• Waldmann
• alpha 1‐antitrypsin
• lymphedema

• Humans
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/complications
• Lymphangiectasis, Intestinal/diet therapy
• Male
• Female

• None

Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy characterized by the loss of proteins, lymphocytes, and immunoglobulins into the intestinal lumen. Increasing evidence has demonstrated an association between PIL and lymphoma.

A 54-year-old man with a 20-year history of abdominal distension and bilateral lower limb edema was admitted. Laboratory investigations revealed lymphopenia, hypoalbuminemia, decreased triglyceride and cholesterol level. Colonoscopy showed multiple smooth pseudo polyps in the ileocecal valve and terminal ileum and histological examination showed conspicuous dilation of the lymphatic channels in the mucosa and submucosa. A diagnosis of PIL was made. Three years later colonoscopy of the patient showed an intraluminal proliferative mass in the ascending colon and biopsy examination confirmed a malignant non-Hodgkin lymphoma. Then the patient was been underwent chemotherapy, and his clinical condition is satisfactory.

Our report supports the hypothesis that PIL is associated with lymphoma development.

• Lymphoma
• Primary intestinal lymphangiectasia
• Protein-losing enteropathy

The primary intestinal lymphangiectasia is a rare exudative enteropathy of unknown etiology that affects the lymphatic system. It causes lymphedema and malabsorption syndrome by the escape of the lymph and its elements into the intestinal lumen.

A female patient, diagnosed at the age of 11 with Waldmann's disease, has initially manifested chronic diarrhea with a stature-ponderal delay at the age of 6 months old; she was treated for a long time as celiac disease patient. Edematous syndrome, chronic diarrhea, staturo-ponderal delay and asymmetric lymphedema of the upper limb are the main clinical symptoms in this case. In addition, the exclusion of secondary intestinal lymphangiectasia was important for the diagnosis. Before and during her follow-up, the patient presented two complications of the disease: warts and osteomalacia. The patient did not respond to treatment with the low-fat diet; therefore, the need to add treatment with octreotide was necessary, which has given quite pleasant results. Octreotide was the therapeutic choice to treat the patient as she was resistant to the appropriate regimen with clinical improvement; nevertheless, certain biological elements of lymphatic leakage persisted.

Waldmann's disease is rare. It can be responsible, besides the typical signs, for complications including warts and osteomalacia. The histopathological study of intestinal biopsies may be normal if lymphangiectasias are localized. The treatment is based on a nutritional diet associated with octreotide. During the patient's follow-up, the evolution after almost two years of the introduction of octreotide compared to the diet alone showed improved outcomes.

The treatment of Waldmann's disease is based on an adapted diet and octreotide. This case highlighted the importance of the long term follow-up in this disease.

-

Waldmann's disease is a rare entity of unknown etiopathogenesis that affects the lymphatic system.

• Case report
• Enteropathy
• Lymphangiectasia
• Octreotide
• Waldmann

• Case report
• Hemihyperplasia
• Intestinal lymphangiectasis
• Lymphedema
• Primary intestinal lymphangiectasia
• Saudi Arabia

• Child, Preschool
• Extremities
• Humans
• Hyperplasia
• Infant
• Lymphangiectasis, Intestinal/complications
• Lymphangiectasis, Intestinal/diagnosis
• Lymphedema/diagnosis
• Lymphedema/etiology
• Male
• Protein-Losing Enteropathies/diagnosis
• Protein-Losing Enteropathies/etiology

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.

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.

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.

• Primary intestinal lymphangiectasia
• Waldmann´s disease
• Protein losing enteropathy
• Hypoproteinemia
• Case report

• Adult
• Child, Preschool
• Diet, Fat-Restricted
• Edema/etiology
• Female
• Humans
• Lymphangiectasis, Intestinal/complications
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/therapy
• Protein-Losing Enteropathies/diagnosis
• Protein-Losing Enteropathies/etiology
• Protein-Losing Enteropathies/therapy
• Triglycerides

Protein losing enteropathy can present as an immunodeficiency. This report describes a rare cause of protein losing enteropathy due to a lymphoenteric fistula and how a novel use of a pre-existing combined imaging technique of single-photon emission computed tomography/computed tomography lymphoscintigraphy helped in making the diagnosis.

• Intestinal lymphangectasia
• Intestinal obstruction
• Lymphoma

• Adolescent
• Female
• Humans
• Ileal Diseases/etiology
• Intussusception/etiology
• Lymphangiectasis, Intestinal/complications
• Lymphangiectasis, Intestinal/diagnosis

• Immunoglobulin deposition
• Lymphangiectasia
• Monoclonal protein
• Rituximab
• Splenic marginal zone lymphoma

• chylous ascites
• electron microscopy
• enteroscopy
• immunohistochemistry
• primary intestinal lymphangiectasia
• protein losing enteropathy
• terminal ileal intubation at colonoscopy

• Aged, 80 and over
• Colonoscopy
• Double-Balloon Enteroscopy
• Endoscopy, Digestive System
• Female
• Humans
• Ileum
• Intubation, Gastrointestinal
• Lymphangiectasis, Intestinal/pathology

