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Tian QJ, Zhang LJ, Zhang Q, Liu FC, Xie M, Cai JZ, Rao W. Protein-losing enteropathy and multiple vasculature dysplasia in LZTR1-related Noonan syndrome: A case report and review of literature. World J Gastroenterol 2025; 31. [DOI: 10.3748/wjg.v31.i17.105347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Revised: 03/31/2025] [Accepted: 04/21/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND
Protein-losing enteropathy (PLE) is a rare cause of hypoalbuminemia that can be attributed to intestinal lymphangiectasia. Patients with Noonan syndrome may present with disorder of lymph vessel formation. However, PLE is rarely reported with Noonan syndrome.
CASE SUMMARY
A 15-year-old female was hospitalized multiple times for recurrent edema and diarrhea secondary to hypoalbuminemia. Additional manifestations included a ventricular septal defect at birth, intermuscular hemangioma, slightly wide interocular and intermammary distances, and absence of the distal phalanx of the left little finger since birth. Abdominal computed tomography revealed cavernous transformation of the portal vein, and liver biopsy indicated “porto-sinusoidal vascular disease”. Whole exome and Sanger sequencing revealed a heterozygous mutation (exon9: C.850C>T:P.R284C) in leucine zipper-like transcription regulator 1, suggesting Noonan syndrome type 10. Further examinations revealed thoracic duct dysplasia and intestinal lymphangiectasia causing PLE in this patient. A multidisciplinary team decided to address thoracic duct dysplasia with outlet obstruction. Approximately two years after the microsurgical relief of the thoracic duct outlet obstruction, the patient achieved persistent normal serum albumin level without edema or diarrhea. Furthermore, the relevant literatures on Noonan syndrome and PLE were reviewed.
CONCLUSION
Herein, we reported the first case of PLE associated with Noonan syndrome caused by a rare genetic mutation in leucine zipper-like transcription regulator 1 (c.850C>T:P.R284C) with newly reported manifestations. This case presented the successful treatment of clinical hypoalbuminemia attributed to thoracic duct dysplasia, intestinal lymphangiectasia and PLE.
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Affiliation(s)
- Qiu-Ju Tian
- Division of Hepatology, Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong Province, China
- Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong Province, China
| | - Lu-Jia Zhang
- Department of Urology, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao 266100, Shandong Province, China
| | - Qun Zhang
- Division of Hepatology, Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong Province, China
- Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong Province, China
| | - Feng-Chao Liu
- Division of Hepatology, Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong Province, China
- Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong Province, China
| | - Man Xie
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong Province, China
| | - Jin-Zhen Cai
- Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong Province, China
| | - Wei Rao
- Division of Hepatology, Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong Province, China
- Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong Province, China
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Yorgun Altunbas M, Kogler H, Abolhassani H, Akkus E, Basturk A, Akkelle E, Sayar E, Polat E, Kara A, Can S, Frohne A, Segarra-Roca A, Jimenez-Heredia R, Babayeva R, Sefer AP, Kiykim A, Bilgic Eltan S, Karakoc-Aydiner E, Ozen A, Beser OF, Boztug K, Rezaei N, Baris S. Clinical and Immunological Prognostic Factors With Novel Variants in a Large Cohort of Diacylglycerol Acyltransferase 1 Deficiency. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2025:S2213-2198(25)00277-6. [PMID: 40154740 DOI: 10.1016/j.jaip.2025.03.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 02/14/2025] [Accepted: 03/17/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Biallelic variants in diacylglycerol acyltransferase 1 (DGAT1) genegene have been implicated congenital diarrhea and protein-losing enteropathy. Insights into the immunopathologic features of this ultrarare disorder remain scarce, with only one cohort published to date. OBJECTIVE To delineate the clinical presentations, laboratory and immunologic profiles, and therapeutic responses associated with DGAT1 deficiency and identify prognostic indicators that affect survival rates. METHODS In this multicenter retrospective analysis of a comprehensive cohort of nine patients carrying seven novel variants, each displaying distinct phenotypic features, we recorded clinical, immunologic, and laboratory data of patients and evaluated the impact of various factors on prognosis. RESULTS A total of 67% of patients (n = 6) exhibited symptoms during the first month of life, whereas one demonstrated symptom onset after 6 months. Moreover, 78% of patients (n = 7) presented with diarrhea, all of whom all had vomiting, failure to thrive, hypoalbuminemia, and hypogammaglobulinemia as the advent of protein-losing enteropathy. Patients with reduced CD4+ T-cell frequency (n = 2) exhibited severe infections with unexpected bacteria during the follow-up. Despite immunoglobulin replacement therapy, 45% of patients (n = 4) died of infective complications. A decreased CD4+/CD8+ T-cell ratio was observed in all deceased patients whose colon biopsy samples showed marked inflammation or apoptosis. Early fat-restricted nutrition extended survival, whereas early symptom onset, recurrent severe infections, and a reduced CD4+/CD8+ T-cell ratio were associated with less favorable outcomes. CONCLUSIONS Our findings advocate early fat restriction as a critical therapeutic strategy. Given the heightened risk of severe infections, antibiotic prophylaxis can be recommended in addition to immunoglobulin replacement therapy for DGAT1-deficient patients exhibiting lymphopenia or diminished CD4+ T cells.
