Cutaneous Porphyria (Vampires Disease)

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Cutaneous Porphyria, or vampires disease, is a disease of the liver that leads to a build up of heme in the blood. Heme can donate electrons and carry gases in the blood stream and contains iron. When it builds up it leads to the symptoms of this disease because the iron becomes toxic. The "porphyria" in the disease name comes from a part of the heme molecule called porphyrin that surrounds the heme molecule. The most obvious symptom is large blisters on the skin resulting from exposure to the sun which is why it has come to be known as Vampires disease. There are treatments for the different types of this disease but there is no known cure.

History

The disease cutaneous porphyria has been around since the beginning of time, however it has just recently been given this name. The disease is one that is a genetically inherited metabolic disorder and the result of this is a deficiency of an enzyme vital in the making of heme [1,2]. The disruption in the production of the heme leads to an over abundance of the heme and this excess amount can reach toxic levels, causing cutaneous porphyria [1,2]. For decades it has been known as the vampires disease. This name comes from the signs and symptoms that the victims would show. When little was known about the disease, people who had the skin altering symptoms would not go out in the sunlight, for fear of being seen by other people and because of the excruciating pain that would occur when the toxic heme in the skin would react with the sunlight [1]. Another "vampire-like" characteristic that brought about its name was that the patients would often become anemic and would then drink the blood of animals to help relieve the pain and symptoms of the anemia. The gums would also swell and recede making the teeth to appear much like fangs giving further visual confirmation of a vampire.

One of the first noted cases was supposedly in King George III of England in 1811. He was diagnosed by his staff of personal medical doctors who were incredibly perplexed by his condition. His disease got to the point that he had to be dethroned because his symptoms altered his state of consciousness so greatly that he could no longer serve as the king [1]. It cannot be said as to who was the soul founder of this disease however all of the known types of porphyria were described between 1911 and 1983 [2].

Mechanisms

This disease is genetic and results from the deficiencies in active enzymes involved in the liver and skin. The deficient enzymes are involved in the heme production pathway. Eight different enzymes are involved in the pathway, and deficiencies of any of the enzymes between the second and eighth result in symptoms of the disease presenting themselves [10]. Certain factors such as diet, alcohol intake, iron metabolism and viral infections can affect the development of this disease. There are multiple different forms of porphyria, each of which involves a different enzyme. The most common type of pophyria is porphyria cutanea tarda. This results from decreased catalytic activity of an enzyme in the liver (uroporphyrinogen decarboxylase), which leads to accumulation of poyphrins [3]. This is affected by not only hereditary factors but acquired factors as well. For example, 30-90% of people with this disease abuse alcohol. This does not mean that alcohol gave them the disease, but because the enzymes that affect it are present in the liver alcohol makes the condition worse. The exact mechanisms that cause alcohol to worsen this condition have not been discovered. 60-65% of patients also have increased iron concentration in the liver as well [3].

Cutaneouschart.jpg

Symptoms

Patients of cutaneous porphyria may experience a variety of different symptoms, however the infamously "vampire-like" symptoms include extreme sensitivity to light, development of lesions in the skin and tightening of the gums, making the teeth appear like fangs [1]. Also, the patient may experience gastrointestinal problems, neurological complications, discoloration of the pigments in the face, anemia with some enlargement of the spleen, and the stool and urine may appear very dark in color [1]. Of these symptoms, the skin lesions are the most characteristic and the reasons for the lesions is an increased photosensitivity due to the photosensitization by the porphyrins [11].

The diagnosis of the disease happens in several steps. One of the first steps involves testing the urine and this step is one of the most commonly used. A simple screening of heme levels in the urine is commonly performed when the urine appears to be dark and abnormally colored [1]. Also, the blood will be tested along with the stool to confirm diagnosis of cutaneous porphyria.

Cutaneous porphyria.jpg

Treatment and Outlook

Cutaneous porphyria is a nonacute porphyria and is also called erythropoietic porphyria. Erythropoietic porphyria can be categorized as two kinds, erythropoietic protoporphyria (EPP) and congenital erythropoietic porphyria (CEP). There are several treatment options for the two kinds of erythropoietic porphyria. However, the only cure to this disease is to do a bone marrow transplant [6]. No matter which types of the porphyria the patient gets, the patient should always avoid sunlight, alcohol, and injuring of the skin. A high-carbohydrate diet may also help to limit the production of porphyrins [7].

EPP is mostly found in children when the patients start suffering from serious skin pain and burning under sunlight. The simplest solution to this problem is to aviod explosure to sunlight. Sunsreen is not always effective because the sunlight can still penetrate and damage the skin [5]. TL-01 therapy is a technique to thicken the skin of the patient and makes it more effective to fight against the sunlight. TL-01 therapy can help patients to obtain a sun protection factor (SPF) of 8 which is very helpful for reducing the suffering of the patient. Also, several possible treatments have been used with beta-carotene, cysteine and antihistamine treatment to keep the patient's skin in a better condition. The liver of an EPP patient cannot function properly as the disease is developing. Use of chlolestyramine treatment to increase the protoporphyrin excretion prevents early liver disease. A liver transplantation has to be done to restore normal liver function if it is not prevented. This cures the liver but not EPP [6].

