What is Porphyria Cutanea Tarda?
Porphyrias are a group of disorders that occur due to changes or defects in the enzymes responsible for a chemical process called heme biosynthesis in the body. These disorders often cause problems related to the nervous system, skin, or both. Porphyria cutanea tarda (PCT), the most common type of porphyria, occurs because of a shortage of an enzyme called uroporphyrinogen decarboxylase (UROD). A standout symptom of this disorder is photosensitivity, which is an extreme sensitivity to light.
This enzyme, UROD, which is primarily found in the liver, is responsible for transforming a substance known as uroporphyrinogen III into another substance called coproporphyrinogen III. If this doesn’t occur, the previous substances pile up in the liver and later show up in the plasma and urine.
Another rare form of porphyria is hepatoerythropoietic porphyria (HEP), which is quite similar to PCT. However, HEP happens due to a double mutation of UROD genes (homozygous mutation), whereas in PCT, any mutation in UROD genes is usually a single mutation (heterozygous).
In this context, we’ll discuss the various causes of UROD deficiency and share useful information to help diagnose and treat patients with PCT.
What Causes Porphyria Cutanea Tarda?
Porphyria cutanea tarda (PCT) is a condition that affects certain enzymes in your body, specifically one called uroporphyrinogen decarboxylase. In people with PCT, this enzyme doesn’t work properly or might not be present. This causes a build-up of certain chemicals, called porphyrinogens, in different parts of the body, especially the liver and skin. When these chemicals build up, they can cause different health problems. Usually, you need to have less than 20% of the normal enzyme activity before you start to see signs of the illness.
There are three types of PCT:
* Type I: This is the most common type and is responsible for about 80% of cases. Patients with Type I PCT generally have normal levels of the UROD enzyme, but it might not work properly in the liver, possibly because of an inhibitor.
* Type II: This type is inherited and makes up about 20% of all cases. In Type II PCT, the enzyme activity is reduced in all cells by 50%. However, you need certain environmental factors or an inhibitor for the symptoms to appear, which is why people carrying the gene can often have no symptoms.
* Type III: This type is very rare and often appears in more than one family member, suggesting some genetic involvement.
One important factor that seems to affect PCT is iron. People with PCT can have altered iron metabolism and high levels of iron in their bodies. This can lead to the production of UROD inhibitors, which can cause the enzyme to not work properly.
A number of factors can contribute to the development of PCT symptoms:
* Alcohol: Regular heavy drinking can increase iron absorption, stimulate the activity of certain enzymes, and inhibit uroporphyrinogen decarboxylase.
* Hepatitis C Virus (HCV): HCV can cause damage to the liver cells, but it’s important to note that this is not due to reduced enzyme activity.
* Estrogen: About two-thirds of people with PCT have used estrogen, but we don’t know how this leads to PCT symptoms.
* HIV: About 13% of people with PCT are infected with HIV. This contributes to PCT mainly because of a higher rate of concurrent HCV infection in these patients.
* Hemochromatosis: More than half of people with PCT have a gene mutation related to a condition called hemochromatosis, which causes iron build-up in the body.
* Smoking: Many people with PCT are smokers. Smoking can induce the synthesis of a UROD inhibitor.
* Chemical Porphyria: This condition presents like PCT and was notably seen in Turkey during a famine in the 1950s when people ate wheat treated with a toxic fungicide.
Risk Factors and Frequency for Porphyria Cutanea Tarda
PCT, or Porphyria Cutanea Tarda, is the most frequently occurring type of porphyria around the globe. Studies indicate that about 1 in 10,000 people suffer from it according to Norwegian research, and it typically affects middle-aged adults. In the United States, it’s estimated to affect 1 in 25,000 people.
The condition generally impacts both men and women equally. However, certain factors may make one sex more susceptible than the other occasionally. For instance, the use of estrogen in women and the consumption of alcohol or presence of Hepatitis C Virus (HCV) in men could elevate their risk.
Signs and Symptoms of Porphyria Cutanea Tarda
Type I and Type II Porphyria Cutanea Tarda (PCT) are conditions with very similar symptoms and they’re usually treated differently, which is why it’s important to tell them apart. Doctors ask patients about their lifestyle and habits, such as whether they consume alcohol, smoke, are exposed to certain chemicals, or use estrogen. They also look for symptoms related to the nervous system and internal organs, which could indicate other types of porphyria. Normal family history won’t help to diagnose PCT, but knowing the patient’s medication history might help rule out skin eruptions caused by drugs. PCT can make the urine reddish-brown, so doctors also ask about any changes in urine color.