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Affiliation(s)
- Melek Yorgun Altunbas
- Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic Center for Primary Immunodeficiency Diseases, Istanbul, Turkey; Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey
| | - Hubert Kogler
- Department of Pediatrics and Adolescent Medicine, St Anna Children's Hospital, Medical University of Vienna, Vienna, Austria
| | - Hassan Abolhassani
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
| | - Erkan Akkus
- Department of Pediatrics Gastroenterology, Hepatology, and Nutrition, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Ahmet Basturk
- Department of Pediatric Gastroenterology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Emre Akkelle
- Department of Pediatric Allergy and Immunology, University of Health Sciences, Sancaktepe Training and Research Hospital, Istanbul, Turkey
| | - Ersin Sayar
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Anadolu Medical Center, Kocaeli, Turkey
| | - Esra Polat
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Sancaktepe Training and Research Hospital, Istanbul, Turkey
| | - Altan Kara
- TUBITAK Marmara Research Center, Gene Engineering and Biotechnology Institute, Gebze, Turkey
| | - Salim Can
- Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic Center for Primary Immunodeficiency Diseases, Istanbul, Turkey; Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey
| | | | | | - Raul Jimenez-Heredia
- St Anna Children's Cancer Research Institute, Vienna, Austria; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Royala Babayeva
- Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic Center for Primary Immunodeficiency Diseases, Istanbul, Turkey; Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey
| | - Asena Pınar Sefer
- Department of Pediatric Allergy and Immunology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
| | - Ayca Kiykim
- Department of Pediatric Allergy and Immunology, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Sevgi Bilgic Eltan
- Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic Center for Primary Immunodeficiency Diseases, Istanbul, Turkey; Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey
| | - Elif Karakoc-Aydiner
- Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic Center for Primary Immunodeficiency Diseases, Istanbul, Turkey; Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey
| | - Ahmet Ozen
- Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic Center for Primary Immunodeficiency Diseases, Istanbul, Turkey; Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey
| | - Omer Faruk Beser
- Department of Pediatrics Gastroenterology, Hepatology, and Nutrition, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Kaan Boztug
- St Anna Children's Cancer Research Institute, Vienna, Austria; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria; Department of Pediatrics, St Anna Children's Hospital, Vienna, Austria
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Primary Immunodeficiency Diseases Network, Universal Scientific Education and Research Network, Tehran, Iran
| | - Safa Baris
- Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic Center for Primary Immunodeficiency Diseases, Istanbul, Turkey; Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.
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Pais-Cunha I, Silva C, Leite de Almeida L, Calejo R, Vasconcelos C, Espinheira C, Pinto Pais I, Trindade E. Primary intestinal lymphangiectasia - A rare cause of growth delay. Pediatr Neonatol 2024; 65:601-602. [PMID: 39127595 DOI: 10.1016/j.pedneo.2024.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 06/25/2024] [Accepted: 07/11/2024] [Indexed: 08/12/2024] Open
Affiliation(s)
| | - Cátia Silva
- Serviço de Pediatria, ULS Alto Minho, Portugal
| | | | - Rita Calejo
- Serviço de Pediatria, ULS Tâmega e Sousa, Portugal
| | | | - Céu Espinheira
- Unidade de Gastroenterologia Pediátrica, Serviço de Pediatria, ULS São João, Portugal
| | - Isabel Pinto Pais
- Unidade de Gastroenterologia Pediátrica, Serviço de Pediatria, ULS São João, Portugal
| | - Eunice Trindade
- Unidade de Gastroenterologia Pediátrica, Serviço de Pediatria, ULS São João, Portugal
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Darmawan D, Raychaudhuri S, Lakshminrusimha S, Dimitriades VR. Hypogammaglobulinemia in neonates: illustrative cases and review of the literature. J Perinatol 2024; 44:929-934. [PMID: 37667006 DOI: 10.1038/s41372-023-01766-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 08/15/2023] [Accepted: 08/23/2023] [Indexed: 09/06/2023]
Abstract
This article presents a review of causes of hypogammaglobulinemia in neonates utilizing illustrative cases to demonstrate commonly seen conditions. Overall, the causes of low immunoglobulin level can be divided into three main categories: decreased maternal transfer or production (due to physiological nadir, transient hypogammaglobulinemia of infancy, medication effects, or immunodeficiency), increased loss of immunoglobulins (from the gastrointestinal (GI) system, lymphatics, kidneys, skin disease, or blood loss) or destruction/suppression (from medication effects). Treatment of hypogammaglobulinemia is generally tailored to the underlying cause and condition of the patient. This can be through supportive care, prophylactic measures, or with immunoglobulin G (IgG) replacement at the recommendation of an immunologist.
