Approach
Acute porphyria should be considered when characteristic but nonspecific symptoms or signs are not explained by other more common diseases. If acute porphyria is not recognized and treated, motor neuropathy may progress to total body paralysis, requiring ventilation.[3] Prompt diagnosis followed by optimal treatment greatly improves outcomes. Patients need long-term follow-up because risks of developing renal impairment and liver cancer are increased.
General history
AIP and other acute porphyrias present with a variety of neurovisceral symptoms and signs that are nonspecific and mimic many other, more common conditions.[15]
Abdominal pain, the most common symptom, is usually severe, steady, and diffuse but may be cramping.
The pain is neuropathic and not accompanied by inflammation. Pain and other symptoms usually occur during acute attacks, but these symptoms may become chronic with repeated attacks. Pain responds poorly to analgesia.
Abdominal pain in women during the luteal phase of the cycle, a preceding intercurrent illness, exposure to a harmful drug or dietary restriction, and dark or reddish urine can be clues to AIP diagnosis.[6] However, this temporal relationship to exacerbating factors cannot always be elicited.
Nausea, vomiting, constipation (less often diarrhea), and pain in the back, chest, and extremities are common. Painful hyperesthesia of the lower extremities may also be noted.
The family history may be negative for AIP because penetrance is low and most carriers of the trait in affected families are asymptomatic. However, a known family history of the disease should increase awareness and can lead to earlier diagnosis.
Muscle weakness usually develops later, but can be an early symptom, and usually begins proximally in the upper extremities.
Seizures may occur during acute attacks and may be due to hyponatremia or acute effects of AIP on the nervous system.
Anxiety, restlessness, agitation, hallucinations, and other psychiatric manifestations are common during acute attacks. These may represent a metabolic encephalopathy that can be accompanied by reversible CT or MRI findings resembling the posterior reversible encephalopathy syndrome.
Chronic pain and depression may occur long-term, and the risk of suicide is increased.
These symptoms and signs mimic other diseases, and other causes must be excluded by thorough clinical evaluation.
Physical examination
Tachycardia and hypertension are the most common signs.[3]
Pain in the abdomen and elsewhere is neuropathic rather than inflammatory, and is characteristically out of proportion to the findings on examination.[3]
Patients may be agitated and disoriented early in an attack.[3]
Testing for proximal muscle weakness by neurologic exam is important for early detection of motor neuropathy.
Reflexes may be normal or hyperactive with clonus early in an attack and become absent later.
Laboratory tests
For prompt diagnosis it is essential to test for increased porphobilinogen (PBG), preferably in a single-void urine sample.[16] Measurement of total porphyrins, which may decrease to normal less rapidly than PBG as an attack resolves, is also recommended as part of first-line testing. A substantial elevation of PBG is highly specific for either AIP, hereditary coproporphyria (HCP), or variegate porphyria (VP). Urine porphyrin elevations, even if marked, are nonspecific. If either PBG or total porphyrins are elevated, additional second-line testing is important to determine whether substantial PBG elevation is due to AIP, HCP, or VP, or whether an increase in porphyrins is due to porphyria. Slight elevations in individual types of porphyrins are not diagnostically significant if the total porphyrin level is normal. All urine results should be normalized to creatinine, although initial results can be expressed per liter.
Additional second-line testing should include:
Erythrocyte porphobilinogen deaminase activity
Urine porphyrins, if not done previously, and delta-aminolevulinic acid
Plasma porphyrins, including a fluorescence scan of diluted plasma at neutral pH
Fecal porphyrins.
After biochemical confirmation of AIP or another type of acute porphyria, DNA studies should be carried out in order to identify a pathogenic mutation (many are often family-specific).[16] This is important for diagnostic confirmation and for facilitating family studies. If there are existing genetic test results, do not perform repeat testing unless there is uncertainty about the existing result, e.g., the result is inconsistent with the patient’s clinical presentation or the test methodology has changed.[17]
Complete medical evaluation in acutely ill patients should include measurement of serum sodium levels, because hyponatremia may be present due to the syndrome of inappropriate ADH secretion.
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