Trusted medical expertise in seconds.

Access 1,000+ clinical and preclinical articles. Find answers fast with the high-powered search feature and clinical tools.

Try free for 5 days
Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer.

Porphyrias

Last updated: June 15, 2021

Summarytoggle arrow icon

Porphyrias are a group of rare, inherited or (less commonly) acquired metabolic disorders in which defective enzymes impair the biosynthesis of heme in the liver and/or bone marrow. All porphyrias are characterized by the accumulation of porphyrin, or intermediates of its biosynthesis, which can cause a variety of symptoms depending on the organs involved (e.g., skin, liver, CNS). Porphyria cutanea tarda (PCT) is the most common form and manifests with chronic, blistering cutaneous photosensitivity and tea-colored urine. The diagnosis of PCT is confirmed by detecting porphyrins in urine or serum. Management consists of rigorous photoprotective measures, regular phlebotomy or low-dose hydroxychloroquine, and avoiding risk factors. The second most common form, acute intermittent porphyria (AIP), is characterized by life-threatening attacks of severe abdominal pain, nausea and vomiting, tachycardia, and neuropsychiatric abnormalities. Attacks are generally triggered by certain medications, alcohol, infections, or fasting. The diagnosis of AIP is confirmed by detecting metabolic heme precursors in urine, which often appears reddish. An important acquired form of porphyria is lead poisoning, which is discussed in another article (see “Metal toxicity”). Patients with a known porphyria should avoid potential triggers. Management of AIP consists of supportive care; acute attacks should be treated with hemin to reduce heme production.

Description

  • Porphyrias are a rare group of inherited or (less commonly) acquired metabolic disorders in which defective enzymes impair the biosynthesis of heme in the liver and/or bone marrow.

Pathophysiology

  • Trigger → ↓ enzyme activity in heme biosynthesis intermediates of heme production accumulate
    • → Deposited into different tissue, such as the skin and/or liver → symptoms
    • → Increased urinary and fecal elimination → metabolite detection
  • The specific intermediates that accumulate depends on which enzymes are affected in the heme biosynthesis pathway.

Classification

Porphyrias can be classified based on inheritance or organ of accumulation.

  • Inheritance: primary (inherited) or secondary (acquired)
  • Organ of accumulation:

Primary porphyrias (hereditary enzyme defect)

Secondary porphyria (acquired)

  • Secondary coproporphyria (caused by e.g., intoxication, hepatic diseases, blood disorders, infections, starvation)
  • Secondary protoporphyrinemia (caused by e.g., anemia, alcohol, or chronic heavy metal poisoning; see metal toxicity)

Epidemiology

  • Most common porphyria [1]
  • Peak incidence: 30–50 years of age [2]

Etiology and pathophysiology [2][3]

Clinical findings [2][3]

PCT manifests clinically as a dermatological disease.

Consider PCT in a patient presenting with a blistering rash on sun-exposed skin.

Diagnosis [2][3]

A high index of suspicion is necessary as the symptoms overlap with several other conditions. Consider PCT in adult patients with a blistering rash on sun-exposed areas (especially the back of the hands) and a known susceptibility factor.

Routine blood studies

Confirmatory diagnostic studies

Management [2][3]

The goal of therapy is to resolve the patient's symptoms by reducing porphyrin levels.

General measures

  • Avoid susceptibility factors; , e.g., smoking, alcohol, and exogenous estrogen.
  • Advise patients on photoprotective measures, including reducing exposure to visible light (e.g., using large particle sunscreens). [6]

Treatment

Ongoing management

Epidemiology

  • Second most common porphyria [1]
  • Peak incidence: 20–30 years of age [2]
  • Sex: >

Etiology and pathophysiology [2]

Triggers of acute porphyric attacks [2][3]

Most triggers increase the demand for hepatic heme, thereby stimulating heme biosynthesis, which, in the setting of an AIP enzyme mutation, results in the accumulation of heme intermediates.

Clinical features [8]

The clinical presentation of AIP is variable and symptoms are often nonspecific. In contrast to some porphyrias, there are no dermatological findings.

The 5 P's of acute intermittent porphyria: Painful abdomen, Polyneuropathy, Psychologic disturbances, Port wine-colored pee, Precipitated by triggers like drugs

The skin is not involved in acute intermittent porphyria.

Diagnosis [2][8]

Diagnosis of AIP is challenging and a high index of suspicion must be maintained. Consider AIP if typical clinical features are seen in the absence of other causes (e.g., unexplained severe abdominal pain accompanied by muscle weakness and dark urine).

Routine studies

Routine laboratory studies and imaging are often normal, and the diagnosis is confirmed with specialized tests.

