Test Faq

GENERAL (ALL PORPHYRIAS)

Most porphyrias are inherited. However, one type, Porphyria Cutanea Tarda (PCT), may either be inherited (also referred to as “familial”) or “sporadic” due to various environmental factors. In each type of porphyria there is a deficiency of a specific enzyme. These enzymes are involved in the synthesis of heme, a substance important to many body functions which is found in large amounts in bone marrow and red blood cells (which contain hemoglobin), and which also has important functions in the liver, muscles, and other tissues. The type of porphyria present is determined by which enzyme is deficient; these enzyme deficiencies are usually inherited. Environmental factors, such as drugs, diet, and sun exposure can, depending on the type of porphyria, greatly influence the severity of symptoms.

The best way to classify a case of porphyria is to determine which enzyme is deficient, or not functioning properly. Normally these enzymes act in a sequence to make heme from simpler molecules. Heme is a vital substance for all body organs and consists of an iron atom surrounded by a porphyrin molecule. If a specific enzyme is not made properly or there is not enough of the enzyme, it cannot function properly and that step in the heme-making process cannot proceed.

Sometimes other classifications are useful. Most commonly the porphyrias are divided into the “acute” and “cutaneous” porphyrias, depending on the cardinal clinical features. The acute porphyrias [Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), and ALA-dehydratase Deficiency Porphyria (ALD)] present with attacks of severe abdominal pain that usually come on gradually over hours and last for several days; VP and HCP may also have skin manifestations of blistering after sun exposure. The cutaneous porphyrias present with blistering and scarring of the skin, pain, and/or redness and swelling in sun-exposed areas. The porphyrias may also be classified as “hepatic” or “erythropoietic”, depending on the organ where the porphyrins or their precursors, called ALA and PBG, are chiefly made:, the liver for the hepatic porphyrias [AIP, HCP, VP, Porphyria Cutanea Tarda (PCT), and Hepatoerythropoietic Porphyria (HEP)] or the bone marrow for the erythropoietic porphyrias [Congenital Erythropoietic Porphyria (CEP), Erythropoietic Protoporphyria (EPP), and X-Linked Protoporphyria (XLP)].

What diagnostic tests are available? Are the diagnostic tests the same for all porphyrias?

There are many laboratory tests available for the porphyrias, and the correct tests to order depend on the type of porphyria the doctor suspects. It is often difficult to decide which tests should be chosen, and the results may be difficult to interpret. The tests vary in sensitivity and specificity. If a test is “sensitive”, it is unlikely to be falsely negative (that is, fail to diagnose porphyria in a patient who has the disorder). If a test is “specific,” it is unlikely to be falsely positive (that is, diagnose porphyria in a patient who does not have the disorder). Certain tests are both sensitive and specific in patients who have symptoms that are suggestive of a porphyria. It is advisable to have the testing performed by a laboratory that has expertise in the clinical aspects of porphyria and can provide a valid interpretation of the test results. If testing has been performed in laboratories other than porphyria laboratories, consultation with a porphyria expert is advised before a final diagnosis is made.

When abdominal and neurological symptoms suggest an acute porphyria, the best screening tests are urinary aminolevulinic acid (ALA) and porphobilinogen (PBG). When there are cutaneous symptoms that suggest porphyria, the best screening test is a plasma porphyrin assay. If one of these screening tests is abnormal, more extensive testing, including urinary, fecal, and red blood cell porphyrins, are often indicated. Urinary, fecal, and red blood cell porphyrin measurements are not very useful for initial screening because they lack either sensitivity or specificity and, therefore, are often difficult to interpret. Measurement of heme biosynthetic enzymes in red blood cells or lymphocytes is not appropriate for screening unless it is part of a family study that is done after someone in the family is already known to have a specific enzyme deficiency. The table below summarizes the tests to be done for each type of porphyria.

Type of Porphyria

Most Common Symptoms

Biochemical Lab Tests

Labs to Use

Acute Porphyrias

Acute Intermittent Porphyria (AIP)

Acute attacks of severe abdominal pain, nausea, vomiting, rapid heartbeat and other symptoms. These attacks generally last for several days or longer and can be frequent or infrequent. They can be triggered by certain medications. Symptoms are very rare before puberty.

  • Urine Porphobilinogen (PBG) done during an acute attack

 

UTMB, ARUP, Mount Sinai**, Mayo, Quest, LabCorp

Variegate Porphyria (VP)

Same as in AIP. Also, can have blistering on sun exposed areas of the skin. Symptoms rare before puberty.

  • Urine PBG done during an acute attack
  • Urine total porphyrins
  • Plasma porphyrins and fluorescence emission peak at 626 nm*
  • *Following excitation by light of 410 nm

UTMB, ARUP, Mayo, Quest, LabCorp

Hereditary Coproporphyria (HCP)

Same as VP, but skin blistering less common.

