What are the other Names for this Condition? (Also known as/Synonyms)

• Dermal Porphyria
• Skin Porphyria

What is Cutaneous Porphyria? (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 disorder, and are described as acute, chronic, and cutaneous
• Cutaneous Porphyria is a genetic condition affecting heme metabolism that is seen in children and adults. It mainly presents with skin symptoms including scarring and blistering on exposure to sunlight
• Some forms of Cutaneous Porphyrias are seen with acute attacks that are triggered by certain internal or external factors. During acute attacks (presentation of severe symptoms), the disorder is characterized by severe abdominal pain, constipation or diarrhea, and neurological symptoms that include muscle pain and weakness
• Cutaneous Porphyria generally consists of the following types:
  • X-Linked Dominant Protoporphyria (XLDPP): It is an extremely rare form that is marked by liver cirrhosis in addition to the skin symptoms
  • Congenital Erythropoietic Porphyria (CEP): It is a rare subtype that is commonly present in young children
  • Porphyria Cutanea Tarda (PCT): It is the most common form of porphyria
  • Erythropoietic Protoporphyria (EPP): EPP typically manifests as a skin condition
  • Hereditary Coproporphyria (HCP): It is an acute form of porphyria that presents skin symptoms in addition to acute attacks
  • Variegate Porphyria (VP): It is another acute form of porphyria that presents skin symptoms in addition to acute attacks
• Acute attacks are not seen with XLDPP, CEP, PCT, and EPP. However, HCP and VP are also Acute Porphyrias (presenting acute attacks) showing cutaneous manifestations (in some cases)
• Cutaneous Porphyria may be inherited in an autosomal dominant or autosomal recessive manner, due to certain gene mutations, which causes a defect in heme production in the bone marrow and liver. The condition may also occur sporadically, or rarely be acquired
• A healthcare provider typically diagnoses this genetic disorder by testing porphyrin levels in urine and blood samples, along-with symptom assessment. During episodes of acute attacks, it can be noted that the urine of the affected individual turns reddish-brown on exposure to sunlight
• The treatments for Cutaneous Porphyria involves the application of topical sunscreens and other measures to protect oneself from direct sunlight exposure. It can also involve the removal/treatment of triggers causing the condition and symptomatic treatment
• The prognosis of Cutaneous Porphyria is determined by the specific subtype, the severity of symptoms, and whether complications have developed. In many individuals, the prognosis is good with accurate diagnosis and adequate treatment

Who gets Cutaneous Porphyria? (Age and Sex Distribution)

• The prevalence and demographics of Cutaneous Porphyria depend on the specific type of porphyria
• The manifestation of symptoms may occur in childhood or adulthood and both male and female genders are affected
• The disorder occurs worldwide without any racial or ethnic bias

What are the Risk Factors for Acute Porphyria? (Predisposing Factors)

• A family history of Cutaneous Porphyria increases the risk of a newborn being diagnosed with the condition

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 Cutaneous Porphyria? (Etiology)

Cutaneous Porphyria is caused by mutations on genes that are involved in the production of “heme”. The gene undergoing mutations may be inherited in an autosomal dominant or autosomal recessive manner. It depends on the specific subtype of porphyria.

• 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
• The gene mutations cause a decrease in porphyrin metabolism. A compromised porphyrin metabolism causes a buildup of precursor porphyrins in the body. These mutations affect the functions of specific enzymes, which disrupts the multistep process of generating heme
• When the activity and levels of the enzyme are 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 acute forms of porphyria, the enzyme dysfunction may not always manifest as symptoms, since the body can manage with reduced enzyme function to some extent. But the presence of other internal or external factors may hinder its function further, resulting in an acute attack (severe symptoms)

The external factors or triggers may include:

• Environmental stimuli
• Eating an unusual diet, starving
• Illegal drug abuse
• Alcoholism
• Use of certain medications

The internal factors may include:

• Emotional or psychological stress
• Menstruation in women
• Any illness or infection
• Other hormonal factors

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.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Cutaneous Porphyria?

The various signs and symptoms of Cutaneous Porphyria are the result of porphyrin buildup in the body. These may be mild or severe and vary from one individual to another. The signs and symptoms depend on the specific subtype of porphyria.

