What are the other Names for this Condition? (Also known as/Synonyms)
- PCT (Porphyria Cutanea Tarda)
What is Porphyria Cutanea Tarda? (Definition/Background Information)
- Porphyrias are disorders resulting from excess porphyrin buildup in the liver and bone marrow. Manufacturing hemoglobin and related proteins (heme synthesis) involves a class of molecules, called porphyrins. Porphyrias are either inherited or acquired, and are described as acute, chronic, and cutaneous
- Porphyria Cutanea Tarda (PCT) is the most common form of porphyria that manifests almost only as a skin condition (form of cutaneous porphyria). In this condition, the skin is severely sensitive to light, which often presents as scarring, blistering, and hair growth on the hands/face
- Porphyria Cutanea Tarda is a genetic condition may be inherited in some cases, or occurs as a sporadic development in majority of the cases. The onset of symptoms may occur in childhood or adulthood (mostly)
- A healthcare provider typically diagnoses this genetic disorder by testing blood or other bodily fluids of the affected individual for porphyrin compounds and gene mutations, in case it is an inherited condition
- The treatments for Porphyria Cutanea Tarda can include phlebotomy (blood draws) to decrease iron from the body, use of anti-malarial drugs in low doses, and application of topical sunscreens. In case the liver is severely affected by cirrhosis or hepatic fibrosis, a liver transplant may be necessary
- The prognosis of Porphyria Cutanea Tarda is determined by the severity of symptoms and extent of liver damage. In many individuals, the prognosis is good with accurate diagnosis and prompt treatment
Who gets Porphyria Cutanea Tarda? (Age and Sex Distribution)
- Porphyria Cutanea Tarda is the most common form of porphyria affecting 1 in 10,000 to 1 in 25,000 individuals globally
- Inherited forms of the disorder report symptom-onset during adulthood, and sometimes during childhood
- The disorder occurs in both male and female genders, and all racial and ethnic groups
What are the Risk Factors for Porphyria Cutanea Tarda? (Predisposing Factors)
- A family history of Porphyria Cutanea Tarda increases the risk of a newborn being diagnosed with the condition
- Individuals with an iron overload disorder, known as hemochromatosis, due to mutations in the HFE gene have an elevated risk for developing PCT
It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.
Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.
What are the Causes of Porphyria Cutanea Tarda? (Etiology)
Porphyria Cutanea Tarda (PCT) is caused by certain gene mutations, which are involved in the production of “heme”.
- Heme is a critical component of iron-containing proteins called hemoproteins. Hemoglobin is one such protein, which is the oxygen carrier in blood. Blood, bone marrow, and liver have the most heme protein in them
- Most of the cases (4 in 5) are acquired or develop through sporadic mutations, when family history is not present. 1 in 5 develop as an autosomal dominant trait, and a family history is seen
- When inherited, the involvement of the UROD gene is noted. The gene involved in sporadic cases is unknown. Studies indicate that all non-inherited cases seem to show some genetic alterations
- Mutations in the defective gene affects porphyrin metabolism. A compromised porphyrin metabolism causes a buildup of porphyrins in the body
- The enzyme involved in end heme synthesis, called uroporphyrinogen decarboxylase (URO. D), is affected and dysfunctional. This enzyme is in the liver and to some extent in red blood cells
- When the activity and levels of URO.D is affected, it leads to abnormal and excess collection of porphyrin compounds in skin. These compounds react with light energy resulting in skin symptoms, termed photosensitivity
- In the presence of internal or external triggers, it results in severe symptoms, due to the abnormal accumulation of the porphyrin compounds in the body
Precipitating factors or triggers of Porphyria Cutanea Tarda:
- The most important trigger is consuming too much alcohol or alcoholism. Since the liver is already involved, excess alcohol can also result in chronic liver disease
- Certain blood disorders
- Estrogen therapy
- infection by some viruses (notably human immunodeficiency virus and hepatic C virus)
- Individuals on long-term kidney dialysis
- Inhaling or ingesting certain insecticides and herbicides that contain compounds, such as chlorinated hydrocarbons, may cause PCT
- Exposure to agent orange
- Overload of iron and iron metabolism defects in the body can make the condition worse or trigger PCT
Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.
What are the Signs and Symptoms of Porphyria Cutanea Tarda?
The signs and symptoms of Porphyria Cutanea Tarda (PCT) due to porphyrin buildup are mostly confined to the skin due to photosensitivity (on exposure to sunlight). These may be mild or severe and vary from one individual to another. The skin signs and symptoms may include:
- Skin gets inflamed with burning sensation
- Blistering of the skin; formation of blisters (vesicles) on the skin
- The blisters are fragile, readily becoming erosions. PCT patients may not have seen a blister
- Recurrent skin infections
- Skin ulceration resulting in scarring of the skin
- Sun-exposed areas of the body are affected the most, such as the face, neck, shoulders, arms (including the wrists and fingers), chest and back
- Weak and fragile skin that is easily broken on minor trauma or injury
- Increased hair growth or hirsutism; hypertrichosis (or abnormal hair growth)
The skin signs and symptoms may be non-specific and can be associated with many other skin disorders. Hence, a differential diagnosis is normally undertaken. In many individuals, no symptoms of PCT may be present.