  • Urine PBG done during an acute attack
  • Urine total porphyrins
  • Plasma porphyrins
  • Stool porphyrins

UTMB, ARUP, Mayo, Quest, LabCorp

Porphyria Cutanea Tarda (PCT)

Blistering and skin fragility (skin that tears easily) on the sun exposed areas. Rare in children.

  • Urine total porphyrins
  • Plasma porphyrins

UTMB, ARUP, Mayo, Quest, LabCorp

Erythropoietic Protoporphyria (EPP) and X-linked Protoporphyria (XLP)

Severe pain on sun exposed areas of the skin, with swelling, lasting several days. Generally, there is no blistering. Symptoms usually start in infancy or childhood.

  • Erythrocyte protoporphyrin
  • Plasma porphyrins

UTMB, ARUP or Mayo

Congenital Erythropoietic Porphyria (CEP)

Severe blistering on sun exposed areas of the skin that can result in infections and scarring. Generally, symptoms start at birth or in early childhood.

  • Urine total porphyrins
  • Plasma porphyrins

UTMB, ARUP, Mayo, Quest, LabCorp

*

**The Mount Sinai Lab only tests for urine PBG

NOTE –; To diagnose all of the porphyrias GENETIC TESTING is also recommended. Information on genetic testing can be found here.

However, many patients have not had an acute attack or are not symptomatic at present, so biochemical testing may be inconclusive. In contrast, DNA testing is the most accurate and reliable method for determining if a person has a specific porphyria and is considered the "gold standard" for the diagnosis of genetic disorders. If a known disease-causing mutation (or change) in the DNA sequence is found in a specific Porphyria-causing gene, the diagnosis of that Porphyria is confirmed. DNA analysis will detect more than 97% of known disease-causing mutations. DNA testing can be performed whether the patient is symptomatic or not. Once a mutation has been identified, DNA analysis can then be performed on other family members to determine if they have inherited that Porphyria, thus allowing identification of individuals who can be counseled about appropriate management in order to avoid or minimize disease complications.

Is the free genetic testing accurate?

This is offered at the present time by the Alnylam Act program. Certain criteria must be met. Testing is by Invitae, which provides very reliable results. Contact the American Porphyria Foundation to learn more about this no-charge testing. 301-APF-3635.

How can it be determined from saliva?

DNA is usually prepared from blood but can also be found in other body fluids including saliva.

What is a Variant of Unknown Significance?

Some differences, or variants, in DNA do not cause disease and are referred to as benign. Those that are known to cause disease are called pathogenic, or disease-causing. Variants of unknown significance are those that need further study to see if they are pathogenic or benign.

Is Enzyme Testing used?

Enzyme testing is used for some porphyrias, such as AIP, but is less reliable than DNA testing.

What are the names of the biochemical testing for blood and stool?

Porphyrins are measured in blood plasma (or serum), red blood cells, urine and stool. ALA and PBG are best measured in urine, because levels are higher than in plasma. But measurement of PBG in plasma is important for diagnosis of AHP in patients with advanced kidney disease.

There are Porphyria experts in the US and outside the US, including the Porphyria Centers in this Physicians Consortium. Information about other experts can be obtained by contacting the American Porphyria Foundation (www.porphyriafoundation.com). If a porphyria is suspected, any physician can order the appropriate tests. Since interpretation of these results may be difficult, it is best for the physician or healthcare professional to consult with a porphyria expert for an accurate interpretation of the results and, if necessary, advice about additional testing, treatment, or prevention and precautionary measures.

Depending on the type of porphyria you have, biochemical testing should be performed prior to genetic testing. For the acute porphyrias, the most important tests are urine delta-aminolevulinic acid and porphobilinogen, which are always elevated during acute porphyria attacks. In the cutaneous porphyrias, urine or plasma fractionated porphyrin testing is recommended. While all porphyrias are inherited, porphyria cutanea tarda can develop in the absence of a genetic mutation in the UROD gene.

Because all porphyrias are rare, it is very unlikely that more than one type of porphyria will occur in the same family, or that a person with one type of porphyria will have an additional type. However, patients with more than one type of porphyria have been reported.

The liver is affected differently for each type of porphyria. Please refer to the disorder definitions page about your type of porphyria for more information on how the liver is involved. Although the different types of porphyria affect the liver differently, liver function tests should be performed routinely (usually annually) on all individuals diagnosed with any type of porphyria.