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Affiliation(s)
- Daphne Darmawan
- Department of Pediatrics, University of California Davis Health, Sacramento, CA, USA
| | - Sanchita Raychaudhuri
- Department of Pediatrics, University of California Davis Health, Sacramento, CA, USA
| | - Satyan Lakshminrusimha
- Division of Neonatology, Department of Pediatrics, University of California Davis Health, Sacramento, CA, USA
| | - Victoria R Dimitriades
- Division of Pediatric Allergy, Immunology and Rheumatology, Department of Pediatrics, University of California Davis Health, Sacramento, CA, USA.
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Abstract
Diet plays an important role in human health and disease. Of all human diseases, diarrheal illnesses bring diet into sharp focus as it has a direct causal and therapeutic relationship. With the advent and widespread use of next generation sequencing, significant advances have been made in unraveling the etiologies of congenital diarrheas and enteropathies, some of which are eminently treatable with dietary modification. Early institution of appropriate dietary therapy is lifesaving in congenital osmotic diarrheas. Chronic diarrhea in older children and adolescents often have an underlying dietary basis, depending on the etiology. Identification and exclusion of the offending food in the diet results in dramatic improvement in symptoms. It is equally important to be prudent and cautious in the use of exclusion diets in management of chronic diarrhea as it is associated with micronutrient deficiencies, needless escalation of cost and enable maladaptive food intake behaviors. In this review, authors discuss etiology specific dietary management of diarrhea in children with emphasis on congenital diarrheas and enteropathies.
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Affiliation(s)
- Sahana Shankar
- Division of Pediatric Gastroenterology, Department of Pediatrics, Mazumdar Shaw Medical Center, Narayana Health, Bangalore, India.
| | - Emmany Durairaj
- Department of Clinical Nutrition and Dietetics, Mazumdar Shaw Medical Center, Narayana Health, Bangalore, India
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Antoine L, Chotard M, Koch S, Aubin F, Puzenat E. Primary intestinal lymphangiectasia: A case report. J Pediatr Gastroenterol Nutr 2024; 78:1197-1198. [PMID: 38695601 DOI: 10.1002/jpn3.12093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 11/15/2023] [Accepted: 11/17/2023] [Indexed: 06/22/2024]
Affiliation(s)
- Léa Antoine
- Service de Dermatologie, CHU, Inserm 1098, Besançon, France
| | | | - Stéphane Koch
- Service de Gastro-Entérologie, CHU, Besançon, France
| | - François Aubin
- Service de Dermatologie, CHU, Inserm 1098, Besançon, France
| | - Eve Puzenat
- Service de Dermatologie, CHU, Inserm 1098, Besançon, France
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Na JE, Kim JE, Park S, Kim ER, Hong SN, Kim YH, Chang DK. Experience of primary intestinal lymphangiectasia in adults: Twelve case series from a tertiary referral hospital. World J Clin Cases 2024; 12:746-757. [PMID: 38322684 PMCID: PMC10841145 DOI: 10.12998/wjcc.v12.i4.746] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 12/17/2023] [Accepted: 01/08/2024] [Indexed: 01/25/2024] Open
Abstract
BACKGROUND While primary intestinal lymphangiectasia (PIL) is considered a rare condition, there have been several reported cases in adults. Nevertheless, the absence of clear guidance from diagnosis to treatment and prognosis poses challenges for both physicians and patients. AIM To enhance understanding by investigating clinical presentation, diagnosis, treatment, complications, and prognoses in adult PIL cases. METHODS We enrolled adult patients diagnosed with PIL between March 2016 and September 2021. The primary outcome involved examining the diagnosis and treatment process of these patients. The secondary outcomes included identifying complications (infections, thromboembolism) and assessing prognoses (frequency of hospitalization and mortality) during the follow-up period. RESULTS Among the 12 included patients, peripheral edema (100%) and diarrhea (75%) were the main presenting complaints. Laboratory tests showed that all the patients exhibited symptoms of hypoalbuminemia and hypogammaglobulinemia. Radiologically, the predominant findings were edema of the small intestine (67%) and ascites (58%). The typical endoscopic finding with a snowflake appearance was observed in 75% of patients. Among the 12 patients, two responded positively to octreotide and sirolimus, and eight who could undergo maintenance therapy discontinued subsequently. Complications due to PIL led to infection in half of the patients, thromboembolism in three patients, and one death. CONCLUSION PIL can be diagnosed in adults across various age groups, with different severity and treatment responses among patients, leading to diverse complications and prognoses. Consequently, tailored treatments will be necessary. We anticipate that our findings will contribute to the management of PIL, an etiology of protein-losing enteropathy.
