Waldmann's disease: Primary intestinal lymphangiectasia diagnosed by 99mTc-labeled albumin macroaggregate scintigraphy-A case report in an adult patient.

Key Clinical Message: Rare yet significant, this case sheds light on the uncommon presentation of Waldmann's disease in adults, showcasing the diagnostic challenges it poses. A multidisciplinary approach, integrating clinical, endoscopic, histological, and radiological evaluations, is crucial for accurate diagnosis and management. Further research is needed to deepen our understanding of this complex disorder. Abstract: Waldmann's disease, or primary intestinal lymphangiectasia, is a rare disorder characterized by protein-losing enteropathy due to dilation and leakage of intestinal lymphatic vessels. Although typically diagnosed in early childhood, we present a case of a 55-year-old male with a complex medical history. The patient's history included intestinal obstruction, multidrug-resistant pulmonary tuberculosis, and primary antiphospholipid syndrome. He presented with a 2-year history of chronic diarrhea, weight loss, and lower limb edema. Endoscopic and histological examination revealed scattered white spots in the duodenum and terminal ileum, indicative of intestinal lymphangiectasia. Nuclear medicine studies confirmed abnormal protein loss. The rarity of Waldmann's disease in adulthood and its association with other significant medical conditions pose diagnostic challenges. The distinct endoscopic and histological findings, coupled with scintigraphy results, contribute to a comprehensive understanding of this complex case. Differential diagnoses and management considerations are discussed. This case highlights the atypical presentation of Waldmann's disease in adulthood, emphasizing the importance of a multidisciplinary approach for accurate diagnosis and management. Further research is warranted to enhance our understanding of this uncommon disorder and its potential implications for patients with complex medical histories.

Renal Lymphangiectasia: The Transcending of Serendipity.

Renal lymphangiectasia, a rare entity of the renal lymphatic system affecting both genders and all ages, can manifest bilaterally or unilaterally and has been referred to by various terms, such as renal lymphangiomatosis, renal lymphangioma, and others. Distinguishing this condition from common pathologies, such as polycystic kidney disease or hydronephrosis, is crucial. This article presents an innovative clinical case of unilateral renal lymphangiectasia in a 67-year-old woman with a relevant medical history. Detection was achieved by ultrasound in primary care using the point-of-care ultrasound (POCUS) technique under the focused assessment with sonography in trauma (FAST) protocol, revealing findings suggestive of renal lymphangiomatosis. This case highlights the utility of advanced technologies, such as bedside ultrasound, in addressing and transforming the approach to rare medical conditions, offering a compelling reminder of the positive influence of technological innovation in clinical practice.

Hypocalcaemic tetany linked to vitamin D deficiency and hypomagnesemia in primary intestinal lymphangiectasia: a literature review.

Primary intestinal lymphangiectasia (PIL) is a rare disorder in children causing protein-losing enteropathy. Vitamin D deficiency and hypomagnesemia contributed to the tetany. The literature review reflects the importance of screening for these deficiencies and regular serum magnesium monitoring in PIL cases with neuromuscular or ionic abnormalities.

A novel classification of senile dermatochalasis: insights from clinical and histological analysis.

PURPOSE: Dermatochalasis is a common disorder of the elderly, often requiring upper blepharoplasty. Although it is mainly accepted as a process of aging, its clinical and histological findings vary among patients. The aim of this study was to classify types of dermatochalasis based on their clinical and histological findings. METHODS: This retrospective study included patients with dermatochalasis who had undergone senile blepharoplasty at a single center. Clinical parameters such as margin-to-reflex distance 1 (MRD1), eyelid contour, visual field, and pre-existing medical conditions were assessed. Histological analysis was conducted of eyelid tissues stained with hematoxylin and eosin (H&E) and D2-40 to evaluate dermal edema, inflammation, lymphatic changes, and stromal depth. RESULTS: This study included 67 eyes of 35 patients. The mean age of the patients was 69.0 ± 8.3 years, and the average MRD1 was 1.8 ± 1.3 mm. In correlation analysis, two distinct types of dermatochalasis based on the histological findings were identified: lymphangiectasia-dominant and stromal edema-dominant types. The difference between nasal and temporal side MRD1(NT-MRD1) showed the area under the ROC curve of 0.718 of for distinguishing the two histological types of dermatochalasis was 0.718. CONCLUSION: Our novel classification of senile dermatochalasis based on morphological and histological analysis provides insights into the underlying pathology and may help to predict surgical outcomes and complications.