Such a situation needs to be dealt with on an individual basis. Whether further testing is recommended depends on how the patient was initially diagnosed and how the porphyria expert made the decision that porphyria is not the diagnosis. The results of biochemical testing are sometimes interpreted incorrectly by a physician who is not an expert in porphyria. Review of the results of the biochemical testing by a porphyria expert may determine that the results are not consistent with what is typically seen in a patient with porphyria during an attack. The results of DNA analysis may also contribute to the porphyria expert saying that it is unlikely that the patient has porphyria. DNA analysis, although considered to be the “gold standard” for diagnosis, is not perfect in that the patient may have a mutation in a part of the porphyria gene that is not analyzed by routine testing or the patient has a mutation in a porphyria gene that was not analyzed. If a diagnosis of porphyria is still suspect, then it is recommended that the patient undergo additional biochemical testing at the time of an acute attack. Additionally, further testing may include DNA analysis for other acute porphyrias (if only one or two were tested).

Yes, we are conducting research about the porphyrias. For additional information about our studies and how to volunteer to participate, please contact the American Porphyria Foundation on 866-APF-3635.

None of the porphyrias are contagious. However, one of the major risk factors for development of acquired PCT, [PCT type 1] is infection with the hepatitis C virus [HCV]. A lesser risk factor for PCT type 1 is infection with the human immunodeficiency virus [HIV]. These common viral infections are contagious.

The heme biosynthetic pathway is one of the key metabolic pathways that leads from the simple building blocks of the amino acid glycine and the dicarboxylic acid succinic acid to the formation first of 5-aminolevulinic acid [ALA], then to the monopyrrole porphobilinogen [PBG], then to porphyrinogens and porphyrins [four pyrrole rings strung together and closed on themselves], and, in the eighth step, to the insertion of an iron atom into the center of the protoporphyrin ring to form heme. Nearly all cells of the human body contain heme, which is essential to carry out many essential functions. Heme functions mainly as a small molecule that binds to proteins to form a large class of proteins called ‘hemoproteins.’ Hemoglobin is one such essential hemoprotein; it is found mainly in developing and adult red blood cells, where it functions to carry oxygen absorbed from air in the lungs to cells and tissue throughout the body. Hemoglobin also functions to carry carbon dioxide, a waste product formed by the metabolic functions of most cells, from these cells back to the lungs, where the carbon dioxide is released into the expired air and where the hemoglobin again picks up more oxygen.

Most of the heme that is synthesized in the human body is made in developing red blood cells, to provide for the formation of heme for hemoglobin. In the erythropoietic porphyrias, the major site of the overproduction of heme precursors is the developing red blood cells. Thus, the name erythropoietic porphyria.

The other major organ where heme is made is the liver. When the major overproduction of heme precursors occurs in the liver, the disorder is called a hepatic porphyria.

For the pain of acute porphyric attacks, prompt treatment of underlying causes of the acute attacks, such as cessation of alcohol intake or stopping drugs or chemicals that can trigger acute attacks, treatment of intercurrent illnesses is essential. Maintenance of adequate nutrition and fluid intake is also important: during acute attacks, patients, who are mostly women between the ages of 15-50 years, often have nausea and vomiting and are unable to eat or drink adequate amounts of food and fluids. In particular, during attacks, an intake of carbohydrates and starches [at least 300 g of sugars/starches per day] is important. If the acute attacks are more severe, they should be treated also with intravenous heme, given at a daily dose of 3 mg/ kg body weight per day.

Acetaminophen [Tylenol and other brands] is the analgesic of first choice, because it is safe if used in amounts that do not exceed 3 grams per day [9 regular strength or 6 extra-strength tablets]. The addition of a phenothiazine, such as promethazine [Phenergan] or prochlorperazine [Compazine] can help to increase the effect of acetaminophen, can help to decrease nausea and vomiting, and can also decrease anxiety and agitation, which are frequent symptoms curing acute attacks. Narcotic analgesics, such as oxycodone, hydrocodone, meperidine, morphine, fentanyl, and others, may be needed for severe attacks. Because of their risks of adverse side effects, such as respiratory depression, constipation, nausea, gastro-esophageal motor dysfunction, narcotic analgesics are best used only for a short time [not more than 5 days]. A major and ongoing problem faced by too many patients with acute porphyrias is that they have been using narcotics chronically and have become addicted to them and thus will suffer withdrawal symptoms when they try to stop them. Patients who are chronically using narcotics should best be managed long-term by specialists in chronic pain management and with a goal of decreasing and stopping their use of chronic narcotics, benzodiazepines, and other habit-forming medications.

For the acute pain of a severe phototoxic reaction, as may occur in EPP or XLP, the key is avoidance of any further sun or strong light exposure and the use of ice packs/cold compresses on the most severely affected areas of the skin. Some patients seem to benefit from a short course of potent, anti-inflammatory medication, such as prednisone [in tapering doses of 30, 25, 20, 15, 10, 5 mg on 6 successive days] or methylprednisolone [Medrol dose pak]. Others may derive some benefit from a combination of H1 [diphenhydramine (Benadryl)] and H2- [cimetidine [Tagamet], famotidine (Pepcid)] antihistamine blockers or from combination histamine and serotonin blockade with cyproheptadine [Periactin].

