset of pain, if at all.” (opens the source at this quote in a new tab)

“Symptoms may seem out of proportion to the visible skin lesions.” (opens the source at this quote in a new tab)

Biliary excretion of protoporphyrin and hepatobiliary injury

“Accumulated protoporphyrin in the bile can form stones, reduce bile flow, and damage the liver.” (opens the source at this quote in a new tab)