A 35-year-old man from Delhi presents with recurrent episodes of photosensitive blistering lesions on the dorsal surfaces of his hands and face, triggered by sun exposure. He also reports dark urine and mild hepatic dysfunction (AST 2× ULN). Urine uroporphyrin is elevated at 800 μmol/24 h (normal <100), and faecal coproporphyrin is elevated. Plasma porphyrins are normal. What is the most appropriate next step in management?

Explanation

## Porphyria Cutanea Tarda (PCT) Management ### Clinical Diagnosis This patient has **Type I PCT** (sporadic, 80% of cases), characterized by: 1. **Photosensitive skin lesions**: blistering, erosions on sun-exposed areas (hands, face, neck) 2. **Dark urine**: due to elevated urinary uroporphyrin (>600 μmol/24 h is diagnostic) 3. **Elevated urinary and faecal porphyrins**: uroporphyrin and coproporphyrin elevated 4. **Normal plasma porphyrins**: distinguishes PCT from other cutaneous porphyrias (e.g., erythropoietic protoporphyria) 5. **Mild hepatic dysfunction**: common in PCT; often associated with iron overload, HCV, or alcohol **Key Point:** PCT is the most common porphyria and is caused by deficiency of uroporphyrinogen decarboxylase (UROD) in the liver, often triggered by iron overload, hepatitis C, HIV, or alcohol. ### Pathophysiology In PCT, hepatic UROD activity is reduced (acquired or inherited), leading to: - Accumulation of uroporphyrinogen and uroporphyrin in the liver - Excretion in urine and faeces - Photosensitivity due to porphyrin-mediated singlet oxygen generation in skin - Iron overload exacerbates the enzyme defect ### Definitive Management: Phlebotomy | Intervention | Rationale | |--------------|----------| | **Phlebotomy (500 mL every 1–2 weeks)** | Reduces iron stores; iron is a cofactor for porphyrin synthesis. Restores UROD activity. | | **Target ferritin** | 50–100 ng/mL (mild iron depletion); haemoglobin >12 g/dL | | **Monitor urinary porphyrins** | Decline indicates remission; usually achieved after 5–10 phlebotomies | | **Avoid triggers** | Alcohol, oestrogens, NSAIDs, hepatotoxins | **High-Yield:** Phlebotomy is the gold standard and only curative treatment for PCT. It works by removing iron, which restores hepatic UROD activity and normalizes porphyrin synthesis. **Clinical Pearl:** Remission is defined as normalization of urinary uroporphyrin and clinical resolution of skin lesions. Relapse can occur if iron reaccumulates or triggers (e.g., alcohol) resume. ### Why Other Options Are Suboptimal or Wrong **Cholestyramine + sun avoidance:** - Cholestyramine may reduce faecal porphyrin excretion slightly but does NOT address the underlying iron overload or restore UROD activity - Sun avoidance is necessary but is supportive only; it does not induce remission - This approach is passive and incomplete **Hydroxychloroquine:** - Low-dose hydroxychloroquine (100–200 mg daily) can be used as an alternative in patients who cannot tolerate phlebotomy (e.g., anaemia, cardiovascular disease) - However, it is NOT first-line and is slower than phlebotomy - It works by forming complexes with porphyrins, increasing urinary excretion, but does not address iron overload - Response takes 3–6 months **Liver biopsy + ursodeoxycholic acid:** - Liver biopsy is not indicated for diagnosis of PCT (clinical + biochemical findings are sufficient) - Ursodeoxycholic acid is used for cholestasis, not for PCT - This approach misdiagnoses the hepatic involvement as cholestatic disease rather than iron overload **Warning:** Avoid oestrogens (oral contraceptives, HRT) and NSAIDs—both can exacerbate PCT. Screen for and treat HCV and HIV.