Porphyria Cutanea Tarda (PCT) is an uncommon disorder occurring in an estimated 5 to 10 persons per 100,000. This condition arises when one of the key enzymes in heme biosynthesis is inhibited. Consequently, porphyrins build up in the liver and blood. Typically diagnosed in people older than 40 years old, PCT occurs more often in men than women. Fun fact: over three quarters of PCT cases do not have a genetic trigger. This is what sets PCT apart from other porphyrias—it can develop even in the absence of a genetic variant.
Doctors usually test for PCT through urine and plasma tests. These tests determine the presence of excess porphyrin levels, which indicates the specific type of disorder. While phlebotomy is a time-tested treatment, patients have few other options. This surgical approach may lead to dramatic symptomatic improvement and eventual return to normal porphyrin levels with time. The implications of PCT go far beyond personal health, affecting the overall management of iron overload and liver function.
The Mechanism Behind PCT
PCT’s pathophysiology focuses on the interruption of heme production. This process disruption results in porphyrins accumulating, most notably in the liver and plasma. The disease commonly presents in men of middle age and older – specifically, over the age of 40.
Rebecca Karp Leaf, MD, emphasizes that “modification of risk factors can be variably helpful: alcohol and smoking cessation, stopping exogenous estrogen, sun-protective clothing, and steroid-containing creams for lesions.” These prevention efforts can help alleviate PCT symptoms and lower the chance of experiencing flare-ups for people with this condition.
Additionally, PCT is unique because it can happen without the presence of a genetic variant. However, this characteristic is what sets it apart from other types of porphyria. Yet, our increasing knowledge of this disease signals the importance of preventing those environmental and lifestyle triggers that can spark its onset.
Diagnosing and Treating PCT
The current diagnostic framework for PCT is centered around urine and plasma tests to identify a high porphyrin level. Once diagnosed, physicians only focus on treating the condition itself through phlebotomy. This process purges the blood to lower iron overload and decrease porphyrin levels.
Dr. Leaf says that “usually, we’ll begin with venesection of 450 ccs of whole blood every 2 weeks. During this treatment, target a ferritin level of 20 ng/mL. They’re OK with the level rising a bit – all the way up to 50 ng/mL. Phlebotomy is very impressive. It can clear skin blisters in as little as two to three months and partially normalize porphyrins levels within approximately 13 months.
Apart from first-line phlebotomy treatment, maintenance therapy involves three phlebotomies annually. Continued treatment is needed to control symptoms and keep porphyrin at acceptable levels.
“Most patients typically require further therapy to reduce liver porphyrins.” – Rebecca Karp Leaf, MD
Managing Associated Risks
PCT is often associated with iron overload, a state that complicates the management of this disease. Fortunately, effective treatment is extremely effective at turning things around for patients, but as you might guess early intervention is key. Girelli emphasizes how safe, inexpensive, and well-tolerated it is. He underscores its life-saving and health-giving potential – particularly if started before a patient develops cirrhosis.
Ferritin levels greater than 1000 µg/L are a very reliable clinical marker of underlying advanced liver fibrosis in PCT patients. Further, the development of arthropathy, or joint disease, makes this diagnosis even more certain. If both conditions are not present and the patient is still asymptomatic, additional work-up may not be warranted. If both are, further investigations including cardiac MRI and a complete endocrine profile should be considered.
“The strongest clinical predictors of advanced liver fibrosis are ferritin higher than 1000 [µg/L] and the presence of arthropathy [joint disease],” – Girelli
Patients diagnosed in the preclinical or early stages of PCT typically have an outstanding prognosis. They should be able to look forward to living a full life expectancy. Girelli emphasizes that “only a small fraction of patients are diagnosed in preclinical or early stage, and prognoses are excellent.”
Future Perspectives on PCT Management
Though recently approved and still under research, more PCT treatment options are emerging. We conclude that low-dose hydroxychloroquine is an effective long-term treatment for most skin lesions of PCT. That’s important because it provides a new option for patients who stand to respond poorly to existing therapies.
Furthermore, safe and effective antiviral treatment for hepatitis C virus (HCV) will likely prevent a significant proportion of PCT cases. This relationship highlights the need to further investigate any cooccurring health conditions that may impact the development and severity of PCT.
“It’s one of my favorite therapies because you don’t have to give somebody a drug. You can just take out iron,” – Rebecca Karp Leaf, MD
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