Porphyria: Difference between revisions
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==Diagnosis== | ==Diagnosis== | ||
''Consider porphyria in patients with abdominal pain that is unexplained after an initial workup has excluded common causes (appendicitis, cholecystitis, pancreatitis, etc).'' | |||
* Recurrent attacks in a patient with proven acute porphyria are usually similar and can be diagnosed on clinical grounds | |||
* Urinary porphobilinogen | |||
**Normal = 0-4 mg/day | |||
**acute attack, spot urine can be 20-200 mg/L | |||
* Recurrent attacks in a patient with proven acute porphyria are usually similar and can be diagnosed on clinical grounds without biochemical reconfirmation. | |||
==Management== | ==Management== |
Revision as of 12:02, 11 May 2016
Background
- 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
- 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
Clinical Features
- History of porphyrinogenic drugs: sulfonamides, barbiturates, rifampin or metoclopramide
- Gastrointestinal symptoms
- Acute abdominal pain (85-90% of attacks)
- Nausea/vomiting
- Constipation and/or diarrhea
- Acute abdominal pain (85-90% of attacks)
- Neurologic symptoms
- Diffuse musculoskeletal pain
- 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
Diagnosis
Consider porphyria in patients with abdominal pain that is unexplained after an initial workup has excluded common causes (appendicitis, cholecystitis, pancreatitis, etc).
- Urinary porphobilinogen
- Normal = 0-4 mg/day
- acute attack, spot urine can be 20-200 mg/L
- Recurrent attacks in a patient with proven acute porphyria are usually similar and can be diagnosed on clinical grounds without biochemical reconfirmation.
Management
- The most effective therapy for the acute attack is hemin (Panhematin®). This drug corrects the deficiency of regulatory heme in the liver and down-regulates ALA synthase. The standard hemin treatment course is 3-4 mg/kg by vein once daily for 4 days. If the diagnosis is confirmed, the first dose can be given in the ED.
- Glucose loading has a similar effect, but is much less potent and effective and should be used only for mild attacks.
- Discontinue any inciting drugs
- Treat any electrolyte abnormalities
- Treat pain with narcotic analgesia and nausea with phenothiazines
- beta blockers can be used to treat tachycardia
- Seizures should be treated with gabapentin, benzodiazepines and vigabatrin. Patients who have a seizure during an acute porphyria attack rarely need long term anticonvulsant therapy.
Disposition
- Admission to a monitored bed
See Also
External Links
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