Herbert L. Bonkovsky, MD, Professor of Medicine; Chief, Liver Services and Laboratory for Liver and Metabolic Disorders, Wake Forest University School of Medicine;Sean R. Rudnick, MD, Assistant Professor, Department of Internal Medicine, Section on Gastroenterology, Wake Forest University School of Medicine
Cutaneous porphyrias result from deficiency (and in one case, excess) of certain enzymes in the heme biosynthetic pathway (see Table: Substrates and Enzymes of the Heme Biosynthetic Pathway and the Diseases Associated With Their Deficiency), resulting in a relatively steady production of phototoxic porphyrins in the liver or bone marrow. These porphyrins accumulate in the skin and, on sunlight exposure (visible light, including near-ultraviolet [UV]), generate cytotoxic radicals that cause recurrent or unremitting cutaneous manifestations.
The acute porphyrias variegate porphyria (VP) and hereditary coproporphyria (HCP) also have cutaneous manifestations. For porphyria etiology and pathophysiology, see Overview of Porphyrias.
In all cutaneous porphyrias except EPP and XLPP, cutaneous photosensitivity manifests as fragile skin and bullous eruptions. Skin changes generally occur on sun-exposed areas (eg, face, neck, dorsal aspects of hands and forearms) or traumatized skin. The cutaneous reaction is insidious, and often patients are unaware of the connection to sun exposure. In contrast, the photosensitivity in EPP and XLPP occurs within minutes or hours after sun exposure, manifesting as a burning pain that persists for hours, without any blistering and often without any objective signs on the skin. However, swelling and erythema may occur. Chronic liver disorders are common in cutaneous porphyrias.
The cutaneous porphyrias are all accompanied by elevated total plasma porphyrins, and are specifically diagnosed by measurements of porphyrins in RBCs, plasma, urine, and stool, as well as by genetic or enzyme analysis. Treatment involves avoidance of sunlight, measures to protect the skin, and sometimes other treatments directed according to the specific diagnosis.