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.  
*The enzyme deficiencies in porphyria limit the capacity of the liver to increase heme synthesis.  
*The enzyme deficiencies in porphyria limit the capacity of the liver to increase heme synthesis.  
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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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{{Extra-abdominal sources of abdominal pain DDX}}
{{Extra-abdominal sources of abdominal pain DDX}}


==Diagnosis==
==Evaluation==
''Consider porphyria in patients with abdominal pain that is unexplained after an initial workup has excluded common causes (appendicitis, cholecystitis, pancreatitis, etc).''
''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)
*Spot urinary porphobilinogen (sendout at most hospitals)
**Normal = 0-4 mg/day
**Normal = 0-4mg/day
**acute attack, spot urine can be 20-200 mg/L
**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.
*Recurrent attacks in a patient with proven acute porphyria are usually similar and can be diagnosed on clinical grounds without biochemical reconfirmation.


==Management==
==Management==
*Narcotic 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
**Recommended for most cases requiring hospitalization, or any with neurologic symptoms
**Recommended for most cases requiring hospitalization, or any with neurologic symptoms
**3-4 mg/kg IV daily x 4 days
**3-4mg/kg IV daily x 4 days
**Can cause significant infusion site phlebitis - minimize by reconstituting in 25% albumin; consider central venous administration
**Can cause significant infusion site phlebitis - minimize by reconstituting in 25% albumin; consider central venous administration
**Very expensive - around $8000 per 313 mg vial
**Very expensive - around $8000 per 313mg vial


==Disposition==
==Disposition==
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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
  1. ↑ https://emedicine.medscape.com/article/205220-treatment
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