Treatment and Prevention
To date, there is no cure for any of the porphyrias. Treatment and prevention depends on the type of porphyria. Preventive measures, which include avoidance of certain drugs and alcohol in the hepatic porphyrias, and sun exposure in the erythropoietic porphyrias, are extremely important in those individuals who are identified as having an inherited porphyria, even if they have never had symptoms.
The Acute Porphyrias (AIP, HCP, VP, and ADP)
For the acute porphyrias, hospitalization is often necessary for acute attacks. Medications for pain, nausea and vomiting, and close observation are generally required with monitoring of salt and water balance. Harmful drugs should be stopped. Attacks are treated with either glucose loading or intravenous administration of hemin (Panhematin®). Attacks can be prevented in many cases by avoiding harmful drugs and adverse dietary practices. Avoidance of sunlight is recommended for all individuals diagnosed with Hereditary Coproporphyria (HCP) or Variegate Porphyria (VP) who have porphyria-related sun sensitivity.
Acute porphyria is particularly dangerous if the diagnosis has not been made and if harmful drugs are administered. The prognosis is usually good if the disease is recognized and if treatment and preventive measures are begun before severe nerve damage has occurred. Although symptoms usually resolve after an attack, some patients develop chronic pain. Nerve damage and associated muscle weakness can improve over a period of months or longer after a severe attack. Mental symptoms may occur during attacks but are usually not chronic.
Wearing a MedicAlert® bracelet is advisable for patients who have been diagnosed with porphyria.
Panhematin®/Hemin
Panhematin®, manufactured by Lundbeck Inc. (formerly Ovation Pharmaceuticals, Inc.), Deerfield, IL, is the only commercially available heme therapy in the United States. (Heme arginate is another preparation, but is only available outside of the U.S.) While a high carbohydrate diet is recommended for patients with porphyria, it is not regarded as highly effective by itself. Intravenous glucose therapy is a treatment option for mild attacks. When heme therapy was introduced as a treatment, it was recommended that it be initiated only after several days of glucose therapy was unsuccessful.
Today, physicians experienced in treating patients with attacks of porphyria recommend early use of Panhematin® rather than waiting to see if glucose alone will be of decisive help. However, not every patient who experiences an attack of porphyria needs Panhematin® since mild attacks may well respond to glucose alone. But a specialist's advice and consultation may first be obtained. This is recommended also for prophylactic infusions of Panhematin® given to prevent attacks.
Many experts recommend reconstituting Panhematin® with albumin as this makes it more stable. This helps prevent phlebitis and an anticoagulant effect. Like Panhematin®, albumin is a biologic product, which is approved and regulated by the FDA.
In addition to Panhematin® therapy, supportive measures such as nursing care and sufficient pain medication help in treating acute attacks. During treatment, attention should be given to salt and water balance. Harmful drugs should be stopped. These include barbiturates, sulfonamide antibiotics, and many others. Respiratory insufficiency may require use of an artificial respirator.
Although it is generally agreed that the outlook for patients with porphyria has improved, an attack can still be life threatening. Therefore, porphyria attacks should be treated as early and effectively as possible. Fortunately, in patients with known porphyria, many attacks can be prevented. However, some patients may have an occasional attack even if they are careful in their lifestyles. And although prophylactic use of Panhematin® to prevent attacks has not been formally studied, Panhematin® is widely used in this manner for patients known to have acute porphyria and attacks that recur frequently. Premenstrual attacks often resolve quickly with the onset of menses. Hormone manipulations may prevent such attacks.
Safety Considerations
Although Panhematin® has few side effects, it does act as a mild anticoagulant. Thus, concurrent use of other anticoagulants such as heparin or Coumadin® (warfarin) should be avoided. Panhematin® may also produce superficial thrombophlebitis, especially if infused into a small vein. Panhematin® is less likely to produce phlebitis if it is mixed with human albumin before it is given. Before Panhematin® is used, it should be clear that the patient indeed suffers from one of the acute porphyrias (AIP, HCP, VP, ADP) and that the patient's symptoms are due to an acute attack. Panhematin® therapy may not be indicated unless the diagnosis of acute porphyria is proven by a marked increase in urine PBG.
The Cutaneous Porphyrias (PCT and HEP, CEP, EPP, and XLP)
Treatment of the cutaneous porphyrias is dependant on the specific porphyria.
