How is erythropoietic protoporphyria (EPP) managed?

Management of Erythropoietic Protoporphyria (EPP)

The primary management of erythropoietic protoporphyria (EPP) focuses on minimizing exposure to sunlight and managing hepatotoxic effects of protoporphyrin accumulation, as treatment of the typically mild anemia is not warranted. 1

Understanding EPP

EPP is a rare genetic disorder of heme biosynthesis characterized by:

• Painful photosensitivity beginning in childhood
• Accumulation of protoporphyrin IX (PPIX) in erythrocytes
• Two main variants: autosomal recessive EPP (FECH deficiency) and X-linked protoporphyria (XLEPP)
• Potential complications including liver disease, gallstones, mild anemia, and vitamin D deficiency

Diagnosis

Diagnosis requires biochemical testing to demonstrate typical patterns of heme precursors:

• Quantification of PPIX in erythrocytes with metal-free PPIX ≥3 times the upper limit of normal confirms diagnosis 2
• Fluorescent erythrocytes visible in fresh, unstained blood smear
• Free protoporphyrin (FPP) found in plasma and erythrocytes
• Zinc protoporphyrin (ZnPP) typically increased in XLEPP due to relative iron deficiency 1

Management Algorithm

1. Prevention and Management of Photosensitivity

• Sun avoidance: Primary strategy to prevent painful photosensitivity reactions
• Protective clothing: Long sleeves, wide-brimmed hats, gloves
• Filters for indoor lighting: Block transmission of light with wavelength below 470 nm during surgery or procedures 3
• Afamelanotide: Currently the only approved specific treatment that increases pain-free sunlight exposure and quality of life 2
• For acute phototoxic reactions: Cold water or cold compresses to relieve pain

2. Monitoring for Complications

• Regular liver function monitoring: Critical as hepatic failure is the most serious complication
• Vitamin D levels: Supplement vitamin D to prevent deficiency
• Bone mineral density: Consider DEXA scans in adults 2
• Iron status: Monitor but approach supplementation differently based on EPP variant

3. Management of Iron Deficiency

• For EPP1 (FECH deficiency): Avoid iron supplementation as it may stimulate PPIX production, increasing photosensitivity and risk of cholestatic liver disease
• For XLEPP: Iron supplementation can reduce PPIX levels, phototoxicity, and liver damage 2

4. Management of Liver Disease

For patients who develop liver complications:

• Early intervention: Eliminate any hepatotoxins
• For progressive disease: Consider phlebotomies, exchange transfusions
• For severe disease: Liver transplantation with subsequent hematopoietic stem cell transplantation (HSCT) 2
• Extracorporeal therapy: MARS (molecular adsorbents recirculating system) or Prometheus may be effective in reducing RBC-PPIX concentration before transplantation 3

Special Considerations

Anemia Management

• Since anemia is typically mild in EPP, specific treatment for anemia is generally not warranted 1

Surgery

• Use filters that block light with wavelength below 470 nm to prevent damage to exposed skin and organs during operations 3

Pregnancy

• Requires specialized monitoring and management

Common Pitfalls to Avoid

1. Delayed diagnosis: EPP often has a long diagnostic delay due to limited expertise among physicians
2. Inadequate monitoring: Regular monitoring of liver function is essential as liver failure can progress rapidly
3. Inappropriate iron supplementation: Treatment approach must differ between EPP1 and XLEPP variants
4. Overlooking vitamin D deficiency: Supplementation is important due to sun avoidance
5. Treating EPP as just a skin condition: EPP is a multisystemic disorder requiring comprehensive monitoring and management

EPP management requires a multidisciplinary approach involving dermatologists, hepatologists, and hematologists with expertise in porphyrias to optimize outcomes and prevent serious complications.