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Affiliation(s)
- Ji Eun Na
- Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan 48108, South Korea
| | - Ji Eun Kim
- Department of Medicine, Samsung Medical Center, Seoul 06351, South Korea
| | - Sujin Park
- Department of Pathology, Samsung Medical Center, Seoul 06351, South Korea
| | - Eun Ran Kim
- Department of Medicine, Samsung Medical Center, Seoul 06351, South Korea
| | - Sung Noh Hong
- Department of Medicine, Samsung Medical Center, Seoul 06351, South Korea
| | - Young-Ho Kim
- Department of Medicine, Samsung Medical Center, Seoul 06351, South Korea
| | - Dong Kyung Chang
- Department of Medicine, Samsung Medical Center, Seoul 06351, South Korea
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Hoskins B, Song W, Guerrerio AL. Secondary Intestinal Lymphangiectasia. J Pediatr Gastroenterol Nutr 2024; 78:166. [PMID: 38291682 DOI: 10.1097/mpg.0000000000003936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 08/30/2023] [Indexed: 09/09/2023]
Affiliation(s)
- Brett Hoskins
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD
| | - Weihua Song
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD
| | - Anthony L Guerrerio
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD
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Awal S, Regmi PR, Awal L. Misty mesentery, ascites, and bowel wall thickening in a child: Diagnostic clue for intestinal lymphangiectasia. Radiol Case Rep 2023; 18:4032-4035. [PMID: 37680662 PMCID: PMC10480635 DOI: 10.1016/j.radcr.2023.08.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 08/04/2023] [Indexed: 09/09/2023] Open
Abstract
Primary intestinal lymphangiectasia (PIL) is a rare congenital disorder characterized by lymphatic system obstruction, resulting in the leakage of lymph into the bowel lumen. We present the case of a 6-year-old boy with recurrent diarrhea and weight loss. On examination, bilateral pitting edema in the lower limbs was observed. Laboratory investigations revealed hypoalbuminemia and lymphopenia. Contrast-enhanced CT of the abdomen showed thickening of the jejunum, echogenic fat islands, and enlarged lymph nodes in the mesentery. The diagnosis was confirmed by endoscopic biopsy. The patient was managed with a high-protein diet and replacement of the long-chain triglycerides with medium-chain triglycerides. Gradual improvement in symptoms was observed with regular follow-up. PIL is a protein-losing enteropathy that causes hypoproteinemia, hypolymphopenia, and hypoglobulinemia. PIL usually presents with peripheral edema, weight loss, abdominal pain, and chronic diarrhea. Diagnosis is based on characteristic endoscopic and histopathologic findings. Management involves a multidisciplinary approach, including nutritional modifications, medical therapy, and, in rare cases, surgical resection. PIL remains a challenging diagnosis due to its nonspecific clinical presentation. Clinicians should maintain awareness of this disorder for prompt identification and management.
