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Acute Porphyria Follow-up

  • Author: Richard E Frye, MD, PhD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
 
Updated: Apr 07, 2016
 

Further Outpatient Care

Regularly monitor blood pressure in patients with acute porphyria.

Monitor renal and liver function.

Folic acid may clinically and biochemically benefit patients with acute intermittent porphyria (AIP).

Physical therapy may be required if significant motor neuropathy persists after the patient's discharge from the hospital.

Central pain syndromes (resulting from sensory neuropathies) can be treated with gabapentin.

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Inpatient & Outpatient Medications

Many medications can induce or worsen porphyria (see Deterrence/Prevention), whereas others have not been associated with worsening porphyria. Many medications have not been tested in patients with known porphyria.

The list of probably safe medications below is not exhaustive; any medication prescribed to a patient with porphyria should be researched.

Drugs not associated with worsening porphyria include the following:

  • Acetaminophen
  • Adrenaline
  • Amitriptyline
  • Aspirin
  • Atropine
  • Bromides
  • Chloral hydrate
  • Chlordiazepoxide
  • Colchicine
  • Diazepam
  • Digoxin
  • Diphenhydramine
  • Ethylenediaminetetraacetic acid (EDTA)
  • Ether
  • Glucocorticoids
  • Guanethidine
  • Ibuprofen
  • Imipramine
  • Indomethacin
  • Insulin
  • Labetalol
  • Lithium
  • Methylphenidate
  • Naproxen
  • Narcotics
  • Neostigmine
  • Nitrous oxide
  • Penicillamine
  • Penicillin
  • Phenothiazines
  • Procaine
  • Propranolol
  • Succinylcholine
  • Tetracycline
  • Thyroxine
  • Tubocurarine

A more extensive list of drugs that are probably safe is available at the University of Queensland Porphyria Research Unit Web site.

Alcohol ingestion can precipitate acute episodes.

Cigarette smoking can increase the risk of acute episode.

Fasting and low-carbohydrate diets are forbidden.

Controlling menses can treat premenstrual exacerbation of porphyria.

Although hormone analogs of luteinizing hormone releasing hormone can suppress menses, these medications essentially induce menopause, which has its own deleterious effects. Therefore, oral contraceptives (eg, a low-dose estrogen-progesterone combination pill) may be useful, if tolerated.

Standard oral contraceptive pills may elicit porphyria symptoms (in 15% of patients) or episodes (in 5% of patients). However, in several cases, further episodes were prevented with the administration of oral contraceptive pills (especially low-dose estrogen or an estrogen-progesterone combination) immediately after a menses-elicited acute episode resolved.

Use of a testosterone implant is reported in 1 case.

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Deterrence/Prevention

Many medications induce or worsen acute and cutaneous porphyria, and many of these are metabolized by the liver, at least to some extent. Liver metabolism may induce the cytochrome P-450 enzymes that require heme, inducing heme production.

Any medication used in a patient with porphyria should be investigated. Many medications have not been used for patients with porphyria; therefore, their potential for worsening porphyria is not known.

The list of common medications below may help to determine whether a medication could have triggered a porphyria reaction in a patient without a diagnosed disorder. Note that the effect of many medications on porphyria is highly idiosyncratic. For example, some patients may tolerate these medications well, and some of these medicines can be used to treat patients with porphyria.

Drugs potentially unsafe in porphyria include the following:

  • Alfaxalone
  • Alkylating agents
  • Antipyrine
  • Arthrotec
  • Barbiturates
  • Busulfan
  • Butalbital
  • Carbamazepine
  • Carisoprodol
  • Chlordiazepoxide
  • Chloroquine
  • Clonidine
  • Danazol
  • Danocrine
  • Dapsone
  • Diclofenac
  • Ergot
  • Erythromycin
  • Erythropoietin
  • Estrogens
  • Ethchlorvynol
  • Fluroxene
  • Griseofulvin
  • Heavy metals
  • Hydralazine
  • Ketamine
  • Mafenide
  • Meprobamate
  • Methoxsalen
  • Methyldopa
  • Metoclopramide
  • Nitrazepam
  • Nortriptyline
  • Pargyline
  • Pentazocine
  • Phenazopyridine
  • Phenobarbital
  • Phenoxybenzamine
  • Phenylbutazone
  • Phenytoin
  • Plaquenil
  • Porfimer
  • Primidone
  • Progestins
  • Pyrazinamide
  • Ranitidine
  • Rifampin
  • Spironolactone
  • Succinimides
  • Sulfonamides
  • Sulfonylureas
  • Theophylline
  • Tolazamide
  • Tranylcypromine
  • Valproate

A more extensive list of unsafe drugs is available at the University of Queensland Porphyria Research Unit Web site.

