Porphyria cutanea tarda

Porphyria cutanea tarda (PCT) presents with blistering and crusted skin lesions on the back of hands and other sun-exposed areas of the body. Other common features include skin fragility, with minor trauma causing blister formation, hypertrichosis, skin hyperpigmentation, and dark or reddish urine.

The main factors that contribute to susceptibility include alcohol use, smoking, hepatitis C, HIV, iron overload, hereditary hemochromatosis gene mutations, estrogen treatment, and uroporphyrinogen decarboxylase (UROD) mutations.

Results from an acquired, substantial deficiency of UROD in the liver.

Diagnosis is established by finding substantial increases in porphyrins in urine or plasma and excluding other blistering cutaneous porphyrias.

Treatment is highly effective and includes direct-acting antivirals (DAAs) if hepatitis C is present, repeated phlebotomy, or low-dose hydroxychloroquine. Remission can usually be achieved within 6 months.

PCT is a blistering cutaneous condition caused by a substantial deficiency of hepatic UROD, the fifth enzyme in the heme biosynthetic pathway. Substrates for the deficient enzyme, which are porphyrinogens (reduced porphyrins), accumulate in the liver, are oxidized to porphyrins, transported in plasma to the skin, and cause photosensitivity.[1]Phillips JD, Anderson KE. The porphyrias (Chapter 59). In: Kaushansky K, Lichtman MA, Prchal JT, et al, eds. Williams Hematology, 10th ed. New York, NY: McGraw-Hill;2020:961-86. PCT is rare (prevalence approximately 1 in 25,000 in the US); however, it is the most common of the porphyrias.[2]Horner ME, Alikhan A, Tintle S, et al. Cutaneous porphyrias part I: epidemiology, pathogenesis, presentation, diagnosis, and histopathology. Int J Dermatol. 2013 Dec;52(12):1464-80. https://onlinelibrary.wiley.com/doi/10.1111/ijd.12305 http://www.ncbi.nlm.nih.gov/pubmed/24261722?tool=bestpractice.com ​ It is usually associated with liver cell damage. Most patients will have at least two risk factors that decrease hepatic UROD activity or increase hepatic iron.[3]Bulaj ZJ, Phillips JD, Ajioka RS, et al. Hemochromatosis genes and other factors contributing to the pathogenesis of porphyria cutanea tarda. Blood. 2000 Mar 1;95(5):1565-71. https://www.sciencedirect.com/science/article/pii/S0006497120669993 http://www.ncbi.nlm.nih.gov/pubmed/10688809?tool=bestpractice.com [4]Dickey AK, Leaf RK, Balwani M. Update on the porphyrias. Annu Rev Med. 2024 Jan 29;75:321-35. https://www.annualreviews.org/content/journals/10.1146/annurev-med-042921-123602 http://www.ncbi.nlm.nih.gov/pubmed/37540847?tool=bestpractice.com ​ Individuals with genetic mutations in UROD have a predisposition to developing the disorder and are classified as having type 2 (familial) PCT, but variants in UROD alone are not sufficient for developing PCT.[3]Bulaj ZJ, Phillips JD, Ajioka RS, et al. Hemochromatosis genes and other factors contributing to the pathogenesis of porphyria cutanea tarda. Blood. 2000 Mar 1;95(5):1565-71. https://www.sciencedirect.com/science/article/pii/S0006497120669993 http://www.ncbi.nlm.nih.gov/pubmed/10688809?tool=bestpractice.com ​ Those without UROD mutations may have type 1 (sporadic) PCT or type 3 PCT (rare instances when more than one family member is affected but there is no UROD mutation).