beta-carotene and Protoporphyria--Erythropoietic

Erythropoietic protoporphyria (EPP) is a semi-dominantly inherited porphyria presenting with photosensitivity during early childhood. Acquired EPP has been reported; however, data regarding this rare disorder are scarce.. To evaluate the characteristics of acquired EPP.. A comprehensive search of PubMed, Google Scholar, ScienceDirect, and clinicaltrials.gov databases was performed by three reviewers. Studies describing patients with acquired EPP were included. Additionally, we present an index case of a 26-year-old patient who acquired clinically and biochemically typical EPP in association with myelodysplastic syndrome (MDS).. We included 20 case reports describing 20 patients. Most (80%) patients were male of mean age 58 ± 13 years. In all patients, acquired EPP was associated with hematological disease, most commonly MDS (85%) followed by myeloproliferative disease (10%). In 86% of cases, hematological disease led to abnormality or somatic mutation in chromosome 18q (the locus of the ferrochelatase gene). The mean erythrocyte protoporphyrin IX concentration was very high (4286 μg/dL). Most (90%) patients presented with photosensitivity, 20% experienced blistering, and 25% presented with hepatic insufficiency, both uncommon in EPP. In 55% of patients, hematological disease was diagnosed after occurrence of cutaneous symptoms. Beta-carotene led to partial control of symptoms in 5 patients and resolution in another patient. Azacitidine treatment of MDS led to resolution of cutaneous symptoms in three patients.. We present the distinct features of acquired EPP and highlight that any patient presenting with new-onset photosensitivity, irrespective of age should be evaluated for porphyria.

Topics: Adult; Aged; Azacitidine; beta Carotene; Chromosomes, Human, Pair 18; Erythrocytes; Female; Ferrochelatase; Genetic Loci; Humans; Male; Middle Aged; Mutation; Myelodysplastic Syndromes; Photosensitivity Disorders; Protoporphyria, Erythropoietic; Protoporphyrins

Erythropoietic protoporphyria (EPP) is a rare inherited disease characterized by dermal photosensitivity due to the accumulation of photosensitizer protoporphyrin IX. We performed a systematic database search on studies related to treatment of EPP. A total of 25 relevant studies were retrieved, 16 of them dealing with the application of beta-carotene. Two studies were found on each of the three substances, n-acetyl-cysteine (NAC), cysteine, and dihydroxyacetone/Lawson (henna). In addition, single studies on vitamin C, canthaxanthin and UVB treatment respectively, were located. The total number of patients in the 25 studies was 454, including 337 patients in the various beta-carotene trials. Most studies were published in the 1970's. Efficacy criteria were not standardized. Only 5 of the 25 studies were randomized and controlled trials; the rest were either open-label, uncontrolled studies or retrospective case reports. Four of the five well-designed studies suggested lack of efficacy of beta-carotene, NAC and vitamin C. The results of the beta-carotene studies were strongly contradictory and efficacy was inversely correlated with study quality. Our data confirm the opinion of experts in the field who are much more skeptical as to its efficacy than were early proponents of treatment with this agent. We conclude, that the available data are insufficient to prove efficacy of any treatments studied so far in EPP. We emphasize the necessity of high quality efficacy studies in porphyrias and in other rare diseases.

Topics: Ascorbic Acid; beta Carotene; Clinical Trials as Topic; Cysteine; Humans; Protoporphyria, Erythropoietic; Treatment Outcome

The porphyrias are a group of rare metabolic disorders that result from defects in heme biosynthesis. Erythropoietic protoporphyria (EPP) is the most common inherited porphyria in children and is diagnosed in most individuals after the onset of cutaneous manifestations. Hepatobiliary disease affects the minority of individuals with EPP and usually manifests in patients with an established diagnosis of EPP. We report on a classic but rare case of EPP that masqueraded as cholestasis. An 8-year-old boy was referred to the Hepatology Clinic after an abrupt onset of jaundice with a longstanding history of dermatitis. The diagnosis of EPP was established with liver biopsy, which revealed dense, dark-brown pigment in hepatocytes and Kupffer cells that, on polarization, displayed bright-red birefringence and centrally located Maltese crosses. Plasma total porphyrins and erythrocyte protoporphyrin were elevated and confirmed a diagnosis of EPP. We hope to raise awareness of this diagnosis among pediatricians, hepatologists, and pathologists and increase the consideration of EPP in patients with cholestatic liver disease and chronic dermatitis.