It is not possible to provide a general or generic answer this question. This requires the thoughtful assessment of each patient by a board-certified specialist in general internal medicine, perhaps, in consultation with selected sub-specialists.

This depends upon the specific type of porphyria and the severity. For most patients, the life expectancy is similar to that of persons without porphyria. In the case of patients with acute hepatic porphyrias, especially those with chronic overproduction of ALA and PBG, there are increased risks of development of systemic arterial hypertension, chronic kidney disease, and, usually later in life [after age 50-55 years] development of hepatocellular carcinoma [primary liver cell cancer]. These conditions can be treated successfully, so such patients should be screened on a regular basis [at least once every 6 months] for the development of these complications. If they are found, they should be treated and controlled.

For most patients with porphyria, there is no contraindication to their having children. Women with an acute porphyria are more prone to have acute attacks during pregnancy and in the post-partum period, and these may require prompt and careful treatment. Such pregnancies are best monitored by an Ob-Gyn specialist with expertise in high-risk pregnancies. The risks of transmitting the genetic abnormalities that usually underlie the porphyrias to children are usually 50/50. If a child inherits an autosomal dominant mutation, such as one that causes AIP, from a parent, the odds that such a child will, in turn, pass the mutation on to his or her child [grandchild of the grandparent] is also 50/50.

There are different treatment options available for acute and cutaneous porphyrias.

Acute Porphyrias:
Treatment for acute attacks requiring hospitalization is hemin (Panhematin) which is given intravenously. During hospitalization, patients typically get one dose a day for about 4 days. In addition to hemin, patients may need intravenous fluids, medications to control nausea, high blood pressure and pain.

Patients who have recurrent (frequent) attacks may sometimes be recommended hemin infusions as an outpatient. This can be given on a regular schedule or when a patient is in early stages of an attack.

Recently a new drug called Givlaari (Givosiran) was approved for patients with acute hepatic porphyrias. This drug was tested in patients with recurrent attacks (> 4 attacks/year) to prevent attacks. Givosiran has not been tested for the management of acute attacks in the hospital.

In addition to these, patients with acute porphyria may develop chronic (daily) symptoms and may need medications to control pain, nausea and other symptoms

The choice of therapy may depend on the patients symptoms and should be made by the treating physician after a complete evaluation.

Cutaneous Porphyrias:
There are different types of cutaneous porphyrias, and the treatment varies by type.

EPP: The primary mode of symptom management for EPP patient has been sun avoidance. Medications such as beta-carotene, cysteine, vitamin C and others have been tried however there is no clear evidence that any of them are effective.

Scenesse (Afamelanotide ) was recently approved by the FDA for the treatment of EPP. This drug is administered in the subcutaneous tissue (just below the skin) through a large needle after numbing the area. The implant is administered once every 2 months and is bioresorbable (dissolves by itself ). This works by increasing the amount of melanin in the skin which makes the skin darker. In addition, this may have some anti-inflammatory properties. Studies show that patients taking this drug can spend longer time in the sun without pain.

There is another medication called MT 7117 in clinical trials for patients with EPP. This medication is in a pill form and is taken daily. It also works by increasing melanin in the skin and may have anti-inflammatory properties.

CEP: CEP is an extremely rare disorder and the symptoms are very variable. Some patients may require a bone marrow transplant, others may need ongoing blood transfusions and other supportive care. In addition, patients should avoid the sun to prevent symptoms and blister formation.

PCT: PCT is one of the most common porphyrias. The primary treatment is phlebotomy (bloodletting) till the blisters disappear and the urine and blood tests normalize. In addition, there is an oral medication chloroquine which can be used to control symptoms. In all cases of PCT, it’s important to treat the underlying factor contributing to the disease manifestations such as hepatitis C, HIV, excessive alcohol consumption etc.

It is important to remember that all patients respond differently to medications and treatment should be individualized to the patient.

Treatment during pregnancy should be administered only after careful evaluation of risk and benefit. For the acute porphyrias, hemin has been safely used during pregnancy and does not appear to impact the fetus. Givlaari has not been tested in pregnant women and should not be used in patients who are pregnant or planning a pregnancy. Scenesse has also not been tested in pregnant women and should not be used during pregnancy.

This depends on the type of porphyria and the severity of symptoms. Most patients with an acute porphyria will not have symptoms or may have only one attack. These patients can live a normal life, particularly if they avoid triggering factors. Patients with recurrent acute attacks may have chronic symptoms such as pain, neuropathy, fatigue and nausea which can be very disabling and may prevent them from leading a normal life. These recurrent attack patients can also develop long term complications such as kidney and liver disease which may impact their health and functioning.