Alcohol ingestion can precipitate acute episodes.

Cigarette smoking can increase the risk of acute episode.

Fasting and low-carbohydrate diets are forbidden.

Controlling menses can treat premenstrual exacerbation of porphyria.

Although hormone analogs of luteinizing hormone releasing hormone can suppress menses, these medications essentially induce menopause, which has its own deleterious effects. Therefore, oral contraceptives (eg, a low-dose estrogen-progesterone combination pill) may be useful, if tolerated.

Standard oral contraceptive pills may elicit porphyria symptoms (in 15% of patients) or episodes (in 5% of patients). However, in several cases, further episodes were prevented with the administration of oral contraceptive pills (especially low-dose estrogen or an estrogen-progesterone combination) immediately after a menses-elicited acute episode resolved.

Use of a testosterone implant is reported in 1 case.

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Complications

Hypertension and chronic renal insufficiency may occur.

Recurrent acute episodes increase the risk of neuropsychiatric symptoms during the symptomless phase of the disease.

For more than 90% of women, pregnancy does not exacerbate symptoms of porphyria or lead to acute episodes. However, approximately 8% of women may have symptoms of porphyria during pregnancy, and approximately 4% have acute episodes after delivery.

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Prognosis

Patients with a history of episodes have an increased risk of future episodes. Persons with histories of multiple acute episodes also have an increased risk of future episodes.

Although urinary excretion of porphobilinogen (PBG) during the symptomless phase is positively correlated with the number of acute episodes, high variability limits its predictive accuracy. However, low PBG urinary excretion during the symptomless phase appears to indicate a low frequency of subsequent acute episodes.

Before 1980, acute episodes were a major cause of death. Improved management of porphyria has since reduced mortality rates during acute exacerbations.

Mortality appears to be associated with increased incidences of cardiovascular disease and hypertension, chronic renal failure, and hepatocellular carcinoma.

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Contributor Information and Disclosures
Author

Richard E Frye, MD, PhD Associate Professor, Department of Pediatrics, University of Arkansas for Medical Sciences

Richard E Frye, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, International Neuropsychological Society, American Academy of Pediatrics

Disclosure: Nothing to disclose.

Coauthor(s)

Thomas G DeLoughery, MD Professor of Medicine, Pathology, and Pediatrics, Divisions of Hematology/Oncology and Laboratory Medicine, Associate Director, Department of Transfusion Medicine, Division of Clinical Pathology, Oregon Health and Science University School of Medicine

Thomas G DeLoughery, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American College of Physicians, American Society of Hematology, International Society on Thrombosis and Haemostasis, Wilderness Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Sharada A Sarnaik, MBBS Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Associate Hematologist/Oncologist, Children's Hospital of Michigan

Sharada A Sarnaik, MBBS is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, Children's Oncology Group, American Academy of Pediatrics, Midwest Society for Pediatric Research

Disclosure: Nothing to disclose.

References
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  2. Ulbrichova D, Hrdinka M, Saudek V, Martasek P. Acute intermittent porphyria--impact of mutations found in the hydroxymethylbilane synthase gene on biochemical and enzymatic protein properties. FEBS J. 2009 Apr. 276(7):2106-15. [Medline].

  3. Besur S, Hou W, Schmeltzer P, Bonkovsky HL. Clinically important features of porphyrin and heme metabolism and the porphyrias. Metabolites. 2014 Nov 3. 4(4):977-1006. [Medline].

  4. Pandey U, Dixit VK. Acute intermittent porphyria in pregnancy: a case report and review of literature. J Indian Med Assoc. 2013 Dec. 111(12):850-1. [Medline].

  5. Kuo HC, Huang CC, Chu CC, Lee MJ, Chuang WL, Wu CL, et al. Neurological complications of acute intermittent porphyria. Eur Neurol. 2011. 66(5):247-52. [Medline].

