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.