How is porphyria treated, including management of acute attacks and chronic disease?

Treatment of Porphyria

For acute hepatic porphyria attacks, immediately discontinue all porphyrinogenic drugs and initiate intravenous hemin (3-4 mg/kg/day) combined with intravenous dextrose, which is the first-line therapy that should be started promptly once diagnosis is confirmed. 1, 2

Acute Attack Management

Immediate Interventions

• Stop all porphyrinogenic medications and chemicals immediately upon suspicion of an acute attack, even before biochemical confirmation is available 1, 3
• Administer intravenous hemin at 3-4 mg/kg/day as the treatment of choice for acute attacks; this should be given via peripherally inserted central catheter 4, 1, 2
• Provide intravenous dextrose (approximately 400 g per day for 1-2 days) to suppress hepatic heme synthesis during the acute phase 1, 3
• Treatment effectiveness is significantly improved when hemin is administered within 24 hours of symptom onset (50% of patients in registry data received treatment within 1 day) 2

Symptomatic Management

• Provide aggressive pain control with analgesics for severe abdominal pain, which is the most common presenting symptom 1, 3
• Administer antiemetics for nausea and vomiting 1, 3
• Monitor and actively correct hyponatremia, which occurs in 25-60% of acute attacks 1, 3

Common Pitfall: Do not delay hemin therapy while awaiting genetic confirmation—biochemical markers (elevated urinary PBG/ALA >10 times upper limit of normal) are sufficient to initiate treatment 1. Oral glucose tablets or concentrated dextrose solutions given early in an attack have not demonstrated clear clinical benefit 1.

Prophylactic Therapy for Recurrent Disease

Indications and Regimens

• Patients experiencing ≥4 attacks per year should receive prophylactic therapy with either intravenous hemin or subcutaneous givosiran 1, 5, 3
• Prophylactic hemin can be administered weekly, bi-weekly, or monthly; however, dosing less frequent than weekly may be insufficient because heme is rapidly catabolized by heme-oxygenase 1
• For menstrual-cycle-related attacks, administer one or two hemin infusions during the luteal phase to reduce crisis frequency 1, 5
• In registry data, 68% (21/31) of patients who received hemin prophylaxis for >1 month did not require subsequent hemin treatment for acute attacks 2

Monitoring During Prophylaxis

• Measure serum ferritin every 3-6 months (or after approximately 12 hemin doses) because each hemin dose contains about 9% iron by weight 1
• Initiate therapeutic phlebotomy when ferritin exceeds 1000 ng/mL, with a target reduction to approximately 150 ng/mL 1

Long-Term Management and Monitoring

Avoidance of Triggering Factors

• All patients must avoid known porphyrinogenic medications, prolonged fasting, alcohol, and tobacco use 1, 5
• Maintain adequate caloric intake and avoid fasting to prevent metabolic decompensation 1, 5
• Before initiating any new medication, consult publicly available drug-interaction databases to ensure the agent is not porphyrinogenic 1
• Patients should receive special identification cards and up-to-date lists of safe drugs 6

Annual Monitoring Requirements

The American Gastroenterological Association recommends the following baseline and annual assessments 4, 1:

• Complete blood count and serum ferritin 1, 3
• Liver function tests (transaminases are elevated in approximately 13% of attacks) 1, 3
• Comprehensive metabolic panel with estimated glomerular filtration rate (eGFR) to monitor renal function 4, 1, 3
• Screen for iron deficiency, especially in young women 1, 3

Surveillance for Long-Term Complications

• Perform liver imaging every 6-12 months after age 50 in patients with recurrent attacks or prior hepatic symptoms to screen for hepatocellular carcinoma (HCC), as these patients have markedly increased risk 4, 1, 3
• Monitor for chronic kidney disease (typically chronic tubulointerstitial nephropathy or focal cortical atrophy) with annual eGFR and urinary protein-to-creatinine ratio 4, 3
• Aggressively control systemic arterial hypertension to help prevent renal damage 4, 3
• Screen for osteoporosis and vitamin D deficiency 1
• Patients with recurrent attacks have a high chronic disease burden: 65% report chronic symptoms (most commonly pain, fatigue, anxiety, nausea), with 46% reporting daily symptoms 4

Enhanced Monitoring for Patients on Givosiran

• Perform comprehensive metabolic panel, plasma homocysteine, urinalysis, urinary protein-to-creatinine ratio, and B12/folate before starting givosiran 4
• Repeat these tests before each monthly injection for 3 months, then every 3 months for the next year if stable, and at least every 6 months thereafter 4
• Monitor eGFR more frequently as givosiran may be associated with worsening renal function in a subset of patients 4

Special Populations

Women of Reproductive Age

• All women with acute hepatic porphyria planning pregnancy should receive pre-conception evaluation 1, 5, 3
• High-risk obstetric care is required during pregnancy because hormonal fluctuations increase attack risk 1, 5, 3
• Avoid progestin-containing contraceptives as they may precipitate attacks; consider alternative low-dose hormonal methods or GnRH analogues 1, 5
• Consider prophylactic hemin during the luteal phase for menstrual-related attacks 1, 5

Perioperative Management

• Administer routine intravenous fluids containing dextrose to fasting patients to prevent metabolic decompensation 1

Definitive Therapy

Transplantation Options

• Orthotopic liver transplantation is curative and should be considered for patients with severe, disabling, or hemin-refractory attacks 1, 5, 3
• Combined liver-kidney transplantation may benefit patients with both recurrent attacks and end-stage renal disease 1, 5, 3
• Kidney transplantation alone is the treatment of choice for patients with end-stage renal disease secondary to acute hepatic porphyria, as ALA and PBG levels can increase significantly between dialysis sessions 4
• Liver transplantation carries significant morbidity and mortality and is regarded as a last-resort option 1

Patient Classification System

The American Association for the Study of Liver Diseases stratifies patients into four subgroups to guide follow-up frequency and management intensity 1, 5, 3:

1. Latent genetic mutation carriers (no symptoms, normal biochemistry)
2. Asymptomatic high excretors (elevated porphyrin precursors but no symptoms)
3. Sporadic attack patients (infrequent attacks, <4 per year)
4. Recurrent attack patients (≥4 attacks per year)

This classification determines the intensity of monitoring, with recurrent attack patients requiring more frequent follow-up and consideration for prophylactic therapy 5, 3.

Treatment of Non-Acute (Cutaneous) Porphyrias

Porphyria Cutanea Tarda

• Iron depletion through phlebotomy is beneficial 7
• Hydroxychloroquine therapy is effective 7
• Elimination of hepatitis C virus if applicable 7

Erythropoietic Protoporphyria and X-Linked Protoporphyria

• α-melanocyte-stimulating hormone analogue can reduce sunlight sensitivity 7