Patients with cutaneous porphyrias need to avoid sun exposure which limits them in performing their daily activities. Patients with CEP and PCT may also develop blisters and other related complications which can be significant and impact their normal life.

It is not possible to provide a general or generic answer this question. This requires the thoughtful assessment of each patient by a board-certified specialist in general internal medicine, perhaps, in consultation with selected sub-specialists.

This depends upon the specific type of porphyria and the severity. For most patients, the life expectancy is similar to that of persons without porphyria. In the case of patients with acute hepatic porphyrias, especially those with chronic overproduction of ALA and PBG, there are increased risks of development of systemic arterial hypertension, chronic kidney disease, and, usually later in life [after age 50-55 years] development of hepatocellular carcinoma [primary liver cell cancer]. These conditions can be treated successfully, so such patients should be screened on a regular basis [at least once every 6 months] for the development of these complications. If they are found, they should be treated and controlled.

For most patients with porphyria, there is no contraindication to their having children. Women with an acute porphyria are more prone to have acute attacks during pregnancy and in the post-partum period, and these may require prompt and careful treatment. Such pregnancies are best monitored by an Ob-Gyn specialist with expertise in high-risk pregnancies. The risks of transmitting the genetic abnormalities that usually underlie the porphyrias to children are usually 50/50. If a child inherits an autosomal dominant mutation, such as one that causes AIP, from a parent, the odds that such a child will, in turn, pass the mutation on to his or her child [grandchild of the grandparent] is also 50/50.

For patients with an acute porphyria it is important to have a healthy, well balanced diet and avoid fasting or dieting. Excessive carbohydrates are not recommended routinely. There are no specific recommendations for vitamins or supplements

Patients with cutaneous porphyrias can have low vitamin D levels as they avoid sunlight. We recommend a daily vitamin D supplement in these patients to maintain bone health

Almost all cells in the body contain heme proteins. Heme proteins, such as hemoglobin, are valuable for transporting oxygen and carbon dioxide throughout the body. Other heme proteins are also important for breaking down drugs, toxins, and other harmful substances.

The process of producing heme in the cells is called porphyrin synthesis. The porphyrin synthesis process requires eight enzymes to produce heme. If there is a defect in any one of these enzymes, less heme is produced and an excess in certain types of proteins occurs which can be toxic to nerves or skin resulting in nerve damage, abdominal pain or skin blistering. The group of genetic diseases associated with defects in the enzymes that produce heme is called Porphyria. There are eight different types of porphyria:

Acute Intermittent Porphyria (AIP) - is a chromosomal dominant inherited gene defect in heme production. Most patients have no symptoms, but if symptoms are present, they can be very debilitating. The most common symptom is vague, crampy abdominal pain that can last over several hours, days or weeks. Associated symptoms include vomiting and constipation. Sometimes the pain can occur in the chest, back or extremities. Severe attacks may lead to loss of movement of an extremity. Attacks are most common in young adult women typically occurring between puberty to menopause. Diagnosis is made by a urine test during an acute attack identifying, an elevated porphyrin protein, porphobilinogen (PBG).

Variegate Porphyria (VP) - is a chromosomal dominant inherited gene defect in heme production that is common that has symptoms like AIP but can also have blistering skin lesions when someone has sun exposure. Diagnosis is made by an elevated urinary PBG during an acute attack. Further testing is needed to identify elevated total urinary and plasma porphyrins to confirm the diagnosis of VP.

Hereditary Coproporphyria (HCP) - is a chromosome dominant inherited gene defect in heme production with symptoms similar to variegate porphyria, including abdominal pain and blistering skin lesions. Diagnosis is made by an elevated urinary PBG during an acute attack. Further testing is needed to identify elevated total urinary, plasma and stool porphyrins to determine the diagnosis of HCP.ALAD Deficiency Porphyria - is a rare chromosomal recessive inherited gene defect in heme production with only a few cases reported world-wide. The symptoms are similar to acute intermittent porphyria. Diagnosis is made during an acute attack by an elevated urinary coproporphyrin and 5-aminolevulinic acid (ALA), rather than PBG.

Porphyria Cutanea Tarda (PCT) - is the most common type of the porphyrias. For some the disease can be acquired over time but for others it can be a chromosomal dominant inherited gene defect in heme production. Environmental factors including alcohol, hepatitis C, smoking, HIV, elevated iron serum levels, and estrogens can trigger the disease. Symptoms include blistering on sun-exposed areas of the skin, usually the hands and face. In addition, the skin can tear easily with mild trauma. Patients are at risk of developing cirrhosis and even liver cancer. Diagnosis is made by elevated plasma and urinary porphyrins.

