Risk factors, effective treatments for PCT identified in study
Disease remission more common with therapeutic bloodletting, antimalarials
Heavy alcohol consumption and hereditary hemochromatosis, a genetic disorder characterized by iron overload, are the leading risk factors for porphyria cutanea tarda (PCT), the most common form of porphyria, according to a retrospective 35-year follow-up study conducted in Scotland.
Disease remission was more commonly achieved by patients who had been treated with a combination of therapeutic phlebotomy, or bloodletting, and antimalarial medications.
Despite these observations, researchers noted “further prospective studies of therapeutic strategies in PCT are required in order to optimize the management of patients with this challenging, rare disease.”
The study, “Porphyria cutanea tarda in Scotland: underlying associations and treatment approaches,” was published in the International Journal of Dermatology.
Like other types of porphyria, PCT is characterized by the buildup of heme precursors and intermediate molecules called porphyrins in the body. PCT specifically is caused by the lack of function of an enzyme called uroporphyrinogen decarboxylase, or UROD, which is involved in the production of heme — a molecule that plays a key role in oxygen transport in the body.
People with PCT are hypersensitive to sunlight
People with PCT have an abnormal sensitivity to sunlight. Upon sun exposure, they may develop blisters or other skin lesions. The disease can be triggered by certain precipitating factors, including alcohol consumption, excessive iron accumulation in the body, infections caused by certain viruses, and intake of estrogen, a female sex hormone.
To shed light on the most common risk factors and therapies used to manage PCT, a team led by researchers in Scotland retrospectively analyzed data from 27 patients who had been diagnosed with PCT from 1987 to 2022 at the Scottish Cutaneous Porphyria Service, which is a national service dedicated to the diagnosis and monitoring of cutaneous porphyrias in Scotland.
Patients were a mean age of 55.6 years at the time of diagnosis, and more than half (66.7%) were men.
The most common disease symptoms included blistering (92%), skin fragility (76%), and tiny white bumps, called milia (52%) on sun-exposed areas, according to clinical data from 25 patients.
Heavy alcohol consumption was identified as a risk factor for the development of PCT in 88.5% of the patients. Other commonly identified risk factors included genetic hemochromatosis (72%) and smoking (45.5%). Most patients (70.4%) had several risk factors present, mainly the three mentioned previously.
For treatments, half of the patients (52%) received phlebotomy in combination with antimalarial medications. Eight patients (32%) were given phlebotomy alone, and four (16%) received only antimalarial agents.
96% of patients reported reduction in skin blistering, fragility after treatment
Nearly all patients (96%) reported a reduction in skin blistering and fragility after treatment.
Biochemical remission — defined as a normalization of the 24-hour levels of porphyrins in the urine, particularly uroporphyrin, or total urine porphyrins — was achieved in 50% of the 22 evaluable patients.
Remission was reached after a median of 19 months in two of the four patients (50%) given antimalarial agents, and in nine of the 13 patients (69.2%) treated with a combination of phlebotomy and antimalarial therapies after a median of 26 months. None of the patients treated with phlebotomy alone attained biochemical remission.
Three patients, all treated with combination therapy, saw their disease relapse, with 24-hour uroporphyrin or total urine porphyrin levels rising above the normal range, after a median of 22 months.
No severe side effects were reported. Nausea, diarrhea, and mild leukopenia — a reduction in the levels of immune cells called leukocytes — were observed in patients treated with antimalarial medications. These effects were reversed when they stopped treatment.
Five patients developed cancer, including lymphoma, lung, liver, and colon cancer, after being diagnosed with PCT.
Overall, “we recommend that the management of PCT should be individualized and that long-term follow-up is needed to monitor for disease relapse, but also with respect to cancer screening, particularly with liver and lung cancer in mind,” the researchers wrote.
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