Porphyria: Difference between revisions

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==Background==
==Background==
*Related to defect(s) in heme synthesis causing a buildup of porphyrins
*Inherited and/or acquired disorders of in which there are enzyme deficiencies involved in heme biosynthesis, resulting in build up of porphyrins
*[[Acute intermittent porphyria]] is most salient to EM
*Autosomal dominant, but poor penetrance
*Autosomal dominant, but poor penetrance
*Inherited and/or acquired disorders of in which there are enzyme deficiencies involved in heme biosynthesis.
*Heme is a component of many essential hemoproteins, such as hemoglobin, myoglobin and cytochromes, including the cytochrome [[P450]] enzymes
*Heme is a component of many essential hemoproteins, such as hemoglobin, myoglobin and cytochromes, including the cytochrome [[P450]] enzymes
*The first enzyme in the heme production pathway is ALA synthase (ALAS), which controls the rate of heme synthesis in the liver. This enzyme is down-regulated by heme.  
*The first enzyme in the heme production pathway is ALA synthase (ALAS), which controls the rate of heme synthesis in the liver. This enzyme is down-regulated by heme.  
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*Infection, metabolic stress
*Infection, metabolic stress
*Carbohydrate deficiency
*Carbohydrate deficiency
*Tobacco, EtOH
*[[Tobacco]], [[ETOH]]
*Porphyrinogenic drugs: sulfonamides, barbiturates, rifampin or metoclopramide
*Porphyrinogenic drugs: [[sulfonamides]], [[barbiturates]], [[rifampin]] or [[metoclopramide]]


==Clinical Features==
==Clinical Features==
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**Acute [[abdominal pain]] (85-90% of attacks)
**Acute [[abdominal pain]] (85-90% of attacks)
***[[Nausea/vomiting]]
***[[Nausea/vomiting]]
***Constipation and/or diarrhea
***[[Constipation]] and/or [[diarrhea]]
*Port wine-colored urine
*Diffuse musculoskeletal pain
*Neurologic symptoms
*Neurologic symptoms
**Diffuse musculoskeletal pain
**[[Headache]]
**[[headache]]
**[[Numbness|Sensory loss]] (40%)
**Sensory loss (40%)
***An indication of a severe and potentially life-threatening attack
***An indication of a severe and potentially life-threatening attack
***Neuropathy can progress to respiratory failure in hours or days
***Neuropathy can progress to [[respiratory failure]] in hours or days
**Bladder paresis
**[[Urinary retention|Bladder paresis]]
**Agitation, confusion, combativeness, seizure
**[[Agitation]], [[confusion]], combativeness, [[seizure]]


==Differential Diagnosis==
==Differential Diagnosis==
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==Management==
==Management==
*Opioid analgesia
*[[Opioid]] analgesia
*Avoid/discontinue offending medications
*Avoid/discontinue offending medications
**Most seizure medications contraindicated: [[Benzodiazepines]], [[gabapentin]], [[levetiracetam]], and [[vigabatrin]] okay
**Most seizure medications are contraindicated
**Avoid [[reglan]]
**Acceptable [[AEDs]] include: [[benzodiazepines]], [[gabapentin]], [[levetiracetam]], and vigabatrin
**Avoid [[Reglan]]
*Treat any [[electrolyte abnormalities]]
*Treat any [[electrolyte abnormalities]]
*[[beta-blockers]] can be used to treat tachycardia
*[[Beta-blockers]] can be used to treat [[tachycardia]]
*Glucose load
===Decrease heme synthesis===
*[[Dextrose|Glucose]] load
**Decreases porphyrin production
**Decreases porphyrin production
**Typical protocol is D10W 3-4 liters daily x 4 days
**E.g. D5NS at 2L/hr x 24h<ref>https://emedicine.medscape.com/article/205220-treatment</ref>==
**Risk of hyponatremia given significant free water load
**Avoid D5/D10W due to risk of hyponatremia given significant free water load
*Hemin (Panhematin®)
*Hemin (Panhematin®)
**Decreases porphyrin production, significantly more potent than glucose
**Decreases porphyrin production, significantly more potent than glucose
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==See Also==
==See Also==
*[[Abdominal pain]]
*[[Abdominal pain]]
*[[Acute intermittent porphyria]]


