Dermatology MCQ - Genetic Disorders - Familial (Type II) Porphyria Cutanea Tarda

A 55-year-old man with a history of chronic hepatitis C and moderate alcohol use presents with increased skin fragility, blisters, and erosions on the dorsal aspects of his hands. He also notes new, hypertrichosis on his temples and hyperpigmentation on his face. His urine appears reddish-brown. Which laboratory finding is most specific for confirming the diagnosis?

A. Elevated total serum porphyrins.
B. Elevated urinary uroporphyrin and heptacarboxyl porphyrin, with normal urinary aminolevulinic acid (ALA) and porphobilinogen (PBG).
C. Elevated urinary aminolevulinic acid (ALA) and porphobilinogen (PBG).
D. Elevated erythrocyte protoporphyrin.
E. Elevated fecal protoporphyrin.

Correct Answer: B. Elevated urinary uroporphyrin and heptacarboxyl porphyrin, with normal urinary aminolevulinic acid (ALA) and porphobilinogen (PBG).

Answer and Explanation

The correct answer is B. This question describes the classic presentation of Familial (Type II) Porphyria Cutanea Tarda, the blistering or cutaneous porphyria. This is due to a heterozygous mutation in the UROD gene inherited in an autosomal dominant manner. The key clues are the skin fragility, blisters, and erosions on sun-exposed areas (dorsal hands), along with hypertrichosis and hyperpigmentation in a patient with liver disease risk factors (hepatitis C, alcohol). The reddish-brown urine is due to excess porphyrins. PCT results from a deficiency of uroporphyrinogen decarboxylase (UROD) in the liver. The diagnostic biochemical hallmark is a specific urinary porphyrin profile: marked elevation of uroporphyrin and heptacarboxyl porphyrin, while ALA and PBG are normal. This distinguishes it from the acute hepatic porphyrias (which have elevated ALA/PBG) and erythropoietic porphyrias.

Why the Other Options are Incorrect:

• A. Elevated total serum porphyrins: This is sensitive but not specific. Serum porphyrins are elevated in all cutaneous porphyrias. The specific pattern (urinary vs. fecal, types of porphyrins) is needed for diagnosis.

• C. Elevated urinary aminolevulinic acid (ALA) and porphobilinogen (PBG): This is the hallmark of the acute hepatic porphyrias (Acute Intermittent Porphyria, Variegate Porphyria, Hereditary Coproporphyria). These cause acute neurovisceral attacks, not the chronic blistering photosensitivity of PCT.

• D. Elevated erythrocyte protoporphyrin: This is diagnostic for Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP), which present with acute, painful, non-blistering photosensitivity, often in childhood.

• E. Elevated fecal protoporphyrin: Markedly elevated fecal protoporphyrin is characteristic of Variegate Porphyria (VP), which can have both blistering skin lesions and acute attacks. Fecal porphyrins in PCT are typically only mildly elevated.

Additional High-Yield Information for Exams:

• Pathogenesis: PCT is due to acquired inhibition of hepatic UROD activity. This is triggered by: Iron overload (most important), Alcohol, Hepatitis C, HIV, Estrogens, and mutations in the HFE gene (hemochromatosis).

• Clinical Features:

  • Cutaneous: Skin fragility and bullae on sun-exposed dorsal hands, forearms, face. Milia, scarring, and hyperpigmentation. Hypertrichosis (especially periorbital). Pseudoscleroderma (sclerodermoid changes on sun-exposed areas).

  • Urine: May be reddish-brown ("port-wine" colored) due to excess porphyrins, especially when left standing.

• Diagnostic Workup:

  • First-line Screening: Plasma or urine porphyrin fluorescence emission spectroscopy. A peak at ~618-620 nm is highly suggestive of a porphyria.

  • Confirmatory: Quantitative 24-hour urine porphyrin analysis showing the specific pattern in answer B. Also check serum ferritin and iron studies (often elevated).

• Differential Diagnosis: Other causes of blistering on sun-exposed skin: Pseudoporphyria (drug-induced, identical skin findings but normal porphyrins), Epidermolysis Bullosa Acquisita, Bullous SLE, and other porphyrias (VP, HCP).

• Associated Conditions & Prognosis:

  • Liver Disease: Underlying liver disease (HCV, alcoholic, hemochromatosis) is common. There is an increased risk of hepatocellular carcinoma.

  • Prognosis: Excellent with treatment. Skin lesions heal without scarring if treated early.

• Management & Rationale:

  • Rationale: The goal is to reduce hepatic iron and eliminate triggering factors to restore UROD activity.

  • First-line/Treatment of Choice: Regular phlebotomy (removing 1 unit of blood every 1-2 weeks) until serum ferritin is at the lower limit of normal. This depletes hepatic iron stores and induces remission in >90% of patients.

  • Alternative: Low-dose oral hydroxychloroquine (or chloroquine). It complexes with porphyrins and promotes their excretion. Used if phlebotomy is contraindicated.

  • Lifestyle/Prevention: Sun protection (clothing, sunscreens with iron oxide), alcohol cessation, discontinuation of estrogens if applicable, and treatment of underlying hepatitis C.

  • Monitoring: Monitor clinical response and serum ferritin. Monitor liver function and screen for hepatocellular carcinoma in patients with cirrhosis.