Erythropoietic Protoporphyria (EPP) - is a chromosomal recessive inherited gene defect in heme production with symptoms that usually occurs in early childhood. Symptoms can include pain, burning, itching, swelling and redness that develops soon after sunlight exposure. Generally, there is no blistering. Other symptoms include iron deficiency and complications from liver disease. Diagnosis is made by elevated plasma porphyrins and red blood cell protoporphyrins.

X-Linked Protoporphyria (XLP) - is a chromosomal X-linked dominant inherited gene defect in heme production. Symptoms are similar to patients with EPP. Diagnosis is made by elevated plasma porphyrins and red blood cell protoporphyrins. Genetic testing is needed to confirm the diagnosis of XLP versus EPP.

Congenital Erythropoietic Porphyria (CEP) - is a chromosomal inherited gene defect in heme production with symptoms that can occur shortly after birth. Symptoms can be severe and include skin photosensitivity with blistering, scarring, and infections. Diagnosis is made by elevated total plasma and urinary porphyrins.

Acute Porphyrias (AIP, VP, HCP and ADP)

Individuals with a disease-causing mutation without symptoms have "latent" acute porphyria. However, this does not mean that such an individual will never have symptoms. Genetic factors (that is, the presence of a porphyria-causing gene mutation) are not the only factors involved. Exposure to certain environmental factors, such as medications can, greatly influence whether an individual with a mutation in a porphyria-causing gene has symptoms This is why it is important that all family members of individuals diagnosed with acute porphyria be tested whether they have symptoms or not, and that all individuals who have a confirmed diagnosis of acute porphyria be educated about and follow the recommended precautionary and preventive measures.

Yes! The diagnosis of porphyria is always an important item of medical information, even when there are no symptoms. It may, for example, influence the choice of drugs to treat other conditions, the choice of anesthesia for surgery, or dietary recommendations.

Surgery and pregnancy may increase the risk of an acute porphyria attack. This risk can be greatly reduced if certain precautions are taken, including the type of anesthesia used in surgeries. The patient’s surgeon and anesthesiologist should consult a porphyria expert prior to hospitalization for surgery. Such consultation may also be helpful during pregnancy. Although attacks of acute porphyria can occur during pregnancy, the risk appears to be less than formally thought. Treatment of acute attacks during pregnancy is also possible.

For information about safe and unsafe drugs in the acute porphyrias, it is best to consult the American Porphyria Foundation Acute Porphyrias Drug Safety Database or the European Porphyria Network. The databases contain expert assessments of the potential of drugs to provoke attacks of acute porphyria (AIP, VP, HCP & ADP) based on the available evidence. However, this evidence is not always complete, which may lead to some degree of uncertainty. The information in these databases is meant as guidance to health care professionals. It must be made clear that the prescription of drugs to a patient with acute porphyria is entirely at the risk of the physician in charge.

Since most commonly used drugs have not been tested, they should be avoided if at all possible. If a question regarding drug safety arises, a physician or medical center specializing in porphyria should be contacted.

Yes. Since the acute porphyrias are inherited in an autosomal dominant pattern, males and females are equally at risk for having an acute porphyria. Exposure to certain environmental factors, such as drugs, chemicals, and diet, greatly influence whether an individual - males and females - with a mutation in a porphyria-causing gene has symptoms and the severity of symptoms. However, one of the environmental factors is hormones, and, therefore, acute attacks are more common in women than in men. Women may experience cyclical acute attacks associated with their menstrual cycle, starting in puberty. Such attacks in women may occur after ovulation and during the last part of the menstrual cycle when progesterone levels are high.

Patients with an acute porphyria should have a healthy balanced diet. Fasting for long periods of time and severe caloric restriction [“crash” dieting] should be avoided. You will find comprehensive information on www.porphyriafoundation.org.

Generally, the acute porphyrias do not affect thinking and memory long term; these can be affected when someone is having an acute attack. Someone with acute porphyria may also experience some neurological effects, including confusion, convulsions, muscle weakness, and, rarely, paralysis, due to effects on the nervous system from an acute attack.

In an individual with an acute porphyria, an acute attack can be brought on by certain drugs, hormones in women, environmental factors, including chemicals of various types, nutrition including fasting and low carbohydrate diets, alcoholic beverages, medical and physical stress, and physical fatigue. Many times, the trigger of an acute attack is unknown.

Flu shots are not contraindicated for individuals diagnosed with acute porphyria and can be taken safely. Any immunizations appear to be okay. In fact, since other illnesses can bring on an acute attack, remaining healthy is one of the most important ways to prevent acute attacks.

There has been no information to date to suggest that CAT scans with or without contrast agents should not be performed on an individual with acute porphyria.

Organ donation would be up to a particular transplant program or network. In acute porphyrias any organ should be acceptable except the liver. A person with an acute porphyria should not donate their liver. Why would they refuse me, specifically?