CEP, as it is described, is a disease found in infancy and rarely in adults. It is a very rare autosomal recessive disorder. CEP is more deadly than EPP because it does not only damage the skin but also the bone. Hyperpigmentation, hypertrichosis and bone resorption are commonly found in CEP patients. The central idea for the treatment of CEP is to reduce porphyrin levels. Several methods can approach this goal. The enterohepatic porphyrin level can be reduced by oral superativation. Injecting or consuming glucose and carbohydrate can helps reduce the porphyrin level [7]. Hypertransfusion is a better method to reduce the entire porphyrin production. Since CEP may cause hemolytic anemia, splenectomy (removal of splen) will help to reduce hemolyses consumption. These methods are just temporarily effective. A bone marrow transplant is the only long term method which is able to remove the main site of the porphyrin, but the treatment requires a suitable donor [6].

Current Research

Cutaneous porphyria is currently being studied to better the therapy of patients. However, this can be challenging because the diagnosis of the many porphyrias “show overlapping clinical and biochemical characteristics” according to Siegesmund. The studies being conducted are using experimental data to show the characteristics of the porphyias. In their research they discuss different challenges among the porphyrias and how they affect the patients. Co-diagnoses of liver cancer, hypertension, renal insufficiency, and kidney complications seem to occur with the acute hepatic porphyria [8]. Assumptions have been made for the diagnosis of acute hepatic porphyrias in female patients and hormone levels. Pregnancy studies also have been conducted in uncertainties that the porphyria would hurt the fetus. However, several studies have been done with women with acute porphyric attacks and with or without the treatment they didn’t have to resort to abortion, and the fetuses were unharmed [8]. Another study on the porphyrias was done on the effects of smoking on both sporadic and familial porphyria cutanea tarda (PCT) [9]. Fontanellas has concluded after their research that smoking leads to the early onset of cutaneous symptoms in patients with sporadic PCT, and familial PCT had no early onset affect from the smoking of the patients.

Some gene therapeutic strategies have been considered for treatment, although they are not ready to be tested on humans currently [8]. Therefore, animal models are being studied to help humans better understand the mechanisms involved in the disease. So far in using mice models Siegesmund concluded that “specific liver-targeted strategies such as hepatic enzyme replacement therapy or gene therapy” might offer an alternative to complete liver transplant for patients. Such gene therapy was done by researchers of the CIMA (Centro de Investigacion Medica Aplicada) at the University of Navarra, Pamplona, Spain, to show the effects of the gene AMT-202 on acute porphyria attacks [8]. “The data showed that the AMT-020 has the potential to protect acute intermittent patients suffering from acute attacks and/or neuropathy” [8]. As more advancement is made in the cellular and microbiological fields on the porphyria and other biomedical diseases, more progress and advancements in the cure and prevention will be made.

Bibliography

[1]Vikramjit S Kanwar, Thomas G DeLoughery, Darius J Adams. 2010. Porphyria, Cutaneous: EMedicine Pediatrics: General Medicine. EMedicine.[1]

[2]Sarkany, Robert P. E. Making Sense of the Porphyrias. School in Photodermatology. 2010. <http://journals.ohiolink.edu/ejc/pdf.cgi/Sarkany_Robert_P._E.pdf?issn=09054383&issue=v24i0002&article=102_msotp>.[2]

[3]Flavia Fedeles, Michael Murphy, Marti J. Rothe, Jane M. Grant-Kels. 2010. Nutrition and Bullous Skin Diseases. Clinics in Dermatology. 28: 627–643[3]

[5]Porphyria. Wikipedia, the Free Encyclopedia. 2010. [4]

[6]Gillian M. Murphy. Diagnosis and management of the erythropoietic porphyrias, Blackwell Publishing, Inc., 2003, P57-64.

[7]Porphyria. Google Health. 2010. [5]

[8]Antonio Fontanellas et al. 2009. Smoking but not homozygosity for CYP1A2 g-163A allelic variant leads to earlier disease onset in patients with sporadic porphyriacutanea tarda. Experimental Dermatology 2010; 19: 326-e328. Retrieved November 3, 2010, from Ohio Link database.[6]

[9]Siegesmund, Marko; van Tuyll van Serooskerken, Anne-Moniek; Poblete-Gutiérrez, Pamela; Frank, Jorge. 2010. The acute hepatic porphyrias: Current status and future challenges. Best Practice & Research Clinical Gastroenterology, 24:593-605. [7]

[10]2010. Porphyria, Cutaneous: EMedicine Pediatrics: General Medicine. EMedicine - Medical Reference. <http://emedicine.medscape.com/article/957765-overview>.[8]

[11] P Poblete-Gutiérrez, T Wiederholt, HF Merk, J Frank. 2006. The porphyrias: clinical presentation, diagnosis and treatment. European Journal of Dermatology. 3:230-40. [9]