What is the management and treatment for porphyria?

Management and Treatment for Porphyria

The management of acute porphyria attacks requires immediate intravenous hemin administration at 3-4 mg/kg body weight daily for typically 4 days, preferably into a high-flow central vein, along with aggressive pain control, antiemetics, and management of electrolyte abnormalities. 1

Types of Porphyria

• Porphyrias are rare inherited disorders of heme biosynthesis caused by specific enzyme deficiencies in the heme pathway 1, 2
• They are classified into two main categories:
  • Acute hepatic porphyrias (AHPs): Include acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and 5-aminolevulinic acid dehydratase deficiency porphyria (ALAD) 1, 3
  • Cutaneous porphyrias: Include porphyria cutánea tarda (PCT), erythropoietic protoporphyria (EPP), and congenital erythropoietic porphyria 2, 4

Acute Attack Management

First-Line Treatment

• Intravenous hemin therapy is the cornerstone of treatment for acute attacks requiring hospitalization 1
  • Dosage: 3-4 mg/kg body weight once daily, typically for 4 days 1
  • Administration: Preferably into a high-flow central vein via a peripherally inserted central catheter or central port 1
  • Heme bound to human serum albumin is preferred to reduce vein irritation 1
  • Collect random urine for ALA, PBG, and creatinine before starting treatment 1

Supportive Care During Acute Attacks

• Aggressive pain management with appropriate analgesics 1
• Antiemetics for nausea and vomiting 1
• Intravenous carbohydrate loading (approximately 300 g/day in adults) during early stages 1
• Monitor and correct electrolyte abnormalities:
  • Hyponatremia (most common) 1, 3
  • Hypomagnesemia 1, 3
• For seizures, use only safe anticonvulsants:
  • Magnesium sulfate, benzodiazepines, and levetiracetam 1
  • Avoid barbiturates, hydantoins, carbamazepine, and valproic acid 1

Prevention of Acute Attacks

• Identify and eliminate precipitating factors 1:
  • Medications that induce cytochrome P450 1
  • Alcohol consumption 1
  • Hormonal fluctuations (particularly progesterone) 1
  • Physical or psychological stress 1
  • Fasting or caloric deprivation 1
  • Infections or acute illnesses 1
• Consult drug safety databases for porphyria (available at porphyria.org and drugs-porphyria.org) 1

Prophylactic Treatment for Recurrent Attacks

• For patients with 4 or more attacks per year, consider prophylactic therapy 1:
  • Scheduled intravenous hemin infusions 1
  • Subcutaneous givosiran (RNA interference therapy targeting ALAS1) 1, 2
• For women with menstrual cycle-associated attacks, consider hormonal suppression therapy (GnRH agonists) 1
• In cases of intractable symptoms that have failed other treatments, liver transplantation may be considered as a curative option 1

Management of Cutaneous Porphyrias

• For porphyria cutanea tarda:
  • Iron depletion therapy 5
  • Hydroxychloroquine 5
  • Treatment of hepatitis C virus if present 5
• For erythropoietic protoporphyria:
  • α-melanocyte-stimulating hormone analogues to reduce sunlight sensitivity 5
  • Sun protection measures 4

Long-Term Monitoring

• Regular monitoring for complications:
  • Hepatocellular carcinoma 1
  • Chronic renal disease 1
  • Hypertension 1, 2
  • Chronic neuropathy 1

Special Considerations

• Genetic testing for family members of affected individuals to identify at-risk relatives 1, 6
• Pregnancy management requires special attention as approximately 50% of women with AIP may experience an attack during pregnancy or postpartum 2
• Careful selection of safe medications for all medical conditions in patients with porphyria 1, 6

Diagnostic Confirmation

• Biochemical testing with urinary porphobilinogen (PBG) and ALA levels during acute attacks 1, 6
• Genetic testing to confirm specific type of porphyria after biochemical confirmation 1