How to diagnose porphyria cutanea tarda?

Diagnosis of Porphyria Cutanea Tarda

The diagnosis of porphyria cutanea tarda (PCT) requires demonstration of typical patterns of heme precursors in urine, with urine porphyrin analysis being the standard initial diagnostic approach. 1

Clinical Presentation

• Characteristic skin findings:

  • Bullae and erosions on sun-exposed areas (particularly hands and face)
  • Skin fragility
  • Hyperpigmentation
  • Hypertrichosis (excessive hair growth)
  • Milia formation (small white cysts)
  • Sclerodermoid plaques in some cases

• Visual examination of urine:

  • Red to brown color in natural light
  • Pink to red fluorescence under fluorescent light 2

Diagnostic Algorithm

First-Line Testing

1. 24-hour urine porphyrin analysis (gold standard initial test)

   • Characteristic pattern: elevated uroporphyrins and hepta-carboxyl porphyrins 3, 1
   • This pattern is essential for confirming PCT diagnosis

2. Plasma fluorescence scanning

   • Particularly useful for patients with active cutaneous symptoms
   • Shows characteristic emission wavelengths specific to PCT 3
   • Can facilitate diagnosis in patients with renal failure who may be anuric

Second-Line Testing

1. Fecal porphyrin analysis

   • Predominance of hepta-, penta-, and isocoproporphyrins 3
   • Helps differentiate PCT from other cutaneous porphyrias

2. Liver function tests

   • Often shows elevated transaminases due to frequent liver involvement 2

3. Iron studies

   • Serum ferritin, transferrin saturation
   • Iron stores are usually elevated in PCT 2, 4

4. Skin biopsy

   • Useful to rule out other blistering disorders
   • Shows subepidermal blistering with minimal inflammation 2

Additional Testing for Risk Factors

Once PCT is confirmed, screen for associated conditions:

1. Hepatitis C testing - strongly associated with PCT 3, 4

   • Particularly important in patients <30 years with high transaminase levels 2

2. Hepatitis B screening 2

3. HIV testing - can be associated with PCT 4

4. Genetic testing for hemochromatosis

   • HFE gene mutations (C282Y, H63D) 5, 4
   • Important for familial PCT cases

5. Assessment for alcohol use disorder 4

6. Medication review - especially estrogens 1, 4

Differentiating PCT Types

• Type I (sporadic PCT) - 80% of cases

  • UROD deficiency limited to liver
  • Normal UROD activity in erythrocytes

• Type II (familial PCT)

  • Autosomal dominant inheritance
  • UROD activity decreased by approximately 50% in all tissues including erythrocytes
  • Consider genetic testing of UROD gene 3, 6

Common Pitfalls to Avoid

1. Relying solely on clinical presentation - clinical features alone are not specific enough to establish a porphyria diagnosis 3

2. Using genomic testing as initial screening - biochemical testing demonstrating increased porphyria-related markers should precede genetic testing 3

3. Failing to screen for hepatitis C - given the strong association, all PCT patients should be screened 3, 2

4. Overlooking simple visual examination of urine - the characteristic color change can provide valuable initial diagnostic clues 2

5. Confusing PCT with other cutaneous porphyrias - proper fractionation of porphyrins is essential for accurate diagnosis 3

By following this systematic diagnostic approach, PCT can be accurately diagnosed, allowing for appropriate management including avoidance of exacerbating factors, phlebotomy for iron reduction, and/or low-dose antimalarial therapy when indicated.