Porphyria cutanea tarda E80.1

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

Actinic-traumatic bullous porphyrin dermatosis; Chronic hepatic porphyria; Chronic porphyry syndrome; Epidermolysis bullosa traumatica in porphyria; Melanoderma Porphyria; MIM 176100; Porphyria bullosa congenita tarda; Porphyria bullosa et erosiva; Porphyria chronic hepatic; Porphyria cutanea tarda symptomatic; Porphyria cutanea tarda toxic; Porphyria hepatica chronica; Porphyria syndrome chronic; Porphyry bovine dermatosis actinic-traumatic bullous

History
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Günther, 1922; Waldenström, 1937

Definition
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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.

Classification
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  • 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).

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

Etiopathogenesis
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  • 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.

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

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

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

Laboratory
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  • 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.

Histology
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Hyperkeratoses, acanthosis, thickened vascular walls, possibly subepidermal bladder with characteristic villi-like bladder floor.

Direct Immunofluorescence
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Deposits of various immunoglobulins as well as of fibrinogen at the dermoepidermal junction zone (homogeneous linear pattern) and especially in the papillary vessel walls (less so in reticular vessel walls). Such fluorescence patterns are also found in patients with chronic dialysis.

Differential diagnosis
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General therapy
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Strict ban on alcohol, as this is the most common trigger! In women, discontinuation of hormonal contraception. Treatment of underlying diseases.

External therapy
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Symptomatic: Textile light protection (wearing suitable headgear), additionally suitable light protection agents. Avoidance of traumatizing loads.

Internal therapy
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  • 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.

Literature
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  1. Bulaj ZJ et al (2000) Hemochromatosis genes and other factors contributing to the pathogenesis of porphyria cutanea tarda. Blood 95: 1565-1571
  2. Fritsch C et al (1998) Porphyria cutanea tarda. dermatologist 49: 870-882
  3. Fritsch S et al (2012) Increased photosensitivity? Case report of porphyria cutanea tarda associated with systemic lupus erythematosus. Rev Bras Reumatol 52:968-97
  4. Günther H (1911) The hematoporphyria. German Arch Klin Med 105: 89-146
  5. Karamfilov T et al (2003) Pansclerotic porphyria cutanea tarda after chronic exposure to organic solvents. dermatologist 54: 448-452
  6. Lee SC et al (2001) A case of porphyria cutanea tarda in association with idiopathic myelofibrosis and CREST syndrome. Br J Dermatol 144: 182-185
  7. Merk HF (2016) Porphyria cutanea tarda. dermatologist 67: 207-210
  8. Schulenburg-Brand D et al (2014) The cutaneous porphyrias. Dermatol Clin 32:369-384
  9. Shaffrali FC et al (2002) Hair darkening in porphyria cutanea tarda. Br J Dermatol 146: 325-329
  10. Sinha A et al (1999) Porphyria cutanea tarda in a patient with systemic lupus erythematosus. Rheumatology (Oxford 38: 1166-1168
  11. Stolzel U et al (2003) Hemochromatosis (HFE) gene mutations and response to chloroquine in porphyria cutanea tarda. Arch Dermatol 139: 309-313
  12. Waldenström J (1937) Studies on porphyria. Acta Med Scand 82 (Suppl): 1-254

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Last updated on: 29.10.2020