Porphyria: Difference between revisions
ClaireLewis (talk | contribs) |
ClaireLewis (talk | contribs) No edit summary |
||
(3 intermediate revisions by 2 users not shown) | |||
Line 1: | Line 1: | ||
==Background== | ==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 | *Autosomal dominant, but poor penetrance | ||
*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. | ||
Line 11: | Line 11: | ||
*Infection, metabolic stress | *Infection, metabolic stress | ||
*Carbohydrate deficiency | *Carbohydrate deficiency | ||
*Tobacco, | *[[Tobacco]], [[ETOH]] | ||
*Porphyrinogenic drugs: sulfonamides, barbiturates, rifampin or metoclopramide | *Porphyrinogenic drugs: [[sulfonamides]], [[barbiturates]], [[rifampin]] or [[metoclopramide]] | ||
==Clinical Features== | ==Clinical Features== | ||
Line 18: | Line 18: | ||
**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 | ||
**[[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== | ||
Line 41: | Line 42: | ||
==Management== | ==Management== | ||
*Opioid analgesia | *[[Opioid]] analgesia | ||
*Avoid/discontinue offending medications | *Avoid/discontinue offending medications | ||
**Most seizure medications contraindicated: [[ | **Most seizure medications are contraindicated | ||
**Avoid [[ | **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]] | ||
*Glucose load | ===Decrease heme synthesis=== | ||
*[[Dextrose|Glucose]] load | |||
**Decreases porphyrin production | **Decreases porphyrin production | ||
** | **E.g. D5NS at 2L/hr x 24h<ref>https://emedicine.medscape.com/article/205220-treatment</ref>== | ||
** | **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 | ||
Line 63: | Line 66: | ||
==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
- Infection, metabolic stress
- Carbohydrate deficiency
- Tobacco, ETOH
- Porphyrinogenic drugs: sulfonamides, barbiturates, rifampin or metoclopramide
Clinical Features
- Gastrointestinal symptoms
- Acute abdominal pain (85-90% of attacks)
- Nausea/vomiting
- Constipation and/or diarrhea
- Acute abdominal pain (85-90% of attacks)
- Port wine-colored urine
- Diffuse musculoskeletal pain
- Neurologic symptoms
- Headache
- Sensory loss (40%)
- An indication of a severe and potentially life-threatening attack
- Neuropathy can progress to respiratory failure in hours or days
- Bladder paresis
- Agitation, confusion, combativeness, seizure
Differential Diagnosis
Diffuse Abdominal pain
- Abdominal aortic aneurysm
- Acute gastroenteritis
- Aortoenteric fisulta
- Appendicitis (early)
- Bowel obstruction
- Bowel perforation
- Diabetic ketoacidosis
- Gastroparesis
- Hernia
- Hypercalcemia
- Inflammatory bowel disease
- Mesenteric ischemia
- Pancreatitis
- Peritonitis
- Sickle cell crisis
- Spontaneous bacterial peritonitis
- Volvulus
Extra-abdominal Sources of Abdominal pain
- MI
- Aortic Dissection
- PNA
- PE
- Testicular Torsion
- Herpes Zoster
- Muscle spasm
- Spinal pathology
- Strep Pharyngitis (peds)
- Mononucleosis
- DKA
- ETOH Ketoacidosis
- Uremia
- Sickle Cell Crisis
- SLE
- Vasculitis
- Glaucoma
- Hyperthyroidism
- Methanol Poisoning
- Heavy Metal toxicity
- Addison's disease
- Porphyria
- Paroxysmal nocturnal hemoglobinuria
- Black widow spider bite
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
- Opioid analgesia
- Avoid/discontinue offending medications
- Most seizure medications are contraindicated
- Acceptable AEDs include: benzodiazepines, gabapentin, levetiracetam, and vigabatrin
- Avoid Reglan
- Treat any electrolyte abnormalities
- Beta-blockers can be used to treat tachycardia
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
- 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.
- 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
- Deacon AC, Peters TJ, Identification of acute porphyria: evaluation of a commercial screening test for urinary porphobilinogen. Ann Clin Biochem. 1998;35:726-32