Confirmatory studies

A 24-hour urine collection is not necessary for the diagnosis of an acute AIP attack and delays diagnosis.

The goal of therapy is to stop the acute attack as quickly as possible while providing supportive and symptomatic care. Hospitalization may be required and specialists (i.e., hematology or hepatology) should be consulted.

Approach [2][3][8]

  • Admit all patients with severe pain, an inability to tolerate oral intake, or a new diagnosis.
  • Identify potential triggers and withdraw unsafe medications if possible (see “Tips & Links” for the drug safety database of the American Porphyria Foundation).
  • Ensure close monitoring (consider ICU admission pending neurological and respiratory status).
  • Monitor daily for:

Treatment

  • Hemin therapy [8]
  • Glucose loading: consider only for mild attacks or as temporizing measure [10][11]

Supportive care [3]

The choice of medications in porphyria patients is complicated and should ideally be agreed upon with a porphyria specialist.

Management of acute attacks of AIP can be challenging; obtain specialist consults early.

Due to the complexity of this rare disease, patients with AIP should receive an evaluation by specialists at a designated porphyria center.

All patients [8]

Severe disease with recurring attacks

Porphyrias vs. lead poisoning
Porphyria cutanea tarda Acute intermittent porphyria Lead poisoning
Defective enzyme
Accumulated substrate
Clinical features
Diagnostics
Treatment

Congenital erythropoietic porphyria (Gunther disease)

Erythropoietic protoporphyria

  1. Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Stroke. In: Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J, eds. Harrisons Manual of Medicine, 20th Edition. McGraw Hill Professional ; 2019.
  2. Caligiuri M, Levi MM, Kaushansky K, et al.. Williams Hematology, 9E. McGraw-Hill Education / Medical ; 2015
  3. Stölzel U, Doss MO, Schuppan D. Clinical Guide and Update on Porphyrias. Gastroenterology. 2019; 157 (2): p.365-381.e4. doi: 10.1053/j.gastro.2019.04.050 . | Open in Read by QxMD
  4. AlGahtani FH, Stuckey R, Alqahtany FS. Secondary hemosiderosis presented by porphyria cutanea tarda in a kidney dialysis patient: A case report. SAGE Open Medical Case Reports. 2020; 8 : p.2050313X2090781. doi: 10.1177/2050313x20907815 . | Open in Read by QxMD
  5. McKane W, Green CA, Farrington K. Porphyria cutanea tarda precipitated by intravenous iron in a haemodialysis patient. Nephrol Dial Transplant. 2001; 16 (9): p.1936-1938. doi: 10.1093/ndt/16.9.1936 . | Open in Read by QxMD
  6. Dawe R. An overview of the cutaneous porphyrias. F1000Res. 2017; 6 : p.1906. doi: 10.12688/f1000research.10101.1 . | Open in Read by QxMD
  7. Baravelli CM, Sandberg S, Aarsand AK, Tollånes MC. Porphyria cutanea tarda increases risk of hepatocellular carcinoma and premature death: a nationwide cohort study. Orphanet J Rare Dis. 2019; 14 (1). doi: 10.1186/s13023-019-1051-3 . | Open in Read by QxMD
  8. Anderson KE, Bloomer JR, Bonkovsky HL, et al. Recommendations for the Diagnosis and Treatment of the Acute Porphyrias. Ann Intern Med. 2005; 142 (6): p.439. doi: 10.7326/0003-4819-142-6-200503150-00010 . | Open in Read by QxMD
  9. Bicknell SG, Stewart JD. Neuroimaging Findings in Acute Intermittent Porphyria. Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques. 2011; 38 (4): p.656-658. doi: 10.1017/s0317167100012221 . | Open in Read by QxMD
  10. Pischik E, Kauppinen R. An update of clinical management of acute intermittent porphyria. The Application of Clinical Genetics. 2015 : p.201. doi: 10.2147/tacg.s48605 . | Open in Read by QxMD
  11. Stein P, Badminton M, Barth J, Rees D, Stewart MF. Best practice guidelines on clinical management of acute attacks of porphyria and their complications. Ann Clin Biochem. 2013; 50 (3): p.217-223. doi: 10.1177/0004563212474555 . | Open in Read by QxMD
  12. Yarra P, Faust D, Bennett M, Rudnick S, Bonkovsky HL. Benefits of prophylactic heme therapy in severe acute intermittent porphyria. Mol Genet Metab. 2019; 19 : p.100450. doi: 10.1016/j.ymgmr.2019.01.002 . | Open in Read by QxMD
  13. Balwani M, Sardh E, Ventura P, et al. Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria. N Engl J Med. 2020; 382 (24): p.2289-2301. doi: 10.1056/nejmoa1913147 . | Open in Read by QxMD