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Minder A, Kluijver LG, Barman‐Aksözen J, Minder EI, Langendonk JG. Erythropoietic protoporphyrias: Pathogenesis, diagnosis and management. Liver Int 2025; 45:e16027. [PMID: 39011756 PMCID: PMC11669082 DOI: 10.1111/liv.16027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 06/22/2024] [Accepted: 06/24/2024] [Indexed: 07/17/2024]
Abstract
The erythropoietic protoporphyrias consist of three ultra-rare genetic disorders of the erythroid heme biosynthesis, including erythropoietic protoporphyria (EPP1), X-linked protoporphyria (XLEPP) and CLPX-protoporphyria (EPP2), which all lead to the accumulation of protoporphyrin IX (PPIX) in erythrocytes. Affected patients usually present from early childhood with episodes of severe phototoxic pain in the skin exposed to visible light. The quantification of PPIX in erythrocytes with a metal-free PPIX ≥3 times the upper limit of normal confirms the diagnosis. Protoporphyria-related complications include liver failure, gallstones, mild anaemia and vitamin D deficiency with reduced bone mineral density. The management is focused on preventing phototoxic reactions and treating the complications. Vitamin D should be supplemented, and DEXA scans in adults should be considered. In EPP1, even in cases of biochemically determined iron deficiency, supplementation of iron may stimulate PPIX production, resulting in an increase in photosensitivity and the risk of cholestatic liver disease. However, for patients with XLEPP, iron supplementation can reduce PPIX levels, phototoxicity and liver damage. Because of its rarity, there is little data on the management of EPP-related liver disease. As a first measure, any hepatotoxins should be eliminated. Depending on the severity of the liver disease, phlebotomies, exchange transfusions and ultimately liver transplantation with subsequent haematopoietic stem cell transplantation (HSCT) are therapeutic options, whereby multidisciplinary management including porphyria experts is mandatory. Afamelanotide, an alpha-melanocyte-stimulating hormone analogue, is currently the only approved specific treatment that increases pain-free sunlight exposure and quality of life.
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Affiliation(s)
- Anna‐Elisabeth Minder
- Division of Endocrinology, Diabetology, and PorphyriaStadtspital Zürich TriemliZurichSwitzerland
- Swiss Reference Centre for PorphyriasStadtspital Zürich TriemliZurichSwitzerland
| | - Louisa G. Kluijver
- Department of Internal Medicine, Porphyria Center Rotterdam, Center for Lysosomal and Metabolic Disease, Erasmus MCUniversity Medical CenterRotterdamThe Netherlands
| | - Jasmin Barman‐Aksözen
- Swiss Reference Centre for PorphyriasStadtspital Zürich TriemliZurichSwitzerland
- Institute of Laboratory MedicineStadtspital Zürich TriemliZurichSwitzerland
- University of ZurichZurichSwitzerland
| | - Elisabeth I. Minder
- Division of Endocrinology, Diabetology, and PorphyriaStadtspital Zürich TriemliZurichSwitzerland
- Swiss Reference Centre for PorphyriasStadtspital Zürich TriemliZurichSwitzerland
- University of ZurichZurichSwitzerland
| | - Janneke G. Langendonk
- Department of Internal Medicine, Porphyria Center Rotterdam, Center for Lysosomal and Metabolic Disease, Erasmus MCUniversity Medical CenterRotterdamThe Netherlands
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2
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Zeng T, Chen SR, Liu HQ, Chong YT, Li XH. Successful treatment of severe hepatic impairment in erythropoietic protoporphyria: A case report and review of literature. World J Hepatol 2024; 16:966-972. [PMID: 38948434 PMCID: PMC11212650 DOI: 10.4254/wjh.v16.i6.966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 05/10/2024] [Accepted: 05/14/2024] [Indexed: 06/20/2024] Open
Abstract
BACKGROUND Erythropoietic protoporphyria (EPP) is a rare genetic disorder stemming from ferrochelatase gene mutations, which leads to abnormal accumulation of protoporphyrin IX primarily in erythrocytes, skin, bone marrow and liver. Although porphyria-related severe liver damage is rare, its consequences can be severe with limited treatment options. CASE SUMMARY This case study highlights a successful intervention for a 35-year-old male with EPP-related liver impairment, employing a combination of red blood cell (RBC) exchange and therapeutic plasma exchange (TPE). The patient experienced significant symptom relief and a decrease in bilirubin levels following multiple PE sessions and an RBC exchange. CONCLUSION The findings suggest that this combined approach holds promise for managing severe hepatic impairment in EPP.