Experience of primary intestinal lymphangiectasia in adults: Twelve case series from a tertiary referral hospital.

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.

A Case of Primary Intestinal Lymphangiectasia Successfully Controlled with a Denver Peritoneovenous Shunt for Refractory Ascites.

A 53-year-old man presented with abdominal symptoms and a fever for 6 months and ascites and lower body edema for 2 months before visiting our clinic. Heart failure, renal failure, inferior vena cava or portal vein obstruction, cirrhosis, and malignancy were suspected, but none were present. We also suspected protein-leakage gastroenteropathy based on the elevated alpha-1 antitrypsin clearance (224 mL/day). Based on the double-balloon endoscopy findings, we diagnosed the patient with primary intestinal lymphangiectasia. Since the patient's ascites were not satisfactorily controlled medically, a Denver peritoneovenous shunt was placed. As a result, the ascites volume was successfully controlled over an extended period.

Newfound features associated with Hennekam Syndrome (Intestinal Lymphangiectasia-Lymphedema-Intellectual-Disability Syndrome) complicated with comorbid Waldmann's Disease resulting in Celiac Disease.

Key Clinical Message: Adequate evaluation of patients with Hennekam Syndrome (HS) is challenging for physicians, because of multi-organ involvement and complex pathophysiology. We report the first case in an African American with lymphedema, who developed protein-losing enteropathy (PLE) and was successfully diagnosed with HS from cause-and-effect complications by Waldmann's Disease (WD) and comorbid Celiac Disease (CD). Abstract: As far as we know, this is the 51st case of HS worldwide and the first one in an African American. The examined patient met all diagnostic criteria for HS, suggesting a dysfunction in the development of the lymphatic system, with associated comorbidities including developmental delay, gastrointestinal pathologies, facial and hearing abnormalities, and cardiac defects. Primary intestinal lymphangiectasia (WD) is a consequence of HS, which ultimately results in PLE and worsening interstitial lymph buildup. Based on our findings, CD, a complication not yet reported in HS, may arise from WD. Other autoimmune diseases may be seen in HS: a previous report demonstrated positive anti-thyroid stimulating hormone antibodies in HS patients. We propose that in HS, increased interstitial lymph (WD, if intestinal) with protein loss induces TNF-α- and IL-6-mediated immune reactions in the affected visceral organs, causing autoimmune pathologies. The interstitial lymph fluid-induced TNF-α and IL-6-mediated immunopathogenic reactions lead to inflammation and subsequent destruction of the intestinal mucosa. The chronic inflammatory increase in TGF-ß causes gastric mucosa hypertrophy, which results in gastric fold thickening. Eventually, wider tight junctions develop, increasing gastric mucosa permeability, and leading to gastropathy. Considering the examined patient's history of gastroenteritis and the literature stating that CD is a non-mucosal cause of gastropathy and PLE, it is suggested that sequelae of GI complications occur in a cause-and-effect chain in HS. HS results in WD, which causes CD, resulting in hypertrophic gastropathy and loss of parietal and chief cells, eventually leading to malabsorption and PLE (Figure 1). HS primarily affects various organs due to inflammatory-mediated damage and accumulation of lymph fluid. Other findings for HS include keratoconjunctivitis sicca (dry eye disease), fibrous lymphedema exhibiting lymphorrhea, chylous ascites, anemia, and parathyroid abnormalities. Immune impairment in HS predisposes patients to autoimmune disorders, therefore autoimmunity (CD) and WD are concomitant comorbidities of HS. HS-associated comorbidities are primarily due to inflammation and damage to immune cell transport or underlying health conditions affecting proper lymphatic function. However, it is suggested that HS mutations may disrupt the development of the lymphatic system leading to further complication. complications can be compound heterozygous, and there is a need for further research to identify nearby genes that can cause concomitant co-morbidity.

