Erythropoietic Protoporphyria (EPP)

Last updated: 25 September 2008.

Introduction

Also known as EPP, Erythropoietic ProtoporphyriaErythropoietic Protoporphyria is a rare inherited metabolic disorder of the heme pathway. Click here for more information. is a rare inherited metabolic disorder of the heme pathway.

Incidence

There has been very limited study completed on the prevalence of EPP because of its extremely low incidence. 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.

Symptoms

Symptoms of EPP usually first present in childhood. They can include swelling, burning, itching and redness of the skin, occurring during or after exposure to sunlight, including light passing through windows. Symptoms usually subside in 12 to 24 hours and heal without significant scarring or discoloration of the skin. This lack of permanent symptoms leads to frequent misdiagnosis by doctors, much to the frustration of parents and their child. Other complications may involve gallstones and liver damage, which results in jaundice and enlargement of the spleen.

Causes

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.

Treatments

Sun avoidance by remaining indoors or wearing sun protective clothing including cotton gloves and a wide brimmed hat is the first line in EPP management. Drugs such as β-carotene, cysteine and cimitedine have been used with various disappointing results and because the disease is inherited, genetic counselling is recommended.

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.

Introduction

EPP belongs to a heterogenous group of disorders 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. The main feature of EPP is ‘burning or prickling’ pain when exposed to sunlight.

Epidemiology and prevalence

EPP is rare, and few studies have been done on its prevalence. It has been shown to occur in 1.75 people per 100,000 in Slovenia but little data exists elsewhere. The disease does occur globally and it is likely that no ethnic group is spared.

Clinical features

Typically, the disease begins in childhood and is 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.

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.

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 EPP 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. 

Etiology and pathogenesis

EPP is inherited and can be autosomal dominant or recessive. 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.

The specific defective enzyme in EPP 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. 

Diagnosis

Diagnosis of EPP 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. 

Treatment

Modifying environmental and behavioural factors are the most important for reducing visible light exposure and controlling symptoms. Most commercially available sunscreens are of no value, but a large particle size titanium dioxide sunscreen may be of some benefit if used with other forms of sun protection.

Beta carotene has often been tried but its efficacy is equivocal with cysteine (an amino acid which has been shown to decrease photosensitivity) and often disappointing.

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 EPP patients. Finally, narrow band UVB phototherapy may provide some protection, presumably through epidermal thickening and tanning. 

Prognosis

Symptoms of EPP are usually with patients for life; however a few people have described symptoms reducing over time.

References

• Marko PB et al., (2007). "Erythropoietic protoporphyria patients in Slovenia", Acta Dermatoven. Vol 16;3, pp99-104.
• Murphy, G M (2003). 'Diagnosis and Management of the Erythropoitetic Porphyrias', Dermatologic Therapy. Vol 16, pp57-64.
• Schneider-Yin et al., (2000). "New insights into the pathogenesis of erythropoietic protoporphyria and their impact on patient care", European Journal of Pediatrics. Vol 125, pp 719-725.
• 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. Vol 60, pp581-604.
• Todd, D J. 'Clinical Implications of the Molecular Biology of Erythropoietic Protoporphyria', Journal of European Academy of Dermatology Venereology. Vol 11, pp207-213.

More References on Erythropoietic Protoporphyria

Clinuvel Photoprotection Reference Library

Associations and online resources

Access to:

American Porphyria Foundation
Australian Porphyria Association
Brazilian Porphyria Association
British Porphyria Association
Canadian Porphyria Foundation
Danish Porphyria Support Group
European Porphyria Initiative
Finnish Porphyria Support Group
French Prophyria Center - Centre Francais des Propyries
Fundacion Colombiana Para La Porfiria
German EPP Association (Selbsthilfe EPP e.V.) - Available in German and English
Italian Porphyria Association
Mount Sinai Department of Genetics and Genomic Sciences
New Zealand Porphyria Support Group
Nordic Porphyria Support Group
Norway Porphyria Foundation
Porphyria Association Denmark
SAKURA - Japanese porphyria patients group
South African Porphyria Association
Spanish Porphyria Foundation
Stowarzyszenia Porfiria Polska (Polish Porphyria Association)
Swedish Porphyria Association
Swiss Porphyria Association

Videos

Absolute light intolerance: Erythropoietic protoporphyria (EPP)