  6. Cederlof M, Bergen SE, Larsson H, Landen M, Lichtenstein P. Acute intermittent porphyria: comorbidity and shared familial risks with schizophrenia and bipolar disorder in Sweden. Br J Psychiatry. 2015 Dec. 207 (6):556-7. [Medline].

  7. Anyaegbu E, Goodman M, Ahn SY, Thangarajh M, Wong M, Shinawi M. Acute Intermittent Porphyria: A Diagnostic Challenge. J Child Neurol. 2011 Dec 21. [Medline].

  8. Bonkovsky HL, Maddukuri VC, Yazici C, Anderson KE, Bissell DM, Bloomer JR, et al. Acute Porphyrias in the USA: Features of 108 Subjects from Porphyria Consortium. Am J Med. 2014 Jul 9. [Medline].

  9. Olutunmbi Y, Gurnaney HG, Galvez JA, Simpao AF. Ultrasound-guided regional anesthesia in a pediatric patient with acute intermittent porphyria: literature review and case report. Middle East J Anaesthesiol. 2014 Jun. 22(5):511-4. [Medline].

  10. [Guideline] Finnish Medical Society Duodecim. Viral hepatitis. In: EBM Guidelines. Evidence-Based Medicine [Internet]. Helsinki, Finland: Wiley Interscience. John Wiley & Sons; 2008 Mar 10. [Full Text].

  11. Aarsand AK, Petersen PH, Sandberg S. Estimation and application of biological variation of urinary delta-aminolevulinic acid and porphobilinogen in healthy individuals and in patients with acute intermittent porphyria. Clin Chem. 2006 Apr. 52(4):650-6. [Medline].

  12. Hift RJ, Meissner PN. An analysis of 112 acute porphyric attacks in Cape Town, South Africa: Evidence that acute intermittent porphyria and variegate porphyria differ in susceptibility and severity. Medicine (Baltimore). Jan 2005. 84(1):48-60. [Medline].

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  15. Onuki J, Chen Y, Teixeira PC, et al. Mitochondrial and nuclear DNA damage induced by 5-aminolevulinic acid. Arch Biochem Biophys. 2004 Dec 15. 432(2):178-87. [Medline].

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Heme production pathway. Heme production begins in the mitochondria, proceeds into the cytoplasm, and resumes in the mitochondria for the final steps. Figure outlines the enzymes and intermediates involved in the porphyrias. Names of enzymes are presented in the boxes; names of the intermediates, outside the boxes. Multiple arrows leading to a box demonstrate that multiple intermediates are required as substrates for the enzyme to produce 1 product.
Table 1. Known Chromosomal Location of Enzymes Involved in Porphyria and Inheritance Patterns
Type of Porphyria Deficient Enzyme Location Inheritance Pattern Band  
ALAD deficiency ALAD Cytosol Autosomal recessive 9q34  
AIP PBG deaminase Cytosol Autosomal dominant 11q23  
HCP Coproporphyrinogen oxidase Mitochondrial Autosomal dominant 3q12  
VP Protoporphyrinogen oxidase Mitochondrial Autosomal dominant 1q22-23  
Table 2. Frequencies of Porphyria
Type of Porphyria Age of Onset Incidence Male-to-Female Ratio
ALAD deficiency Mostly adolescence to young adulthood, but variable (2-63 y) 6 cases total 6:0
AIP After puberty (third decade) General 0.01/1000



Sweden 1/1000



Finland 2/1000



France 0.3/1000



M>F
HCP Predominantly adulthood (youngest patient aged 4 y) Japan 0.015/1000



Czech 0.015/1000



Israel 0.007/1000



Denmark 0.0005/1000



1:20



1:4



2:1



1:1



VP Heterozygous mutation: after puberty (fourth decade) Homozygous mutation (rare): childhood South Africa 0.34/1000 1:1
Table 3. Quantitative Urine Porphyrin Levels
Level ALAD Deficiency Acute Intermittent Porphyria (AIP) Congenital Erythropoietic Porphyria (CEP) and Porphyria Cutanea Tarda (PCT) HCP and VP
ALA Significantly increased Significantly increased Normal Significantly increased
PBG Increased Significantly increased Normal Significantly increased
Uroporphyrin Normal Increased Significantly increased Increased
Coproporphyrin Significantly increased Increased Increased Significantly increased
Table 4. Quantitative Stool Porphyrin levels
Level HCP VP
Coproporphyrin Significantly increased Increased
Protoporphyrin Increased Significantly increased
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