Mechanisms of photosensitivity in porphyric patients with special emphasis on erythropoietic protoporphyria.
In erythropoietic protoporphyria, protoporphyrin overproduction occurs mainly in erythroid tissue. Protoporphyrin can be released from erythrocytes in the dark, but the release is greatly increased if the erythrocytes are exposed to small amounts of light. Protoporphyrin can be bound in plasma either to albumin or to low density or high density lipoprotein. The cutaneous symptoms in erythropoietic protoporphyria are primarily elicited by protoporphyrin-sensitized photodamage of endothelial cells due to the presence of protoporphyrin in lipid structures. Which structures are damaged first in endothelial cells is unknown. Endothelial cells probably accumulate protoporphyrin from albumin or lipoproteins present in the plasma. A direct transfer from the erythrocyte membrane to the endothelial cell membrane can also occur. The transfer processes are probably facilitated by light exposure. Degranulation of mast cells, invasion of neutrophils into interstitial tissue and complement activation seem to be of less importance than endothelial cell injury in the pathogenesis of erythropoietic protoporphyria. These processes may, however, participate in the final expression of the cutaneous symptoms. Uroporphyrin and coproporphyrin are hydrophilic and are probably unbound in plasma, although weak binding to plasma proteins cannot be excluded. In the hepatic porphyrias and in erythropoietic porphyria, the clinical symptoms are probably evoked by uroporphyrin and coproporphyrin present in the interstitial tissue. Very little is known about the primary targets of uroporphyrin and coproporphyrin photodamage in these disorders, but photodamage to intercellular structures probably represents the initial event. Activation of complement may contribute to the final expression of the cutaneous symptoms.
Brun
A
A
Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
Sandberg
S
S
D004730:Endothelium, Vascular / Q000503:physiopathology; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology*; D004920:Erythropoiesis; D006801:Humans; D010787:Photosensitivity Disorders / Q000209:etiology / Q000503:physiopathology*; D011164:Porphyrias / Q000097:blood / Q000503:physiopathology*; D011166:Porphyrins / Q000097:blood / Q000378:metabolism*; D011524:Protoporphyrins / Q000097:blood
D011166:Porphyrins; D011524:Protoporphyrins