Wednesday, July 12, 2017

Updates on PCT Porphyria

Porphyria cutanea tarda

Created 1997.

What is porphyria cutanea tarda?

Porphyria cutanea tarda (PCT) is the most common type of porphyria.
An increase in porphyrins in the skin result in photosensitivity, ie, the skin is damaged by light.

What are the symptoms of porphyria cutanea tarda?

Individuals with PCT present with increasingly fragile skin on the back of the hands and the forearms. Features include:
  • Sores (erosions) following relatively minor injuries
  • Fluid filled blisters (vesicles and bullae)
  • Tiny cysts (milia) arising as the blisters heal
  • Increased sensitivity to the sun
Although these features may also occur on the face and neck as well, it is more common to notice mottled brown patches around the eyes and increased facial hair (hypertrichosis). Occasionally the skin becomes hardened (scleroderma) on the neck, face or chest. There may be small areas of permanent baldness (alopecia) or ulcers.
Characteristically, the urine is darker than usual, with a reddish or tea-coloured hue.
The clinical appearance of variegate porphyria is similar but the biochemical abnormality is different.








What is the cause of porphyria cutanea tarda?

PCT is due to a defective enzyme in the liver (uroporphyrinogen decarboxylase). This is involved in synthesis of the red pigment in blood cells (haem). Some families carry an enzyme that is prone to oxidation under certain circumstances, most often due to iron accumulation.
There are basically two forms of PCT, type 1 and type 2.
Type 1 PCT generally begins in mid-adult life after exposure to certain chemicals that increase the production of porphyrins (precursors of haem) in the liver. These include:
  • alcohol (in 50% patients)
  • oestrogen eg oral contraceptive, hormone replacement (in 50% of affected women) or liver disease
  • polychlorinated aromatic hydrocarbons (eg, dioxins, when PCT is associated with chloracne).
  • iron overload, due to excessive intake (orally or by blood transfusion), viral infections (hepatitis, especially hepatitis C, in 15%) or chronic blood disorders such as thalassaemia (acquired haemochromatosis), or hereditary haemochromatosis (in 20%)
Type 2 PCT is familial and associated with abnormal genetic variants of uroporphyrinogen decarboxylase. Trigger factors are less often involved and onset of PCT is often younger than in type 1 PCT.

What investigations should be done?

  • Skin biopsy : characteristic changes are seen which differentiates PCT from other blistering diseases.
  • Examination of the urine with a Wood's lamp: may reveal coral pink fluorescence due to excessive porphyrins.
  • 24 hour urine porphyrin profile: total porphryins are usually elevated 5- to 20-fold above the upper reference limit. Most of the excreted porphyrins are uroporphyrin and a 7-carboxyl porphyrin.
Other important tests include:
  • Complete blood count to assess haemoglobin levels.
  • Measurement of iron stores, which may be increased in over 30% of patients.
  • Liver enzymes because the liver sometimes does not function normally.
  • Fasting blood sugar because of the increased incidence of diabetes.
  • Antinuclear antibodies because of the increased incidence of lupus erythematosus.
  • Viral hepatitis studies
If a blood ferritin shows iron stores are increased, further investigations may include transferrin saturation and genotyping for hereditary haemochromatosis.

What is the management of porphyria cutanea tarda

  • Avoid alcohol, oestrogen, and iron.
  • If using pesticides, be very careful to avoid contact with polychlorinated aromatic hydrocarbons (eg. 2,4,5T).
  • Apply an opaque sun-block and cover up when outside; the responsible light is the "Soret" band at 400 nm which is unfortunately not blocked by most sunscreens.
  • Use tanning cream containing dihydroxyacetone: this can block the responsible light to some extent.
  • Phlebotomy (removal of blood) — up to 500 ml blood is removed every one to two weeks until the haemoglobin and iron levels drop to low normal levels. It may take 3 to 6 months to improve. Venesection may need to be repeated after a year or more.
  • Antimalarial tablets, ie, low-dose chloroquine or hydroxychloroquine may be recommended, but must be used cautiously. This medication makes the porphyrins more soluble so more are excreted in the urine.
  • Autologous red cell transfusion (this is a blood transfusion using the patient's own red cells that have been washed to remove plasma thereby reducing the circulating porphyrins).

 

  1. Deferasirox for Porphyria Cutanea Tarda
    Graeme M. Lipper, MD, Medscape, 2012
  2. A porphomethene inhibitor of uroporphyrinogen decarboxylase causes porphyria cutanea tarda.
    John D Phillips et al., Proc Natl Acad Sci U S A, 2007
  3. Porphyria variegata and porphyria cutanea tarda in siblings: chemical and genetic aspects.
    C J Watson et al., Proc Natl Acad Sci U S A, 1975
  4. Alcohol and Skin Disorders: With a Focus on Psoriasis
    Natalia Kazakevich et al., Medscape, 2011
  5. Fingernail and Toenail Abnormalities: Nail the Diagnosis
    Mark P. Brady, PA-C, Medscape, 2015

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