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Cutaneous Porphyria Treatment & Management

  • Author: Richard E Frye, MD, PhD; Chief Editor: Robert J Arceci, MD, PhD  more...
 
Updated: Nov 13, 2014
 

Medical Care

Iron depletion can treat several of the cutaneous porphyrias. High plasma iron levels inactivate uroporphyrinogen decarboxylase, the enzyme deficient in porphyria cutanea tarda (PCT), and induce 5-aminolevulinate, a major regulatory enzyme in the heme biosynthetic pathway. Thus, the activity of the deficient enzyme is reduced further, and porphyrins that cannot be metabolized are produced in increased quantities. Iron depletion also induces the synthesis of porphyrin pathway enzymes. In addition, iron overload resulting from chronic renal failure, a condition not uncommonly seen in association with PCT, is improved by this therapy.

Phlebotomy and apheresis can remove excessive iron in patients with PCT.[24] Standard phlebotomy for adults consists of removal of 250-500 mL of blood once or twice per week. The patient's tolerance and clinical response regulate the exact amount. In patients with chronic renal failure, more frequent small-volume phlebotomies and high-dose erythropoietin combined with phlebotomy are effective.

Monthly neocyte RBC exchange transfusions are reportedly useful in PCT, variegate porphyria (VP), and erythropoietic protoporphyria (EPP).

Erythropoietin is reportedly effective in PCT. By stimulating erythrogenesis, excess iron stored is mobilized and a drop in serum iron, ferritin, and plasma porphyrins is observed. Combining higher doses of erythropoietin with phlebotomy is effective in patients with renal failure.[25]

Deferoxamine forms a stable complex with iron, thereby preventing it from entering into further chemical reactions in PCT and congenital erythropoietic porphyria (CEP).[26] Long-term therapy slows hepatic iron accumulation and retards progression of hepatic fibrosis. Iron is chelated from ferritin and hemosiderin but not from transferrin, cytochromes, or hemoglobin. The chelate readily passes through the kidney, giving the urine a characteristic reddish color.

Iron oxidizes vitamin C, causing patients with iron overload to become deficient in vitamin C. Vitamin C supplements also increase the availability of iron.

Toxic metabolites have deleterious effects. Porphyrin levels can be reduced by direct methods or with medications that bind porphyrins. These methods are useful adjuncts to iron load reduction therapy or when such therapy is ineffective or limited because of comorbid conditions, such as severe renal disease.

Therapeutic erythrocytapheresis has been combined with plasma exchange to reduce uroporphyrin blood levels. The procedure is continued until urine uroporphyrins are less than 600 mcg/d.[27]

Chloroquine and hydroxychloroquine, 2 antimalarial medications, chelate and remove hepatic-bound porphyrins by forming water-soluble complexes that are eliminated in the urine.

Cholestyramine is a polymeric resin that binds bile acids to form a nonabsorbable complex, which is excreted unchanged in the feces. This compound also binds carboxylated porphyrins excreted in the bile. By preventing enterohepatic circulation, porphyrins do not reenter the systemic circulation.

Oral photoprotection can be achieved with free radical scavengers, thereby reducing free radicals, singlet oxygen formation, and the photosensitizing effect of porphyrins.

Beta-carotene is a pigment found in various green and yellow fruits and vegetables and can decrease the severity of photosensitivity reactions in patients with porphyria. Beta-carotene does not alter stool concentrations of protoporphyrins, and plasma or erythrocyte concentrations are not affected. Laboratory evidence suggests that beta-carotene quenches free radicals and singlet oxygen, which are produced when porphyrins are exposed to light and air. Carotenodermia (yellowing of the skin) usually develops after 4-6 weeks and coincides with the start of photoprotection. Protection decreases within 1-2 weeks after discontinuation of therapy. Plasma concentrations of 4-6 mcg/mL are therapeutic for most patients.

Cysteine was found to reduce photosensitivity in patients with protoporphyria.[28] Cysteine is believed to inactivate free radicals. Cysteine is a precursor to glutathione, a free radical scavenger.

N -acetylcysteine has been used, but the efficacy is questionable. Studies have used N -acetylcysteine in PCT elicited by HIV, HCV, and hemodialysis with some benefit.[29]

Sunscreen protection agents should be used if sun exposure is expected. Sun E45 lotion sun protection factor (SPF) 15 and Sun E45 cream SPF 25 have superior ultraviolet (UV)-A and blue light protection than Report on Carcinogens (RoC) 15+A+B, although all have good UV-B protection for photosensitive patients with EPP. In general, sun-blocking creams containing titanium dioxide or zinc oxide are useful. Sunless tanning agents that impart a pigment to the stratum corneum, especially those containing dihydroxyacetone, can also help.

Acute scleritis in PCT is treated with indomethacin or systemic steroids when standard treatment does not improve the condition.[30]

There have been case reports that radiation therapy can result in significant cutaneous and soft tissue morbidity in PCT, and this should be considered while discussing risks of this therapy.[31]

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Surgical Care

Many anesthetics can exacerbate porphyria, requiring an experienced anesthesiologist for proper treatment during surgery.

Cholecystectomy may be required for severe cholelithiasis in CEP.

Splenectomy may be required if severe hemolytic anemia develops in CEP.

CEP has been cured with allogenic bone marrow transplant. Risks of this procedure must be carefully considered.

EPP is not curable with liver transplant, although combined liver and bone marrow transplant may be curative in the future.