Drugs on the “unsafe” list are those drugs that should be avoided by individuals diagnosed with an acute porphyria because they have been found to provoke an acute attack in some individuals. If a drug prescribed for an individual diagnosed with an acute porphyria is on the “unsafe” list, the prescribing physician should check the Drug Database for a safe alternative. No drug should be withheld if it is judged essential for optimum treatment of a life-threatening condition (e.g. chemotherapy for cancer). The risk versus the benefit should be assessed and discussed with the patient. For help with this assessment you may wish to contact a Porphyria expert. It may be recommended that a patient undergo biochemical monitoring in the early stages of treatment. It must also be noted that response to drugs in patients with an acute porphyria is extremely variable and individuals may be encountered who have used an unsafe drug without adverse effect.

Donation of blood might not be harmful to you if you are in good health and have not had a recent attack. Your blood would also not be harmful to a recipient. However, a blood bank might have a policy of not taking blood from anyone with a chronic condition, just to be on the safe side.

Acute porphyrias are hepatic porphyrias, so your liver should not be donated, because the recipient would be likely to develop porphyria. Because acute porphyrias can damage the kidneys, you should probably not be a living kidney donor, and losing a kidney would reduce your reserve kidney function. A transplant program might have a policy of not transplanting certain organs from anyone with a chronic condition, just to be on the safe side. But transplanting some tissues, such as skin and cornea, should not be a problem.

The circumstances should be discussed with your doctor. The drug lists maintained by the American Porphyria Foundation and European Porphyria Network can be accessed to try to find a safe alternative. No drug should be withheld if it is judged essential for optimum treatment (e.g. chemotherapy for a life-threatening condition such as cancer). In such instances, the risks and potential benefits should be assessed and discussed with your doctor. A porphyria expert can be contacted for additional advice. It must also be noted that response to drugs in patients with an acute porphyria is extremely variable and sometimes a needed unsafe drug can be given without an adverse effect. Monitoring of urine PBG in the early stages of treatment is sometimes helpful.

This may be as short as a few days but is highly variable. Multiple triggers may be present, so the timing of symptoms may be governed by the triggering factor that was most recently added.

Attack symptoms are nonspecific and can be mimicked by many other medical conditions. If an individual has been diagnosed already as having acute porphyria, the diagnosis of an acute attack is based on the symptoms and physician judgement. The levels of porphobilinogen and porphyrins are not determining factors because these often remain high between attacks.

If you are vomiting, have severe pain, seizures or other neurological symptoms, it is often best to go the ER. But it is preferable to first call your doctor to discuss whether going to the ER is the best option.

Yes. A seizure can be due to effects of acute porphyria on the brain or be a consequence of decreased sodium in the bloodstream, which is itself a complication of the attack. Seizures generally indicate that the attack is severe and requires medical attention as soon as possible.

Attacks cause increases in the heart rate and blood pressure, due to effects on the autonomic nervous system, and these will generally return to normal with treatment of the attack. Acute porphyria patients may develop chronic hypertension, which needs to be managed in the usual manner.

Your doctor can advise on managing your diabetes using pills and/or insulin. A dietitian is also helpful for designing a diet with the proper amounts of carbohydrate and fat.

Premenstrual attacks are likely due at least in part to the high levels of progesterone that occur during the second half of the cycle. If these are frequent, and no other factors are contributing, such attacks may be prevented using a GnRH analogue (e.g. Lupron). Removal of the ovaries is not considered unless there are other medical indications and the patient is interested in permanent sterilization.

Yes. Other conditions that decrease food intake or cause fever and metabolic stress can trigger an attack.

This is not indicated if a healthy diet containing all required nutrients is maintained. A multivitamin tablet containing the daily requirements is not harmful, however.

It may be best to consult a dietitian to be sure you get an adequate amount of all required nutrients. A vegetarian diet generally will contain adequate amounts of carbohydrates and fiber, but may be low in protein, some vitamins and minerals such as iron and zinc.

Checking levels of urine porphobilinogen and porphyrin at least yearly is advisable to have some idea how active acute porphyria is.

There is no simple answer. There are now a number of treatment options for acute porphyrias. Advice from your doctor is important, and advice from a porphyria expert may also be valuable.

Acute porphyria can cause chronic symptoms. But advice from a doctor and sometimes a porphyria specialist is necessary to answer this question.

Cutaneous Porphyrias (CEP, EPP, XLP, PCT)

Sun sensitivity is the main symptom in CEP, EPP, XLP and PCT. VP and HCP, which are acute porphyrias, can also have blistering sun sensitivity. The degree of sensitivity to sunlight varies considerably. Patients with sun sensitivity have high levels of porphyrins in the blood plasma which, depending on the type of porphyria, have originated from the liver or the bone marrow. Ultraviolet light interacts with porphyrins in such a way as to damage skin tissue. In general, for patients with CEP, EPP, XLP and PCT they should protect themselves from sun exposure. For patients with VP and HCP, only if they have sun sensitivity do, they need to protect themselves from sun exposure.

