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Cutaneous Porphyria Workup

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

Laboratory Studies

Demonstration of elevated porphyrins in plasma (particularly for congenital erythropoietic porphyria [CEP]), urine, and stool are very useful for diagnosis of the porphyrias.[19]

Qualitative urine examination can identify urine porphyrins. However, normal urine contains porphyrins, making comparison with a control sample essential. In both the amyl alcohol and talc tests, the urine must be adjusted to a pH of 4 by mixing 3 mL of urine with 1 mL of 1 mol/L acetate buffer.

For the amyl alcohol test, 4 mL of amyl alcohol is added to the 4-mL buffered urine solution. After vigorous shaking or low-speed centrifuge, the mixture is examined under a Wood lamp.[20] A pink-to-red fluorescence in the upper organic layer indicates a positive result.

For the talc test, 100 mg of talc is added to 10 mL of the buffered urine solution and shaken vigorously. Low-speed centrifuge for about 10 minutes produces a talc pellet, which can be examined under a Wood lamp. A pink or red color indicates a positive result.

Protoporphyria can be diagnosed by identifying numerous fluorescent erythrocytes in blood examined microscopically with a 100-watt iodine-tungsten lamp.

Qualitative stool studies can help guide the diagnosis. Mix 1-2 g of stool in 2 mL of an amyl alcohol, glacial acetic acid, and ether mixture. Red fluorescence under a Wood lamp indicates that porphyrins are present.

Stool porphyrin levels that are combined with other laboratory values and clinic correlation help guide the diagnosis. However, levels of porphyrins widely vary, and, in most cases, exact values for each disorder have not been established.

Table 3. Quantitative Fecal Porphyrins by Type of Porphyria (Open Table in a new window)

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

 

Quantitative urine porphyrin levels can be useful, but prior qualitative urine testing is desirable. Although hereditary coproporphyria (HCP) and variegate porphyria (VP) have identical urine porphyrin profiles, stool porphyrin testing can differentiate them. CEP and porphyria cutanea tarda (PCT) also have identical porphyrin patterns; however, erythrocyte examination results are positive only for CEP.

Table 4. Quantitative Urine Porphyrins (Open Table in a new window)

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

 

Iron overload is almost always present in PCT and is reflected by abnormally high serum iron levels, low total iron-binding capacity, and high serum ferritin levels. Hemolytic anemia with polychromasia, poikilocytosis, anisocytosis, and basophilic stippling is observed in CEP. Thrombocytopenia and leukopenia are observed if hypersplenism develops in CEP.

Functional enzyme assays are not widely available and, therefore, are not commonly used in cutaneous porphyria diagnosis. ALAD and AIP assays are useful, and, at specialized centers, assays for other cutaneous porphyria types (eg, coproporphyrinogen oxidase) may be available. Although these other enzyme assays may be available, differential tissue expression of the enzymes makes these assays less useful in some individuals and they are not reliable for diagnostic purposes.

Many genetic defects responsible for porphyria have been identified. However, in general, a large number of defects account for each porphyria type, limiting the practical use of these tests. For example 121 mutations in the PPOX gene result in VP. In the future, advances in microarray technology may make routine DNA testing for multiple mutations possible. Currently, genetic testing is useful in 2 situations, as follows:

  • If a genetic defect is known to be present in an individual, family members can be tested for the defect.
  • Certain ethnic groups have a high incidence of a particular mutation (founder effect). For example, many South African families demonstrate a specific mutation for VP, and in the Swiss most VP patients show a single PPOX gene mutation. [21] Similarly, a limited number of mutations account for CEP in the United Kingdom. [22]
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Imaging Studies

Imaging studies have no direct value.

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Procedures

Skin biopsy is not routinely indicated for the diagnosis of cutaneous porphyria and may lead to further scarring and poor healing.

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Histologic Findings

Porphyria cutanea tarda

Skin lesions examined under light microscopy reveal subepidermal bullae with dermal papillae at the bases, elastosis and periodic acid-Schiff (PAS)-positive vessels in the dermis, and acid mucopolysaccharides at the dermal-epidermal junction. Immunofluorescence reveals accumulation of immunoglobulin G (IgG) and immunoglobulin M (IgM) and complement around dermal vessels and at the dermal-epidermal junction.[23]

Liver tissue reveals siderosis, fatty changes, necrosis, chronic inflammatory changes, and granuloma formation. Red autofluorescence and needlelike inclusion bodies are also observed. Cirrhosis and neoplastic changes are not uncommon.

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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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