Most common form of the porphyrias and is due to a partial deficiency of hepatic uroporphyrinogen decarboxylase activity.
Incidence is unclear.
Usually begins in middle or late adult life.
A chronic hepatic porphyria.
No racial predilection except for South African Bantus with their high incidence of hemosiderosis.
Incidence probably equal among the sexes.
Most cases acquired, while some cases occur associated an inherited disease.
Hallmark of the disease is skin photosensitivity secondary to increased accumulation of uroporphyrin and 7-carboxylic porphyrin.
Patients excrete large amounts of 8 and 7 carboxylated porphyrins in their urine and isocoproporphyrin in their stool, but not ALA or PBG.
Three subtypes
Type I-family history negative with normal erythrocyte uroporphyrinogen decarboxylase levels, but with decreased levels of enzyme activity in the liver, adult presentation, and frequently associated with alcohol, estrogens, drug use, excess iron levels and other disorders.
Type II-activity and concentrations of uroporphyrinogen decarboxylase are both about 50% of normal in erythrocytes and liver and indicates an autosomal dominance.
Type III-patients have normal erythrocyte uroporphyrinogen decarboxylase levels and activity but have decreased hepatic uroporphyrinogen decarboxylase activity and is found in multiple members of a family.
Porphyrin synthesis in the skin is increased and the initial clinical event is formation of membrane limited vacuoles in the superficial dermis.
The porphyrins can be derived from production in the skin and the liver and activation of complement in the skin after exposure to sun radiation results in the generation of reactive oxygen species.
The fluid in the bullous skin lesions contains prostaglandin E2.
Photo activation of urophorphyrins damages lysosomes causing inflammation and autolysis.
Most patients with type I disease have cirrhosis.
Liver biopsy of most patients show hemosiderosis (80%) and this is particularly true for patients with type I disease.
Crystallized porphyrins frequently seen on liver biopsies of patients with PCT.
Incidence of hepatocellular cancer increased in patients.
Sporadic cases associated with alcohol, estrogens, exposure to iron, and polychlorinated aromatic hydrocarbons..
25-100% of patients report heavy alcohol use.
Estrogen administration and pregnancy and other hyperestrogenic processes can precipitate acute process.
Serum iron and f2242itin levels are frequently elevated in patients with PCT, while iron absorption and turnover is normal or elevated.
The administration of iron may lead to exacerbation of symptoms.
Phlebotomy can induce clinical remission.
High prevalence of C282Y mutation suggests involvement of the HFE gene seen in hereditary hemochromatosis is also related to the pathogenesis of PCT.
Polyhalogenated aromatic hydrocarbons associated with events indicted metabolic activation of such compounds that decrease uroporphyrinogen decarboxylase activity.
Reported to occur in patients on hemodialysis, with SLE, Sjögren syndrome, rheumatoid arthritis, diabetes, Wilson’s disease, hemophilia, thalassemia minor, viral hepatitis and AIDS.
While patients may have mild to severe photosensitivity and often have overt liver abnormalities they do not have neurologic manifestations.
Sporadic cases of type I occur almost exclusively in adults while types II and III may occur n childhood associated well.
Associated with increased skin fragility with erosions.
Sun exposure may lead to vesicle and bullae formation which may take weeks to heal and leave scarring.
May be associated with milia, hyperpigmentation, hypopigmentation, melanosis, brownish discolorations, alopecia and facial hypertrichosis.
Examination of urine for fluorescence under UV light and quantification of porphyrins leads to diagnosis.
Uroporphyrin greater than coproporhyrin favors diagnosis of PCT, while the reverse favors variegate porphyria or hereditary coproporhyria.
May be associated with elevated urinary ALA and PBG levels and invariably with increased plasma porphyrins.
Isocoproporphyrin in feces important diagnostic feature.
Treatment involves the detection and avoidance of factors that precipitate events.
Phlebotomy decreases urinary porphyrin and induces clinical remissions by decreasing body iron stores.
Remission by phlebotomy usually occurs after 4-10 liters of blood have been removed, with initial application of phlebotomy 1-2 times per week.
The goal of phlebotomy treatment is to reduce f2242itin levels to the lower limits of normal.
Chloroquine has been used in the past, in patients who have contraindication to phlebotomy, with reduction in porphyrin secretion.