Wednesday, May 31, 2017

Erythropoietic Protoporphyria (EPP)

Erythropoietic Protoporphyria (EPP)

Other common terms:EPP, protoporphyria, erythropoietic porphyria
ICD-10 classification:E80.0
Prevalence:Rare; between 1:58,000-200,000. Estimates of between 5000-10,000 globally
Causes:Inherited disease; defective enzyme causes inability to properly produce haem (heme).
Symptoms:Phototoxicity: swelling, burning, itching and redness of the skin, occurring during or after exposure to sunlight, including light passing through windows. Liver toxicity in 5% of cases. Microcytic anaemia can occur.
Treatments/cures:None proven fully effective to date. Phototoxicity can be avoided by complete avoidance of sunlight and certain artificial lights.
Differential diagnosis:Solar urticaria, polymorphous light eruption, porphyria cutanea tarda
Erythropoietic protoporphyria (EPP) is a rare inherited metabolic disorder of the haem (heme) pathway causing severe phototoxicity (toxic reactions to light) in skin due to the build up of a phototoxic chemical in the skin.
EPP belongs to a heterogenous group of disorders (porphyrias) that result from a dysfunction of specific enzymes involved in the haem biosynthesis. Haem serves many essential functions in the body one of which is oxygen transport via haemoglobin.
Erythropoietic Protoporphyria (EPP) reaction
Erythropoietic protoporphyria is rare, and few studies have been done on its prevalence. Geographic location generally doesn’t seem to bias the incidence of EPP, although one study has suggested that the incidence in Slovenia is 1:58,000. Other studies include incidence that range from 1:75,000 to 1:200,000. Case reports suggest that EPP is prevalent globally.
It is estimated that between 5,000-10,000 individuals worldwide have EPP.
Typically, erythropoietic protoporphyria symptoms begin in childhood and are characterized by episodes of phototoxicity. The main symptoms are pain, which is often described as heat, prickling, itch or extreme sensitivity of skin exposed to light. The pain is often very severe, and swelling and blistering of the skin may result. Skin lesions resolve slowly often leaving waxy or pitted scars. Repeated exposure leads to scarring and waxy thickening of the skin on the backs of the knuckles and nose.
Erythropoietic Protoporphyria (EPP) reaction
As little as a few minutes of sunlight (which may overcast or window transmitted) may be sufficient to evoke symptoms. Symptoms are due to visible light (at wavelength above 400 nanometers, part of the electromagnetic spectrum). In most affected individuals, skin involvement persists throughout life, although some people become less symptomatic with time. Symptoms can be seasonal, starting early in the spring, continuing through summer and diminishing in winter. Some patients report that wind may exacerbate their symptoms.
Erythropoietic protoporphyria patients will sometimes have a mild microcytic anaemia, presumably due to the inability or reduced ability to form haem. This should not be confused with iron deficiency anaemia and patients should not take iron replacement for this as it may actually exacerbate the porphyria. Gall stones, usually pigment stones, are more common at an earlier age in EPP.
Liver failure occurs in 5% of erythropoietic protoporphyria patients; this is thought to be related to the increased work of the liver to clear the excessive intermediate by-products from the defective haem pathway. If liver failure occurs it can be fatal.
This lack of permanent symptoms in erythropoietic protoporphyria leads to frequent misdiagnosis by doctors, much to the frustration of parents and their child.
Protoporphyrin IX molecule
Erythropoietic protoporphyria is inherited and can be autosomal dominant or recessive. This disorder causes a chemical known as protoporphyrin IX to accumulate in the skin. When the skin is exposed to the sun, these molecules undergo a chemical reaction that results in swelling, severe and intolerable pain and scarring, a condition known as phototoxicity.
The pain is sometimes described as like having hot needles stuck into the skin. The lifelong pain experienced by these patients typically resigns them to become socially isolated, due to the lack of an efficacious treatment and their need to continuously avoid sunlight.
Ferrochelatase deficiency
The specific defective enzyme in erythropoietic protoporphyria is ferrochelatase, the last of eight enzymes in the porphyrin-haem pathway. Consequently there is an inability to chelate iron with protoporphyrin IX to form haem. Intermediates from the pathway accumulate before this final step and cause toxic effects which are involved in the dermal symptoms of EPP.
The gene for the ferrochelatase enzyme, which shares the same name, is located on chromosome 18q21.3. Molecular studies on the gene indicate that more than 60 different mutations exist, most of which are insertions or deletions.
Diagnosis of erythropoietic protoporphyria is based on the detection of increased levels of free protoporphrin IX in red blood cells. Monitoring of liver function tests and red cell porphyrins are sometimes performed to pick up any early signs of liver failure.
