The Challenges Of Testing For And Diagnosing Porphyrias

epidermis
papillae
vessels
thickened basement
membrane zone
dermis
Photo 2. This slide shows the thickened vessels, visible as
bright-green donut shapes, and the thickened basement
membrane zone that are characteristic of a diagnosis of
porphyria.
Porphyria Cutanea Tarda
Porphyria cutanea tarda (PCT) is the most common
porphyria and is most amenable to treatment. It is unique
in that it may be an acquired (sporadic, type I) or an
inherited (familial, types II and III) condition. About 75%
of patients have type I PCT. In these cases, symptoms are
precipitated by complications from liver diseases, such as
hepatitis C and hereditary hemochromatosis, or by
environmental exposures including certain medications,
estrogens, alcohol abuse, iron overload, smoking, and
occupational exposures to polychlorinated cyclic
hydrocarbons. Historically, outbreaks have been caused
by toxic exposure to certain organic chemicals.
Observed less commonly is familial PCT. It is estimated
that 25% of patients are affected with this autosomal
dominant condition. In type II PCT, uroporphyrinogen
decarboxylase activity is approximately 50% of normal
in all tissues, while in type III the enzyme is deficient
only in hepatic cells. In the absence of a positive family
history, type III PCT is virtually indistinguishable from
the sporadic form.
PCT is characterized by photosensitivity and skin fragility.
Patients experience blistering lesions in sun-exposed areas
resulting in cutaneous thickening and scarring. The face,
neck, forearms, and backs of hands are areas most often
affected. Minor trauma may also trigger lesions. Twothirds
of patients experience hypertrichosis (excessive hair
growth) on the face, and less frequently on the ears and
arms. Approximately half of individuals with PCT have
hyperpigmentation in sun-exposed areas, while one-third
of patients develop patches of alopecia as a result of
scarring from large blisters on the scalp. In most cases,
patients exhibit abnormal liver function tests. Long-term
complications include an increased risk for hepatic
cirrhosis and hepatocellular carcinoma. Iron overload may
occur in association with PCT. Hemosiderosis is usually
mild or moderate, although can be severe. Interestingly,
patients with hereditary hemochromatosis are more likely
to experience symptoms of PCT than individuals in the
general population.
PCT is observed more frequently in males than in
females. It is hypothesized that this may be related to
varying levels of alcohol consumption and other
environmental exposures between men and women. A
second theory postulates that menses may provide a level
of protection for women as it acts as a form of
phlebotomy, which is an effective treatment for PCT.
The diagnosis of PCT is easily established through
elevations of uroporphyrin and heptacarboxylporphyrin
in 24-hour urine porphyrins (#8562 Porphyrins,
Quantitative, Urine) and uroporphyrin in plasma (#8733
Porphyrins, Fractionation, Plasma). In PCT urine
uroporphyrin levels are typically elevated to at least 4
times the upper limit of normal, but concentrations may
reach as high as 250 times the upper limit of normal. In
general, heptacarboxylporphyrin is at least 25% of the
uroporphyrin value. (Elevated uroporphyrin without a
concomitant elevation of heptacarboxylporphyrin is often
observed in the acute porphyrias, rather than PCT.)
A urine uroporphyrin level twice the upper limit of
normal is suspicious for PCT and justifies further
investigation. Thus, subsequent plasma and fecal (#81652
Porphyrins, Feces) porphyrin analyses and a repeat urine
porphyrin analysis are recommended, particularly if
symptoms develop or continue to persist. Plasma testing
in cases of PCT demonstrates plasma porphyrin levels
that are typically elevated at least 5 times the upper limit
of normal. Conversely, mild elevations in plasma levels
are associated with renal disease.
Sporadic versus familial PCT can be distinguished by
enzyme analysis (#8599 Uroporphyrinogen Decarboxylase
[Upg D], Erythrocytes) and eliciting a thorough family
history. Enzymatic assay is not an appropriate first-level
assay as the majority of cases are sporadic and the enzyme
exhibits normal activity in these cases.
The cutaneous symptoms of PCT are more amenable to
treatments than are similar complications seen in other
forms of porphyria. Phlebotomy therapy and low-dose
chloroquine, an antimalarial drug, result in complete
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11/02