The primary symptoms of PCT relate to the skin, particularly areas exposed to the sun. Commonly affected areas are the backs of the hands, forearms, neck, face, and feet. Symptoms include:
- Photosensitivity (skin reacting to sunlight)
- Formation of skin blisters, vesicles, and bullae
- Fragile skin
- Scarring, which can lead to skin tightening similar to another condition called scleroderma
- Changes in skin pigment, ranging from blue to purplish-brown, especially on the face
- Unusual hair growth on the cheeks, temples, and forearms in women, which might be the only visible symptom of PCT in some cases
The skin lesions caused by PCT often occur after minor injuries and can get infected, leading to severe pain and inflammation. Over time, these lesions heal, leaving behind scars and small, hard, yellow or white lumps known as milia.
In some cases, PCT patients lose hair on their scalps due to scarring alopecia, which causes widespread hair loss. Depending on the individual, the skin might look similar to that of a person with a condition known as polycythemia vera – a reddish coloring on areas of skin exposed to the sun.
Testing for Porphyria Cutanea Tarda
To understand more about porphyria, a disorder related to our body’s process of making proteins, doctors often look at urine or blood samples. If they see that these samples have a high level of substances called porphyrins, it could be a sign of this disease. Doctors usually also check levels of specific kinds of porphyrin called uroporphyrin and heptacarboxyl porphyrin. If these substances are also elevated, it could be a sign of Porphyria Cutanea Tarda (PCT) or Hepatoerythropoietic porphyria, two types of the disease. However, it’s worthwhile to note that the amounts of other substances related to porphyria in the urine – ALA and Porphobilinogen – would typically be normal.
In certain cases, doctors may check for porphyrins in the stool, especially in patients who are on hemodialysis, a process used to clean the blood of those whose kidneys don’t function properly.
Once doctors establish that porphyrin levels are elevated, they perform additional tests to confirm whether PCT is the cause of skin lesions in the patient. If tests find water-soluble porphyrins in the urine, it could be a sign of PCT and Hepatoerythropoietic porphyria (HEP).
Doctors also look for a very high level of a substance called erythrocyte protoporphyrin as it indicates HEP. By observing the level of fluorescence peak wavelength – light emission – in a patient’s blood plasma at a neutral pH level, doctors could differentiate PCT from variegate porphyria, another type of the disease.
A typical pattern of porphyrin accumulation, specific to PCT, in a patient’s body might look like this:
– Urine samples have an increased amount of Uroporphyrin and Coproporphyrin, while Porphobilinogen and ALA levels remain normal.
– Stool samples have an increased amount of Uroporphyrin, Isocoproporphyrin, and Protoporphyrin.
– Red blood cells show normal levels of Uroporphyrin, Coproporphyrin, and Porphobilinogen.
– Blood plasma samples reveal a heightened level of Uroporphyrin.
Lastly, it’s worth mentioning that skin biopsies are not necessary to diagnose porphyria. However, they can be helpful to rule out other skin conditions. If a biopsy is performed, doctors might see things like blisters beneath the skin surface or deposits stuck in the walls of blood vessels.
Treatment Options for Porphyria Cutanea Tarda
To manage Porphyria cutanea tarda (PCT), a condition causing blistering on your skin after sunlight exposure, the first step is to avoid triggers. This includes staying out of the sun until your porphyrin levels, which measure the severity of PCT, are back to normal. Certain sunscreens containing either titanium dioxide or zinc oxide can protect your skin from sunlight between 400-410nm, which triggers porphyrin. Also, protective clothing can help shield your skin from harmful sunlight. Keep any affected skin areas clean to prevent infections and manage any associated pain with over-the-counter painkillers. You should avoid alcohol, smoking, and estrogen therapy, and try to limit iron intake.
Treatments for PCT often involve phlebotomy and hydroxychloroquine, with the choice depending on specific health conditions you may have.
Phlebotomy is a process of removing some of your blood. This treatment method is preferred for individuals with excess iron. Different protocols involve removing a certain amount of blood every week or two, while regularly monitoring your ferritin (iron storage protein) levels to ensure they are decreasing. The goal of phlebotomy is to lower ferritin levels to less than 20 ng/ml. It’s important not to remove too much blood, as doing so can lead to anemia, a condition where you don’t have enough healthy red blood cells. Improvement in skin symptoms is typically seen within four months, but it may take up to a year for porphyrin levels to fully normalize. Ferritin levels can be used to monitor for any relapses in your condition. However, people with diseases affecting the lungs or the heart should not undergo phlebotomy.
