Porphyria

The signs and symptoms of porphyrias by type of porphyria are:

Porphyria cutanea tarda. The most common form of porphyria in the U.S. and elsewhere in the world is called porphyria cutanea tarda (PCT). PCT does not usually occur until middle age, and it affects the skin in sun-exposed areas, causing fluid-filled blisters to develop. Over time, the skin becomes scarred, brown, blotchy, and fragile. Sometimes excess hair grows in the affected areas. Most cases of PCT are sporadic, but the disease also can run in families. Even in cases where it appears to be inherited from a parent, another factor is usually required before it causes symptoms. The most common factor is excessive alcohol consumption, but the presence of other diseases such as hemochromatosis and hepatitis C may trigger PCT symptoms.

Acute intermittent porphyria. The next most common form of porphyria is acute intermittent porphyria (AIP). AIP causes only neurological symptoms and does not affect the skin. AIP is a hereditary disorder, but many people who inherit the gene for AIP never get any symptoms. AIP virtually never appears prior to puberty. Affected people get attacks that develop over hours or days and last for days or weeks if untreated.

The most common symptom is pain in the abdomen (often severe), but the pain may affect other areas of the body as well. Muscle weakness of the arms and legs may occur and, in severe cases, weakness of the breathing muscles may require the person to be placed on a ventilator. A variety of other symptoms may occur, depending upon which parts of the nervous system are affected. These include areas of reduced or altered sensation, confusion, seizures, palpitations, high blood pressure, and constipation or diarrhea. Attacks of AIP are often precipitated by drugs, hormones, starvation or crash diets, and the stress caused by infections, surgery, accidents or even psychological stress.

Erythropoietic protoporphyria. The third most common form of porphyria is erythropoietic protoporphyria (EPP). EPP is also inherited, and signs and symptoms usually start in childhood or adolescence. Children with EPP are unusually sensitive to the sun and develop itching, burning pain, redness and swelling in sun-exposed skin within minutes of sun exposure. Over time, the skin may become thickened and waxy in appearance, but permanent spots and scarring are unusual. A small number of affected children also develop gallstones and liver disease, which in some cases can be very serious.

Other forms of porphyria are very rare. Variegate porphyria (VP - more common in Caucasian people of South African ancestry) and hereditary coproporphyria (HCP) can cause neurological symptoms like AIP and skin symptoms like PCT. Most affected persons get either neurological or skin symptoms, but a few unlucky persons get both. Both of these diseases are inherited as autosomal dominant conditions like AIP. There are several even more rare forms of porphyria that cause some combination of the symptoms described above, sometimes in a more severe manner.

Measurements of porphyrins and porphyrin precursors in blood, urine, and stool are the main tests for assessing people with symptoms that may be caused by a porphyria. These tests are available in many hospital and reference laboratories. Measurement of individual enzyme activities and DNA testing for mutations are only available in a limited number of specialized centers. They are most useful for assessing people who have a family history of the disease but do not currently have symptoms.

• Measurement of porphobilinogen, a porphyrin precursor, in urine is the most important test for diagnosing an acute neurological porphyria (AIP, VP or HCP).
• Measurement of porphyrins in urine and red blood cells is used to detect and diagnose porphyrias that affect the skin (PCT is by far the most common).
• Measurement of enzyme activity in red blood cells may be used to confirm the diagnosis of AIP and to identify relatives of persons with AIP who have inherited the disease.
• Identification of specific mutations (DNA testing) is the most definitive way to diagnose or exclude a porphyria in family members of an affected person. This type of testing is not widely available at present.

Once a person is known to have a particular porphyria, there are precautions that can be taken to limit or prevent signs and symptoms from occurring.

For the acute neurological porphyrias (AIP, VP and HCP), the most important precaution is to avoid using drugs that are known to precipitate attacks. Lists of drugs that are considered safe and unsafe for people with a neurologic porphryria are available. If attacks are related to the menstrual cycle, hormone therapy to change the menstrual cycle may prevent attacks. Avoidance of strict dieting may be important in some people.

For people having an attack, treatment involves identifying and removing any precipitating factors, giving an intravenous infusion of a heme derivative such as hematin or heme arginate, and supplying enough nutrition by intravenous infusion if necessary. Intensive medical care may be required in severe cases.

People with PCT need to avoid alcohol consumption. Sun protection with clothing and complete sunblock lotions is also very important. The treatment for PCT is phlebotomy (removal of blood), which rids the body of excess iron. People who do not have hepatitis or other transmissible diseases may become regular blood donors. Patients who cannot tolerate phlebotomy may be treated with chloroquine to help remove excess porphyrins.

Children and adults with EPP benefit from sun protection with clothing that blocks lights in the ultraviolet part of the spectrum. Conventional sunscreens have limited effectiveness. Treatment with beta-carotene may reduce sun sensitivity and skin symptoms.

People with VP and HCP need to take the same precautions as people with AIP to avoid neurological symptoms. They also need sun protection with clothing and sunblock lotions if they suffer from sun sensitivity.