Profound and selective lymphopaenia in primary lymphatic anomaly patients demonstrates the significance of lymphatic-lymphocyte interactions.

Introduction: The lymphatic system has a pivotal role in immune homeostasis. To better understand this, we investigated the impact of Primary Lymphatic Anomalies (PLA) on lymphocyte numbers and phenotype. Methods: The study comprised (i) a retrospective cohort: 177 PLA subjects from the National Primary Lymphatic Anomaly Register with clinical and laboratory data, and (ii) a prospective cohort: 28 patients with PLA and 20 healthy controls. Patients were subdivided using established phenotypic diagnostic categories and grouped into simplex (localised tissue involvement only) and systemic (involvement of central lymphatics). Further grouping variables included genital involvement and the likelihood of co-existent intestinal lymphangiectasia. Haematology laboratory parameters were analysed in both cohorts. In the prospective cohort, prospective blood samples were analysed by flow cytometry for markers of proliferation, differentiation, activation, skin-homing, and for regulatory (CD4+Foxp3+) T cells (Treg). Results: In patients with PLA, lymphopaenia was frequent (22% of subjects), affected primarily the CD4+ T cell subset, and was more severe in subjects with systemic versus simplex patterns of disease (36% vs 9% for lymphopaenia; 70% vs 33% for CD4+ cells). B cells, NK cells and monocytes were better conserved (except in GATA2 deficiency characterised by monocytopaenia). Genital oedema and likelihood of concomitant intestinal lymphangiectasia independently predicted CD4+ T cell depletion. Analysing CD4+ and CD8+ T cells by differentiation markers revealed disproportionate depletion of naïve cells, with a skewing towards a more differentiated effector profile. Systemic PLA conditions were associated with: increased expression of Ki67, indicative of recent cell division, in naïve CD4+, but not CD8+ T cells; increased levels of activation in CD4+, but not CD8+ T cells; and an increased proportion of Treg. Skin-homing marker (CCR10, CLA and CCR4) expression was reduced in some patients with simplex phenotypes. Discussion: Patients with PLA who have dysfunctional lymphatics have a selective reduction in circulating lymphocytes which preferentially depletes naïve CD4+ T cells. The presence of systemic disease, genital oedema, and intestinal lymphangiectasia independently predict CD4 lymphopaenia. The association of this depletion with immune activation and increased circulating Tregs suggests lymphatic-lymphocyte interactions and local inflammatory changes are pivotal in driving immunopathology.

Idiopathic Chylous Pericardial Effusion Due to Lymphatic Malformation of Mediastinum.

Chylopericardium can be due to a variety of secondary causes like trauma, radiation, tumors, following cardiac surgery, etc., or may be idiopathic due to abnormal lymphatic system and mediastinal lymphangiectasia, which is a rare entity. Here, we present a case of a 34-year-old previously healthy male presenting with idiopathic chylopericardium. 2D echocardiography revealed massive pericardial effusion without features of cardiac tamponade. Following pericardiocentesis, a CT scan of the thorax and MR lymphangiogram were done to arrive at a diagnosis of idiopathic chylopericardium. In addition to medical management, surgical treatment included partial pericardiectomy and sclerotherapy of the mediastinal lymphatic sac. The patient had an uneventful post-operative period.

Small intestinal mucosal abnormalities using video capsule endoscopy in intestinal lymphangiectasia.

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.

A late diagnosis of primary intestinal lymphangiectasia in a Syrian girl.

Primary intestinal lymphangiectasia is a rare disease that affects children and young adults, causing mainly gastrointestinal disorders that lead to edema and immunologic abnormalities. The majority of patients typically present bilateral lower limb edema, along with pericarditis, pleural effusion, or chylous ascites. The goal of the treatment is to restrict the consumption of long-chain fats and administer a formula that includes protein and medium-chain triglycerides. Here, we report 11-year-old Syrian girl presented to the hospital with 2 years history of diarrhea and generalized edema. Furthermore, investigation showed ascites and pleural effusion. The disease was detected by several biopsies from duodenum that showed dilation of the lymph vessels within the lamina propria without any evidence for inflammation. She was managed by modifying her diet and albumin transfusion, which caused significant improvement in the child's condition.

