Congenital Erythropoietic Porphyria Publications (826)

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Congenital Erythropoietic Porphyria Publications

2017Jan
Clin Pharmacokinet
Clin Pharmacokinet 2017 Jan 6. Epub 2017 Jan 6.
Stadtspital Triemli, Institute of Laboratory Medicine, Zurich, Switzerland.

Afamelanotide, the first α-melanocyte-stimulating hormone (MSH) analogue, synthesized in 1980, was broadly investigated in all aspects of pigmentation because its activity and stability were higher than the natural hormone. Afamelanotide binds to the melanocortin-1 receptor (MC1R), and MC1R signaling increases melanin synthesis, induces antioxidant activities, enhances DNA repair processes and modulates inflammation. The loss-of-function variants of the MC1R present in fair-skinned Caucasians are less effectively activated by the natural hormone. Read More

Afamelanotide was the first α-MSH analogue to be applied to human volunteers. Ten daily doses of between 0.08 and 0.21 mg/kg in saline injected subcutaneously resulted in long-lasting skin pigmentation and enabled basic pharmacokinetics. Subcutaneous application had full bioavailability, but neither oral nor transdermal application resulted in measurable plasma concentrations or pigmentation response. Two trials in human volunteers showed that neither MC1R variants nor fair skin reduced the afamelanotide-induced increase in skin pigmentation. A controlled-release formulation optimizes administration in man and is effective at a lower dose than the daily saline injections. Promising therapeutic results were published in polymorphic light eruption, erythropoietic protoporphyria (EPP), solar urticaria, Hailey-Hailey disease and vitiligo. In 2014, afamelanotide was approved by the European Medicines Agency for the prevention of phototoxicity in adult patients with EPP. No late effects were reported in volunteers 25 years after the first exposure or after continuous long-term application of up to 8 years in EPP patients, and an immunogenic potential has been excluded. Generally, adverse effects were benign in all trials.

2016Dec
Appl Clin Genet
Appl Clin Genet 2016 12;9:179-189. Epub 2016 Dec 12.
Department of Internal Medicine, Section on Gastroenterology.

Erythropoietic protoporphyria (EPP) and the phenotypically similar disease X-linked protoporphyria (XLPP) are inherited cutaneous porphyrias characterized clinically by acute non-blistering photosensitivity, intolerance to sunlight, and significantly reduced quality of life. They are due to marked overproduction of protoporphyrin (PP) chiefly by erythroblasts and reticulocytes. In EPP, the underlying genetic defect is in the ferrochelatase gene, which encodes the final enzyme in the heme synthetic pathway. Read More

In XLPP, the genetic defect is a gain-of-function mutation, usually a four-base deletion, in the gene that encodes the enzyme 5-aminolevulinic acid synthase-2, the first and rate-controlling enzyme of heme synthesis in developing red blood cells. The excess PP causes acute and painful photosensitivity, being activated by light in the long ultraviolet to blue spectrum (380-420 nm, the Soret band). Although several treatments have been proposed, presently no very effective treatment exists for EPP or XLPP. Afamelanotide (Scenesse(®)) is a first-in-class synthetic analog of α-melanocyte stimulating hormone. Afamelanotide mimics the naturally occurring hormone to increase skin pigmentation by increasing melanin production in melanocytes, resulting in increased sunlight tolerance in those with EPP/XLPP. Afamelanotide is currently approved for use in the European Union and Switzerland, and it is under review in the United States by the Food and Drug Administration for use in patients with EPP/XLPP. This paper provides a review of the clinical characteristics and current therapies for EPP/XLPP. We discuss the pharmacology, clinical efficacy, safety, and tolerability of afamelanotide and summarize the results of several key Phase II and III clinical trials. These data indicate that afamelanotide is a promising therapy for those with these debilitating diseases.

2016Dec
Br. J. Dermatol.
Br J Dermatol 2016 Dec;175(6):1144-1145
Scottish Cutaneous Porphyria Service, Photobiology Unit, Level 8, Ninewells Hospital, Dundee, DD1 9SY, U.K.
2016Nov
J Cutan Med Surg
J Cutan Med Surg 2016 Nov 11. Epub 2016 Nov 11.
Department of Internal Medicine, College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.

Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. There is a clear association between BCC development and ultraviolet (UV) radiation. Erythropoietic protoporphyria (EPP) is an inherited porphyria disorder that is a result of protoporphyrin accumulation, typically manifesting with phototoxicity. Read More


We report a case of a 24 year-old man with both EPP and BCC diagnoses. At the age of 4 years, the patient was diagnosed with EPP. The patient presented with a BCC on his nose at age 24 years, despite sun avoidance as the primary treatment for his EPP diagnosis.
Consider the diagnosis of BCC in a patient with EPP, despite sun avoidance.

2016Nov
Indian J Gastroenterol
Indian J Gastroenterol 2016 Nov 31;35(6):405-418. Epub 2016 Oct 31.
Department of Internal Medicine, UAB University of Alabama in Birmingham, Birmingham, AL, USA.