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Affiliation(s)
- Shila Awal
- Suryabinayak Municipal Hospital, Bhaktapur, Nepal
| | - Pradeep Raj Regmi
- Department of Radiology, Tribhuvan University Teaching Hospital, Kathmandu, Nepal
| | - Lila Awal
- Rangpur Medical College, Rangpur, Bangladesh
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Lin L, Liu K, Liu H, Xin J, Sun Y, Xia S, Shen W, Wu J. Small intestinal mucosal abnormalities using video capsule endoscopy in intestinal lymphangiectasia. Orphanet J Rare Dis 2023; 18:308. [PMID: 37784188 PMCID: PMC10544442 DOI: 10.1186/s13023-023-02914-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 09/07/2023] [Indexed: 10/04/2023] Open
Abstract
BACKGROUND Intestinal lymphangiectasia (IL) is a rare protein-losing enteropathy caused by disorders of the intestinal lymphatics. There are only a few case reports and case series concerning the VCE (video capsule endoscopy) findings of IL. This work aimed to evaluate the VCE characteristics of small intestinal mucosal abnormalities in patients with IL, and to investigate the relationship between clinical and VCE characteristics. METHODS Consecutive patients with IL who underwent VCE were enrolled in this retrospective study. The cases were classified into the white villi group and non-white villi group according to mucosal abnormalities detected by VCE. Clinical and endoscopic characteristics were investigated and analyzed. RESULTS A total of 98 patients with IL with a median onset age of 26.3 ± 19.2 years were included. VCE revealed the following small intestinal lesions: (i) white villi type (57/98, 58.2%), i.e.: white-tipped or granular villi, white nodular villi or plaques; (ii) non-white villi type (41/98, 41.8%), i.e.: diffused low and round villi; (iii) complications (46/98, 46.9%), i.e.: bleeding, ulcers, protruding or vesicular-shaped lesions, stenosis and lymphatic leakage. A total of 58.2% (57) and 41.8% (41) of the cases were classified into the white villi and non-white villi groups respectively. The percentage of chylothorax in the white villi group was significantly lower than that in the non-white villi group (12/57 vs. 19/41, p = 0.008). In VCE, there were no significant differences in the involved segments and total detected rate of complications between the white villi and non-white villi groups (p > 0.05), while the detected rate of lymphatic leakage in the white villi group was significantly higher than that in the non-white villi group (31.6% vs. 12.2%, p = 0.026). CONCLUSIONS Our study evaluated the entire small intestinal mucosal abnormalities of IL by VCE, especially endoscopic complications. IL has specific VCE abnormalities in addition to classical endoscopic findings.
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Affiliation(s)
- Lin Lin
- Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Haidian District, Beijing, China
| | - Kuiliang Liu
- Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Haidian District, Beijing, China
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hong Liu
- Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Haidian District, Beijing, China
| | - Jianfeng Xin
- Department of Lymphatic Surgery, Beijing Shijitan Hospital, Capital Medical University, Haidian District, Beijing, China
- Clinical Center for Lymphatic Disorders, Capital Medical University, Beijing, China
| | - Yuguang Sun
- Department of Lymphatic Surgery, Beijing Shijitan Hospital, Capital Medical University, Haidian District, Beijing, China
- Clinical Center for Lymphatic Disorders, Capital Medical University, Beijing, China
| | - Song Xia
- Department of Lymphatic Surgery, Beijing Shijitan Hospital, Capital Medical University, Haidian District, Beijing, China
- Clinical Center for Lymphatic Disorders, Capital Medical University, Beijing, China
| | - Wenbin Shen
- Department of Lymphatic Surgery, Beijing Shijitan Hospital, Capital Medical University, Haidian District, Beijing, China.
- Clinical Center for Lymphatic Disorders, Capital Medical University, Beijing, China.
| | - Jing Wu
- Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Haidian District, Beijing, China.