Other signs and symptoms of PCT may include:
- Abnormal color of urine (turns reddish after hours in natural light)
- Urine that glows pinkish under ultraviolet light
- Inflammation of the liver is commonly noted in those with sporadic cases of PCT
- Hemolytic anemia (destruction of red blood cells)
- Splenomegaly (spleen enlargement) seen in the case of advanced liver disease
How is Porphyria Cutanea Tarda Diagnosed?
The diagnosis of Porphyria Cutanea Tarda may be complicated, because it is confused with other porphyria disorders, such as hereditary coproporphyria (HCP) and variegate porphyria (VP), even with lab urine test results. Also, the cutaneous symptoms are non-specific and may be present in many skin conditions. Due to this, blood and stool tests are usually performed. The differentiation is important because some of the triggering medications may be avoided/prescribed. Also, some medications for PCT are contraindicated for VP, and hence an accurate diagnosis is critical with respect to employing suitable treatment measures.
The diagnosis of Porphyria Cutanea Tarda is made by the following tools:
- A complete physical examination and an assessment of symptoms
- An evaluation of the affected individual’s full medical history
- Measurement of the porphyrin levels in blood, urine, or feces: Excess amounts of porphyrin compounds (uroporphyrins) are produced, and therefore, seen in urine and feces during the attacks. But, ALA and PBG are not affected and secretions in urine are normal, but may be increased in blood
- Measurement of uroporphyrinogen decarboxylase (URO.D) enzyme activity
- Molecular genetic testing before or after birth, to confirm UROD gene mutation(s), in case of a family history of PCT
- A differential diagnosis is often necessary to exclude other conditions, such as lead poisoning, pseudoporphyria, and iron overload disorder
Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.
What are the possible Complications of Porphyria Cutanea Tarda?
The potential complications of Porphyria Cutanea Tarda may include:
- Diffuse thickening and pigment changes of the skin of extremities over time
- Severe emotional stress due to cosmetic concerns
- Bacterial infections following characteristic blistering of the skin
- Chronic liver conditions, such as scarring and fibrosis, are noted in individuals with sporadic PCT
- Individuals with PCT are generally found to be deficient in certain important vitamins and minerals particularly, vitamins A and C, retinol, and beta-carotene
How is Porphyria Cutanea Tarda Treated?
Unlike other forms of porphyria, Porphyria Cutanea Tarda is not difficult to treat, once an accurate diagnosis is established. The treatment involves controlling the factors that cause or trigger PCT, and undertaking treatment of the symptoms.
The treatment measures of Porphyria Cutanea Tarda may include:
- Phlebotomy (blood draws) helps reduce iron load in the body. A unit (500 ml) of blood is drawn, with the technique used by blood banks. This blood cannot be transfused into other patients, so it is safely discarded. As the body forms more blood, iron is mobilized from the liver. Draws are done every two weeks for 2-4 months. Treatment is paused if short term anemia develops
- Use of oral anti-malarial drug chloroquine and hydroxychloroquine (low-dose) has proven to be effective in removing excess buildup of porphyrins in liver. However, it takes a period of 6-12 months for the treatment to be effective
- Avoiding direct exposure to sunlight and the application of topical sunscreen creams
- Use of suitable medications to treat HCV infection if hepatitis C is present
- Addressing vitamin and mineral deficiencies
- Undertaking treatment for liver disorders; in some cases, a partial or complete liver transplant may be necessary
- Cessation of exposure to triggering agents must be complete. Consuming alcohol must be discontinued
How can Porphyria Cutanea Tarda be Prevented?
- Currently, there are no specific methods or guidelines to prevent Porphyria Cutanea Tarda (PCT), since it is a genetic condition
- Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
- If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
- Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Porphyria Cutanea Tarda
Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.
Once the triggers or precipitating factors for Porphyria Cutanea Tarda are identified, certain steps may be taken to avoid them to the extent possible, such as:
- Having a healthy lifestyle and a regular diet
- Avoid the use of illegal drugs; avoiding alcohol
- Stress avoidance, when possible
- Discontinuing medicines that trigger PCT, instead using alternatives
- Undertaking prompt treatment for any illness or infection
What is the Prognosis of Porphyria Cutanea Tarda? (Outcomes/Resolutions)
- The prognosis of Porphyria Cutanea Tarda varies with the severity of the condition. It is assessed on a case-by-case basis
- However, with an early and accurate diagnosis and appropriate treatment, the prognosis is good in many individuals
Additional and Relevant Useful Information for Porphyria Cutanea Tarda:
The other forms of cutaneous porphyria include X-linked dominant protoporphyria (XLDPP), congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP), hereditary coproporphyria (HCP), and variegate porphyria (VP).