Acute Intermittent Porphyria
Acute intermittent porphyria is an uncommon cause of abdominal pain that frequently confounds the diagnostic efforts of even the most astute clinician. The porphyrias are disorders of heme synthesis that can produce a wide range of clinical symptoms. Many different types of porphyrias occur, each of which manifests in a distinct clinical manner that reflects the specific enzyme deficiency of the heme biosynthetic pathway. The porphyrias can be inherited or acquired. The main clinical manifestations of the porphyrias are neurological dysfunction and the unique clinical finding of cutaneous sensitivity to sunlight.
Acute intermittent porphyria is an autosomal dominant trait with variable clinical expression. The incidence of the gene responsible for acute intermittent porphyria is thought to be 1 in 100,000 individuals. This enzyme responsible for the clinical manifestation of acute intermittent porphyria is hydroxymethylbilane synthase, which is the third enzyme in the heme synthesis pathway. The disease rarely manifests before puberty. Acute abdominal pain is usually the first clinical expression of the disease. As the name implies, the pain of acute intermittent porphyria is intermittent and colicky. The pain may be localized to the abdomen or may radiate to the flanks. The patient also may exhibit neurological symptoms, suggesting dysfunction of the central and peripheral nervous systems. Port wine urine, which is characteristic of hepatic porphyrias, including acute intermittent porphyria, is often seen during acute attacks.
Signs and Symptoms
Although the reports of abdominal pain are often quite impressive in patients with acute intermittent porphyria, the abdominal examination is often nondescript. Vomiting occasionally occurs. Tachycardia and autonomic dysfunction, including sweating, are common, as is labile hypertension. Occasionally urinary retention may occur and may confuse the clinical diagnosis, especially if port wine urine is present. Neurological findings, including attenuated deep tendon reflexes and decreased distal sensation suggestive of peripheral neuropathy, are often present and seizures often occur. Cranial nerve involvement is less common, but can be severe. Mental disturbance ranging from agitation to frank psychosis can occur in one-third of patients with acute intermittent porphyria. The presence of nervousness and anxiety often makes the care of these patients difficult. Alcohol, smoking, pregnancy, barbiturates, and oral contraceptives may precipitate attacks of acute intermittent porphyria, as may dehydration, calorie restriction, hormonal alterations, and infection.
Given the usual delay in the diagnosis of acute intermittent porphyria, a considerable amount of testing is done. Most standard laboratory testing does not point the clinician toward a diagnosis of acute intermittent porphyria, however. Specifically, liver function tests are normal. A mild normocytic, normochromic anemia is sometimes present. Freshly passed urine is colorless, but it turns a port wine color if exposed to light. Given the low incidence of porphyria, qualitative urine screening tests, such as the Watson-Schwartz and Hoesch tests, are a reasonable first step in diagnosing porphyria. If the qualitative tests are positive, quantitative testing, such as gas chromatographic measurements for aminolevulinic acid, should be performed. Magnetic resonance imaging may reveal transient abnormalities during attacks of acute intermittent porphyria
Essentially all causes of acute intermittent abdominal pain must be included in the differential diagnosis. The clinician needs to take a detailed history and perform a careful physical examination to rule out life-threatening causes of acute, intermittent abdominal pain, such as ischemic bowel, volvulus, and acute appendicitis. The key distinguishing factor in acute intermittent porphyria is that the patient’s report of severe abdominal pain and the benign abdominal examination do not correlate. Given the high incidence of psychiatric abnormalities in patients with acute intermittent porphyria, psychogenic causes of abdominal pain must be included in the differential diagnosis.
Attacks of acute intermittent porphyria can be aborted by the intravenous administration of large quantities of carbohydrates, such as glucose. Hematin can be given intravenously and seems to be well tolerated. Cimetidine, a histamine-2 inhibitor, also may be useful in ameliorating acute attacks. Avoidance of barbiturates, anticonvulsants, and alcohol is imperative to avoid exacerbating the symptoms of acute intermittent porphyria attacks. Careful attention to fluid and electrolyte balance also is important. Despite careful treatment, fatalities during attacks do occur. Orthotopic liver transplant has the potential to actually correct the enzyme defect responsible for the disease and provide both biochemical and clinical remission.
Complications and Pitfalls
The major complications surrounding acute intermittent porphyria relate to misdiagnosis and failure to correct metabolic and electrolyte abnormalities during acute attacks. Barbiturates and anticonvulsants are often erroneously given to control seizures associated with acute intermittent porphyria, which worsen the porphyria, creating a vicious negative feedback cycle that ultimately may kill the patient.CLINICAL PEARLS
The cause of abdominal pain in acute intermittent porphyria is thought to be the result of intermittent autonomic dysfunction, causing abnormal gut motility with alternating spasm and obstruction. The incidence of psychiatric abnormalities in patients with acute intermittent porphyria often confounds the clinician and complicates treatment. It has been said that to make a diagnosis, the clinician must think of it first. Nowhere is this statement more true than in the case of acute intermittent porphyria.