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
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Yan J, Xie C, Chen Y. Surgical Treatment of Mesenteric Lymphatic Malformations in Children: An Observational Cohort study. J Pediatr Surg 2023; 58:1762-1769. [PMID: 36931944 DOI: 10.1016/j.jpedsurg.2023.02.041] [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: 07/29/2022] [Revised: 01/17/2023] [Accepted: 02/03/2023] [Indexed: 02/23/2023]
Abstract
BACKGROUND Few studies have analyzed the cyst characteristics and complications of mesenteric lymphatic malformations (ML). This study aimed to compare ML's cyst characteristics and preoperative complications at different locations and suggest a modified ML classification for patients requiring surgery. METHODS In total, 157 ML patients underwent surgery at Beijing Children's Hospital between January 2010 and December 2021. The cyst characteristics and preoperative complications were reviewed. The surgical methods for ML were analyzed according to the modified ML classification (Type I, n = 87, involving the intestinal wall; Type II, n = 45, located in the mesenteric boundaries; Type III, n = 16, involving the root of the mesentery; Type IV, n = 7, multicentric ML; Type V, n = 2, involving the upper rectum). RESULTS Overall, 111 (70.7%) ML were located at the intestinal mesentery and 44 (28.0%) at the mesocolon. Type I and type II ML mainly involved intestinal mesentery (64.9%) and mesocolon (56.8%), respectively (P < 0.001). Microcystic-type ML and ML with chylous fluid were only located in the intestinal mesentery. Intestinal volvulus was only found in patients with ML in the intestinal mesentery (P < 0.001), whereas ML in the mesocolon were more prone to hemorrhage (P = 0.002) and infection (P = 0.005). ML in the jejunal mesentery was an independent risk factor for intestinal volvulus (OR = 3.5, 95% CI 1.5-8.3, P = 0.003). The surgical methods significantly differed between Type I and type II ML (P < 0.001). CONCLUSIONS ML at different locations have different characteristics. For patients requiring surgery, the new ML classification can be used to select an appropriate surgical method. LEVEL OF EVIDENCE Level III.
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Affiliation(s)
- Jiayu Yan
- Department of General Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Chuanping Xie
- Department of General Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Yajun Chen
- Department of General Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
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Abu Shtaya A, Sukenik-Halevy R, Bazak L, Lidzbarsky GA, Gonzaga-Jauregui C, Lagovsky I, Goldberg Y, Basel-Salmon L. Possible biallelic inheritance in TIE1 in a family with congenital lymphedema, intestinal lymphangiectasia and cutis aplasia. Clin Genet 2023. [PMID: 37096293 DOI: 10.1111/cge.14344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 04/10/2023] [Accepted: 04/12/2023] [Indexed: 04/26/2023]
Abstract
A short report of two male siblings born with cutis aplasia, lymphedema and intestinal lymphangiectasia, one found to carry bi-allelic variants in the TIE1 gene known to be associated with congenital lymphedema.
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Affiliation(s)
- Aasem Abu Shtaya
- Recanati Genetic Institute, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
| | - Rivka Sukenik-Halevy
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Genetics Institute, Meir Medical Center, Kfar Saba, Israel
| | - Lily Bazak
- Recanati Genetic Institute, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
| | | | | | - Irina Lagovsky
- Felsenstein Medical Research Center, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
| | - Yael Goldberg
- Recanati Genetic Institute, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Lina Basel-Salmon
- Recanati Genetic Institute, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Felsenstein Medical Research Center, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
- Pediatric Genetics Clinic, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
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13
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Zhao Q, Sun X, Liu K, Peng Y, Jin D, Shen W, Wang R. Correlation between capsule endoscopy classification and CT lymphangiography of primary intestinal lymphangiectasia. Clin Radiol 2023; 78:219-226. [PMID: 36509551 DOI: 10.1016/j.crad.2022.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 09/21/2022] [Accepted: 10/05/2022] [Indexed: 12/13/2022]
Abstract
AIM To investigate the correlation between capsule endoscopy (CE) classification of primary intestinal lymphangiectasia (PIL) and computed tomography (CT) lymphangiography (CTL). MATERIALS AND METHODS A total of 52 patients with diagnosed PIL were enrolled. All patients were examined using CTL and small intestinal CE before surgery. CE assessments included the morphology, scope, colour, and size of lesions. CTL assessments included intestinal wall, lymphatic vessel dilatation, lymph fluid reflux, and lymphatic fistula. Patients were divided into three groups according to type diagnosed by CE, and the CTL characteristics were analysed among the groups. RESULTS CE showed 15 patients with type I, 27 with II, and 10 with type III. Intestinal wall thickening was observed in 15 type I, 21 type II, and seven type III. Pericardial effusion was observed in only three type I patients; the difference among types was statistically significant (p=0.02). Abnormal contrast agent distribution in the intestinal wall and mesentery was observed in 15 type II patients, and the difference was significantly greater than that of types I and III (p=0.02). Abnormal contrast agent distribution in the abdominal cavity was observed in 12 type II, and the difference was statistically significant (p=0.03). CONCLUSION The CE PIL classification reflects the extent and scope of intestinal mucosa lesions; CTL more systematically demonstrates abnormal lymphatic vessels or reflux, and its manifestations of PIL are related to the CE classification. The combination of CTL with CE is useful for accurately evaluating PIL, and provides guidance for preoperative assessment and treatment management of PIL patients.
