Management of Porphyria
The management of acute hepatic porphyrias centers on immediate discontinuation of porphyrinogenic triggers, administration of intravenous hemin and dextrose during acute attacks, and prophylactic therapy with hemin or givosiran for patients experiencing 4 or more attacks per year. 1
Acute Attack Management
Immediate Interventions
- Stop all porphyrinogenic drugs and chemicals immediately upon suspicion of an acute attack, even before biochemical confirmation 1
- Administer oral or intravenous dextrose (glucose) to suppress hepatic heme synthesis 1, 2
- Initiate intravenous hemin therapy early in the acute phase, which is the treatment of choice for acute attacks 1, 3
- Provide aggressive symptomatic management with analgesics for severe abdominal pain and antiemetics for nausea/vomiting 1
- Monitor and correct hyponatremia, which occurs in 25-60% of acute attacks 1, 4
- Ensure intensive care monitoring for cardiovascular symptoms (tachycardia, hypertension) and neurological complications 1, 5
Common Pitfall
The average diagnostic delay is 15 years from symptom onset, so maintain a high index of suspicion in women aged 15-50 years with recurrent unexplained severe abdominal pain 6. Do not wait for complete diagnostic workup to discontinue suspected porphyrinogenic medications 3.
Long-Term Prevention Strategies
Trigger Avoidance (All Patients)
- Strictly avoid porphyrinogenic drugs - provide patients with identification cards and updated safe drug lists 1, 7, 3
- Limit alcohol consumption and avoid smoking 7
- Maintain adequate caloric intake and avoid fasting, as caloric restriction can precipitate attacks 7
- Manage stress appropriately through counseling and support 7
- Exercise caution with hormonal treatments, particularly progestins, which frequently trigger attacks 7, 4
Prophylactic Therapy for Recurrent Attacks
- Patients with 4 or more acute attacks per year should receive prophylactic therapy with either intravenous hemin or subcutaneous givosiran 1
- Prophylactic hemin can be administered weekly or once-twice during the luteal phase for menstrual cycle-related attacks 7
- Patients on prophylactic hemin or givosiran require additional monitoring including comprehensive metabolic panel, plasma homocysteine, B12/folate levels, and amylase/lipase 4
Patient Classification and Monitoring
Risk Stratification
The American Association for the Study of Liver Diseases classifies patients into four subgroups that determine management intensity 7, 4:
- Latent genetic mutation carriers (minimal monitoring)
- Asymptomatic high excretors (annual monitoring)
- Sporadic attack patients (annual follow-up)
- Recurrent attack patients (close monitoring tailored to attack frequency)
Baseline and Annual Monitoring (All Confirmed Cases)
- Complete blood count and ferritin levels at baseline and yearly 1
- Liver function tests (aminotransferases elevated in ~13% during attacks) 1
- Metabolic panel including estimated glomerular filtration rate (eGFR) for renal function 1, 4
- Screen for iron deficiency, which is common in young women and should be treated 1
Long-Term Complication Surveillance
- Screen for hepatocellular carcinoma in all patients with confirmed acute hepatic porphyria, as they carry increased risk 1, 4
- Monitor for chronic kidney disease, typically chronic tubulointerstitial nephropathy or focal cortical atrophy 1, 4
- Aggressively monitor and treat hypertension, which may help prevent renal damage 1, 4
- Screen for osteoporosis, vitamin D deficiency, and anemia 4
- Refer to nephrology if hypertension is not controlled by first-line treatment or when renal dysfunction is first recognized 1
Neurological Assessment
- Obtain neurological consultation for persistent neurological findings or unexplained symptoms between attacks 1
- Perform nerve conduction and electromyographic studies if chronic neuropathy is suspected as the cause of ongoing pain, sensory loss, or muscle weakness 1
- More than 50% of patients with recurrent attacks develop chronic neurologic symptoms requiring neurology involvement 6
Special Populations
Women of Childbearing Age
- Provide pre-conception evaluation for all women with acute hepatic porphyrias planning pregnancy 7, 4
- Arrange high-risk obstetrical care during pregnancy, as hormonal changes increase attack risk 7, 4, 6
- Carefully select contraceptives - progestin-containing contraceptives may trigger attacks and should be avoided 7, 4
Genetic Testing and Family Screening
- Confirm diagnosis after initial treatment by genetic testing for pathogenic variants in HMBS, CPOX, PPOX, and ALAD genes 1
- Once a mutation is identified in an index case, test at-risk family members 1
- Genetic testing is not first-line because there are no common mutations (except founder mutations in Scandinavia for AIP and South Africa for VP) 1
Definitive Treatment Options
Liver Transplantation
- Orthotopic liver transplantation is curative and should be considered for patients with intractable symptoms who have failed other treatment options 1, 7
- Reserved for patients with severe, disabling attacks or attacks refractory to hemin therapy 7
Renal Transplantation
- Renal transplantation benefits patients with advanced renal disease 7
- Combined liver-kidney transplantation may benefit patients with both recurrent attacks and end-stage renal disease 7, 6
Cutaneous Porphyrias (Non-Acute Types)
Porphyria Cutanea Tarda
- Avoidance of triggering factors including alcohol and estrogens 8
- Iron depletion through phlebotomy is the hallmark treatment 8
- Low-dose chloroquine therapy for porphyrin elimination - safe and effective but has limits in cases with HFE gene mutations 8
- Eliminate hepatitis C virus if applicable 9
- In chronic hemodialysis-associated PCT, chloroquine is ineffective; use erythropoietin, desferroxamine, or small-volume phlebotomy 8