Hydroxychloroquine or chloroquine are preferred if your ferritin levels are not too high or if you don’t have an HFE mutation, a genetic condition that can cause iron overload. These drugs work by stopping the creation and release of porphyrins, which are the chemicals causing PCT. These drugs should be taken twice a week and it usually takes between six to nine months for complete recovery. However, certain individuals, such as pregnant women, people with liver or eye diseases, and those taking other drugs that harm the liver should not use these drugs. If prescribed these, you should have regular eye exams and liver function tests.
Chelation therapy, which uses medication to remove excess iron from your body, is another method to treat PCT if phlebotomy and hydroxychloroquine are not suitable. However, this treatment method can be quite expensive and often fails to restore normal porphyrin levels even after a year of treatment.
What else can Porphyria Cutanea Tarda be?
When a patient is suspected to have porphyria cutanea tarda (PCT), a type of skin condition, doctors will often consider other similar conditions. These include:
- Hereditary coproporphyria
- Variegate porphyria
- Congenital erythropoietic porphyria
These conditions all have skin symptoms and elevated porphyrin levels like PCT, but each disease has a specific pattern of porphyrin elevation that helps to identify it. For example, if a patient has variegate porphyria, they would have increased levels of coproporphyrins, ALA, and porphobilinogen in their urine. But if they have congenital erythropoietic porphyria, their urinary ALA and porphobilinogen levels would be normal. Additionally, both variegate porphyria and hereditary coproporphyria can be told apart from PCT because patients with these conditions often have symptoms related to the nervous system and organs, which are absent in PCT.
There are a few skin conditions that can cause similar blisters but they can be distinguished from PCT because they don’t increase porphyrin levels. These include:
- Pseudoporphyria cutanea tarda: looks like PCT under the microscope and in person, but without the elevated porphyrin levels. It’s often linked with certain medications.
- Epidermolysis bullosa acquisita: an immune system disorder that causes widespread blisters, even on skin that’s not exposed to the sun.
- Polymorphous light eruption: a skin rash that appears shortly after sun exposure, and presents as red bumps, blisters, or plaque without scarring.
High porphyrin levels can also be seen in liver disease, advanced kidney disease, and other types of porphyria. However, these diseases wouldn’t show the typical skin symptoms seen in PCT patients.
What to expect with Porphyria Cutanea Tarda
People with PCT (porphyria cutanea tarda), a type of skin condition, can generally expect to live a normal lifespan unless they also have other health issues like HCV (hepatitis C virus), which can cause liver disease or cancer.
Complete recovery from PCT is possible, but the disease may return. In fact, up to 35% of patients have experienced a relapse within an 11-year period.
If you have high iron levels in your blood, you may need to go through a procedure called a phlebotomy, which helps remove some of the iron from your blood. Lifestyle factors like drinking alcohol excessively and smoking can increase the chance of the disease returning.
To catch a relapse of the disease early, before any symptoms show up, doctors recommend checking the levels of uroporphyrin (a chemical that’s usually high in people with PCT) in your urine and blood every year.
Possible Complications When Diagnosed with Porphyria Cutanea Tarda
Even though the symptoms of PCT largely affect the skin, people with this condition are also at significant risk for liver problems. Typically, a liver biopsy may show a build up of fats and porphyrins, sometimes even leading to localized liver tissue death. In addition to this, PCT also increases the person’s risk of developing liver cirrhosis and liver cancer. This risk may be amplified if the person also has Hepatitis C virus (HCV) infection, alcohol-related hepatitis, or an excessive amount of iron in their bodies.
Common Complications of PCT:
- Liver problems
- Fatty deposits in the liver
- Deposits of porphyrins in the liver
- Liver tissue necrosis
- Increased risk of liver cirrhosis
- Increased risk of liver cancer
- Complications with Hepatitis C virus infection
- Complications with alcohol-related hepatitis
- Complications with iron overload
Preventing Porphyria Cutanea Tarda
Patients should be given detailed information about their illness, with reassurance that the condition isn’t life-threatening. The procedure known as phlebotomy, which is simply the process of drawing blood, and the need for regular checkups to monitor the amount of porphyrins (a type of substance in your blood) should be explained. Patients should also be told to steer clear of factors that could make their condition worse. This includes stopping smoking, refraining from alcohol intake, and not taking estrogen and iron therapies. Using sun-protective strategies such as sunscreens, hats, and clothing that covers the skin is crucial and needs emphasis.
If patients have a history of HCV (a viral infection that causes liver inflammation) or HIV (a virus that attacks the immune system), it’s important that they disclose this information. Following the treatment plan created by the doctor is vital for their recovery.
As part of the treatment plan for this condition, known as PCT, patients should anticipate tests for a protein called ferritin, check for any infections, as well as genetic tests. All these are essential to manage their condition better and they should be made aware of them.