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Affiliation(s)
- Tao Zeng
- Department of Infectious Diseases, Key Laboratory of Liver Disease of Guangdong Province, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Shu-Ru Chen
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Hao-Qiang Liu
- Department of Blood Transfusion, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Yu-Tian Chong
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Xin-Hua Li
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China.
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3
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Dickey AK, Naik H, Keel SB, Levy C, Beaven SW, Elmariah SB, Erwin AL, Goddu RJ, Hedstrom K, Leaf RK, Kazamel M, Mazepa M, Philpotts LL, Quigley J, Raef H, Rudnick SR, Saberi B, Thapar M, Ungar J, Wang B, Balwani M, Porphyrias Consortium of the Rare Diseases Clinical Research Network. Evidence-based consensus guidelines for the diagnosis and management of erythropoietic protoporphyria and X-linked protoporphyria. J Am Acad Dermatol 2023; 89:1227-1237. [PMID: 36041558 PMCID: PMC9968824 DOI: 10.1016/j.jaad.2022.08.036] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 07/07/2022] [Accepted: 08/15/2022] [Indexed: 11/16/2022]
Abstract
Erythropoietic protoporphyria and X-linked protoporphyria are rare genetic photodermatoses. Limited expertise with these disorders among physicians leads to diagnostic delays. Here, we present evidence-based consensus guidelines for the diagnosis, monitoring, and management of erythropoietic protoporphyria and X-linked protoporphyria. A systematic literature review was conducted, and reviewed among subcommittees of experts, divided by topic. Consensus on guidelines was reached within each subcommittee and then among all members of the committee. The appropriate biochemical and genetic testing to establish the diagnosis is reviewed in addition to the interpretation of results. Prevention of symptoms, management of acute phototoxicity, and pharmacologic and nonpharmacologic treatment options are discussed. The importance of ongoing monitoring for liver disease, iron deficiency, and vitamin D deficiency is discussed with management guidance. Finally, management of pregnancy and surgery and the safety of other therapies are summarized. We emphasize that these are multisystemic disorders that require longitudinal monitoring. These guidelines provide a structure for evidence-based diagnosis and management for practicing physicians. Early diagnosis and management of these disorders are essential, particularly given the availability of new and emerging therapies.
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Affiliation(s)
- Amy K Dickey
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
| | - Hetanshi Naik
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Siobán B Keel
- Division of Hematology, University of Washington School of Medicine, Seattle, Washington
| | - Cynthia Levy
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida
| | - Simon W Beaven
- Vatche & Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, California
| | - Sarina B Elmariah
- Harvard Medical School, Boston, Massachusetts; Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts
| | - Angelika L Erwin
- Center for Personalized Genetic Healthcare, Cleveland Clinic, Cleveland, Ohio
| | - Robert J Goddu
- Division of Continuing Education, University of Colorado Boulder, Boulder, Colorado
| | - Karli Hedstrom
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Rebecca K Leaf
- Harvard Medical School, Boston, Massachusetts; Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Mohamed Kazamel
- Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Marshall Mazepa
- Division of Hematology and Oncology, University of Minnesota Medical Center, Minneapolis, Minnesota
| | | | - John Quigley
- Division of Hematology/Oncology, Department of Medicine, University of Illinois Chicago, Chicago, Illinois
| | - Haya Raef
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts
| | - Sean R Rudnick
- Department of Internal Medicine, Section on Gastroenterology and Hepatology, Atrium Health Wake Forest Baptist, Winston-Salem, North Carolina
| | - Behnam Saberi
- Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Manish Thapar
- Division of Gastroenterology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | - Jonathan Ungar
- Department of Dermatology, Mount Sinai Hospital, New York, New York
| | - Bruce Wang
- Department of Medicine, University of California San Francisco Medical Center, San Francisco, California
| | - Manisha Balwani
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
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Huang H, Cai L, Li X, Chen S. Diagnosis and treatment of icteric hepatitis caused by erythropoietic protoporphyria: A case report. LIVER RESEARCH (BEIJING, CHINA) 2022; 6:116-120. [PMID: 39958623 PMCID: PMC11791850 DOI: 10.1016/j.livres.2022.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 03/22/2022] [Accepted: 05/16/2022] [Indexed: 11/27/2022]
Abstract
Erythropoietic protoporphyria (EPP) is a rare inherited disease caused by partial deficiency activity of the enzyme ferrochelatase (FECH), resulting in excessive accumulation of protoporphyrin IX in erythrocyte and tissues. Here, we report a patient with photosensitive dermatitis and acute icteric hepatitis caused by EPP, whose clinical and biochemical results successfully improved following 2-month treatment with glucose load, ursodeoxycholic acid capsules, and cholestyramine powder. This case provides a reference for a combination therapy strategy for patients with liver and skin injury caused by EPP.
