Highlights
- •Porphyrias are a group of 8 metabolic diseases of the heme synthesis pathway.
- •Clinically, they are divided in neurovisceral, cutaneous bullous and non-bullous.
- •Each porphyria has its own pattern of porphyrin excretion, allowing easy diagnosis.
- •Treatment relies on patient education, trigger removal and support therapy.
- •As rare diseases, physician awareness is vital to timely and adequate management.
Abstract
Background
Porphyrias are a group of metabolic diseases, individually rare but with an important
combined prevalence. Because of their pathological complexity and clinical heterogeneity,
they present a challenging diagnosis. The present review aims to provide a clinically
based approach to the recognition and treatment of these disorders.
Methods
We carried out a search in PubMed, with the keyword “porphyria”, for reviews published
in English from 2010 until 2017.
Results
The research yielded 196 papers, of which 64 were included in the final narrative
review.
Conclusions
Porphyrias can be divided based on clinical presentation in acute neurovisceral, chronic
cutaneous bullous, chronic cutaneous non-bullous and acute neurovisceral/chronic cutaneous
bullous. Each individual porphyria presents a characteristic pattern of porphyrins
in plasma, urine, stool and red blood cells. As such, diagnosis is easily obtained
by following a simple diagnostic algorithm. Early recognition is key in managing these
diseases. Neurovisceral porphyrias require acute support therapy and chronic eviction
of precipitating factors. Cutaneous prophyrias, as photosensitivity disorders, rely
on sunlight avoidance and, in some cases, specific therapeutic interventions. Given
the rarity of these conditions, physician awareness is crucial.
Keywords
Abbreviations:
ALA (delta-aminolevulinic acid), ALAD (delta-aminolevulinic acid dehydratase), ALAS2 (delta′-aminolevulinate synthase 2), CPOX (coproporphyrinogen oxidase), FECH (ferrochelatase), GATA1 (erythroid transcription factor), HFE (human hemochromatosis), PBG (porphobilinogen), PBGD (porphobilinogen deaminase), PCT (porphyria cutanea tarda), PPOX (protoporphyrinogen oxidase), RBC (red blood cells), UROD (uroporphyrinogen decarboxylase), UROS (uroporphyrinogen III synthase)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of Internal MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Acute hepatic porphyria.J Clin Transl Hepatol. 2015; 3: 17-26
- Complex gene-chemical interactions: hepatic uroporphyria as a paradigm.Chem ResToxicol. 2010; 23: 712-723
- Porphyria and its neurologic manifestations.Handb Clin Neurol. 2014; 120: 839-849
- Variegate porphyria. 2013 Feb 14.in: Pagon R.A. Adam M.P. Ardinger H.H. Wallace S.E. Amemiya A. Bean L.J.H. GeneReviews(R) [Internet]. University of Washington, Seattle, Seattle (WA)1993–2018 (All rights reserved)
- Porphyrias at a glance: diagnosis and treatment.Intern Emerg Med. 2010; 5: S73-S80
- Liver disease and erythropoietic protoporphyria: a concise review.World J Gastroenterol. 2010; 16: 4526-4531
- Porphyria cutanea tarda—when skin meets liver.Best Pract Res Clin Gastroenterol. 2010; 24: 735-745
- Purple pigments: the pathophysiology of acute porphyric neuropathy.Clin Neurophysiol. 2011; 122: 2336-2344
- The neurologic manifestations of the acute porphyrias.J Clin Neurosci. 2011; 18: 1147-1153
- Psychiatric signs and symptoms in treatable inborn errors of metabolism.J Neurol. 2014; 261: S559-S568
- Drugs in porphyria: from observation to a modern algorithm-based system for the prediction of porphyrogenicity.Pharmacol Ther. 2011; 132: 158-169
- Diagnostic and treatment implications of psychosis secondary to treatable metabolic disorders in adults: a systematic review.Orphanet J Rare Dis. 2014; 9: 65
- Drugs and acute porphyrias: reasons for a hazardous relationship.Postgrad Med. 2014; 126: 108-120
- A challenging diagnosis for potential fatal diseases: recommendations for diagnosing acute porphyrias.Eur J Intern Med. 2014; 25: 497-505
- A review of the clinical presentation, natural history and inheritance of variegate porphyria: its implausibility as the source of the ‘Royal Malady’.J Clin Pathol. 2012; 65: 200-205
- Porphyrin and heme metabolism and the porphyrias.Compr Physiol. 2013; 3: 365-401
- Acute porphyrias.J Emerg Med. 2015; 49: 305-312
- Liver transplantation in the management of porphyria.Hepatology. 2014; 60: 1082-1089
- Dermatologic extrahepatic manifestations of hepatitis C.J Clin Transl Hepatol. 2015; 3: 127-133
- Porphyrias: a 2015 update.Clin Res Hepatol Gastroenterol. 2015; 39: 412-425
- Porphyrias.Lancet. 2010; 375: 924-937
- The porphyrias: advances in diagnosis and treatment.Hematology Am Soc Hematol Educ Program. 2012; 2012: 19-27
- Clinically important features of porphyrin and heme metabolism and the porphyrias.Metabolites. 2014; 4: 977-1006
- The cutaneous porphyrias.Dermatol Clin. 2014; 32 ([ix]): 369-384
