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Overview of Cutaneous Porphyrias

by Herbert L. Bonkovsky, MD, Vinaya Maddukuri, MD

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.

Cutaneous porphyrias include

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.

Some Less Common Porphyrias


Symptoms and Signs



Congenital erythropoietic porphyria (Günther disease)

Severe deficiency of uroporphyrinogen III cosynthase (UROS)

In utero or shortly after birth: Severe cases manifesting as nonimmune hydrops

Soon after birth: Skin blistering, hemolytic anemia, hyperbilirubinemia, red urine, dark diapers that show a red fluorescence under UV light

Phototherapy for hyperbilirubinemia leads to severe skin blistering.

In adulthood: Facial disfiguration, increased hair growth, corneal scarring (possibly severe), hemolytic anemia, splenomegaly, erythrodontia, deposition of porphyrins in bone, bone demineralization (possibly substantial)

Porphyrins in plasma, urine, and stool elevated to levels higher than those in other porphyrias, with uroporphyrin I and coproporphyrin I the predominant porphyrins in urine and stool :

Urinary ALA and PBG virtually normal

Can be confirmed by low RBC UROS activity (<10%), but test not readily available

Genetic analysis of UROS gene, which reveals homozygous or compound heterozygous mutations on chromosome 10 (most common mutation is C73R)

For in utero diagnosis: Measurement of amniotic porphyrins or genetic analysis

Avoidance of sunlight (including lights for treating neonatal hyperbilirubinemia)

Use of sun-protective clothing

Avoidance of skin trauma

Prompt treatment of secondary bacterial infections to help prevent scarring

Splenectomy possibly beneficial for patients with hemolytic anemia

Repeated RBC transfusions and hydroxyurea to keep bone marrow porphyrin production low; deferoxamine for transfusion-related iron overload

Bone marrow transplantation potentially curative

Hepatoerythropoietic porphyria

Severe deficiency of uroporphyrinogen decarboxylase (UROD)

Skin blistering

Red urine


Elevated isocoproporphyrin in stool and urine

Elevated zinc protoporphyrin in RBCs (to differentiate from PCT)

Confirmed by very low RBC UROD activity

Genetic analysis of UROD gene, which reveals homozygous or compound heterozygous mutations

Avoidance of sunlight

Phlebotomy possibly beneficial to patients with milder cases

Treatment of severe disease similar to that of congenital erythropoietic porphyria

Dual porphyria

Disorders resulting from deficiencies of > 1 enzyme of the heme biosynthetic pathway

Clinical and biochemical manifestations of both disorders

In acute porphyrias: Neurovisceral symptoms triggered by porphyrogenic agents

In cutaneous porphyrias: Hypersensitivity to sunlight with blistering and fragile skin

Porphyrin and porphyrin precursor excretion patterns

Confirmed by family history and enzyme analyses

In acute porphyrias: Avoidance of triggering agents

In cutaneous porphyrias: Skin protection and avoidance of sunlight

ALA =δ-aminolevulinic acid; PBG = porphobilinogen; PCT = porphyria cutanea tarda; UV = ultraviolet.

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