Most patients with a cutaneous type of porphyria must learn to avoid sunlight as much as possible. Transparent topical sunscreens which block ultraviolet light are ineffective. Physical sunscreens (e.g., zinc oxide) maybe helpful.

Protective clothing may also be recommended. For patients with EPP, treatment with pharmaceutical grade ?-carotene (Lumitene, Tishcon) or cysteine may improve sunlight tolerance but does not lower porphyrin levels. Over-the-counter sunscreens and over-the-counter beta carotene (vitamin A) are not effective.

Patients with EPP and XLP experience photosensitivity that starts in infancy or early childhood and is characterized by pain, redness, and itching of sun exposed skin. The time after sun exposure to onset of symptoms is variable among patients. Variegate porphyria and rarely hereditary coproporphyria (both acute hepatic porphyrias) can also experience photosensitivity that manifests differently than in EPP and XLP patients and analogously to porphyria cutanea tarda (a hepatic cutaneous porphyria) with skin friability and blistering skin lesions on sun exposed areas.

The photosensitivity in porphyria is to light in the blue-violet spectrum of visible light (VIBGYOR - violet, indigo, blue, green, yellow, orange, red). The peak wavelength for light-mediated porphyrin excitation is ~ 410 nm. Indoor light sources (including lights for surgical or dental procedures) that emit within this spectrum can be problematic. Yellow filters (which block out wavelengths below ~ 470 nm) can be used to protect patients if needed. Fluorescent bulbs have little light within this spectrum and typical LED lights used for lighting purposes also lack wavelengths of light within this spectrum.

Avoidance of sun exposure, including through windows, is the most effective way of preventing photosensitivity reactions. Opaque, tightly knitted clothing, which blocks exposure to visible light,[Solumbra and other brands] provide some protection (goggles, hats, gloves).

Afamelanotide was recently (October 2019) approved by the FDA for the prevention of phototoxicity in erythropoietic protoporphyria. It is a selective agonist of the melanocortin receptor and increases production of the skin pigment, eumelanin, which is photoprotective. It is administered as a sustained-release subcutaneous implant. Its administration results in skin darkening within a few days after placement of the implant and which persists for weeks. It improves the length of time patients remain pain-free in direct sunlight and reduces the incidence of phototoxic reactions.

Oral beta-carotene which causes a yellowish skin discoloration may improve sunlight tolerance in some patients.

The efficacy of cimetidine therapy in this disease remains unknown.

Monitoring for hepatic complications is recommended. Treatment of severe hepatic complications (cholestatic liver failure) requires specialty care at a center with expertise in EPP and XLP and with liver and bone marrow transplant expertise.

Synthesis of vitamin D by the skin in response to exposure to ultraviolet light (in sunlight) is the major source of this vitamin. As a consequence of avoiding sunlight, patients are therefore at risk for vitamin D deficiency and may require supplementation.

Mild anemia, with laboratory studies suggestive of iron deficiency, are observed in some patients. It remains unknown whether iron therapy improves the anemia in this setting and/or may worsen photosensitivity.

Use of tanning beds in general are not recommended, even for persons without porphyrias. Some patients with EPP or XLP have found that they are able to use tanning beds or to cultivate natural sun tans and gradually to increase their own melanin production and to tolerate more light exposure.

Monitoring for hepatic complications is recommended. Treatment of severe hepatic complications (cholestatic liver failure) requires specialty care at a center with expertise in EPP and XLP and with liver and bone marrow transplant expertise.

A patient's sensitivity to light is dependent on the light quality, the duration of exposure, and patient-specific variables (including geographic latitude and altitude, natural skin pigmentation, and other factors which are not fully understood).

In EPP and XLP the source of the majority of the phototoxic substances that result in disease originate from red blood cells and their parent cells in the bone marrow. Thus, bone marrow transplantation from a donor who lacks EPP or XLP is curative for the recipient. As bone marrow transplantation is associated with significant risk to patients (including death and potentially multiple life-altering complications), it is reserved for a very rare subset of patients for whom the benefit is thought to out weight the risks of this procedure. In EPP and XLP the source of the majority of the phototoxic substances that result in disease originate from red blood cells and their parent cells in the bone marrow. Thus, bone marrow transplantation from a donor who lacks EPP or XLP is curative for the recipient. As bone marrow transplantation is associated with significant risk to patients (including death and potentially multiple life-altering complications), it is reserved for a Mild anemia, with laboratory studies suggestive of iron deficiency, are observed in some patients. It remains unknown whether iron therapy improves the anemia in this setting and/or may worsen photosensitivity.