==External Links==
==External Links==
{{#widget:YouTube|id=VQHz0Qu-OjA}}
http://www.porphyriafoundation.com/
http://www.porphyriafoundation.com/
==References==
==References==
#NR Pimstone, KE. Anderson, B Freilich. (n.d.). Emergency Room Guidelines for Acute Porphyria. American Porphyria Foundation. Retrieved January 11, 2016. From http://www.porphyriafoundation.com/for-healthcare-professionals/emergency-guidelines-for-acute-porphyria#Treatment.
#NR Pimstone, KE. Anderson, B Freilich. (n.d.). Emergency Room Guidelines for Acute Porphyria. American Porphyria Foundation. Retrieved January 11, 2016. From http://www.porphyriafoundation.com/for-healthcare-professionals/emergency-guidelines-for-acute-porphyria#Treatment.

Revision as of 17:50, 1 October 2019

Background

  • Inherited and/or acquired disorders of in which there are enzyme deficiencies involved in heme biosynthesis, resulting in build up of porphyrins
  • Acute intermittent porphyria is most salient to EM
  • Autosomal dominant, but poor penetrance
  • Heme is a component of many essential hemoproteins, such as hemoglobin, myoglobin and cytochromes, including the cytochrome P450 enzymes
  • The first enzyme in the heme production pathway is ALA synthase (ALAS), which controls the rate of heme synthesis in the liver. This enzyme is down-regulated by heme.
  • The enzyme deficiencies in porphyria limit the capacity of the liver to increase heme synthesis.
  • When drugs, hormones or other factors that induce ALAS and CYPs are given, ALA and porphobilinogen (PBG) are overproduced and accumulate, and a neurovisceral attack may develop

Triggers

Clinical Features

Differential Diagnosis

Diffuse Abdominal pain

Extra-abdominal Sources of Abdominal pain

Evaluation

Consider porphyria in patients with abdominal pain that is unexplained after an initial workup has excluded common causes (appendicitis, cholecystitis, pancreatitis, etc).

  • Spot urinary porphobilinogen (sendout at most hospitals)
    • Normal = 0-4mg/day
    • acute attack, spot urine can be 20-200mg/L
  • Recurrent attacks in a patient with proven acute porphyria are usually similar and can be diagnosed on clinical grounds without biochemical reconfirmation.

Management

Decrease heme synthesis

  • Glucose load
    • Decreases porphyrin production
    • E.g. D5NS at 2L/hr x 24h[1]==
    • Avoid D5/D10W due to risk of hyponatremia given significant free water load
  • Hemin (Panhematin®)
    • Decreases porphyrin production, significantly more potent than glucose
    • Recommended for most cases requiring hospitalization, or any with neurologic symptoms
    • 3-4mg/kg IV daily x 4 days
    • Can cause significant infusion site phlebitis - minimize by reconstituting in 25% albumin; consider central venous administration
    • Very expensive - around $8000 per 313mg vial

Disposition

  • Admission to a monitored bed

See Also

External Links

{{#widget:YouTube|id=VQHz0Qu-OjA}}

http://www.porphyriafoundation.com/

References

  1. NR Pimstone, KE. Anderson, B Freilich. (n.d.). Emergency Room Guidelines for Acute Porphyria. American Porphyria Foundation. Retrieved January 11, 2016. From http://www.porphyriafoundation.com/for-healthcare-professionals/emergency-guidelines-for-acute-porphyria#Treatment.
  2. Anderson KE, Bloomer, JR Bonkovsky HL, Kushner JP, Pierach CA, Pimstone NR and Desnick RJ. Recommendations for the Diagnosis and Treatment of the Acute Porphyrias. Ann Intern Med 2005; 142:439-450
  3. Deacon AC, Peters TJ, Identification of acute porphyria: evaluation of a commercial screening test for urinary porphobilinogen. Ann Clin Biochem. 1998;35:726-32