Discussion
Clinically overt PCT is due to hepatic accumulation of uroporphyrin,
which consequently circulate in the plasma and capillaries, get
activated on exposure to sun light, results in immune-mediated reaction,
release of free radicals, and damage of the lower dermis and basement
membranes 2. Characteristics of PCT skin lesions
include increased photosensitivity, skin fragility, painful
vesicles/bullae and erosions/crusts on sun-exposed sites such as face,
dorsum of hands and forearms. Crusting of lesions take weeks to heal,
resulting in atrophic scars with milia formation. Post-inflammatory
hyperpigmentation, scarring alopecia, hypertrichosis, and sclerodermoid
changes are also observed.
The diagnosis of PCT depends on a detailed history, characteristic
symptoms, and laboratory tests. High level of urine and serum
uroporphyrin and heptacarboxyl porphyrin is important for diagnosis. In
our cases, we did not measure urine level of porphyrins but instead
adopted qualitative examination of porphyrins using Wood’s lamp as
previously reported 4. All three patients were tested
positive by Wood’s light, suggesting that Wood’s light is a convenient
and useful test for clinical screening of PCT. Histological examination
of involved skin is not required to confirm the diagnosis of any
cutaneous porphyria, but it help to exclude other entities in the
differential diagnosis, including epidermolysis bullosa acquisita (EBA),
drug-induced pseudoporphyria, and phototoxic drug eruptions.
There are multiple environmental triggers of PCT including alcohol
abuse, smoke, estrogens therapy, hepatitis and liver disease5. Other factors, including HIV infection6, systemic lupus erythematosus 7and end-stage renal disease on hemodialysis 8 are also
associated with the development of PCT. Heavy alcohol use of
>40 g per day has been considered an important
susceptibility factor and was reported in about 60 to 90% of PCT cases9, although only about 2% of subjects with chronic
heavy alcohol were reported to have PCT 2. Mechanisms
of PCT development triggered by alcohol are unclear. It was suggested
that alcohol increased iron absorption and resulted in iron accumulation
in liver that subsequently stimulated the production of
hepaticδ-aminolevulinate synthase (ALA) and free radicals10. The three patients in our report were heavy
drinkers of alcohol. Notably, patient 1 achieved complete remission of
skin lesions purely by cessation of drinking, suggestive of cessation of
alcohol as a general treatment for PCT. A recent study showed that
patients with PCT had high mortality, which was attributed to
gastrointestinal diseases and cancers of gut, liver/gallbladder, and
lungs 11. Further studies are warranted to investigate
how lifestyles such as alcohol consumption affect the long-term
complications and mortality of PCT.
Hereditary hemochromatosis (HH) is defined as an inherited iron overload
disorder characterized by excessive absorption of iron. High frequency
of hereditary hemochromatosis gene mutations including C282Y and H63D,
occurs in patients with PCT 12. Ideally, patients with
PCT should be offered genetic test to uncover possible HH. Serum level
of ransferrin saturation were raised in two of our cases, suggestive of
overloaded iron and potential association with high risk of C282Y
homozygotes 13. However, the two patients demonstrated
good response to therapy, thus gene test was not performed.
PCT can be treated efficiently by phlebotomy or a low dose regimen of
either HCQ or chloroquine14. Patients showed equal improvement as comparing
those received 200 mg chloroquine per week to those with 450 ml
phlebotomy per 2 weeks, whereas the former group showed better
compliance. The mechanism of action of HCQ or chloroquine remains
unclear. The most accepted concept is that the drugs act as mobilizers
of porphyrins and transform hepatocyte porphyrins into water-soluble
complexes that are subsequently excreted in urine 15.
It is suitable for patients who have anemia, blood vessel disorders or
are unwilling to have multiple phlebotomies. To be noted, excessive
dosage might cause worsening of the photosensitivity and elevation of
porphyrin. The suggested dose is 100 mg HCQ or 125 mg chloroquine twice
a week. In our cases, HCQ of 200 mg per week showed great efficacy on
control of skin lesions.