Porphyria cutanea tarda E80.1

Günther, 1922; Waldenström, 1937

Photodermatosis with massive actinic elastosis (wrinkle formation), increased vulnerability, hyperpigmentation, blistering and scarring in chronically exposed skin areas. Most common porphyria (hepatic porphyria) with reduced activity of uroporphyrinogen-1-decarboxylase.

• Type I Sporadic or acquired Porphyria cutanea tarda (acquired uroporphyrinogen-1-decarboxylase deficiency, e.g. Porphyria turcica: form described in the Türkey 1954 after consumption of hexachlorobenzene displaced seed wheat, also called hexachlorobenzene porphyria - clinical: conspicuous hypertrichosis = monkey children), digoxin or estrogen induced forms (see also pseudoporphyria).
• Type II Familial Form
  • Familial, autosomal dominant porphyria cutanea tarda (heterozygous; mutation in the URO-D gene).
  • Special forms:
    • Sporadic or acquired porphyria cutanea tarda with familial accumulation.
    • Porphyria hepatoerythropoetica (severe mutating porphyria with initial manifestation in childhood; autosomal recessive, homozygous).

Incidence: 1/30.000 - 1/70.000 inhabitants/year. Prevalence: 15/100,000 inhabitants. Proportion of all porphyrias: 30-40%.

• In hereditary forms: Autosomal-dominant or autosomal-recessive inheritance of mutations of the uroporphyrinogen decarboxylase (URO-D), which is mapped on gene locus 1p34 (currently >100 mutations are known).
• In autosomal dominant PCT, UROD inhibition is found in all tissues and not only in the liver. The enzyme activity in the erythrocytes is reduced to 5% of the normal value in the (rare) homozygous form of PCT and to 50% in the heterozygous form.
• In the hereditary forms, in addition to mutations in the UROD gene, mutations in the HFE gene (leading to hemochromatosis) may also occur. The increase in the iron level caused by haemochromatosis leads to an additional functional reduction of UROD activity, which in turn increases the disease symptoms.
• In acquired forms: a genetic defect of URO-D alone does not lead to the manifestation of the disease. Catalytic inhibition of URO-D in the liver is effected by trigger factors. Trigger factors: alcoholism, liver diseases (hepatitis C and B), HIV infection, drugs (barbiturates, arsenic, androgens, griseofulvin, hydantoin, nalidixic acid, phenytoin, rifampicin, sulphonamides, tetracyclines, steroids, oral contraceptives, oestrogens), hexachlorobenzene, dioxin, vinyl chloride, iron, haemodialysis. An impressive example of exogenously induced PCT was hexachlorophene poisoning of larger population groups in Anatolia at the end of the 1950s. This was triggered by a mix-up of seed (containing the pesticide hexachlorophene) and baking wheat. Hexachlorophen leads to an inhibition of UROD and to massive disease patterns.
• Hemodialysis-induced PCT is one of the rare indications for porphyrin determination in serum or plasma.
• Cytochrome P450 polymorphism(cytochrome p450 plays an important role in the metabolism of prophyrin)
• In about half of the so-called sporadic or acquired PCT cases (family history negative), a genetic predisposition can be suspected due to reduced enzyme activity in the erythrocytes and verified by family examinations.

Occurrence mainly between 40 and 70 years of age, more frequent in men than in women (m:w=2/3:1).

Skin changes in the areas exposed to light, especially on the face, the sides of the forearm and the back of the hands.

Seasonal (spring, summer) skin changes that occur more frequently and are also caused by low mechanical stress.

• Blistering: Especially on the backs of the hands and fingers, blisters of varying sizes, with a coarse covering and serous or haemorrhagic content. Nikolski phenomenon II is positive. Hemorrhagic crusts, erosions, atrophic scars, hyperpigmentation and hypopigmentation, postbullous milia.
• Hyperpigmentation: diffuse melanosis of the face and neck (Melanodermie-Porphyrie Brugsch).
• Hypertrichosis of the zygomatic region and cheeks, dense eyebrows.
• Elastosis: pronounced wrinkling, telangiectasia, comedones (similar to elastoidosis cutanea nodularis et cystica), cutis rhomboidalis nuchae, keratosis actinica in chronic cases.
• Urine discoloration (wine-red dark)
• Pseudoscleroderma, scleroporphyria.
• Sclerovitiligo.
• Cyanosis, lid edema, conjunctivitis. Also: hepatic metabolic disorders, porphyrinuria (beer brown urine).

• Pathological liver enzymes (transaminases, gamma-GT); often through alcohol abuse
• Urine: Uroporphyrin(III) excretion is 10-20 times increased, red fluorescence in Wood light. Coproporphyrin III is elevated. Possibly dark urine!
• Stool: Coproporphyrin III.
• Serum: uroporphyrin I is elevated, hypersiderinemia; in acute attacks elevated transaminases; usually elevated iron levels.

Addison's disease; hemochromatosis; epidermolysis bullosa group or epidermolysis bullosa acquisita; erythema elevatum diutinum; leprosy lepromatosa.

Pseudoporphyria: Porphyria cutanea tarda in haemodialysis patients.

• Chloroquine (e.g. Resochin) causes mobilization of prophyrins in tissues with subsequent excretion through urine. Chloroquine initially twice a week 250 mg for 1 month, then reduced to 125 mg twice a week. Duration of therapy: Several months.
• Bloodletting is performed under the idea that siderosis and sideremia are pathogenetically relevant factors. Initial bloodletting: 1 time per week 500 ml. Maintenance dose after 4 weeks: 500 ml once a month (Hb 10-12 g/dl). In case of severe cutaneous symptoms and total porphyrin excretion > 8 μmol/day: start of bloodletting therapy once/week 500 ml. After 4 weeks 500 ml once a month (set Hb to 10-12 g/dl). In combination low-dose chloroquine therapy (125-250 mg once/week) for 8-12 months. Under this therapy skin symptoms decrease after 3 months and porphyrinuria after 6 months.
• Deferoxamine (e.g. Desferal) 1-4 g/day i.v. to reduce the amount of iron.

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