From the Guidelines
The workup for porphyria cutanea tarda (PCT) should begin with a comprehensive clinical evaluation and specific laboratory tests to confirm the diagnosis, including measurement of total porphyrins in urine, plasma porphyrin levels, and fecal porphyrins, as recommended by the most recent study 1. The most characteristic finding in PCT is elevated urinary uroporphyrin levels, typically exceeding coproporphyrin levels.
- Initial testing should include:
- Measurement of total porphyrins in urine
- Plasma porphyrin levels
- Fecal porphyrins
- Plasma fluorescence scanning showing a characteristic emission peak at 620 nm is also diagnostic.
- Skin biopsy may reveal subepidermal blistering with festooning of dermal papillae and periodic acid-Schiff (PAS)-positive thickening of blood vessel walls. Once PCT is confirmed, additional testing should be performed to identify underlying contributors, including:
- Hepatitis C serology
- HIV testing
- Hemochromatosis genetic testing (HFE gene mutations)
- Liver function tests
- Ferritin levels to assess iron overload
- Complete blood count
- Renal function tests
- Estrogen levels may also be relevant depending on clinical presentation. Abdominal ultrasound should be considered to evaluate for hepatic involvement, as PCT is often triggered by multiple factors including alcohol use, estrogens, iron overload, and viral hepatitis, and identifying these factors is crucial for effective management of the condition, as highlighted in the recent study 1. It is essential to note that clinical features alone are not specific enough to establish a porphyria diagnosis, and diagnosis in a symptomatic patient depends on demonstration of typical patterns of haem precursors, for most diagnoses in urine, faeces, and blood, as stated in the study 1. Genomic testing should not be used for diagnostic screening in a symptomatic patient without prior biochemical testing having demonstrated increased porphyria-related diagnostic markers, as recommended in the study 1.
From the Research
Diagnosis of Porphyria Cutanea Tarda
- The diagnosis of porphyria cutanea tarda (PCT) is usually fairly straightforward due to its characteristic clinical findings, including blisters and erosions on sun-exposed skin, hypertrichosis, abnormal pigmentation, and milia formation 2.
- Gross examination of the urine can provide a valuable clue, as the urine of PCT patients is red to brown in natural light and pink to red in fluorescent light 2.
- Biopsy of a bullous lesion is useful to rule out other diseases, and confirmation of PCT requires measurement of porphyrin levels in a 24-hour urine collection 2.
Laboratory Tests
- Urinary porphyrins show a stronger correlation with total plasma porphyrin levels than with the free fraction of plasma porphyrins 3.
- Patients with PCT have a higher mean level of total plasma porphyrins and a lower mean percentage of free plasma porphyrins than those in remission 3.
- The urinary profile of porphyrin isomers may remain abnormal even after clinical remission of PCT, with decreased coproporphyrin-to-uroporphyrin ratio and/or inversion of the normal coproporphyrin III-to-coproporphyrin I ratio 4.
Screening for Underlying Conditions
- It is reasonable to screen all patients with PCT for hepatitis C and possibly B, especially those less than 30 years old with extremely high liver transaminase levels 2.
- PCT is associated with haemochromatosis, diabetes mellitus, and hepatitis C infection, and treatment should take these underlying conditions into account 5.
Treatment
- Therapeutic measures for PCT include avoidance of exacerbating factors, such as ultraviolet light, ethanol, and certain medications 2.
- Phlebotomy or chloroquine therapy is reserved for patients in whom conservative measures fail, and the treatment is safe and effective but has its limits in cases with haemochromatosis (HFE) gene mutations 5.