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Affiliation(s)
- Hanqing Huang
- Department of Infectious Diseases and Key Laboratory of Liver Disease of Guangdong Province, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Gastroenterology, People's Hospital of Longhua District of Shenzhen, Shenzhen, Guangdong, China
| | - Leiqin Cai
- Guang Dong Clinical Research Center for Metabolic Diseases, Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xinhua Li
- Department of Infectious Diseases and Key Laboratory of Liver Disease of Guangdong Province, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Shuru Chen
- Department of Infectious Diseases and Key Laboratory of Liver Disease of Guangdong Province, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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Di Pierro E, Granata F, De Canio M, Rossi M, Ricci A, Marcacci M, De Luca G, Sarno L, Barbieri L, Ventura P, Graziadei G. Recognized and Emerging Features of Erythropoietic and X-Linked Protoporphyria. Diagnostics (Basel) 2022; 12:diagnostics12010151. [PMID: 35054318 PMCID: PMC8775248 DOI: 10.3390/diagnostics12010151] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/31/2021] [Accepted: 01/06/2022] [Indexed: 02/06/2023] Open
Abstract
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inherited disorders resulting from defects in two different enzymes of the heme biosynthetic pathway, i.e., ferrochelatase (FECH) and delta-aminolevulinic acid synthase-2 (ALAS2), respectively. The ubiquitous FECH catalyzes the insertion of iron into the protoporphyrin ring to generate the final product, heme. After hemoglobinization, FECH can utilize other metals like zinc to bind the remainder of the protoporphyrin molecules, leading to the formation of zinc protoporphyrin. Therefore, FECH deficiency in EPP limits the formation of both heme and zinc protoporphyrin molecules. The erythroid-specific ALAS2 catalyses the synthesis of delta-aminolevulinic acid (ALA), from the union of glycine and succinyl-coenzyme A, in the first step of the pathway in the erythron. In XLP, ALAS2 activity increases, resulting in the amplified formation of ALA, and iron becomes the rate-limiting factor for heme synthesis in the erythroid tissue. Both EPP and XLP lead to the systemic accumulation of protoporphyrin IX (PPIX) in blood, erythrocytes, and tissues causing the major symptom of cutaneous photosensitivity and several other less recognized signs that need to be considered. Although significant advances have been made in our understanding of EPP and XLP in recent years, a complete understanding of the factors governing the variability in clinical expression and the severity (progression) of the disease remains elusive. The present review provides an overview of both well-established facts and the latest findings regarding these rare diseases.
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Affiliation(s)
- Elena Di Pierro
- Dipartimento di Medicina Interna, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (F.G.); (G.D.L.); (G.G.)
