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Erythropoietic Protoporphyria: Differential Diagnoses & Workup

Author: Maureen B Poh-Fitzpatrick, MD, Professor Emerita of Dermatology and Special Lecturer, Columbia University; Professor of Medicine (Dermatology), University of Tennessee
Contributor Information and Disclosures

Updated: Feb 23, 2009

Differential Diagnoses

Drug-Induced Photosensitivity
Lupus Erythematosus, Drug-Induced
Erythropoietic Porphyria
Lupus Erythematosus, Subacute Cutaneous
Hydroa Vacciniforme
Polymorphous Light Eruption
Lupus Erythematosus, Acute
Porphyria Cutanea Tarda
Lupus Erythematosus, Bullous
Urticaria, Solar
Lupus Erythematosus, Discoid
Variegate Porphyria

Other Problems to Be Considered

Other porphyrias (see also Erythropoietic Porphyria, Porphyria Cutanea Tarda, Pseudoporphyria, and Variegate Porphyria)
Prurigo aestivalis

Workup

Laboratory Studies

  • Protoporphyrin concentration is elevated in red blood cells, plasma, bile, and feces. The diagnosis is usually made by finding the abnormal levels in erythrocytes and plasma. Urinary porphyrin levels are normal in patients without liver dysfunction. Abnormal coproporphyrinuria develops when liver function is deteriorating.23,24
    • Erythrocyte and plasma protoporphyrin levels are increased several-fold over the reference range. Fecal protoporphyrin excretion may be increased, but, in many patients, it remains within the reference range.
    • In impending liver failure, the dynamic equilibrium between rates of protoporphyrin production and excretion is altered, producing progressively rising erythrocyte and plasma porphyrin levels and progressively diminishing fecal porphyrin excretion.23,25
  • Obtain a complete blood cell count and serum liver function panel at diagnosis. Monitor serum indices of liver function at 6- to 12-month intervals if baseline values are normal. If liver function is abnormal, complicating factors (eg, gallstones, viral hepatitis, alcohol or drug abuse, other toxic, infectious, immunologic, or metabolic storage disorders) should be excluded by appropriate testing.
  • Perform a hematological assessment of anemia. Individuals with protoporphyria often have mildly lowered hemoglobin and hematocrit levels, which do not cause symptoms and do not require treatment.3,26 The mean corpuscular volume may be below the normal limit.

Imaging Studies

  • If cholelithiasis is suspected, abdominal ultrasonography or other imaging procedures are indicated.

Other Tests

  • Impending liver failure may be signaled by progressively rising levels of urinary coproporphyrin.24  Urinary porphyrin levels are within normal limits in persons with uncomplicated erythropoietic protoporphyria. Protoporphyrin, being lipophilic, is not excreted by renal mechanisms and does not normally appear in urine. Coproporphyrin, which accumulates as a result of liver disease, has intermediate water solubility, and levels become abnormally elevated in the urine of patients developing protoporphyrin-induced hepatotoxicity.23
  • Measurement of ferrochelatase enzyme activity remains a research procedure. Mutation analysis of the ferrochelatase gene (ie, DNA testing) is performed at several porphyria research units in various countries and is now commercially available in the United States. See the American Porphyria Foundation for further information.

Procedures

  • In the event of liver dysfunction, liver biopsy may be indicated.17
  • Liver transplantation may be life saving, but it does not cure protoporphyria because the source of most of the excess protoporphyrin is the bone marrow. Continued overproduction of protoporphyrin eventually leads to protoporphyrin deposition in the engrafted liver, which may again become dysfunctional.20 While bone marrow transplantation is potentially curative, its risks have warranted its application in only a few cases to date.11,19,27 Research in animal models has shown promising developments in gene therapy strategies that may eventually be transferrable to humans.

Histologic Findings

Light microscopy examination of the acute skin reaction shows perivascular and interstitial neutrophilic dermal infiltrates. Ultrastructural findings in the acute reaction include damage of endothelial cells with extravasation of intravascular contents and degranulated mast cells.28

Biopsy specimens of chronically damaged skin show deposition of hyaline masses in the upper dermis and markedly thickened walls of upper dermal capillaries.29 Ultrastructural findings in chronically damaged skin include replicated basal laminae around dermal vessels, degranulated mast cells, and amorphous dermal deposits.29 Direct immunofluorescence studies show deposition of immunoglobulins and complement in and around upper dermal vessel walls and, to a lesser extent, at the dermoepidermal junction.29

Liver biopsy typically reveals brown pigment in hepatocytes, Kupffer cells, portal macrophages, and small biliary structures.15,20 Many of these protoporphyrin deposits are crystalline when examined under electron microscopy and birefringent when examined under polarization microscopy.15,20 Cirrhotic changes are seen in advanced disease, including fibrous expansion of portal areas and regenerative nodules.15,20

More on Erythropoietic Protoporphyria

Overview: Erythropoietic Protoporphyria
Differential Diagnoses & Workup: Erythropoietic Protoporphyria
Treatment & Medication: Erythropoietic Protoporphyria
Follow-up: Erythropoietic Protoporphyria
References
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References

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Further Reading

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Keywords

erythropoietic protoporphyria, erythrohepatic protoporphyria, congenital erythropoietic protoporphyria, protoporphyria, porphyria, light sensitivity, photoprotection, end-stage liver disease, endstage liver disease, ESLD, ferrochelatase, FECH

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Contributor Information and Disclosures

Author

Maureen B Poh-Fitzpatrick, MD, Professor Emerita of Dermatology and Special Lecturer, Columbia University; Professor of Medicine (Dermatology), University of Tennessee
Maureen B Poh-Fitzpatrick, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and New York Academy of Medicine
Disclosure: Nothing to disclose.

Medical Editor

Günter Burg, MD, Professor and Chairman Emeritus, Department of Dermatology, University of Zürich School of Medicine; Delegate of The Foundation for Modern Teaching and Learning in Medicine Faculty of Medicine, University of Zürich, Switzerland
Günter Burg, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, International Society for Dermatologic Surgery, North American Clinical Dermatologic Society, and Pacific Dermatologic Association
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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