Action spectrum of PPIX
Sun avoidance by remaining indoors or wearing sun protective clothing including cotton gloves and a wide brimmed hat is the first line in erythropoietic protoporphyria management. The remaining treatment is focused upon symptomatic relief, although no effective symptomatic treatments have been reported. Patients have reported immersing affected skin in water (both hot and cold) to try and relieve the phototoxicity.
Most commercially available sunscreens are of no value as a treatment, but a large particle size titanium dioxide sunscreen may be of some benefit if used with other forms of sun protection.
Drugs such as β-carotene, cysteine (an amino acid which has been shown to decrease photosensitivity) and cimitedine have been used with various disappointing results and because the disease is inherited, genetic counselling is recommended.
Hematin infusion may temporarily decrease the production of haem and may also result in a decrease of plasma and faecal porphyrins. Also, there is sporadic evidence that autologous blood cell transfusion with washed red blood cells may successfully induce clinical and biochemical remission for erythropoietic protoporphyria patients. Finally, narrow band UVB phototherapy as a treatment option may provide some protection, presumably through epidermal thickening and tanning.
Since sun avoidance is recommended, patients lead lives where they are in the sun for very limited time. This can prevent normal social activities and the intense pain that is experienced interferes with normal daily activities and can prevent adequate sleep.
Liver transplantation in EPP
Liver failure occurs in 2-5% of patients with erythropoietic protoporphyria; this is thought to be related to the increased workload of the liver to clear excessive intermediate by-products from the defective haem pathway. If liver failure occurs it can be fatal.
31 European liver transplants in EPP patients have been reported in medical literature from 1983 and 2008. A 2005 US study followed up 20 patients who had undergone the procedure. 
When conducting transplants and other surgery in EPP patients, it has been recommended that yellow filters be fixed to surgical lights to remove light wavelengths below 470nm and prevent phototoxic reactions resulting from exposure.
Psychological and social impact
EPP has been widely recognised as having a serious impact on the quality of patients’ lives due to sun avoidance leading to social exclusion. Depression, anxiety due to fear of reactions and suicidal thoughts have been reported by EPP patients in the literature. A 2010 UK study has also shown that individuals with photosensitive disorders, including EPP, have a greater unemployment rate. 
Misdiagnosis and ‘invisible’ reaction symptoms can compound these issues as patients also report accusations of hypochondria when experiencing reactions or avoiding situations which may cause the onset of symptoms.
Symptoms of erythropoietic protoporphyria are usually with patients for life; however a few people have described symptoms reducing over time. 
·       Lecha, M et al., (2009). ‘Erythropoietic protoporphyria’, Orphanet Journal of Rare Diseases. 14(9) available online at 
·       Marko PB et al., (2007). ‘Erythropoietic protoporphyria patients in Slovenia’, Acta Dermatoven. 16(3):99-104.
·       McGuire BM, et al, (2005). Liver transplantation for erythropoietic protoporphyria liver disease. Liver Transpl. 11(12):1590-6.
·       Murphy GM, (2003). 'Diagnosis and Management of the Erythropoitetic Porphyrias', Dermatologic Therapy. 16:57-64.
·       Rufener EA (1987). ‘Erythropoietic protoporphyria: a study of its psychosocial aspects’, British Journal of Dermatology. 116:703-708.
·       Schneider-Yin et al., (2000). "New insights into the pathogenesis of erythropoietic protoporphyria and their impact on patient care", European Journal of Pediatrics. 125:719-725.
·       Stafford R, et al., (2010). ‘The impact of photosensitivity disorders on aspects of lifestyle.’ British Journal of Dermatology. 163(4):817-822.
·       Thunell S, Harper P & Brun A, (2000). 'Porphyrins, Porphyrin Metabolism and Porphyrias, IV, Pathophysiology of Erythropoietic Protoporphyria - Dianosis, Care and Monitoring of the Patient', Scandinavian Journal of Clinical and Laboratory Investigation. 60:581-604.
·       Todd DJ. 'Clinical Implications of the Molecular Biology of Erythropoietic Protoporphyria', Journal of European Academy of Dermatology Venereology. 11:207-213.
·       Wahlin S, et al, (2008). “Protection from phototoxic injury during surgery and endoscopy in erythropoietic protoporphyria.” Liver Transpl. 14(9):1340-6.
·       Wahlin S, et al, (2011). “Liver transplantation for erythropoietic protoporphyria in Europe.” Liver Transpl. epublished May 20.
Erythropoietic protoporphyria associations and online resources
·       German erythropoietic protoporphyria Association (Selbsthilfe EPP e.V.) - Available in German and English
Tagged under 
·       skin