• Waldmann’s disease
• intestinal
• malabsorption
• primary intestinal lymphangiectasia

Protein losing enteropathy (PLE) refers to excessive intestinal protein loss, resulting in hypoalbuminemia. Underlying pathologies include conditions leading to either reduced intestinal barrier or lymphatic congestion. We describe the case of a patient with long-lasting diffuse abdominal problems and PLE. Repetitive endoscopies were normal with only minimal lymphangiectasia in biopsies. Further evaluations revealed an indolent marginal zone lymphoma with minor bone marrow infiltration. Monotherapy with rituximab decreased bone marrow infiltration of the lymphoma but did not relieve PLE. Additional treatments with steroids, octreotide, a diet devoid of long-chain fatty-acids, and parenteral nutrition did not prevent further clinical deterioration with marked weight loss (23 kg), further reduction in albumin concentrations (nadir 8 g/L), and a pronounced drop in performance status. Finally, immunochemotherapy with rituximab and bendamustine resulted in hematological remission and remarkable clinical improvement. 18 months after therapy the patient remains free of gastrointestinal complaints and has regained his body weight with normal albumin levels. We demonstrate a case of PLE secondary to indolent marginal zone lymphoma. No intestinal pathologies were detected, contrasting a severe and almost lethal clinical course. Immunochemotherapy relieved lymphoma and PLE, suggesting that a high suspicion of lymphoma is warranted in otherwise unexplained cases of PLE.

Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy with lymphatic leakage into the small intestine. Dilated lymphatics in the small intestinal wall and mesentery are observed in this disease. Laboratory tests of PIL patients revealed hypoalbuminemia, lymphocytopenia, hypogammaglobulinemia and increased stool α-1 antitrypsin clearance. Cell-mediated immunodeficiency is also present in PIL patients because of loss of lymphocytes. As a result, the patients are vulnerable to chronic viral infection and lymphoma. However, cases of PIL with chronic viral infection, such as human papilloma virus-induced warts, are rarely reported. We report a rare case of PIL with generalized warts in a 36-year-old male patient. PIL was diagnosed by capsule endoscopy and colonoscopic biopsy with histological tissue confirmation. Generalized warts were observed on the head, chest, abdomen, back, anus, and upper and lower extremities, including the hands and feet of the patient.

• Protein-losing enteropathy
• Lymphocytopenia
• Cell-mediated immunodeficiency
• Primary intestinal lymphangiectasia
• Warts

• Adult
• Biopsy
• Capsule Endoscopy
• Chronic Disease
• Colonoscopy
• Diet, Fat-Restricted
• Dietary Proteins/administration & dosage
• Humans
• Immunocompromised Host
• Immunohistochemistry
• Lymphangiectasis, Intestinal/complications
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/immunology
• Lymphedema/complications
• Lymphedema/diagnosis
• Lymphedema/diet therapy
• Lymphedema/immunology
• Male
• Opportunistic Infections/diagnosis
• Opportunistic Infections/immunology
• Opportunistic Infections/virology
• Papillomavirus Infections/diagnosis
• Papillomavirus Infections/immunology
• Papillomavirus Infections/virology
• Tomography, X-Ray Computed
• Treatment Outcome
• Triglycerides/administration & dosage
• Warts/diagnosis
• Warts/immunology
• Warts/virology

• Adult
• Humans
• Lymphangiectasis, Intestinal/complications
• Lymphangiectasis, Intestinal/diagnostic imaging
• Lymphangiectasis, Intestinal/therapy
• Lymphedema/complications
• Lymphedema/diagnostic imaging
• Lymphedema/therapy
• Male
• Melena/etiology
• Protein-Losing Enteropathies/diet therapy
• Protein-Losing Enteropathies/etiology
• Radiography

• Adults
• Intestinal lymphangiectasia
• Submucosa

Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and “secondary” changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple’s disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohn’s disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial diagnosis of intestinal lymphangiectasia. Treatment has been historically defined to include a low fat diet with medium-chain triglyceride supplementation that leads to portal venous rather than lacteal uptake. A number of other pharmacological measures have been reported or proposed but these are largely anecdotal. Finally, rare reports of localized surgical resection of involved areas of small intestine have been described but follow-up in these cases is often limited.

• Intestinal lymphangiectasia
• Adults
• Submucosa

• Adults
• Intestinal lymphangiectasia
• Submucosa

• Adults
• Intestinal lymphangiectasia
• Submucosa

• Adults
• Intestinal lymphangiectasia
• Submucosa

• Adults
• Intestinal lymphangiectasia
• Submucosa

• Adults
• Intestinal lymphangiectasia
• Submucosa

• Adults
• Intestinal lymphangiectasia
• Submucosa

• Capsule Endoscopy
• Child
• Child, Preschool
• Dilatation, Pathologic
• Female
• Humans
• Immunoglobulin E/blood
• Lymphangiectasis, Intestinal/blood
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/pathology
• Lymphangiectasis, Intestinal/therapy
• Lymphatic Vessels/pathology
• Male
• Retrospective Studies