Porphyrias are a group of metabolic disorders, which result from a specific abnormality in one of the eight enzymes of the heme biosynthetic pathway. These have been subdivided based on the predominant site of enzyme defect into hepatic and erythropoietic types and based on clinical presentation into acute neurovisceral and cutaneous blistering porphyrias. This review focuses on hepatic porphyrias, which include acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), aminolevulinic acid dehydratase deficiency porphyria (ADP), and porphyria cutanea tarda (PCT). Read More

Of these, AIP and ADP are classified as acute porphyria, PCT as cutaneous, while VP and HCP present with both acute and cutaneous clinical manifestations. Porphobilinogen levels in a spot urine sample is the initial screening test for the diagnosis of acute hepatic porphyria, and plasma with spot urine porphyrin levels is the initial screening test to approach patients suspected of cutaneous porphyria. Specific biochemical porphyrin profile for each porphyria helps in determining the specific diagnosis. Pain relief and elimination of triggering agents are the initial steps in managing a patient presenting with an acute attack. Intravenous glucose administration terminates the mild episode of acute porphyria, with intravenous hemin needed for management of moderate to severe episodes. Liver transplantation is curative and may be needed for patients with a life-threatening acute porphyria attack or for patients with recurrent acute attacks refractory to prophylactic treatment. Of the cutaneous porphyrias, PCT is the most common and is frequently associated with a combination of multiple susceptibility factors such as alcohol use, smoking, hepatitis C virus infection, HIV infection, estrogen use, and mutations of the hemochromatosis gene. Regular phlebotomy schedule and low-dose hydroxychloroquine are effective and safe treatment options for management of PCT.

2016Sep
Adv Clin Exp Med
Adv Clin Exp Med 2016 Mar-Apr;25(2):361-8
Department of Haemostasis and Metabolic Disorders of the Institute of Haematology and Transfusion Medicine, Warszawa, Poland.

Porphyrias are diverse disorders that arise from various inherited enzyme defects in the heme biosynthesis pathway, except for porphyria cutanea tarda (PCT), in which the enzyme deficiency in most cases is acquired. The biosynthetic blocks resulting from the defective enzymes are largely expressed either in the liver or bone marrow, the sites where the majority of heme is produced. Although the pathophysiologic mechanisms of the clinical manifestations of the porphyrias are not fully understood, two cardinal features prevail: skin photosensitivity and neurologic symptoms of intermittent autonomic neuropathy, acute neurovisceral attacks, and disorders of the nervous system. Read More

The primary diagnosis of the proband is based on biochemical testing, which is not always able to identify acute porphyrias, especially in asymptomatic family carriers when heme precursors and porphyrins excretion is normal, low-normal and high-reduced values of enzyme activity overlap, and hematological diseases responsible for abnormal blood cells distribution coexist. Molecular analysis of gene mutations responsible for each type of porphyria is the best diagnostic approach for symptomatic as well as presymptomatic gene carriers.

2016Aug
Indian J Dermatol
Indian J Dermatol 2016 Jul-Aug;61(4):467
Department of Dermatology, Army College of Medical Sciences, New Delhi, India.

Hereditary porphyrias are a group of metabolic disorders of heme biosynthesis pathway that are characterized by acute neurovisceral symptoms, skin lesions, or both. Congenital erythropoietic porphyria (CEP) is an extremely rare disease with a mutation in the gene that codes for uroporphyrinogen III synthase leading to accumulation of porphyrin in different tissues and marked cutaneous photosensitivity. We report a case of CEP with infancy onset blistering, photosensitivity, red colored urine, and teeth along with scarring. Read More

Examination revealed an undescended testis of the left side. Mutation analysis revealed mutation in the uroporphyrinogen III synthase gene (UROS) resulting in c. 56 A > G (Tyr19Cys). The presence of undescended testis with a rare mutation in a case of CEP which itself is an extremely rare condition make the case interesting.

2016Nov
JAMA Dermatol
JAMA Dermatol 2016 Nov;152(11):1258-1261
Department of Dermatology, Stanford University, Stanford, California.

Erythropoietic protoporphyria (EPP) is a rare hereditary disease of heme biosynthesis that manifests as severe photosensitivity and hepatotoxicity. There have been no effective treatments to date. Cimetidine has been shown to inhibit heme biosynthesis and results in symptomatic improvement in patients with acute intermittent porphyria (AIP) and porphyria cutanea tarda (PCT). Read More

There is only 1 report in the literature describing the use of cimetidine in the effective treatment of an adult patient with EPP.
To describe the successful use of cimetidine in pediatric patients with EPP.
Retrospective medical record review carried out in a pediatric dermatology practice at an academic institution of patients diagnosed with EPP who were younger than 18 years and treated with systemic cimetidine in the past 3 years.
Systemic cimetidine.
Resolution of skin photodamage was evaluated on clinical examination. Subjective measures including tolerability to sun exposure, ability to participate in outdoor activities, and objective evaluation including serum erythrocyte protoporphyrin levels and liver function tests following treatment were assessed.
All 3 cases reported a rapid reduction in photosensitivity within weeks following initiation of systemic therapy. Their skin photodamage were also improved or resolved completely on subsequent examination. Laboratory study results also revealed reduction in serum erythrocyte protoporphyrin levels and improved liver function. None of the patients have reported any adverse effects of the systemic treatment after more than 2 years of treatment.
Children with EPP currently have limited therapeutic options and experience substantial disease impact on their quality of life. This is the first case series demonstrating that cimetidine, a readily available oral medication, can be a promising treatment for children with EPP.

2016Jul
Proc (Bayl Univ Med Cent)
Proc (Bayl Univ Med Cent) 2016 Jul;29(3):311-2
Department of Pathology, University of South Carolina, Charleston (Lindsey); and the Departments of Hematology/Oncology (Burch) and Pathology (Krause), Baylor University Medical Center at Dallas and Baylor Sammons Cancer Center, Dallas, Texas.

A 53-year-old Texas rancher developed a blistering skin rash that was sensitive to exposure to sunlight. He was referred to hematology with a presumptive diagnosis of porphyria. His peripheral blood counts were within normal limits, and a bone marrow examination revealed erythroid dyspoiesis and ringed sideroblasts. Read More

Serum, plasma, and erythrocyte protoporphyrin levels were elevated, the findings of which are consistent with a diagnosis of erythropoietic protoporphyria. This paper discusses the diagnosis and etiology of the porphyrias.