Porphyria Cutanea Tarda

Porphyria cutanea tarda (PCT) is the most common porphyria, caused by reduced hepatic uroporphyrinogen decarboxylase (UROD) activity, leading to accumulation of uroporphyrins and photosensitising porphyrins.

• Types: sporadic (type I, 80 to 90%, no UROD mutation), familial (type II, UROD mutation, autosomal dominant with low penetrance), and type III (family clustering without mutation).
• Precipitants: alcohol, hepatitis C, HIV, iron overload (HFE variants C282Y and H63D), oestrogens (oral contraceptives, hormone therapy), smoking, and polyhalogenated aromatic compounds.
• Complications: liver disease (siderosis, cirrhosis), and increased risk of hepatocellular carcinoma.

• Blistering, skin fragility, erosions, crusts, milia, and scarring on sun exposed skin, especially dorsal hands and forearms, face, and ears.
• Hypertrichosis (periorbital), hyperpigmentation, scleroderma like thickening, and calcification.
• Dark or reddish brown urine.
• No acute neurovisceral attacks.

• Urine porphyrins: markedly raised uroporphyrin and heptacarboxylporphyrin (urine pink orange fluorescence under Wood lamp).
• Plasma porphyrin fluorescence scan with peak at about 620 nm; faecal isocoproporphyrin raised.
• Workup for precipitants: hepatitis C RNA and antibody, HIV, HFE genotype, ferritin, transferrin saturation, liver tests, fasting glucose, and alcohol history.
• Biopsy: subepidermal blister with festooning of dermal papillae, thickened vessel walls (PAS positive), and DIF with IgG and C3 around vessels.
• UROD gene sequencing in suspected familial disease.
• Exclude pseudoporphyria, variegate porphyria, hereditary coproporphyria, bullous pemphigoid, and epidermolysis bullosa.

• Eliminate triggers: stop alcohol, smoking, oestrogens, and iron supplements; treat hepatitis C with direct acting antivirals (sofosbuvir-velpatasvir) and manage HIV.
• Photoprotection: avoid sunlight, wear protective clothing, and use opaque sunscreens (zinc oxide, titanium dioxide).
• Phlebotomy (first line if iron overload): remove 450 mL every 2 weeks until ferritin reaches 20 to 50 ng/mL (haemoglobin not below 10 to 11 g/dL), then maintain with periodic checks; clinical remission occurs after 2 to 3 months (up to 6 to 12 months for biochemical remission).
• Low dose hydroxychloroquine 100 mg (or 200 mg) twice weekly until urinary porphyrins normalise (higher doses can trigger acute hepatotoxicity and porphyrin release); use if phlebotomy is contraindicated.
• Iron chelation (deferasirox 10 to 20 mg/kg/day) when phlebotomy not possible; erythropoietin with phlebotomy in dialysis related PCT.
• Surveillance for hepatocellular carcinoma (ultrasound every 6 months) in cirrhosis, and avoid known porphyrinogenic factors.