- Cutaneous porphyrias part I: epidemiology, pathogenesis, presentation, diagnosis, and histopathology.Int J Dermatol. 2013; 52: 1464-1480
- The acute hepatic porphyrias: current status and future challenges.Best Pract Res Clin Gastroenterol. 2010; 24: 593-605
- Photosensitivity disorders in children: part I.J Am Acad Dermatol. 2012; 67 (1093.e1-18; quiz 1111-2)
- Acute ntermittent porphyria. 2005 Sep 27 [Updated 2013 Feb 7].in: Pagon R.A. Adam M.P. Ardinger H.H. GeneReviews(R) [Internet]. University of Washington, Seattle, Seattle (WA)1993-2016
- Hereditary coproporphyria. 2012 Dec 13 [updated 2018 Nov 8].in: Pagon R.A. Adam M.P. Ardinger H.H. Wallace S.E. Amemiya A. Bean L.J.H. GeneReviews(R) [Internet]. University of Washington, Seattle, Seattle (WA)1993–2016
- An update of clinical management of acute intermittent porphyria.Appl Clin Genet. 2015; 8: 201-214
- The neuropsychiatry of inborn errors of metabolism.J Inherit Metab Dis. 2013; 36: 687-702
- Emergency management of acute abdomen in children.Indian J Pediatr. 2013; 80: 226-234
- Psychiatric manifestations of treatable hereditary metabolic disorders in adults.Ann Gen Psychiatry. 2014; 13: 27
- Metabolic pancreatitis: etiopathogenesis and management.Indian J Endocrinol Metab. 2013; 17: 799-805
- Medical conditions with neuropsychiatric manifestations.Med Clin North Am. 2014; 98: 1193-1208
- Acute intermittent porphyria presenting solely with psychosis: a case report and discussion.Psychosomatics. 2012; 53: 494-498
- Hepatitis C, porphyria cutanea tarda and liver iron: an update.Liver Int. 2012; 32: 880-893
- Cutaneous porphyrias part II: treatment strategies.Int J Dermatol. 2014; 53: 3-24
- The role of nutrition in dermatologic diseases: facts and controversies.Clin Dermatol. 2013; 31: 677-700
- Review of hepatocellular cancer, hypertension and renal impairment as late complications of acute porphyria and recommendations for patient follow-up.J Clin Pathol. 2012; 65: 976-980
- Risk of HCC: genetic heterogeneity and complex genetics.J Hepatol. 2010; 52: 252-257
- Advances in understanding the pathogenesis of congenital erythropoietic porphyria.Br J Haematol. 2016; 173: 365-379
- Cutaneous manifestations of hepatitis C in the era of new antiviral agents.World J Hepatol. 2015; 7: 2740-2748
- Non-HFE hepatic iron overload.Semin Liver Dis. 2011; 31: 302-318
- Dermatologic manifestations of hepatitis C infection and the effect of interferon therapy: a literature review.Arch Iran Med. 2012; 15: 43-48
- Update on photodermatoses.Semin Cutan Med Surg. 2011; 30: 229-238
- Erythropoietic protoporphyria, autosomal recessive. 2012 Sep 27 [Updated 2017 Sep 7].in: Pagon R.A. Adam M.P. Ardinger H.H. GeneReviews(R) [Internet]. University of Washington, Seattle, Seattle (WA)1993–2016
- Nutrition and bullous skin diseases.Clin Dermatol. 2010; 28: 627-643
- Congenital erythropoietic porphyria. 2013 Sep 12 [Updated 2016 Apr 7].in: Pagon R.A. Adam M.P. Ardinger H.H. GeneReviews(R) [Internet]. University of Washington, Seattle, Seattle (WA)1993-2018
- Hepatoerythropoietic porphyria. 2013 Oct 31. [Updated 2016 Dec 22].in: Pagon R.A. Adam M.P. Ardinger H.H. GeneReviews(R) [Internet]. University of Washington, Seattle, Seattle (WA)1993–2018
- Porphyrias consortium of the rare diseases clinical research network. 2013 Jun 6 [Updated 2016 Sep 8].in: Pagon R.A. Adam M.P. Ardinger H.H. GeneReviews(R) [Internet]. University of Washington, Seattle, Seattle (WA)1993-2018
- Diagnosis of common dermopathies in dialysis patients: a review and update.Semin Dial. 2012; 25: 408-418
- Cutaneous manifestations of common liver diseases.J Clin Exp Hepatol. 2011; 1: 177-184
- Current applications of therapeutic phlebotomy.Blood Transfus. 2014; 12: s75-s83
- Heme and erythropoieis: more than a structural role.Haematologica. 2014; 99: 973-983
- Morphologic features of extrahepatic manifestations of hepatitis C virus infection.Clin Dev Immunol. 2012; 2012: 740138
- Role of genetic testing in the management of patients with inherited porphyria and their families.Ann Clin Biochem. 2013; 50 (Pt 3): 204-216
- Structure and function of enzymes in heme biosynthesis.Protein Sci. 2010; 19: 1137-1161
- Skin biopsy: biopsy issues in specific diseases.J Am Acad Dermatol. 2016; 74 ([quiz 17-8]): 1-16
- Complement in skin diseases.Acta Dermatovenerol Alp Pannonica Adriat. 2011; 20: 3-11
- Cutaneous deposits.Am J Dermatopathol. 2014; 36: 1-48
- Direct and indirect immunofluorescence.An Bras Dermatol. 2010; 85: 490-500
- Role of therapeutic apheresis and phlebotomy techniques in anaesthesia and critical care.Indian J Anaesth. 2014; 58: 672-678
- Afamelanotide (CUV1647) in dermal phototoxicity of erythropoietic protoporphyria.Expert Rev Clin Pharmacol. 2015; 8: 43-53
Article info
Publication history
Published online: June 27, 2019
Accepted:
June 21,
2019
Received in revised form:
June 19,
2019
Received:
January 18,
2019
Identification
Copyright
© 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