·       epp

·       treatment

·       light

·       porphyria

·       patient

·       sun

·       pain
·       disease

·       symptoms

·       sunlight

·       liver
·       phototoxicity

·       haem

·       light intolerance

Friday, May 26, 2017

Important EPP Survey URGENT ASAP!!!

Important EPP Survey

Dear EPP Community,
As you know, the diagnosis of EPP is often delayed for many years. Researchers at the Icahn School of Medicine at Mount Sinai are conducting a survey study to learn more about the delayed diagnosis of EPP and how to better educate providers. This is a short survey (~5 min) for adults with EPP, or parents of children with EPP. If you would like to learn more and participate, click on the link below.

Sajel Lala, MD

Hetanshi Naik, MS, CGC
Manisha Balwani, MD

Comprehensive Porphyria Diagnostic and Treatment Center

Icahn School of Medicine at Mount Sinai
Department of Genetics and Genomic Sciences

"Remember....Research is the key to your cure!" 

NORD! Learn the facts

NORD's Rare Disease Database provides brief introductions for patients and their families to more than 1,200 rare diseases. This is not a comprehensive database since there are nearly 7,000 diseases considered rare in the U.S. We add new topics as we are able to do so, with the help of rare disease medical experts.
If you are seeking information about a rare disease that is not in this database, we would suggest contacting the Genetic and Rare Diseases Information Center (GARD) at the National Institutes of Health. NIH has the most complete database of rare diseases in the U.S.
Representatives of patient organizations whose medical advisors are interested in assisting NORD in creating a report on a disease not currently covered in this database may write to
                                 " Remember....Research Is Your Key To A Cure"

Thursday, May 25, 2017

ACT NOW! Important EPP Survey

Important EPP Survey

Dear EPP Community,
As you know, the diagnosis of EPP is often delayed for many years. Researchers at the Icahn School of Medicine at Mount Sinai are conducting a survey study to learn more about the delayed diagnosis of EPP and how to better educate providers. This is a short survey (~5 min) for adults with EPP, or parents of children with EPP. If you would like to learn more and participate, click on the link below.

Sajel Lala, MD
Hetanshi Naik, MS, CGC
Manisha Balwani, MD

Comprehensive Porphyria Diagnostic and Treatment Center
Icahn School of Medicine at Mount Sinai
Department of Genetics and Genomic Sciences

"Remember....Research is the key to your cure!" 

