Acute Porphyria Follow-up
- Author: Richard E Frye, MD, PhD; Chief Editor: Max J Coppes, MD, PhD, MBA more...
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.
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.
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.
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.
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.
Patient Education
The following resources are useful for patient reference and education:
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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].
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Gordon N. The acute porphyrias. Brain Dev. Sep 1999;21(6):373-7. [Medline].
Gross U, Honcamp M, Daume E, et al. Hormonal oral contraceptives, urinary porphyrin excretion and porphyrias. Horm Metab Res. Aug 1995;27(8):379-83. [Medline].
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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Kappas A, Sassa S, Galbraith RA. The porphyrias. In: Scriver CR, et al, eds. The metabolic basis of inherited disease. New York, NY: McGraw-Hill; 1995:2103-2159.
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Krauss GL, Simmons-O'Brien E, Campbell M. Successful treatment of seizures and porphyria with gabapentin. Neurology. Mar 1995;45(3 Pt 1):594-5. [Medline].
Logan GM, Weimer MK, Ellefson M, Pierach CA, Bloomer JR. Bile porphyrin analysis in the evaluation of variegate porphyria. N Engl J Med. May 16 1991;324(20):1408-11. [Medline].
Meyer UA, Schuurmans MM, Lindberg RL. Acute porphyrias: pathogenesis of neurological manifestations. Semin Liver Dis. 1998;18(1):43-52. [Medline].
Onuki J, Chen Y, Teixeira PC, et al. Mitochondrial and nuclear DNA damage induced by 5-aminolevulinic acid. Arch Biochem Biophys. Dec 15 2004;432(2):178-87. [Medline].
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Sadeh M, Blatt I, Martonovits G, et al. Treatment of porphyric convulsions with magnesium sulfate. Epilepsia. Sep-Oct 1991;32(5):712-5. [Medline].
Schoenfeld N, Mamet R. Individualized workup: a new approach to the biochemical diagnosis of acute attacks of neuroporphyria. Physiol Res. 2006;55 Suppl 2:S103-8. [Medline].
Solis C, Martinez-Bermejo A, Naidich TP, et al. Acute intermittent porphyria: studies of the severe homozygous dominant disease provides insights into the neurologic attacks in acute porphyrias. Arch Neurol. Nov 2004;61(11):1764-70. [Medline].
Soonawalla ZF, Orug T, Badminton MN, et al. Liver transplantation as a cure for acute intermittent porphyria. Lancet. Feb 28 2004;363(9410):705-6. [Medline].
Suarez JI, Cohen ML, Larkin J, et al. Acute intermittent porphyria: clinicopathologic correlation. Report of a case and review of the literature. Neurology. Jun 1997;48(6):1678-83. [Medline].
Vaughan CJ, Delanty N. Hypertensive emergencies. Lancet. Jul 29 2000;356(9227):411-7. [Medline].
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Yamamori I, Asai M, Tanaka F, et al. Prevention of premenstrual exacerbation of hereditary coproporphyria by gonadotropin-releasing hormone analogue. Intern Med. Apr 1999;38(4):365-8. [Medline].
| 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 |
| 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 |
| 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 |
| Level | HCP | VP |
| Coproporphyrin | Significantly increased | Increased |
| Protoporphyrin | Increased | Significantly increased |
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