Erythropoietic protoporphyria

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Erythropoietic protoporphyria
Classification and external resources
Chronic skin lesions of EPP.jpg
Chronic skin lesions of EPP
ICD-10 E80.0 (ILDS E80.010)
ICD-9 277.1
OMIM 177000
DiseasesDB 4484
eMedicine derm/473
MeSH C06.552.830.812

Erythropoietic protoporphyria (EPP) is a form of porphyria, which varies in severity and can be very painful. It arises from a deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the tissue.[1]:525 The severity varies significantly from individual to individual.

Both autosomal dominant and autosomal recessive inheritance have been reported with this disorder[2] as has an acquired form of the disease.[3] A clinically similar form of porphyria, known as X-Linked dominant protoporphyria, was identified in 2008.[4]

Presentation[edit]

Acute photosensitivity reaction in EPP.

A common symptom is very painful photosensitivity, manifesting itself as a burning and itching sensation on the surface of the skin. At times the itching sensations are almost unbearable. Rubbing the affected areas with ice can be the only relief, and that is only temporary. The usual anti-itch remedies, including cortisone anti-histamine topical preparations, and Calomine lotion generally provide little or no relief. If a patient presents with a history of anti-itch preparation inefficacy, EPP should be considered.

EPP usually first presents in childhood, and most often affects the face and the upper surfaces of the arms, hands, and feet and the exposed surfaces of the legs. Most patients, if the EPP is not as severe, manifest symptoms with onset of puberty when the male and female hormone levels elevate during sexual development and maintenance. More severe EPP can manifest in infancy. Exposure to even indoor light sources can cause the reaction, and the infant, if clothed only in a diaper, will break out everywhere except under the diaper. EPP can be triggered through exposure to sun even though the patient is behind glass. Even the UV emissions from arc welding with the use of full protective mask have been known to trigger EPP. EPP can also manifest between the ages of 3 and 6.

EPP is so rare that it has been mentioned on an episode of the popular American TV show, HOUSE M.D. It is over-dramatised, and much of the description of EPP is incorrect. Exposure to powerful surgical lights is enough to trigger the reaction. As a precaution, individuals with EPP should tell their close friends and family to make sure that if they ever are taken to the hospital for emergency surgery that the staff be notified of the condition so they can adjust the lighting accordingly.

Prolonged exposure to the sun can lead to oedema of the hands, face, and feet, rarely with blistering and petechiae. Skin thickening can sometimes occur over time.

People with EPP are also at increased risk to develop gallstones.[5] One study has noted that EPP patients suffer from vitamin D deficiency.[6]

Liver failure in EPP[edit]

In a small percentage of cases, protoporphyrin accumulates to toxic levels in the liver, leading to liver failure. A lack of diagnostic markers for liver failure makes it difficult to predict which patients may experience liver failure, and the mechanism of liver failure is poorly understood. A retrospective European study identified 31 EPP patients receiving a liver transplant between 1983 and 2008, with phototoxic reactions in 25% of patients who were unprotected by surgical light filters. The same study noted a 69% recurrence of the disease in the grafted organ. Five UK liver transplants for EPP have been identified between 1987 and 2009.

Frequent liver testing is recommended in EPP patients where no effective therapy has been identified to manage liver failure to date.

Prevalence[edit]

Case reports suggest that EPP is prevalent globally. The prevalence has been estimated somewhere between 1 in 75,000 and 1 in 200,000[7] however it has been noted that the prevalence of EPP may be increasing due to a better understanding of the disease and improved diagnosis.[8] An estimated 5,000-10,000 individuals worldwide have EPP.[9] EPP is considered the most common form of porphyria in children.[10] The prevalence in Sweden has been published as 1:180,000.[11]

EPP and pregnancy[edit]

EPP photosensitivity symptoms are reported to lessen in some female patients during pregnancy and menstruation, although this phenomenon is not consistent, and the mechanism is not understood.[12]

Treatment and prognosis[edit]

There is no cure for this disorder; however, symptoms can usually be managed by limiting sun exposure. Protective clothing is also very helpful. Since the photosensitivity results from light in the visible spectrum, most sunscreens (with the exception of light-reflecting substances such as zinc oxide) are of little use. Some individuals may decrease their sun sensitivity with daily doses of beta carotene, though a recent meta analysis of carotene treatment has called its effectiveness into question.[13] Some patients gradually build a protective layer of melanin by regularly exposing themselves for short times to ultraviolet radiation.

EPP is considered one of the least severe of the porphyrias. Unless there is liver failure, it is not a life-limiting disease.

Experimental treatments[edit]

Clinuvel Pharmaceuticals Ltd., an Australian pharmaceutical company, has successfully completed Phase III clinical trials [14] with a melanocyte-stimulating hormone called afamelanotide (SCENESSE)[15] (formerly CUV1647).[16] In May 2010 afamelanotide (SCENESSE) was approved by the Italian Medicines Agency (AIFA) for reimbursement, for the treatment of EPP.[17] The treatment is also available in Switzerland.[18]

History[edit]

Erythropoietic protoporphyria was first described in 1953 by Kosenow and Treibs[19] and completed in 1960 by Magnus et al. at the St John's Institute of Dermatology in London.[20]

Pop Culture[edit]

In the 9th episode of season 3 of House entitled "Finding Judas", the primary patient is a young girl who is ultimately diagnosed with erythropoietic protoporphyria.[citation needed]

In series 14 episode 26 of Casualty entitled Seize the Night, one of the patients admitted to the department was a young girl who had erythropoietic protoporphyria. She got brought in after being hit by a car.

