1
|
Lipiński P, Lipniacka A, Klaudel-Dreszler M, Ziółkowska L, Kostrzewa G, Odnoczko E, Wasilewski R, Płoski R, Tylki-Szymańska A. Case Report: Cholestatic liver disease in the course of erythropoietic protoporphyria associated with renal hypodysplasia and atrial septal defect. Front Pediatr 2025; 13:1504181. [PMID: 40007872 PMCID: PMC11851339 DOI: 10.3389/fped.2025.1504181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 01/17/2025] [Indexed: 02/27/2025] Open
Abstract
Erythropoietic protoporphyria (EPP) is an autosomal recessive disorder of the heme biosynthesis pathway caused by pathogenic variants in FECH gene resulting in a decreased activity of ferrochelatase. Liver involvement is observed in 5%-20% of patients harbouring loss-of-function FECH variants and its manifestations are heterogeneous, ranging from mildly elevated liver transaminases, cholelithiasis to severe acute cholestatic hepatitis/liver failure. This paper presents the case of a Polish infant with EPP associated with two novel missense FECH variants accompanied by other congenital anomalies, namely atrial septal defect and renal hypodysplasia. Progressive cholestatic liver disease (with subsequent congestive heart failure) was observed in the course of EPP. Erytropoietic protoporphyria should be considered in patients with hepatosplenomegaly and cholestasis accompanied by skin damage. The natural history of liver disease in the course of EPP could be determined by other factors, like the co-existence of congenital anomalies.
Collapse
Affiliation(s)
- Patryk Lipiński
- Institute of Clinical Sciences, Maria-Skłodowska-Curie Medical Academy, Warsaw, Poland
| | - Agnieszka Lipniacka
- Department of Haemostasis and Metabolic Diseases, Institute of Haematology and Transfusion Medicine, Warsaw, Poland
| | - Maja Klaudel-Dreszler
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children’s Memorial Health Institute, Warsaw, Poland
| | - Lidia Ziółkowska
- Department of Cardiology, The Children’s Memorial Health Institute, Warsaw, Poland
| | - Grażyna Kostrzewa
- Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland
| | - Edyta Odnoczko
- Department of Haemostasis and Metabolic Diseases, Institute of Haematology and Transfusion Medicine, Warsaw, Poland
| | - Robert Wasilewski
- Department of Disorders of Hemostasis and Internal Medicine, Institute of Haematology and Transfusion Medicine, Warsaw, Poland
| | - Rafał Płoski
- Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland
| | - Anna Tylki-Szymańska
- Department of Pediatrics, Nutrition and Metabolic Diseases, The Children’s Memorial Health Institute, Warsaw, Poland
| |
Collapse
|
2
|
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.
Collapse
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.
| |
Collapse
|
3
|
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.
Collapse
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.
| |
Collapse
|
4
|
Rodrigues-Fernandes CI, de Cáceres CBL, Sant'Ana MSP, Soares CD, de Carvalho MGF, van Heerden WFP, Robinson L, Radhakrishnan R, Hunter KD, Gomez RS, de Almeida OP, Vargas PA, Günhan Ö, Tomasi RA, Alawi F, Pontes HAR, Fonseca FP. Oral lesions containing amyloid-like material. Oral Surg Oral Med Oral Pathol Oral Radiol 2021; 132:190-201. [PMID: 33737015 DOI: 10.1016/j.oooo.2021.01.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Accepted: 01/13/2021] [Indexed: 02/07/2023]
Abstract
During oral pathology daily practice, true amyloid may be identified in oral amyloidosis and several odontogenic tumors. However, histologic examination often reveals other oral and perioral diseases with similar eosinophilic, acellular, amorphous substances. These include extensive areas of collagenous sclerosis, fibrin deposition, elastic fiber degeneration, and dentinoid material, which may resemble amyloid under light microscopic examination. These materials are often termed "amyloid-like" due to their close histologic resemblance to true amyloid. The rarity of most of these conditions and their strong histologic similarity may hamper an accurate diagnosis. Definitive diagnosis of these lesions may require clinical correlation; laboratory evaluation; histochemical or immunohistochemical reactions; and, in some cases, genetic investigation. In this review, we describe the main clinicopathologic features of this group of diseases that may manifest in the oral and/or perioral regions and that have in common the presence of amyloid-like material deposition.