Cryptococcal meningitis and cerebral vasculitis in a patient with primary intestinal lymphangiectasia: a case report.

Primary intestinal lymphangiectasia (Waldmann's disease) is a rare exudative enteropathy without precisely assessed infectious risk. We report the case of a 49-year-old male patient with meningitis and cerebral vasculitis due to Cryptococcus neoformans complicating Waldmann's disease diagnosed 12 years ago. The treatment combined liposomal amphotericin B, 3 mg/kg daily plus flucytosine 25 mg/kg/6 h, both intravenously during 15 days, then fluconazole 800 mg daily during 8 weeks, and finally 200 mg daily indefinitely. Dexamethasone 0.4 mg/kg daily during the first week was gradually decreased over 2 months. The outcome was good, and the patient is still followed 3 years later without any recurrence.

Randomized controlled trial of hydrolyzed fish diets in dogs with chronic enteropathy.

BACKGROUND: The role of diet in the pathogenesis and treatment of chronic enteropathies (CE) in dogs is unresolved. OBJECTIVES: To compare the ability of diets composed of hydrolyzed fish, rice starch, and fish oil without (HF) or with prebiotics, turmeric, and high cobalamin (HF+) against a limited ingredient diet containing mixed nonhydrolyzed antigens and oils (control) to resolve clinical signs and maintain serum cobalamin and folate concentrations in dogs with nonprotein losing CE (non-PLE). To determine the ability of hydrolyzed fish diets to support recovery and remission in dogs with PLE. ANIMALS: Thirty-one client-owned dogs with CE: 23 non-PLE, 8 PLE. METHODS: Randomized, blinded, controlled trial. Diets were fed for 2 weeks; responders continued for 12 weeks. Nonresponders were crossed over to another diet for 12 weeks. Response was determined by standardized clinical evaluation with long-term follow-up at 26 weeks. Concurrent medications were allowed in PLE. RESULTS: Nineteen of 23 (83%; 95% confidence interval [CI], 60%-94%) non-PLE CE responded clinically to their initial diet, with no difference between diets (P > .05). Four nonresponders responded to another diet, with sustained remission of 18/18 (100%; 95%CI, 78%-100%) at 26 weeks. Serum cobalamin concentration was increased (P < .05) and maintained by diet. Serum folate concentration decreased posttreatment (P < .05) but was restored by dietary supplementation. Hydrolyzed fish diets supported weight gain, serum albumin concentration, and recovery (P < .05) in dogs with PLE. CONCLUSIONS AND CLINICAL IMPORTANCE: Changing diet, independent of antigen restriction or supplemental ingredients, induced long-term remission in dogs with non-PLE CE. Serum cobalamin and folate concentrations were maintained by diet. Hydrolyzed fish diets supported clinical recovery and remission in PLE.

Misty mesentery, ascites, and bowel wall thickening in a child: Diagnostic clue for intestinal lymphangiectasia.

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.

Solitary Intestinal Lymphangiectasia Causing Transient Intussusception.

Lymphangiectasia is the benign malformation of lymphatic channels associated with either focal or diffuse dilation of vessels and impaired lymph drainage. This malformation has the potential to create a cystic mass due to the accumulation of lymphatic fluid. While rare in adults, intussusception, the telescoping of the proximal bowel into the distal bowel, can be caused by a mass within the bowel. In this case, a near-obstructing cystic colon mass developed in a 74-year-old man; this was later found to be a large lymphangiectasia. In addition, this near-obstructing colonic lymphangiectasia served as the lead point in a colo-colonic intussusception. Due to this complication, the mass was immediately removed by a laparoscopic oncologic right-extended hemicolectomy which proved to be both diagnostic and therapeutic.

Development of unilateral renal peripelvic lymphangiectasia after renal vein thrombosis.

Renal peripelvic lymphangiectasia is a rare entity that can mimic hydronephrosis on routine contrast-enhanced computer tomography (CT). While it may remain asymptomatic, symptomatic cases can exhibit refractory hypertension (HTN) and recurrent abdominal pain. Diagnostic challenges stem from its nonspecific symptoms and imaging characteristics, which can overlap with other renal disorders. Thereby, adequate protocolling of CT or magnetic resonance (MR) imaging is important for accurate diagnosis. In this report, we present a case of renal lymphangiectasia that developed in a medically complex patient following renal vein thrombosis.

