Porphyria
(Redirected from Acute intermittent porphyria)
Background
- Inherited and/or acquired disorders in which there are enzyme deficiencies involved in heme biosynthesis, resulting in build up of porphyrins (Porphobilinogen and δ-Aminolevulinic acid [ALA])
- Heme is a component of many essential hemoproteins, such as hemoglobin, myoglobin and cytochromes, including the cytochrome P450 enzymes
- Acute intermittent porphyria is most salient to EM
- 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
- Seizure
- 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
- Psychiatric symptoms
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.
- Hyponatremia has been documented in up to 60% of acute attacks & is attributed to elevated levels of antidiuretic hormone[3]
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[4]==
- 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
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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
- ↑ Fredrick, Thomas, M. D., et al. “Turning Purple with Pain.” The New England Journal of Medicine, vol. 385, no. 6, 2021, pp. 549–54, doi:10.1056/NEJMcps2105278.
- ↑ Fredrick, Thomas, M. D., et al. “Turning Purple with Pain.” The New England Journal of Medicine, vol. 385, no. 6, 2021, pp. 549–54, doi:10.1056/NEJMcps2105278.
- ↑ Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011;159(2):332-9.e1. doi:10.1016/j.jpeds.2011.02.039
- ↑ https://emedicine.medscape.com/article/205220-treatment