See also[edit]

References[edit]

  1. ^ James, William D.; Berger, Timothy G.; and others (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.  Missing |last3= in Authors list (help)
  2. ^ Rüfenacht, U.B.; Gouya, L.; Schneider-Yin, X.; Puy, H.; Schäfer, B.W.; Aquaron, R.; Nordmann, Y.; Minder, E.I.; Deybach, J.C. (1998). "Systematic Analysis of Molecular Defects in the Ferrochelatase Gene from Patients with Erythropoietic Protoporphyria". The American Journal of Human Genetics 62 (6): 1341. doi:10.1086/301870. 
  3. ^ Blagojevic, Daniel; Schenk, Thomas; Haas, Oskar; Zierhofer, Brigitte; Konnaris, Christophoros; Trautinger, Franz (2009). "Acquired erythropoietic protoporphyria". Annals of Hematology 89 (7): 743–4. doi:10.1007/s00277-009-0859-7. PMID 19902211. 
  4. ^ Seager, M. J.; Whatley, S. D.; Anstey, A. V.; Millard, T. P. (2014). "X-linked dominant protoporphyria: A new porphyria". Clinical and Experimental Dermatology 39 (1): 35–7. doi:10.1111/ced.12202. PMID 24131146. 
  5. ^ 12-160d. at Merck Manual of Diagnosis and Therapy Home Edition
  6. ^ Spelt, JM; De Rooij, FW; Wilson, JH; Zandbergen, AA (2010). "Vitamin D deficiency in patients with erythropoietic protoporphyria". Journal of Inherited Metabolic Disease. 33 Suppl 3: S1–4. PMID 24137761. 
  7. ^ Arceci, Robert.; Hann, Ian M.; Smith, Owen P. (2006). Pediatric hematolog. Malden, Mass.: Blackwell Pub. ISBN 978-1-4051-3400-2. [page needed]
  8. ^ Elder, George; Harper, Pauline; Badminton, Michael; Sandberg, Sverre; Deybach, Jean-Charles (2012). "The incidence of inherited porphyrias in Europe". Journal of Inherited Metabolic Disease 36 (5): 849–57. doi:10.1007/s10545-012-9544-4. PMID 23114748. 
  9. ^ http://www.clinuvel.com/skin-conditions/rare-skin-conditions/erythropoietic-protoporphyria[full citation needed]
  10. ^ Michaels, BD; Del Rosso, JQ; Mobini, N; Michaels, JR (2010). "Erythropoietic protoporphyria: A case report and literature review". The Journal of clinical and aesthetic dermatology 3 (7): 44–8. PMC 2921755. PMID 20725556. 
  11. ^ Wahlin, S.; Floderus, Y.; Stål, P.; Harper, P. (2011). "Erythropoietic protoporphyria in Sweden: Demographic, clinical, biochemical and genetic characteristics". Journal of Internal Medicine 269 (3): 278–88. doi:10.1111/j.1365-2796.2010.02236.x. PMID 20412370. 
  12. ^ Wahlin, S.; Marschall, H.-U.; Fischler, B. (2013). "Maternal and fetal outcome in Swedish women with erythropoietic protoporphyria". British Journal of Dermatology 168 (6): 1311–5. doi:10.1111/bjd.12242. PMID 23738640. 
  13. ^ Minder, EI; Schneider-Yin, X; Steurer, J; Bachmann, LM (2009). "A systematic review of treatment options for dermal photosensitivity in erythropoietic protoporphyria". Cellular and molecular biology 55 (1): 84–97. PMID 19268006. 
  14. ^ Clinuvel reports positive results in phase III erythropoietic protoporphyria (EPP) clinical trial PDF (273 KB)
  15. ^ http://www.clinuvel.com/scenesse
  16. ^ "World Health Organisation assigns CUV1647 generic name" (PDF). Clinuvel. 2008. Retrieved 2008-06-17. 
  17. ^ Italian Medicines Agency (AIFA) provides reimbursement for the treatment of EPP with afamelanotide (SCENESSE) PDF (273 KB)
  18. ^ http://lifescientist.com.au/content/biotechnology/news/swiss-insurers-to-reimburse-clinuvel-s-scenesse-468721759[full citation needed]
  19. ^ Kosenow, W; Treibs, A (1953). "Light hypersensitivity and porphyrinemia". Zeitschrift fur Kinderheilkunde 73 (1): 82–92. doi:10.1007/BF00438257. PMID 13103364. 
  20. ^ Magnus, I; Jarrett, A; Prankerd, TA; Rimington, C (1961). "Erythropoietic protoporphyria. A new porphyria syndrome with solar urticaria due to protoporphyrinæmia". The Lancet 278 (7200): 448–51. doi:10.1016/S0140-6736(61)92427-8. PMID 13765301. 

External links[edit]