GeneHealth - Your precision medicine

Porphyria Cutanea Tarda

Disease Details

Family Health Simplified

Buy Membership

Description: Porphyria cutanea tarda (PCT) is a disorder characterized by photosensitivity, leading to blistering lesions on sun-exposed skin areas due to a deficiency in the enzyme uroporphyrinogen decarboxylase.
Type: Porphyria cutanea tarda (PCT) is the most common type of porphyria, a group of disorders caused by abnormalities in the chemical steps leading to the production of heme. PCT can be inherited in an autosomal dominant fashion, meaning only one copy of the altered gene is necessary to increase the risk of developing the condition. However, PCT often also has an acquired component, influenced by environmental factors such as alcohol consumption, hepatitis C infection, or exposure to certain chemicals.
Signs And Symptoms: Porphyria cutanea tarda (PCT) is characterized by the following signs and symptoms:

1. **Skin Symptoms**:
- Blistering on sun-exposed areas of the skin, chiefly the hands, forearms, face, neck, and ears.
- Increased skin fragility, leading to easily torn or blistered skin.
- Hyperpigmentation and hypopigmentation, causing darkening or lightening of the skin.
- Excessive hair growth (hypertrichosis), particularly on the face (cheeks and temples).

2. **Other Symptoms**:
- Liver abnormalities, which may be discovered incidentally during routine blood tests or in the evaluation of other conditions.
- Red or brown urine due to the presence of porphyrins.

PCT occurs due to the decreased activity of the enzyme uroporphyrinogen decarboxylase, typically combined with environmental factors such as alcohol consumption, estrogen use, hepatitis C infection, or iron overload.
Prognosis: Porphyria cutanea tarda (PCT) prognosis is generally favorable with appropriate management. The condition is chronic but can be controlled effectively. Key strategies include avoiding alcohol, estrogen, iron supplements, and sun exposure. Phlebotomy or low-dose hydroxychloroquine may be used to reduce iron overload. Monitoring and managing associated conditions like hepatitis C and HIV are also crucial. With proper treatment, many patients experience significant improvement, and some may achieve remission.
Onset: Porphyria cutanea tarda (PCT) typically has an onset in adulthood, most commonly between the ages of 30 and 50. The condition is characterized by increased sensitivity to sunlight, leading to blistering, fragility, and scarring of the skin, especially on sun-exposed areas.
Prevalence: The prevalence of porphyria cutanea tarda (PCT) is estimated to be about 1 in 20,000 individuals. PCT is the most common type of porphyria.
Epidemiology: PCT prevalence is estimated at 1 in 10,000. An estimated 80% of porphyria cutanea tarda cases are sporadic. The exact frequency is not clear because many people with the condition never experience symptoms and those that do are often misdiagnosed with anything ranging from idiopathic photodermatitis and seasonal allergies to hives.
Intractability: Porphyria cutanea tarda (PCT) is not generally considered intractable. It is the most common type of porphyria and can often be effectively managed and treated. Treatment options include phlebotomy to reduce iron levels in the body, low-dose hydroxychloroquine, and lifestyle changes such as avoiding alcohol and sun exposure. Identifying and managing underlying factors, such as hepatitis C or excessive alcohol consumption, can also help control the disease.
Disease Severity: Porphyria cutanea tarda (PCT) severity can vary significantly among individuals. It is generally considered a chronic condition that mainly affects the skin, leading to increased sensitivity to sunlight, blistering, and skin fragility. The severity can range from mild skin symptoms to more severe and disfiguring skin lesions. Factors such as alcohol consumption, estrogen use, and exposure to sunlight can exacerbate the condition. While PCT is not usually life-threatening, it can cause significant discomfort and complications if not managed properly.
Healthcare Professionals: Disease Ontology ID - DOID:3132
Pathophysiology: Porphyria cutanea tarda (PCT) is a type of porphyria that primarily affects the skin. The pathophysiology of PCT involves a deficiency of the enzyme uroporphyrinogen decarboxylase (UROD). This enzyme deficiency leads to the accumulation of porphyrins and their precursors in the liver. When these compounds are exposed to sunlight, they cause damage to the skin, resulting in blistering, fragility, and increased photosensitivity. Contributing factors can include genetic mutations, liver disease, alcohol consumption, iron overload, and certain medications.
Carrier Status: Porphyria cutanea tarda (PCT) is typically not discussed in terms of "carrier status" as it is primarily an acquired condition. However, it can also have a hereditary component. Mutations in the UROD gene can predispose individuals to PCT, increasing their susceptibility when exposed to certain environmental factors, but possessing a mutation does not guarantee onset of the disease.
Mechanism: Porphyria cutanea tarda (PCT) is primarily caused by deficient activity of the enzyme uroporphyrinogen decarboxylase (UROD). This enzyme is essential in the heme biosynthesis pathway, converting uroporphyrinogen to coproporphyrinogen. When UROD activity is diminished, porphyrins accumulate, particularly uroporphyrinogen and heptacarboxylporphyrinogen, leading to their increased presence in the liver, plasma, and skin.