• Age Factors
• Diarrhea/diagnosis
• Diarrhea/diet therapy
• Diarrhea/pathology
• Diet, Fat-Restricted/methods
• Humans
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/pathology
• Lymphedema/diagnosis
• Lymphedema/diet therapy
• Lymphedema/pathology
• Malabsorption Syndromes/diagnosis
• Malabsorption Syndromes/diet therapy
• Malabsorption Syndromes/pathology

• Age Factors
• Diarrhea/diagnosis
• Diarrhea/diet therapy
• Diarrhea/pathology
• Diet, Fat-Restricted/methods
• Humans
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/pathology
• Lymphedema/diagnosis
• Lymphedema/diet therapy
• Lymphedema/pathology
• Malabsorption Syndromes/diagnosis
• Malabsorption Syndromes/diet therapy
• Malabsorption Syndromes/pathology

• Age Factors
• Diarrhea/diagnosis
• Diarrhea/diet therapy
• Diarrhea/pathology
• Diet, Fat-Restricted/methods
• Humans
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/pathology
• Lymphedema/diagnosis
• Lymphedema/diet therapy
• Lymphedema/pathology
• Malabsorption Syndromes/diagnosis
• Malabsorption Syndromes/diet therapy
• Malabsorption Syndromes/pathology

• Age Factors
• Diarrhea/diagnosis
• Diarrhea/diet therapy
• Diarrhea/pathology
• Diet, Fat-Restricted/methods
• Humans
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/pathology
• Lymphedema/diagnosis
• Lymphedema/diet therapy
• Lymphedema/pathology
• Malabsorption Syndromes/diagnosis
• Malabsorption Syndromes/diet therapy
• Malabsorption Syndromes/pathology

• Age Factors
• Diarrhea/diagnosis
• Diarrhea/diet therapy
• Diarrhea/pathology
• Diet, Fat-Restricted/methods
• Humans
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/pathology
• Lymphedema/diagnosis
• Lymphedema/diet therapy
• Lymphedema/pathology
• Malabsorption Syndromes/diagnosis
• Malabsorption Syndromes/diet therapy
• Malabsorption Syndromes/pathology

• Age Factors
• Diarrhea/diagnosis
• Diarrhea/diet therapy
• Diarrhea/pathology
• Diet, Fat-Restricted/methods
• Humans
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/pathology
• Lymphedema/diagnosis
• Lymphedema/diet therapy
• Lymphedema/pathology
• Malabsorption Syndromes/diagnosis
• Malabsorption Syndromes/diet therapy
• Malabsorption Syndromes/pathology

• Age Factors
• Diarrhea/diagnosis
• Diarrhea/diet therapy
• Diarrhea/pathology
• Diet, Fat-Restricted/methods
• Humans
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/pathology
• Lymphedema/diagnosis
• Lymphedema/diet therapy
• Lymphedema/pathology
• Malabsorption Syndromes/diagnosis
• Malabsorption Syndromes/diet therapy
• Malabsorption Syndromes/pathology

Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool α1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum) or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other inconsistently effective treatments have been proposed for PIL patients, such as antiplasmin, octreotide or corticosteroids. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. The need for dietary control appears to be permanent, because clinical and biochemical findings reappear after low-fat diet withdrawal. PIL outcome may be severe even life-threatening when malignant complications or serous effusion(s) occur.

• Adult
• Female
• Follow-Up Studies
• Humans
• Lymphangiectasis, Intestinal/complications
• Lymphangiectasis, Intestinal/pathology
• Lymphoma, B-Cell/etiology
• Lymphoma, B-Cell/therapy
• Lymphoma, Large B-Cell, Diffuse/etiology
• Lymphoma, Large B-Cell, Diffuse/therapy
• Protein-Losing Enteropathies/etiology

• Chest Pain/etiology
• Child
• Cryptococcosis/diagnosis
• Cryptococcosis/microbiology
• Female
• Humans
• Immunologic Deficiency Syndromes/complications
• Lung Diseases, Fungal/diagnosis
• Lung Diseases, Fungal/microbiology
• Lymphangiectasis, Intestinal/complications
• Lymphangiectasis, Intestinal/pathology

• Agammaglobulinemia/etiology
• Diagnosis, Differential
• Flow Cytometry
• Humans
• Leukocyte Common Antigens/analysis
• Lymphangiectasis, Intestinal/diagnosis
• Lymphopenia/etiology
• Male
• Middle Aged
• Skin Diseases/etiology
• T-Lymphocytes/immunology
• Warts/etiology

• Adult
• Biopsy
• Duodenum/pathology
• Extremities
• Humans
• Lymphangiectasis, Intestinal/complications
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/pathology
• Lymphedema/complications
• Lymphedema/diagnostic imaging
• Lymphedema/therapy
• Male
• Radionuclide Imaging

• Adolescent
• Child
• Child, Preschool
• Diagnosis, Differential
• Diet, Fat-Restricted
• Female
• Follow-Up Studies
• Humans
• Infant
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/pathology
• Male
• Prognosis
• Treatment Outcome
• Triglycerides