- Correspondence: or ; Tel.: +39-0255036155
| | - Francesca Granata
- Dipartimento di Medicina Interna, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (F.G.); (G.D.L.); (G.G.)
| | - Michele De Canio
- Porphyria and Rare Diseases Centre, San Gallicano Dermatological Institute IRCCS, 00144 Rome, Italy; (M.D.C.); (L.B.)
| | - Mariateresa Rossi
- Department of Dermatology, ASST Spedali Civili di Brescia, University of Brescia, 25123 Brescia, Italy; (M.R.); (L.S.)
| | - Andrea Ricci
- Internal Medicine Unit, Department of Medical and Surgical Science for Children and Adults, University of Modena e Reggio Emilia, 41124 Modena, Italy; (A.R.); (M.M.); (P.V.)
| | - Matteo Marcacci
- Internal Medicine Unit, Department of Medical and Surgical Science for Children and Adults, University of Modena e Reggio Emilia, 41124 Modena, Italy; (A.R.); (M.M.); (P.V.)
| | - Giacomo De Luca
- Dipartimento di Medicina Interna, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (F.G.); (G.D.L.); (G.G.)
| | - Luisa Sarno
- Department of Dermatology, ASST Spedali Civili di Brescia, University of Brescia, 25123 Brescia, Italy; (M.R.); (L.S.)
| | - Luca Barbieri
- Porphyria and Rare Diseases Centre, San Gallicano Dermatological Institute IRCCS, 00144 Rome, Italy; (M.D.C.); (L.B.)
| | - Paolo Ventura
- Internal Medicine Unit, Department of Medical and Surgical Science for Children and Adults, University of Modena e Reggio Emilia, 41124 Modena, Italy; (A.R.); (M.M.); (P.V.)
| | - Giovanna Graziadei
- Dipartimento di Medicina Interna, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (F.G.); (G.D.L.); (G.G.)
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6
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Zhao C, Guan JX, Hui DY, Zhang NN, Lu LR, Tang LY, Shao CK, Chen JN. Liver involvement in patients with erythropoietic protoporphyria: retrospective analysis of clinicopathological features of 5 cases. Ann Diagn Pathol 2021; 56:151859. [PMID: 34844099 DOI: 10.1016/j.anndiagpath.2021.151859] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 11/11/2021] [Indexed: 01/24/2023]
Abstract
Erythropoietic protoporphyria (EPP) is a rare inherited disease whose morbidity is about 1:75,000 to 1:200,000. It is caused by the deficiency of porphyrin ferrochelatase (FECH). Liver involvement in EPP is even rarer. The diagnosis of EPP with liver involvement mainly relies on clinical manifestations, laboratory examinations, histopathological examinations and genetic testing, which is still a huge challenge for both clinicians and pathologists. Here, 5 cases of EPP with liver injury were collected, and the clinicopathological features of these patients were analyzed. The clinical manifestations and laboratory examinations varied from person to person, whereas the liver biopsies showed that there were dark brown deposits within the hepatocytes, Kupffer cells, bile canaliculi and the lumen of bile ducts, which was a constant finding by histopathological examination. Gene tests were conducted in two of the five cases, and the results confirmed the diagnosis. Fully understanding of the diseases can help us reduce the rate of missed diagnosis and provide proper treatment as early as possible.
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Affiliation(s)
- Chang Zhao
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China
| | - Jie-Xia Guan
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China
| | - Da-Yang Hui
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China
| | - Na-Na Zhang
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China
| | - Li-Rong Lu
- Department of Special Inspection, Guangzhou KingMed Center for Clinical Laboratory Co., Ltd., Guangzhou 510000, China
| | - Lu-Ying Tang
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China
| | - Chun-Kui Shao
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China.
| | - Jian-Ning Chen
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China.