Molecular Mechanisms:
1. Genetic Mutation: There are genetic and sporadic forms of PCT. In the familial type, mutations in the UROD gene lead to a hereditary deficiency. In the sporadic form, no such mutation is present, but enzyme activity is still reduced due to acquired factors.

2. Iron Overload: An excess of iron in the liver, often due to factors like chronic hepatitis C, alcohol consumption, or genetic conditions like hemochromatosis, plays a pivotal role by promoting oxidative stress and further inhibiting UROD activity.

3. Oxidative Stress: Reactive oxygen species (ROS) can oxidize UROD, reducing its functional capacity. This oxidation is often exacerbated by iron overload and other environmental factors.

4. Estrogens and Hepatotoxins: Exogenous estrogens (e.g., in oral contraceptives) and certain industrial chemicals can also inhibit UROD, contributing to the onset of PCT.

Cumulatively, these molecular mechanisms lead to the accumulation of porphyrins, which are photoreactive and can cause the characteristic photosensitivity and skin blistering seen in PCT when exposed to sunlight.
Treatment: Since PCT is a chronic condition, a comprehensive management of the disease is the most effective means of treatment. Primarily, it is key that patients diagnosed with PCT avoid alcohol consumption, iron supplements, excess exposure to sunlight (especially in the summer), as well as estrogen and chlorinated cyclic hydrocarbons, all of which can potentially exacerbate the disorder. Additionally, the management of excess iron (due to the commonality of hemochromatosis in PCT patients) can be achieved through phlebotomy, whereby blood is systematically drained from the patient. A borderline iron deficiency has been found to have a protective effect by limiting heme synthesis. In the absence of iron, which is to be incorporated in the porphyrin formed in the last step of the synthesis, the mRNA of erythroid 5-aminolevulinate synthase (ALAS-2) is blocked by attachment of an iron-responsive element (IRE) binding cytosolic protein, and transcription of this key enzyme is inhibited.Low doses of antimalarials can be used. Orally ingested chloroquine is completely absorbed in the gut and is preferentially concentrated in the liver, spleen, and kidneys. They work by removing excess porphyrins from the liver via increasing the excretion rate by forming a coordination complex with the iron center of the porphyrin as well as an intramolecular hydrogen bond between a propionate side chain of the porphyrin and the protonated quinuclidine nitrogen atom of either alkaloid. Due to the presence of the chlorine atom, the entire complex is more water-soluble allowing the kidneys to preferentially remove it from the blood stream and expel it through urination. Chloroquine treatment can induce porphyria attacks within the first couple of months of treatment due to the mass mobilization of porphyrins from the liver into the blood stream. Complete remission can be seen within 6–12 months as each dose of antimalarial can only remove a finite amount of porphyrins and there are generally decades of accumulation to be cleared. Originally, higher doses were used to treat the condition but are no longer recommended because of liver toxicity. Finally, due to the strong association between PCT and Hepatitis C, the treatment of Hepatitis C (if present) is vital to the effective treatment of PCT.
Chloroquine, hydroxychloroquine, and venesection are typically employed in the management strategy.
Compassionate Use Treatment: Porphyria cutanea tarda (PCT) can be managed with several treatment options, including some that might be considered off-label or experimental under compassionate use conditions:

1. **Phlebotomy**: Regular removal of blood to reduce iron levels, which can help decrease porphyrin production.