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Affiliation(s)
- Q Zhao
- Department of Radiology, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - X Sun
- Department of Radiology, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - K Liu
- Department of Gastroenterology, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Y Peng
- Beijing Jiaotong University, China
| | - D Jin
- Peking University Third Hospital, China
| | - W Shen
- Department of Lymph Surgery, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - R Wang
- Department of Radiology, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
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14
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Jablonski SA. Pathophysiology, Diagnosis, and Management of Canine Intestinal Lymphangiectasia: A Comparative Review. Animals (Basel) 2022; 12:2791. [PMID: 36290177 PMCID: PMC9597800 DOI: 10.3390/ani12202791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 10/05/2022] [Accepted: 10/13/2022] [Indexed: 11/06/2022] Open
Abstract
Intestinal lymphangiectasia was first described in the dog over 50 years ago. Despite this, canine IL remains poorly understood and challenging to manage. Intestinal lymphangiectasia is characterized by variable intestinal lymphatic dilation, lymphatic obstruction, and/or lymphangitis, and is a common cause of protein-losing enteropathy in the dog. Breed predispositions are suggestive of a genetic cause, but IL can also occur as a secondary process. Similarly, both primary and secondary IL have been described in humans. Intestinal lymphangiectasia is definitively diagnosed via intestinal histopathology, but other diagnostic results can be suggestive of IL. Advanced imaging techniques are frequently utilized to aid in the diagnosis of IL in humans but have not been thoroughly investigated in the dog. Management strategies differ between humans and dogs. Dietary modification is the mainstay of therapy in humans with additional pharmacological therapies occasionally employed, and immunosuppressives are rarely used due to the lack of a recognized immune pathogenesis. In contrast, corticosteroid and immunosuppressive therapies are more commonly utilized in canine IL. This review aims toward a better understanding of canine IL with an emphasis on recent discoveries, comparative aspects, and necessary future investigations.
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Affiliation(s)
- Sara A Jablonski
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA
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15
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Cabrerizo M, Hidalgo-Montes I, Mendez-Echevarria A, Rodrieguez-Pena R, Ruiz-Carrascoso G, Martinez-Ojinaga E, Del Rosal T, Pastrian LG, Fernandez-Garcia MD. Severe vaccine-acquired rotavirus infection in an infant with primary intestinal lymphangiectasia. Pediatr Allergy Immunol 2022; 33:e13834. [PMID: 36003052 DOI: 10.1111/pai.13834] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 07/04/2022] [Accepted: 07/07/2022] [Indexed: 01/01/2023]
Affiliation(s)
- Maria Cabrerizo
- Enterovirus and Viral Gastroenteritis Unit, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.,CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | | | - Ana Mendez-Echevarria
- Pediatric Infectious and Tropical Diseases Department, La Paz University Hospital, Madrid, Spain.,Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain.,CIBERINFEC (CB21/13/00049), Instituto de Salud Carlos III, Madrid, Spain
| | - Rebeca Rodrieguez-Pena
- Immunology Department, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.,Center for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III
| | | | - Eva Martinez-Ojinaga
- Department of Pediatric Gastroenterology, University Hospital La Paz, Madrid, Spain
| | - Teresa Del Rosal
- Pediatric Infectious and Tropical Diseases Department, La Paz University Hospital, Madrid, Spain.,Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain.,Center for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III
| | - Laura G Pastrian
- Department of Pathology, Hospital Universitario La Paz, Madrid, Spain
| | - Maria Dolores Fernandez-Garcia
- Enterovirus and Viral Gastroenteritis Unit, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain
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16
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Montoro-Huguet MA, Belloc B, Domínguez-Cajal M. Small and Large Intestine (I): Malabsorption of Nutrients. Nutrients 2021; 13:1254. [PMID: 33920345 PMCID: PMC8070135 DOI: 10.3390/nu13041254] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 04/06/2021] [Accepted: 04/07/2021] [Indexed: 02/06/2023] Open
Abstract
Numerous disorders can alter the physiological mechanisms that guarantee proper digestion and absorption of nutrients (macro- and micronutrients), leading to a wide variety of symptoms and nutritional consequences. Malabsorption can be caused by many diseases of the small intestine, as well as by diseases of the pancreas, liver, biliary tract, and stomach. This article provides an overview of pathophysiologic mechanisms that lead to symptoms or complications of maldigestion (defined as the defective intraluminal hydrolysis of nutrients) or malabsorption (defined as defective mucosal absorption), as well as its clinical consequences, including both gastrointestinal symptoms and extraintestinal manifestations and/or laboratory abnormalities. The normal uptake of nutrients, vitamins, and minerals by the gastrointestinal tract (GI) requires several steps, each of which can be compromised in disease. This article will first describe the mechanisms that lead to poor assimilation of nutrients, and secondly discuss the symptoms and nutritional consequences of each specific disorder. The clinician must be aware that many malabsorptive disorders are manifested by subtle disorders, even without gastrointestinal symptoms (for example, anemia, osteoporosis, or infertility in celiac disease), so the index of suspicion must be high to recognize the underlying diseases in time.