Tuesday, May 23, 2017

Andreea Miller and her Struggle with AIP

Andreea Miller
Type of Porphyria: 
Acute Intermittent Porphyria (AIP)
I started getting symptoms in 2010 after my 19th birthday. Every few months, I would get the “flu,” but it was worse than the flu, because it would knock me out to the point that I couldn’t get out of bed without help. My muscles and bones would not cooperate. This went on for about 2 years. It would always start with a bellyache and what seemed like heartburn. I always felt lethargic, and my bones would hurt. I needed someone to physically force me out of bed. Only hot baths would help, but it would end up being too hot and would worsen my stomach pain. I went to a few urgent care clinics but nothing popped up.
Around the middle of 2011, I began going to both of the two ERs in my town. They would do a full work-up, including blood work, CT scans, EKG, etc. Upon finding nothing, I would then head to the other ER. At one point I was told I had an ovarian cyst and removal would cure my symptoms. I agreed with everything they said. After removal, I was in even more pain than before. Hydrocodone would make me sick when they would give it to me for pain, so I began to refuse it.
In mid-2011, I started to get sick more often. I began experiencing symptoms more and more frequently. I would constantly go from one ER to the other, and they would all tell me nothing was wrong. This continued for about 6 months. Beginning in 2012, it got worse and worse. Finally, the doctors were convinced it was in my head and said I couldn’t keep coming back and forth to the ER if nothing was wrong. They said they needed to perform a psychological evaluation or send me to another place because I was becoming an issue at the hospital by taking away from other patient’s time. My mom fought back and said, “What 20 year old WANTS to be sick this badly?”
My condition deteriorated and by mid-2012, I was having monthly attacks. In September 2012, my grandmother passed away and that was the final straw. We were very close, as she was the one that raised me. About a week before she passed, I was in a walker, at my own request. I had been having spinal taps, more blood work, and many other tests, so I was not able to spend much time with my grandmother in her last days. Many specialists visited me from all over town, but nothing popped up. Many suggested “dehydration” as the cause of my symptoms.
I had a nervous breakdown when my grandmother passed away. I went to the ER in early October 2012, a few weeks after the burial. I had lost so much hope but told my mom I thought we should try the ER “one more time.” While we were there, one of the doctors decided that gallstones were causing my symptoms. They operated immediately and removed my gallbladder. I was released on October 10, 2012. The next day, after leaving the hospital, everything became too overwhelming for me to handle. I went back on October 12, 2012 and called my surgeon to see if my symptoms were possibly the result of surgical complications. He told me to just take more pain medication and that they would not admit me. The last thing I remember is walking into the ER; the staff was well familiar with me at this point. I was admitted for dehydration, malnutrition, etc. While I was in my room I asked my husband to help me to the restroom, I remember my heartbeat in my head, the walls turning black around me and me telling my husband I was going to pass out. I had 3 seizures over a few hours and I had no memory of any of the next three days after that. Supposedly, I drifted in and out, but I remembered nothing. When I woke up, I couldn’t speak to my mom. It felt like my tongue was stuck and I couldn’t move anything. I began choking on my spit, because I had become paralyzed. Later I realized I was having neurological symptoms as a result of not being treated for porphyria. When they all realized I was not faking it anymore they began calling other doctors for a consultation. They called the Texas Tech unit and by that time, I was paralyzed from the mouth down.
Starting on October 12th, I spent 62 consecutive days in hospital without leaving. Dr. Urban came in from Texas Tech. He pulled up a chair and asked my mom if I was having my cycle and when she said no, he concluded that dehydration was not my problem. He said he had a friend that was a blood specialist in NY. He sent my blood to another specialist. A few days later he told me he knew what I had. I was ecstatic. We wanted something manageable, fixable, curable, etc. He sat us down and said, “You have Acute Intermittent Porphyria” and explained it all. He said it’s not curable, however, there are treatments. He said he was not a specialist, but had witnessed this before. I remained paralyzed for a while, but slowly regained functions such as swallowing, which returned first, and then eventually all speaking abilities.
I am still in a wheelchair because of this experience. I have attacks monthly, sometimes even twice a month. I attend physical therapy, and I would be walking if I didn’t have regular attacks that practically erase any progress I have made over the last month. If I had a break from the attacks, I would be able to walk again. I mainly just experience drop foot at this point.
I always get Panhematin for attacks in my Lubbock, TX hospital. Weekly infusions would help tremendously with attacks, but since I cannot afford the treatment, the doctors apologetically told me I will have to wait until I’m in an attack to get my hemin. I have had roughly 85 hospital admissions in my lifetime. I have lost count of the exact number. For over a year and a half, I spent up to 30 consecutive hours going between ERs before I received my diagnosis.

I flew to see Dr. Anderson for the first time in August 2014. I flew to UTMB to get Panhematin and establish a relationship with a porphyria specialist. While I was there, he asked me to be part of a research trial and Dr. Ede explained what the benefits there are to joining the research. I am now enrolled in every possible study that I qualify for and have no regrets about joining the studies.
To learn more about signing up for research studies in your area please visit:

                                                          "Remember....Research Is Your Key To A Cure"

What is δ-Aminolevulinic Acid Dehydratase Porphyria (ADP)?

What is δ-Aminolevulinic Acid Dehydratase Porphyria (ADP)? ADP is more severe than the other acute porphyrias and can present in childhoo...