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Hashmi SK, Harstead E, Sachdev M, Black DD, Clark I, Ortanca I, Triplett BM, Talleur AC. Hematopoietic cell transplant for reversal of liver fibrosis in a pediatric patient with erythropoietic protoporphyria. Pediatr Transplant 2021; 25:e13966. [PMID: 33405342 DOI: 10.1111/petr.13966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 12/16/2020] [Indexed: 01/19/2023]
Abstract
BACKGROUND EPP is a rare disorder of heme biosynthesis in which patients present with disabling photosensitivity. A subset of patients develop severe liver disease with progressive liver failure necessitating an OLT. A HCT can potentially cure EPP by replacing the native bone marrow, which is the primary site of heme synthesis. However, due to concerns for inherent risks of treatment-related toxicities, the use of HCT has been reserved for patients undergoing an OLT to avoid disease recurrence in the hepatic graft. Data for HCT in EPP are lacking, particularly in the pediatric population. CASE (METHODS/RESULTS) We present the case of a 12-year-old patient with EPP photosensitivity and cirrhosis, whom we successfully treated with pre-emptive allogeneic HCT, significantly improving the patient's quality of life. We used a matched-unrelated donor bone marrow-derived graft. Our patient achieved full donor peripheral blood chimerism and has not had any evidence of GVHD. In addition to resolution of photosensitivity, our patient had reversal of liver fibrosis which we feel was largely due to intervention at an early stage of compensated cirrhosis. CONCLUSION Our case highlights the successful application of a known RIC regimen to this rare disorder that was well tolerated with sustained donor engraftment. It also emphasizes the importance of timing for HCT in patients with EPP and liver fibrosis. HCT should be considered early in pediatric patients with EPP-hepatopathy to prevent progression to liver failure and need for OLT with lifelong immunosuppression.
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Affiliation(s)
- Saman K Hashmi
- Department of Oncology, Hospitalist Medicine, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Elaine Harstead
- Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Mansi Sachdev
- Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Dennis D Black
- Division of Gastroenterology, Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, TN, USA
| | - Ian Clark
- Department of Pathology and Laboratory Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA
| | - Ibrahim Ortanca
- Department of Pathology and Laboratory Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA
| | - Brandon M Triplett
- Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Aimee C Talleur
- Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA
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Wang Y, Karamchandani DM. Erythropoietic protoporphyria- associated hepatopathy: expanding the spectra of brown pigments encountered in hepatic specimens. Histopathology 2021; 79:122-124. [PMID: 33475175 DOI: 10.1111/his.14340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/17/2021] [Accepted: 01/19/2021] [Indexed: 12/01/2022]
Affiliation(s)
- Ying Wang
- Department of Pathology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Dipti M Karamchandani
- Department of Pathology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA
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Kunz BC, Center SA, Randolph JF, Walker JD, Choi AE, Anderson KE. Congenital erythropoietic protoporphyria and protoporphyric hepatopathy in a dog. J Am Vet Med Assoc 2021; 257:1148-1156. [PMID: 33226294 DOI: 10.2460/javma.2020.257.11.1148] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
CASE DESCRIPTION A 6-month-old sexually intact male Clumber Spaniel was evaluated because of small stature, recurrent dermatitis of the head, and progressive pigmentary hepatopathy. CLINICAL FINDINGS Clinicopathologic findings included nonanemic hypochromic microcytosis, hypocholesterolemia, persistently high serum liver enzyme activities, and anicteric hyperbilirubinemia. Histologic examination of liver biopsy specimens collected when the dog was 6 months and 2 years of age revealed expansion and bridging of portal tracts, occasional centrilobular parenchymal collapse, scattered lymphoplasmacytic infiltrates, and dark red to brown pigment within large aggregates of macrophages, engorged bile canaliculi, and hepatocytes. The pigment failed to stain for the presence of iron, copper, bile, and glycoprotein and, when examined with polarized microscopy, emitted a yellow to green birefringence with occasional Maltese cross configurations. Further analyses confirmed marked porphyrin accumulation in blood, urine, feces, and liver tissue; protoporphyrin accumulation in RBCs and liver tissue; and a signature porphyrin profile and fluorescence peak consistent with erythropoietic protoporphyria. Advanced protoporphyric hepatopathy was diagnosed. The chronic dermatopathy was presumed to reflect protoporphyric photosensitivity. TREATMENT AND OUTCOME Management was focused on avoiding conditions known to induce heme synthesis and catabolism, administrating ursodeoxycholic acid and antioxidants S-adenosylmethionine and vitamin E, and avoiding sunlight exposure. At follow-up at 4 years of age, the dog was stable without evidence of jaundice but with probable persistent erythropoietic protoporphyria-related solar dermatopathy. CLINICAL RELEVANCE Clinical and histologic features of congenital erythropoietic protoporphyria and resultant protoporphyric hepatopathy, the diagnosis, and the successful management of a dog with these conditions over 4 years were described. Veterinarians should consider porphyric syndromes when unusual pigmentary hepatopathies are encountered.
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