The Challenges Of Testing For And Diagnosing Porphyrias

attacks rarely occur before puberty, and attack frequency
and severity decline after menopause. Interestingly, a
subset of female patients experience regular, cyclical,
exacerbations of disease in conjunction with menses.
A variety of drugs, including alcohol, have been
implicated in the induction of acute porphyric attacks.
There is consensus regarding the use and safety of
many common medications in patients with AIP. Other
drugs are not as well understood. Some commonly used
drugs, which have been classified as safe or unsafe for
use by patients with an acute porphyria, are listed in
Table 1. More extensive lists, including drugs whose
safety is still in question, are available elsewhere. 3
Medications previously established as safe should be
used whenever possible in patients with asymptomatic
or symptomatic AIP.
Nutritional status, in particular decreased caloric intake,
has been shown to induce the onset of an acute attack.
Intercurrent illnesses and surgery exhibit a causal
relationship, possibly due to increased energy requirements
during these times. Additionally, psychological stress
has been reported to contribute to AIP symptomology,
though the underlying mechanisms are not understood.
Precipitating factors likely act in an additive fashion,
and the trigger(s) of a particular crisis, cannot always be
ascertained.
Table 1. Medications and the acute porphyrias
Treatment for Acute Porphyrias
Hospitalization is often necessary for the treatment of
acute attacks. Crises are treated with increased
carbohydrate intake that may occur via intravenous
administration. Heme (hematin or heme arginate)
therapy allows for the excretion of ALA and PBG.
Efficacy is compromised if heme therapy is delayed, so
treatment should commence as soon as possible after
the onset of a crisis. Symptomatic treatment includes
frequent doses of analgesics to control pain, and
phenothiazines may be administered to control nausea,
vomiting, and anxiety. Given that pain tends to be
severe, narcotics are typically the analgesia of choice, as
nonnarcotic agents are usually inadequate.
Treatment for asymptomatic patients or between acute
porphyria crises largely relies upon the prevention of
potentially life-threatening episodes. At-risk individuals
should be counseled to avoid medications known to
precipitate attacks (Table 1), to avoid excessive alcohol
intake, to seek prompt treatment for other intercurrent
illnesses, and to maintain proper nutritional status,
including the avoidance of crash dieting. Patients
should be encouraged to wear a medical alert bracelet
allowing for proper management in the event that the
patient becomes temporarily incapacitated as a result of
an accident or acute crisis. Photosensitivity can be
minimized in VP and HCP patients by avoidance of sun
exposure, protective clothing, and pharmacotherapy in
the form of a beta-carotene analog, canthaxanthine.
Testing for Porphyria
By following our suggested testing strategy, the quality
of patient care and cost-effectiveness of testing can be
maximized. Depending upon the specific type of
porphyria suspected, certain tests are more informative
than other assays. In general, a 24-hour urine
porphyrins (#8562 Porphyrins, Quantitative, Urine)
analysis that includes porphobilinogen is the most
effective screening tool. However, when EPP is the
potential diagnosis, an erythrocyte porphyrin (#8536
Porphyrins, Total, Erythrocytes and #8735 Porphyrins,
Fractionation, Erythrocytes) and protoporphyrin
fractionation (#8739 Protoporphyrins, Fractionation,
Erythrocytes) are the most appropriate tests to perform.
For a listing of informative biochemical findings for
each type of porphyria, please refer to Table 2.
Testing strategies for each suspected porphyria are
outlined in Table 3, page 10. Ordering a battery of tests
does not enhance the quality of patient care. Rather, a
stepwise diagnostic approach is the most effective
means of ruling in/out a specific porphyria. In most
cases, when the result of the urine porphyrins test is
normal, subsequent testing in the form of fecal, plasma,
and erythrocyte porphyrin analyses and enzyme assay
are not recommended. As shown, the 24-hour urine
porphyrins (#8562 Porphyrins, Quantitative, Urine)
analysis is the most appropriate starting point. If a
8 11/02