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Consultations

Contact a porphyria expert to assist in diagnosis and management of short-term and long-term treatments. Because porphyria spans many disciplines, experts may be certified in the area of metabolic disease, gastroenterology, or hematology.[32]

A hematologist may be particularly helpful if phlebotomy, apheresis, or exchange transfusion procedures are being used. In addition, management of deferoxamine and erythropoietin therapy may also require such an expert. A hematologist should be consulted if bone marrow transplant or splenectomy is considered for CEP.

Seek dermatologist consultation for management of cutaneous lesions.

Seek ophthalmologist consultation if ocular manifestations arise.

Gynecologist consultation may be necessary for menses control because estrogens should be avoided.

Anesthesiology consultation is necessary before sedation in minor procedures or surgery.

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Diet

A high-carbohydrate diet can reduce disease severity. A low-carbohydrate diet is strictly forbidden.

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Activity

Contact with direct sunlight should be minimized. Sunscreen protection should be used when skin is exposed to the sun.

Shading of glass windows in cars can minimize light exposure during driving.

Activities that could damage skin lesions should be avoided.

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Contributor Information and Disclosures
Author

Richard E Frye, MD, PhD Associate Professor, Department of Pediatrics, University of Arkansas for Medical Sciences

Richard E Frye, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, International Neuropsychological Society, American Academy of Pediatrics

Disclosure: Nothing to disclose.

Coauthor(s)

Thomas G DeLoughery, MD Professor of Medicine, Pathology, and Pediatrics, Divisions of Hematology/Oncology and Laboratory Medicine, Associate Director, Department of Transfusion Medicine, Division of Clinical Pathology, Oregon Health and Science University School of Medicine

Thomas G DeLoughery, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American College of Physicians, American Society of Hematology, International Society on Thrombosis and Haemostasis, Wilderness Medical Society

Disclosure: Nothing to disclose.

Darius J Adams, MD Director, Personalized Genomic Medicine, Atlantic Health System; Director, Division of Genetics and Metabolism, Goryeb Children's Hospital

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD Director, Children’s Center for Cancer and Blood Disorders, Department of Hematology/Oncology, Co-Director of the Ron Matricaria Institute of Molecular Medicine, Phoenix Children’s Hospital; Editor-in-Chief, Pediatric Blood and Cancer; Professor, Department of Child Health, University of Arizona College of Medicine

Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Association for Cancer Research, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Additional Contributors

Sharada A Sarnaik, MBBS Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Associate Hematologist/Oncologist, Children's Hospital of Michigan

Sharada A Sarnaik, MBBS is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, Children's Oncology Group, American Academy of Pediatrics, Midwest Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

Vikramjit S Kanwar, MD, MBA, MRCP(UK), FAAP Associate Professor of Pediatric Hematology and Oncology, Department of Pediatrics, Albany Medical Center; Faculty, Alden March Bioethics Institute

Vikramjit S Kanwar, MD, MBA, MRCP(UK), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and Royal College of Physicians of the United Kingdom

Disclosure: Nothing to disclose.

References
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The heme production pathway. Heme production begins in the mitochondria, proceeds into the cytoplasm, and is then resumed in the mitochondria for the final steps. This figure outlines the enzymes and intermediates involved in the porphyrias. Enzymes names are presented in the boxes. Names of the intermediates are outside the boxes, between arrows. Multiple arrows leading to a box demonstrate that multiple intermediates are required as substrates for the enzyme to produce one product.
Table 1. Frequency Varies with the Specific Porphyria
Type of Porphyria Age of Onset Incidence per 100,000 Population Male-to-Female Ratio
CEP Infancy to early childhood; rare in adults 300 cases total 1:1
PCT Type I: Adulthood



Type II (heterozygous mutations): Adulthood



Type III (homozygous mutations): Childhood



United States: 4



United Kingdom: 0.05



1:1
HCP Predominantly adulthood



Youngest report was child aged 4 y



Japan: 1.5



Czech: 1.5



Israel: 0.7



Denmark: 0.05



1:20



1:4



2:1



1:1



VP Heterozygous mutation: After puberty



Homozygous mutation: Childhood (rare)



South Africa: 34 1:1
EPP Infancy to childhood 0.02 1:1
Table 2. Causes by Type of Porphyria
Porphyria Deficient Enzyme Location Inheritance Chromosome Band
CEP Uroporphyrinogen III synthase Cytosol Autosomal recessive (AR) 10q25.3-26.3
PCT Uroporphyrinogen decarboxylase Cytosol Autosomal dominant (AD) 1p34
HEP Uroporphyrinogen decarboxylase Cytosol AR 1p34
HCP Coproporphyrinogen oxidase Mitochondrial AD 3q12
VP Protoporphyrinogen oxidase Mitochondrial AD 1q22-23
EPP Ferrochelatase Mitochondrial AD, AR 18q22
Table 3. Quantitative Fecal Porphyrins by Type of Porphyria
Porphyrin Type CEP PCT HCP VP EPP
Uroporphyrin Significantly increased Increased Within reference range Within reference range Within reference range
Coproporphyrin Significantly increased Increased Significantly increased Increased Within reference range
Protoporphyrin Within reference range Within reference range Increased Significantly increased Significantly increased
Table 4. Quantitative Urine Porphyrins
Porphyrin type CEP and PCT HCP and VP
5-Aminolevulinate Within reference range Significantly increased
PBG Within reference range Significantly increased
Uroporphyrin Significantly increased Increased
Coproporphyrin Increased Significantly increased
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