Porphyria cutanea tarda

PCT & HEP are cutaneous porphyrias occur due to decreased activity of the heme biosynthetic enzyme uroporphyrinogen decarboxylase (UROD). PCT ptns cou

 

 

 

 

 

Porphyria cutanea tarda (PCT) & hepatoerythropoietic porphyria (HEP)

  

Porphyria Cutanea Tarda & Hypertrichosis

PCT & HEP are cutaneous porphyrias occur due to decreased activity of the heme biosynthetic enzyme uroporphyrinogen decarboxylase (UROD). PCT ptns could be classified as inherited or sporadic (about 20 & 80 % of cases, resp.) according to the presence/absence of heterozygous UROD mutation. In both familial & sporadic cases, various acquired factors e.g., alcohol abuse, smoking, oestrogen administration, & HCV is commonly involved, in addition to hemochromatosis (HFE) mutations. HEP that is extremely rare, is related to the developed mutations of both UROD alleles. PCT is iron-related and generally observed in adulthood; HEP can present in children or adulthood according to the degree of UROD deficit levels.

 

Typical manifestations of PCT may include chronic blistering photosensitivity, particularly involving the back of the hands & other sun-exposed area that can invite infection, scarring, hyper- & hypopigmentation. Many ptns show rise in serum transaminases, but neurovisceral episodes do not occur. Plasma & urine total porphyrins are raised, with a characterizing pattern. Criteria of HEP are simulating PCT but more intense, and usually seen in early childhood.  As followed in other porphyrias, assessment of PCT is performed in a stepwise pattern, with measuring plasma or urinary total porphyrins as 1^st-line testing tool. Normal total urine/plasma porphyrins can exclude PCT as well as other blistering cutaneous porphyrias. If total plasma or urine porphyrins are rising, more extensive 2^nd-line should be proceeded.  

 

Medical disorders that can lead to oxidative liver damage (e.g., DM, hepatic steatosis) have been observed in some PCT cases. PCT also has been observed in late pregnancy; however, an increased prevalence with pregnancy or a causative relation remain to be identified. PCT has been reported in ptns with myeloproliferative disorders, often associated with evident iron overload.

Renal disease: PCT can be seen in ptns on maintenance HDX or PD for severe CKD, usually with iron overload. The disorder is often particularly intense in these cases, reflecting plasma porphyrin levels that may be so high as compared to ptns with PCT & normal kidney function.

 

Dgx of PCT is made by reporting its rising biochemical pattern of porphyrin that include higher plasma & urine porphyrins + predominant high carboxylated porphyrins. Plasma peak fluorescence = 620 nm DD PCT from variegate porphyria (VP); total fecal porphyrins in PCT may be normal or raised with a characterising fashion including isocoproporphyrins. Molecular analysis > UROD mutations in almost 20 % of ptns; this is NOT required for Dgx. HEP Dgx: same porphyrin raised that are usually more intense than PCT, and a marked rise of RBCs zinc protoporphyrin. HEP should be documented by molecular testing that show biallelic UROD mutations.  DD of PCT includes:

1)    Other causes of blistering cutaneous porphyrias,

2)    Other causes of urinary/plasma porphyrin rising, &

3)    Other causes of phototoxic skin lesions including pseudoporphyria,

 

Ttt: All PCT ptns having active cutaneous lesion should be ttt with:

(1)  Phlebotomy or

(2)  Low doses of hydroxychloroquine &

(3)  Limitation of the susceptibility factors.

-       Optional choice between phlebotomy & hydroxychloroquine relied mainly on the degree of iron overload & other liability factors. Whether PCT ptns with HCV should be ttt primarily with direct-acting antiviral medications still investigational.