Collapse
Affiliation(s)
| | | | - Maria Sissa Pereira Sant'Ana
- Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Ciro Dantas Soares
- Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas
| | | | - Willie F P van Heerden
- Department of Oral Pathology and Oral Biology, School of Dentistry, University of Pretoria, Pretoria, South Africa
| | - Liam Robinson
- Department of Oral Pathology and Oral Biology, School of Dentistry, University of Pretoria, Pretoria, South Africa
| | - Raghu Radhakrishnan
- Department of Oral Pathology, Manipal College of Dental Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Keith D Hunter
- Department of Oral Pathology and Oral Biology, School of Dentistry, University of Pretoria, Pretoria, South Africa; Academic Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, The University of Sheffield, Sheffield, UK
| | - Ricardo Santiago Gomez
- Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | - Pablo Agustin Vargas
- Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas; Department of Oral Pathology and Oral Biology, School of Dentistry, University of Pretoria, Pretoria, South Africa
| | - Ömer Günhan
- Department of Pathology, TOBB ETU Medical School, Ankara, Turkey
| | - Ramiro Alejandro Tomasi
- Department of Pathology, School of Dentistry, National University of Córdoba, Córdoba, Argentina
| | - Faizan Alawi
- Division of Dermatopathology, Department of Dermatology, University of Pennsylvania, Philadelphia, PA
| | | | - Felipe Paiva Fonseca
- Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Department of Oral Pathology and Oral Biology, School of Dentistry, University of Pretoria, Pretoria, South Africa.
| |
Collapse
|
5
|
Systemic lupus erythematosus and hydroxychloroquine-related acute intermittent porphyria. Rheumatol Int 2019; 40:777-783. [PMID: 31865445 DOI: 10.1007/s00296-019-04500-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 12/11/2019] [Indexed: 12/16/2022]
Abstract
Porphyrias, particularly acute intermittent porphyria (AIP), are rare disorders which could be associated with systemic lupus erythematosus (SLE). Although the association with AIP has been known since 1952, only 11 cases have been published to date. It is widely known that precipitating causes such as infections, hormonal changes, sunlight exposure, stress and drugs could provoke an AIP crisis. Hydroxychloroquine (HCQ) is usually used in lupus patients, but rarely appears to trigger AIP crises even in SLE patients. The case of a 51-year-old man in whom AIP onset was probably due to hydroxychloroquine use during SLE management is presented. SLE onset was accompanied by fever, pleural, lung and joint involvement with a characteristic SLE autoantibody panel. Although prednisone was given, the joint symptoms did not subside. HCQ was then started; however, some days later the patient suffered anxiety, vomiting and severe abdominal pain refractory to pain-relief drugs and liver function had worsened. No cutaneous lesions were observed. The patient suffered similar episodes accompanied by paralytic ileus and dark-coloured urine, the sediment of which showed no abnormalities. In addition, no myoglobinuria was found. This finding raised the suspicion of AIP and urine tests revealed elevated values of delta-aminolevulinic acid and porphobilinogen. Hydroxychloroquine was preventively suspended and the patient improved notably within a few days. In the following months, the patient suffered no relapse and the prednisone dose could be lowered. Finally, a review of the literature on this topic highlighted the exceptional nature of an API/ SLE association particularly in men. Interestingly, porphyria may present first followed by SLE, or vice versa. The latency period between drug administration and disease onset varies from days to 2 years. Both chloroquine and HCQ may induce PAI in SLE patients. Clinicians should be alerted to a possible association with AIP when a patient with SLE recently put on HCQ presents acute onset of abdominal and/or neurological symptoms and dark urine. Appropriate tests and prompt HCQ cessation are mandatory.
Collapse
|
6
|
Wensink D, Wagenmakers MAEM, Wilson JHP, Langendonk JG. Letter to the editor: Diagnosis of erythropoietic protoporphyria with severe liver injury - a case report. World J Gastroenterol 2019; 25:4292-4293. [PMID: 31435180 PMCID: PMC6700695 DOI: 10.3748/wjg.v25.i30.4292] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 07/17/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Erythropoietic protoporphyria (EPP) is an extremely rare disease which is often unrecognized as diagnosis. In the recent article Lui et al describe a patient with a new diagnosis of EPP with severe liver injury. Approximately 5%-20% of patients with EPP develop liver manifestations. The most severe complication of EPP is an hepatic crisis, which is a medical emergency requiring urgent treatment. Intensive treatment should consist of (exchange) transfusions and preferably in a center that performs liver transplantations.
Collapse
Affiliation(s)
- Debby Wensink
- Porphyria Center Rotterdam, Center for lysosomal and metabolic disease, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam 3015 GD, Netherlands
| | - Margreet AEM Wagenmakers
- Porphyria Center Rotterdam, Center for lysosomal and metabolic disease, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam 3015 GD, Netherlands
| | - JH Paul Wilson
- Porphyria Center Rotterdam, Center for lysosomal and metabolic disease, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam 3015 GD, Netherlands
| | - Janneke G Langendonk
- Porphyria Center Rotterdam, Center for lysosomal and metabolic disease, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam 3015 GD, Netherlands
| |
Collapse
|