Cutaneous signs and symptoms may include:

• Skin gets burned on sun exposure resulting in sunburns and blister formation
• The skin becomes weak and fragile over time
• Change of skin pigmentation and thickening
• Recurrent skin infections
• 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 damaged on minor trauma or injury
• Increased hair growth or hirsutism; hypertrichosis, or abnormal hair growth

The skin manifestations may be categorized into the following two types:

• Immediate photosensitivity:
  • The skin symptoms are observed within a short span of time, usually by half an hour, after exposure to sunlight
  • However, in many individuals, these may be mild (with skin inflammation and redness); while in some, it can be severe (presenting severe irritation, burning, and pain) on the exposed areas
  • It is observed in XLDPP and EPP forms of Cutaneous Porphyria
• Vesiculo-erosive skin disease:
  • It is characterized by the formation of fluid-filled blisters that are confined to the sun-exposed areas, and these may be mild, moderate, or severe depending on the specific subtype
  • It is observed in CEP, PCT, HCP, and VP forms of Cutaneous Porphyria

Additionally, the following signs and symptoms may be observed:

• Stomach pain and cramping abdominal pain
• Diarrhea or constipation
• Retention of urine
• Neurological signs and symptoms may include:
  • Peripheral neuropathy
  • Muscular pain and weak muscles
  • If the respiratory muscles are affected, it may cause breathing difficulties
  • Seizures in some cases
• When the nervous system of the internal organs is affected, it gives rise to neurovisceral crises
• Psychiatric signs and symptoms may include:
  • Change in sensation
  • Feeling confused
  • Hallucinations
• Abnormal color of urine (reddish) on exposure to sunlight; which tends to resolve following treatment, or when the symptoms go away
• When liver involvement is present, yellowing of skin and eyes may be observed

How is Cutaneous Porphyria Diagnosed?

The diagnosis of Cutaneous Porphyria 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
• Measurement of activity of the involved enzyme
• Molecular genetic testing before or after birth, to confirm gene mutation

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 Cutaneous Porphyria?

The potential complications of Cutaneous Porphyria may include:

• Cosmetic issues due to skin of the face, neck, arms being chronically affected
• Severe deformation of the skin or extremities over time
• Bacterial infections following characteristic blistering of the skin
• Severe pain and emotional stress during periods of acute attacks
• Anemia and related conditions, due to low levels of oxygen transport
• Increased heart rate and increased blood pressure may be the outcome of autonomic nervous system being affected

How is Cutaneous Porphyria Treated?

The treatment measures for Cutaneous Porphyria are based on the specific subtype. The treatment also involves controlling the factors that cause or trigger porphyria, and undertaking treatment of the symptoms. The treatment considerations may involve:

• Skin protection by avoiding direct sunlight and use of topical sunscreen creams
• Beta carotene analogues which make the skin less sensitive to sun’s rays
• Oral/intravenous glucose and carbohydrate-rich diet
• Painkillers, including narcotics if necessary, may be given for severe pain
• Antipsychotic medication (chlorpromazine) to treat some of the neurological symptoms
• Beta-blockers, such as propranolol, for cardiovascular conditions such as hypertension and tachycardia
• Anti-seizure medications, such as gabapentin, for seizures
• Blood disorder medications (intravenous heme) may be used to treat accumulation of porphyrin compounds
• If the symptoms are because of normal menstrual cycles, birth control hormonal pills or synthetic peptide drugs may be helpful
• Blood transfusions, based on the degree of anemia
• A splenectomy (removal of the spleen) to alleviate bleeding and worsening anemia (due to spleen enlargement)
• Bone marrow transplant for severe cases

In many individuals, the symptoms of an acute attack subside on their own. Sometimes, it may be severe as to requiring treatment in a hospital setting. The treatment also involves removing or treating any internal or external triggers

How can Cutaneous Porphyria be Prevented?

• Currently, there are no specific methods or guidelines to prevent most forms of Cutaneous Porphyria, since these are genetic conditions
• 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 Acute Intermittent Porphyria

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

Once the triggers or precipitating factors for some subtypes of Cutaneous Porphyria are identified, certain steps may be taken to avoid them to the extent possible. These include:

• Having a healthy lifestyle and a regular diet
• Stress avoidance when possible
• Avoiding the use of illegal drugs; avoiding alcohol
• Discontinuing medicines that trigger porphyria, instead using alternatives
• Undertaking prompt treatment for any illness or infection

What is the Prognosis of Cutaneous Porphyria? (Outcomes/Resolutions)

• The prognosis of Cutaneous Porphyria depends on the subtype of porphyria and varies with the severity of the condition. It may be assessed on a case-by-case basis
• The prognosis is generally good for mild cases and the symptoms go away with adequate treatment. If neurological symptoms are severe involving the muscle and sensory faculties, then recovery may be prolonged

Additional and Relevant Useful Information for Cutaneous Porphyria:

It is believed that the fable of werewolves, vampires, and Dracula originated from cutaneous forms of porphyria, wherein the skin spontaneously reacts upon sunlight exposure by reddening, swelling, and causing the formation of blisters.