History and exam

Key diagnostic factors

common

presence of risk factors

Common risk factors include males, women taking oestrogen, middle age, white, alcohol use, smoking, hepatitis C, hereditary haemochromatosis gene (HFE) mutation, other causes of iron overload, inherited partial deficiency or uroporphyrinogen decarboxylase (UROD), and HIV.

blistering skin lesions

These are most common on the backs of the hands, and also occur in other sun-exposed areas such as arms, face, ears, and feet (e.g., in women who wear open shoes).[Figure caption and citation for the preceding image starts]: Blistering and crusted skin lesions on the back of hands in patient with porphyria cutanea tardaFrom the personal collection of Gagan Sood, MD [Citation ends].com.bmj.content.model.Caption@7dc427e6

Other diagnostic factors

common

skin hyperpigmentation

Studies have reported hyperpigmentation in 25% to 55% of patients with PCT.[17][18] It is a manifestation of skin photosensitivity.

hypertrichosis

Hypertrichosis is a manifestation of skin photosensitivity.

scarring alopecia

Scarring alopecia is a manifestation of skin photosensitivity.

red urine

Red urine is due to large concentrations of porphyrins.

Risk factors

strong

male, middle-aged, white people

Most common in these groups of patients.[5][6]

alcohol use

Long recognised as an important contributor, alcohol may act by decreasing hepcidin, increasing hepatic iron, inducing cytochrome P450 (CYP) enzymes, and increasing oxidative stress in hepatocytes.[5] Up to 90% of PCT patients are alcohol drinkers.[5][6]

smoking

Can induce hepatic CYPs (especially CYP1A2) that may be involved in generation of a uroporphyrinogen decarboxylase inhibitor.[5] Up to 90% of PCT patients are smokers.[5][6]

oestrogen therapy

Oestrogen therapy has been described as the precipitating factor in 20% to 63% of women diagnosed with PCT.[6][7][8] Oestrogen may increase oxidative stress in hepatocytes.

hepatitis C

In PCT, the prevalence exceeds 70% in southern Europe, compared to 20% in northern Europe and 56% in the US.[5][9] Hepatic steatosis, low hepcidin, intracellular iron redistribution, and oxidative damage may explain the contribution of this viral infection in PCT.[5]

HIV

Probably an independent risk factor for PCT. How it may contribute is not understood.[9] Reported in up to 13% of patients with PCT.[6]

hereditary haemochromatosis gene (HFE) mutation

Predisposes to increased iron absorption by impairing hepcidin production by the liver.[5] Patients with PCT are homozygous or heterozygous for HFE gene mutations more commonly than expected by chance. About 10% to 20% of PCT patients of northern European origin may be homozygous for the C282Y mutation, which is commonly associated with hereditary haemochromatosis, and a corresponding number are C282Y/H63D compound heterozygotes.[10] C282Y heterozygotes and H63D homozygotes have some increase in iron absorption, making them somewhat more susceptible for developing PCT.

uroporphyrinogen decarboxylase (UROD) mutations

Half-normal UROD in all tissues from birth increases susceptibility to inhibition of hepatic UROD.[1] These patients with type 2 disease are identified by finding reduced erythrocyte UROD activity, or most reliably by DNA studies.

exposure to halogenated polycyclic aromatic hydrocarbons

These chemicals are rarely documented as causing PCT in humans, but can cause hepatic UROD inhibition due to generation of a UROD inhibitor and the biochemical abnormalities of PCT in laboratory animals.

weak

reduced levels of antioxidants

Low levels of vitamin C and carotenoids reported in small case series.[11][12]

end-stage renal disease

PCT in patients with end-stage renal disease is commonly associated with iron overload and other factors such as hepatitis C.

diabetes mellitus

Diabetes mellitus may predispose to PCT due to increased fat and oxidative stress in hepatocytes.[13] Changes in glucose metabolism are prevalent in patients with PCT, developing around 12 to 13 years after diagnosis.[9]

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