Topics: beta Carotene; Child; Cholagogues and Choleretics; Cholestasis; Cholestyramine Resin; Chronic Disease; Diagnosis, Differential; Humans; Male; Photosensitivity Disorders; Protoporphyria, Erythropoietic; Provitamins; Pruritus; Ursodeoxycholic Acid

Topics: Aged; Azacitidine; Benzoates; beta Carotene; Deferasirox; Humans; Male; Myelodysplastic Syndromes; Protoporphyria, Erythropoietic; Triazoles

To investigate the demographic, clinical, biochemical and genotypic features of patients with erythropoietic protoporphyria (EPP) in a Swedish cohort.. Cross-sectional questionnaire, biochemical and genetic study.. Sweden.. Fifty-one Swedish individuals known in 2008 to have EPP confirmed by molecular diagnosis. There were no exclusion criteria; all patients were included in the demographic and genetic study. A total of 92% participants completed the questionnaire study and 82% the biochemical study.. The prevalence of EPP was 1 : 180,000. Nine novel ferrochelatase gene mutations were found. The most commonly reported age at onset of symptoms was the first year of life and the mean age at diagnosis was 22 years. Painful photosensitivity was the main symptom. Exogenous factors other than sunlight were frequently reported to cause cutaneous symptoms. One in five patients reported a positive effect of beta-carotene therapy. A marked impact of EPP on quality of life was reported. Women had a significantly lower mean erythrocyte protoporphyrin concentration than men. Of all participants, 84% had insufficient vitamin D concentrations, 44% had below normal serum ferritin or transferrin saturation levels and red cell abnormalities were common.. The notably delayed diagnosis suggests the need for an increased awareness of EPP. Disturbed erythropoiesis, biochemical signs of iron deficiency and low vitamin D levels are frequent findings in this disease. New and better treatments are needed as current treatment options for symptom amelioration are limited. Vitamin D supplementation should be considered.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta Carotene; Child; Cross-Sectional Studies; Erythropoiesis; Female; Ferrochelatase; Genotype; Humans; Male; Middle Aged; Mutation; Photosensitivity Disorders; Porphyrins; Protoporphyria, Erythropoietic; Sweden; Vitamin D; Young Adult

Topics: Aged; beta Carotene; Humans; Male; Myelodysplastic Syndromes; Protoporphyria, Erythropoietic; Protoporphyrins; Sunlight; Vitamins

Erythropoietic protoporphyria (EPP) is an inborn error of heme biosynthesis with high levels of protoporphyrin in red cells and is characterized by mild to moderate photosensitivity. High-dose beta-carotene therapy has been reported to afford photoprotection in patients with EPP. We report the case of a 5-year-old Caucasian female with EPP who presented with a long-standing 3-year history of recurrent facial blisters and erythematous swelling and lesions of other sun-exposed areas of the skin. She was treated with a topical sunblocker (PreSun Ultra-SP45) but continued to show moderate to severe photosensitivity despite 3 months (March to May) of vigorous photoprotection. She was then started on increasing doses of beta-carotene (90-180 mg/day) over a period of 3 months (June to September) which resulted in a marked improvement of both facial and forearm lesions, but only modest improvement in her hand lesions.. High-dose beta-carotene appears to provide photoprotection in erythropoietic protoporphyria, resulting in improved but highly variable tolerance to sunlight.

Topics: Antioxidants; beta Carotene; Child, Preschool; Female; Humans; Photosensitivity Disorders; Protoporphyria, Erythropoietic

Topics: beta Carotene; Carotenoids; Combined Modality Therapy; Erythropoiesis; Humans; Liver Diseases; Porphyrias; Porphyrins; Protoporphyria, Erythropoietic; Protoporphyrins; Skin Diseases