Overview

Porphyria is a group of rare genetic disorders characterised by abnormalities in the production and accumulation of porphyrins, which are essential components of haem synthesis. Haem is a red pigment found in haemoglobin, the protein in red blood cells that carries oxygen throughout the body. These disorders can affect multiple body systems and result in a wide range of symptoms.

Porphyria Cutanea Tarda (PCT) is a specific type of porphyria and is considered the most common form worldwide. It is characterised by a deficiency of the enzyme uroporphyrinogen decarboxylase (UROD), which is necessary for the normal synthesis of haem. As a result, porphyrins accumulate in the body, particularly in the skin. PCT primarily affects the skin, leading to increased skin sensitivity and fragility.

Another type of porphyria is congenital erythropoietic porphyria, which is characterised by a deficiency of the enzyme uroporphyrinogen III cosynthase. This deficiency results in the accumulation of porphyrins in various body tissues, including the skin. Congenital erythropoietic porphyria is a rare and severe form of porphyria which typically presents early in life and affects multiple body systems.

Erythropoietic protoporphyria is another type of porphyria caused by a defect in the enzyme ferrochelatase. This defect leads to the accumulation of protoporphyrins, another type of porphyrin, primarily in the skin. Erythropoietic protoporphyria is characterised by extreme sensitivity to sunlight, causing pain, redness, and swelling upon sun exposure.

In all forms of porphyria, the accumulation of porphyrins or their precursors can result in various symptoms depending on the specific type and distribution of porphyrins in the body. These symptoms can include abdominal pain, neurological disturbances, photosensitivity, skin changes, and in some cases, liver disease.¹

Causes of porphyria cutanea tarda

Porphyria Cutanea Tarda (PCT) is primarily considered an acquired form of porphyria, meaning it is often not inherited but rather triggered by environmental factors. However, genetic factors can still play a role in determining an individual's susceptibility to PCT. The development of PCT is influenced by a combination of genetic and environmental factors.

Various triggers have been identified that can contribute to the development of PCT in susceptible individuals. Excessive alcohol consumption is a well-known trigger, as it can disrupt liver function and impair the metabolism of porphyrins, leading to their accumulation. Oestrogen therapy, such as hormone replacement therapy or oral contraceptives, can also be a trigger for PCT, particularly in people assigned female at birth. The exact mechanism is not fully understood, but it is believed that oestrogen may interfere with the normal synthesis and metabolism of porphyrins.

Iron overload is another significant trigger for PCT. Excessive iron in the body can lead to increased production and accumulation of porphyrins. This can occur in individuals with conditions such as hereditary haemochromatosis or those who receive frequent blood transfusions.

Certain medications or chemicals can also induce or exacerbate PCT in susceptible individuals. Examples include chloroquine, a medication used for malaria treatment, and certain industrial chemicals like hexachlorobenzene and trichloroethylene.

In individuals with HIV infection, PCT may be associated with hepatitis C virus (HCV) co-infection and immune dysfunction. The exact relationship between HIV, HCV, and PCT is not fully understood, but it is believed that the presence of both infections and compromised immune function can contribute to the development of PCT in these patients.

It's important to note that while these triggers increase the risk of developing PCT, not everyone exposed to these factors will develop the condition. Susceptibility to PCT can vary among individuals based on their genetic makeup and other underlying factors.^2,3

Signs and symptoms of porphyria cutanea tarda

Patients with PCT experience photosensitivity, resulting in blistering, redness, itching, and pain upon sun exposure. The skin manifestations primarily occur in sun-exposed areas. Other symptoms include hypertrichosis, skin fragility leading to bruising and bleeding, and hyperpigmentation. In severe cases, patients may present with liver disease, such as fibrosis or cirrhosis.⁴

Management and treatment for porphyria cutanea tarda

The management of PCT focuses on reducing porphyrin production, alleviating symptoms, and preventing complications. Lifestyle modifications, including alcohol avoidance and protection from sunlight, are essential. Phlebotomy, which involves the removal of blood, effectively reduces iron levels and porphyrin accumulation. Hydroxychloroquine, an antimalarial drug, can also reduce porphyrin production and improve symptoms.^8,9

Diagnosis of porphyria cutanea tarda

Diagnosing PCT involves a combination of clinical evaluation and laboratory tests. Increased levels of uroporphyrin and heptacarboxylporphyrin in blood, urine, and stool samples are characteristic findings. Genetic testing can identify mutations in the UROD gene, confirming the diagnosis of PCT. In cases of acute attacks, the detection of increased porphyrin levels can aid in the differentiation from other acute porphyrias.^5,6.

Risk factors

Alongside genetic predisposition, several risk factors can trigger PCT development. Alcohol consumption, oestrogen therapy, iron overload, and certain medications (such as chloroquine and sulfonamides) are known triggers. Additionally, patients with HIV infection and HCV co-infection are at an increased risk of developing PCT.⁷

Complications

PCT can lead to various complications, including chronic liver disease, such as fibrosis, cirrhosis, and an increased risk of hepatocellular carcinoma (liver cancer). Regular monitoring of liver function and hepatocellular carcinoma screening is crucial, especially in patients with long-standing and untreated PCT. Acute attacks of porphyria may require hospitalisation and management of symptoms, including pain control and supportive care.^10,11

FAQs

How can I prevent porphyria cutanea tarda?

To prevent Porphyria Cutanea Tarda (PCT), follow these steps:

• Limit alcohol consumption to prevent PCT triggers.
• Protect your skin from sunlight using sunscreen, protective clothing, and seeking shade.
• Avoid oestrogen therapy, as it can trigger PCT.
• Manage iron levels if you require transfusions or iron supplementation.
• Consult a healthcare professional experienced in porphyrias for personalised prevention advice. By being aware of triggers and taking preventive measures, you can reduce the risk of developing or worsening Porphyria Cutanea Tarda symptoms.

How common is porphyria cutanea tarda?

PCT is the most common type of porphyria worldwide, but its occurrence varies between populations. Generally, PCT is relatively rare, with approximately 1 to 2 cases per 10,000 people in the general population. However, certain factors like HCV infection or excessive alcohol consumption can increase its prevalence in specific regions or groups. PCT is more commonly diagnosed in middle-aged or older people assigned male at birth. It's important to note that the actual number of cases may be higher as PCT is often misdiagnosed or overlooked due to similarities with other skin conditions.

When should I see a doctor?

If you're concerned about Porphyria Cutanea Tarda (PCT), it's important to see a doctor in the following cases:

• Persistent skin symptoms: If you have ongoing skin issues like blistering, redness, itching, or skin fragility, especially in sun-exposed areas.
• Family history or risk factors: If you have a family history of PCT or known risk factors such as alcohol consumption, oestrogen therapy, or HCV.
• Unexplained liver abnormalities: If you have unexplained liver problems or signs of liver disease.
• Suspected triggers or exposure: If you've been exposed to known triggers of PCT and develop symptoms or skin changes. Early diagnosis and management are crucial, so consult a healthcare professional experienced in porphyrias if you have concerns about PCT.

Summary

Porphyria cutanea tarda is a rare genetic disorder characterised by skin manifestations due to the accumulation of porphyrins. Environmental triggers, along with genetic factors, play a significant role in its development. Early diagnosis, lifestyle modifications, and appropriate management strategies are essential for symptom relief and prevention of complications in patients with PCT.