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Affiliation(s)
- Miguel A. Montoro-Huguet
- Departamento de Medicina, Psiquiatría y Dermatología, Facultad de Ciencias de la Salud y del Deporte, University of Zaragoza, 50009 Zaragoza, Spain
- Unidad de Gastroenterología, Hepatología y Nutrición, Hospital Universitario San Jorge de Huesca, 22004 Huesca, Spain; (B.B.); (M.D.-C.)
- Aragonese Institute of Health Sciences (IACS), 50009 Zaragoza, Spain
| | - Blanca Belloc
- Unidad de Gastroenterología, Hepatología y Nutrición, Hospital Universitario San Jorge de Huesca, 22004 Huesca, Spain; (B.B.); (M.D.-C.)
- Aragonese Institute of Health Sciences (IACS), 50009 Zaragoza, Spain
| | - Manuel Domínguez-Cajal
- Unidad de Gastroenterología, Hepatología y Nutrición, Hospital Universitario San Jorge de Huesca, 22004 Huesca, Spain; (B.B.); (M.D.-C.)
- Aragonese Institute of Health Sciences (IACS), 50009 Zaragoza, Spain
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17
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Huber R, Semmler G, Mayr A, Offner F, Datz C. Primary intestinal lymphangiectasia in an adult patient: A case report and review of literature. World J Gastroenterol 2020; 26:7707-7718. [PMID: 33505146 PMCID: PMC7789053 DOI: 10.3748/wjg.v26.i48.7707] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 11/29/2020] [Accepted: 12/06/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Primary intestinal lymphangiectasia (PIL), first described in 1961, is a rare disorder of unknown etiology resulting in protein-losing enteropathy. The disease is characterized by dilatation and leakage of intestinal lymph vessels leading to hypoalbuminemia, hypogammaglobulinemia, and lymphopenia. Since the severity and location of lymph vessels being affected can vary considerably, the range of associated symptoms is wide from mild lower-limb edema to generalized edema, abdominal and/or pleural effusion, and recurrent diarrhea, among others. Although usually developing in early childhood, we present the case of a 34-year-old woman with PIL. Moreover, we performed a literature review systematically assessing clinical presentation, and provide a practical approach to facilitate diagnosis and therapy of PIL in adults.
CASE SUMMARY Our patient presented with unspecific symptoms of abdominal discomfort, fatigue, nausea, and recurrent edema of the lower limbs. Interestingly, a striking collinearity of clinical symptoms with female hormone status was evident. Additionally, polyglobulia, hypoalbuminemia, hypogammaglobulinemia, and transient lymphocytopenia were evident. Due to suspicion of a bone marrow disease, an extensive diagnostic investigation was carried out excluding secondary causes of polyglobulinemia and hypoalbuminemia. The diagnosis of primary intestinal lymphangiectasia was established after 22 wk by histological analysis of biopsy samples obtained via enteroscopy. Consecutively, the patient was put on a high-protein and low-fat diet with medium-chain triglycerides supplementation leading to significant improvement of clinical symptoms until 2 years of follow-up.
CONCLUSION PIL can be the reason for cryptogenic hypoalbuminemia, hypogammaglobulinemia, and lymphopenia in adulthood. Due to difficulty in correct diagnosis, treatment initiation is often delayed despite being effective and well-tolerated. This leads to a significant disease burden in affected patients. PIL is increasingly been recognized in adults since the majority of case reports were published within the last 10 years, pointing towards an underestimation of the true prevalence. The association with female hormone status warrants further investigation.
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Affiliation(s)
- Rudolf Huber
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf 5110, Austria
| | - Georg Semmler
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf 5110, Austria
| | - Alexander Mayr
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf 5110, Austria
| | - Felix Offner
- Department of Pathology, General Hospital Feldkirch, Feldkirch 6800, Austria
| | - Christian Datz
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf 5110, Austria
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