2. **Low-dose Hydroxychloroquine or Chloroquine**: These antimalarial drugs are used to help clear porphyrins from the body but must be administered carefully to avoid liver toxicity.

3. **Iron Chelators**: Deferasirox has been used off-label to reduce iron levels in some cases where phlebotomy is not suitable.

4. **Ursodeoxycholic Acid**: Sometimes used off-label to improve liver function and reduce the buildup of porphyrins.

5. **Hematin**: While more commonly used to treat acute porphyrias, hematin has been tried in PCT as an experimental approach to reduce porphyrin levels.

6. **Investigational Drugs**: Compounds like Polymerized Hemoglobin (PolyHeme), gene therapies, and other experimental medications may be accessible under compassionate use programs for those with severe or refractory cases.

Always consult with a healthcare provider for personalized medical advice.
Lifestyle Recommendations: For porphyria cutanea tarda (PCT), here are some lifestyle recommendations:

1. **Avoid Alcohol**: Limit or eliminate alcohol consumption as it can exacerbate symptoms.
2. **Sun Protection**: Use sunscreen, wear protective clothing, and avoid sun exposure to prevent skin damage.
3. **Iron Management**: Avoid iron supplements and foods high in iron if you have iron overload.
4. **Healthy Diet**: Maintain a balanced diet to support liver health.
5. **Avoid Smoking**: Smoking can worsen symptoms and overall health.
6. **Regular Monitoring**: Keep up with regular medical appointments to monitor liver function and manage symptoms.

Maintaining a healthy lifestyle can help manage PCT symptoms and reduce flare-ups.
Medication: The primary medication used to treat porphyria cutanea tarda is hydroxychloroquine or chloroquine, which are antimalarial drugs that help reduce the levels of porphyrins. Another treatment option is phlebotomy, which involves periodically removing blood to decrease iron levels and, consequently, reduce porphyrin production.
Repurposable Drugs: For Porphyria Cutanea Tarda (PCT), some drugs that have been considered for repurposing include:

1. **Hydroxychloroquine (Plaquenil):** Originally used for malaria and autoimmune diseases.
2. **Chloroquine:** Another antimalarial drug similar to hydroxychloroquine.
3. **Deferasirox:** An iron chelator used in conditions with iron overload.

These medications help to reduce the accumulation of porphyrins or manage the underlying iron overload seen in PCT.
Metabolites: Porphyria cutanea tarda (PCT) is primarily associated with the abnormal accumulation of porphyrins and their precursors. Key metabolites that are typically elevated in PCT include uroporphyrin and heptacarboxylporphyrin in the urine. These porphyrins are involved in the heme biosynthesis pathway, and their buildup is due to a deficiency or inhibition of the enzyme uroporphyrinogen decarboxylase. This enzyme deficiency can lead to the characteristic symptoms of PCT, such as photosensitivity and blistering on sun-exposed areas of the skin.
Nutraceuticals: There is limited evidence supporting the use of nutraceuticals for the management of Porphyria Cutanea Tarda (PCT). Common treatment approaches typically focus on reducing iron levels through phlebotomy and using medications like hydroxychloroquine. Patients are also advised to avoid factors that can exacerbate symptoms, such as alcohol, estrogens, and exposure to sunlight. While some nutraceuticals like antioxidants (e.g., vitamins C and E) could theoretically help by reducing oxidative stress, there is no strong clinical evidence backing their efficacy specifically for PCT. Always consult with a healthcare provider for personalized advice and treatments.
Peptides: Porphyria cutanea tarda (PCT) is primarily associated with a deficiency in the enzyme uroporphyrinogen decarboxylase. Specific peptides are not typically the focus in the context of PCT, but the enzyme's malfunction leads to the buildup of porphyrins, which cause the skin-related symptoms. Nanotechnology is not a mainstream treatment or diagnostic tool for PCT currently, but research in nanomedicine could potentially offer future advancements in detection or therapy.