Porphyria Cutanea Tarda (PCT), both familial and sporadic, and Hepatoerythropoietic Porphyria (HEP) can be treated with regularly scheduled phlebotomies (removal of blood) to lower the amount of iron in the liver or a low dose regimen of hydroxychloroquine, as well as removal of factors (for example, certain medications) that activated the disease.
For Congenital Erythropoietic Porphyria (CEP), avoidance of sunlight and fluorescent lights is recommended. Vitamin D supplements should be prescribed to avoid complications due to sunlight restrictions and associated vitamin D deficiency. Blood transfusions to correct anemia are often needed. Bone marrow transplant (BMT) has also been performed in severe cases with good results.
For the protoporphyrias, Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP), treatment with pharmaceutical grade β-carotene (LumiteneTM) or cysteine may improve sunlight tolerance. Avoidance of sunlight is recommended for all individuals diagnosed with protoporphyria. Vitamin D supplements should be prescribed to avoid complications due to sunlight restrictions and associated vitamin D deficiency.
LumiteneTM/Beta-carotene
Beta-carotene, a natural product found in green plants, can be used as a protective measure to lessen symptoms of photosensitivity. In the treatment of protoporphyrias, it functions to neutralize the reactive chemical compounds formed by protoporphyrin. Interestingly, beta- carotene and other related carotenoid pigments function in plants in a similar fashion by neutralizing the reactive compounds formed by the plants' own chlorophyll.
Beta-carotene is the most effective therapy to date for protoporphyria. It is important, however, for patients diagnosed with protoporphyria to ingest the proper formulation of beta-carotene to obtain its greatest beneficial effect. It is also important to make sure the preparation is made with pharmaceutical grade beta-carotene. The pharmaceutical grade formulation having the highest effective absorption is the "dry beta-carotene beadlets, 10%" made by Roche and distributed by Tishcon with the trade name, LumiteneTM. LumiteneTM can be ordered by calling 1-800-848-8442 or via their website www.epic4health.com.
Please also note that preparations using beta-carotene crystals dissolved in vegetable oil, or beta- carotene-containing algae preparations, or dry beadlets made by other manufacturers are not suitable for use in treating protoporphyria, because these preparations are erratically absorbed by the body, and in the case of algae preparations may contain algal components which might act as photosensitizers. Most brands of over-the-counter beta-carotene use these less-effective preparations, or may mix Roche beadlets with others which are not as well-absorbed. It is, therefore, recommended that individuals diagnosed with protoporphyria use only LumiteneTM and not purchase other brands of beta-carotene pills. These other brands may work well for cancer prevention but do not deliver the high absorption, and thus the high blood levels, needed for the effective treatment of protoporphyria.
There have been articles in the press about a National Academy of Sciences panel report on vitamin requirements, discouraging the overuse of supplements. Beta-carotene was mentioned, again talking about the finding reported several years ago that in certain people who were heavy smokers and also asbestos workers who were taking beta-carotene in a cancer-prevention study, there seemed to be in some cases an increase in lung cancer, but in another study, heavy smokers also taking beta-carotene in a cancer prevention study did not develop lung cancer. The studies also found that people who stopped smoking did not develop excessive lung cancer. If a person does not stop smoking and continues to take Lumitene, that person is taking a chance of developing lung cancer.
The following table summarizes treatment and preventive measures, including recommendations for monitoring patients diagnosed with porphyria. For all individuals diagnosedwith porphyria, medical alert bracelets and wallet cards can help notify emergency medical personnel and ensure that unsafe drugs are not given to patients in emergencies.
Future treatment
There are clinical trials underway in the US, starting May 2010, investigating the effectiveness and safety of another drug, Alfamelanotide, for the treatment of the symptoms of photosensitivity of the erythropoietic protoporphyrias. Alfamelanotide, manufacured by Clinuvel Pharmaceuticals, Melbourne, Australia, is administered as an implant inserted under the skin. The study is a double-blind placebo-controlled study, meaning that some of the people participating in the clinical trial will get the medication, some will not. Clinical trials in Europe showed that the drug is effective and safe. Several Centers in the US are participating in the trial, and it is hoped that the results will lead to approval by the Federal Drug Administration (FDA) for commercial use in the US. Anyone who is interested in additional information should contact one of the Participating Clinical Centers of the Porphyrias Consortium or the American Porphyria Foundation.