ADAMTS3 and FLT4 gene mutations result in congenital lymphangiectasia in newborns: A case report.

BACKGROUND: Congenital lymphangiectasia is a rare disease characterized by dilated interstitial lymphatic vessels and cystic expansion of the lymphatic vessels. Congenital lymphangiectasia can affect various organ systems; however, it frequently occurs in the lungs accompanied with unexplained pleural effusion. Further, it might not be diagnosed during prenatal examination owing to the absence of pronounced abnormalities. However, after birth the newborn rapidly develops respiratory distress that quickly deteriorates. Genetic variations in proteins controlling the development of lymphatic vessels contribute to the pathophysiology of this disease. We report a rare case of heterozygous mutation of ADAMTS3 and FLT4 genes, which have not been reported previously. CASE SUMMARY: We analysed the case of a neonate who had presented with only pleural effusion at a late gestational age and eventually died due to its inability to establish spontaneous breathing after birth. An autopsy revealed lymphangiectasia of the organ systems. Further, whole exome sequencing revealed heterozygous mutations of the lymphangiogenesis-controlling genes, ADAMTS3 and FLT4, and Sanger verification revealed similar lesions in the mother with no symptoms. CONCLUSION: Considering the presented case, obstetricians should observe unexplained foetal pleural effusion, and perform pathology analysis and whole exome sequencing for a conclusive diagnosis and prompt treatment.

Small Bowel Lymphangiectasia Leading to Massive Gastrointestinal Bleeding: A Case Report.

Lymphangiomas are benign lymphatic system abnormalities that can appear anywhere on the skin and mucous membranes. Lymphangiomas are caused by congenital or acquired lymphatic system disorders. In the congenital form, although the cause is unknown it is said that it is formed by the incorrect attachment of lymphatic channels to the main lymphatic drainage duct before the age of 5 years. lymphangiectasia as a subgroup of lymphangioma occurs seldom in the small bowel, especially in adults. If that happens, protein-losing enteropathy will be the most common presenting sign. In the present study, we introduce a case of a 40-year-old man without a history of any congenital or acquired diseases who was admitted to the emergency room due to long-lasting obscure overt gastrointestinal (GI) bleeding. Normal upper and lower GI endoscopies were suggestive of GI bleeding originating from the small intestine. Despite receiving iron supplements, he continued to have melena and remained anemic. Further evaluation of the small intestine by deep enteroscopy revealed multiple white spots histologically consistent with dilated lymphatics. Intestinal lymphangiectasia was eventually introduced to be the final diagnosis of the patient.

A Rare Case of Transplanted Kidney Lymphangiectasia in a Patient With Joubert Syndrome.

Renal lymphangiectasia is one of the rarest surgical complications in post-transplant kidney patients. A few patients may clinically complain of nonspecific symptoms, and the other few might be diagnosed incidentally. We report the case of a 32-year-old female patient with a known case of Joubert syndrome who presented with nonspecific clinical manifestations. The patient underwent ultrasound, magnetic resonance imaging (MRI), and nuclear medicine (NM) imaging to confirm the diagnosis, which showed radiologic features of renal lymphangiectasia. Conservative medical management was delivered to the patient.

Polypoid Lymphangiectasia in the Sigmoid Colon: A Case Report of a Rare Entity.

Intestinal polypoid lymphangiectasia is an uncommon disorder involving an improperly formed enteric lymphatic system. It is characterized by lymphatic vessel dilatation with impaired drainage or obstruction of the lymph from the intestine. In this report, we present a case of a 73-year-old male patient with chronic intermittent left lower quadrant abdominal pain for one year who was found to have a sigmoid colon polyp on a colonoscopy. Upon microscopic examination, the polyp revealed dilated lymphatic vessels staining strongly for D2-40 (lymphatic vessel marker), supporting the diagnosis of polypoid lymphangiectasia. Intestinal lymphangiectasia has a broad differential diagnosis, warranting histopathological examination for a definitive diagnosis.--------------.