Primary intestinal lymphangiectasia as a component of autoimmune polyglandular syndrome type I: A report of 2 cases.

Primary intestinal lymphangiectasia as a component of autoimmune polyglandular syndrome type I: A report of 2 cases.

Indian J Gastroenterol. 2007 Nov-Dec

Makharia GK, Tandon N, Stephen Nde J, Gupta SD, Tandon RK.
Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110 029, India. govindmakharia@gmail.com.

Correspondence Address: Makharia Govind KDepartment of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110 029 India

Abstract

Chronic diarrhea and steatorrhea occur frequently in patients with autoimmune polyglandular syndrome (APS) type I. Intestinal lymphangiectasia has been reported earlier as a cause of steatorrhea in a young girl with APS Type I. We describe 2 patients with APS Type I who were found to have intestinal lymphangiectasia, one of whom had symptomatic protein-losing enteropathy.

Chronic diarrhea and steatorrhea occur in 18-24% of patients with autoimmune polyglandular syndrome (APS) type I. Intestinal lymphangiectasia has been described earlier as a cause of steatorrhea in a young girl with APS Type I. We describe 2 patients with APS Type I who were found to have intestinal lymphangiectasia.

Case 1

A 38-year-old woman had been having generalized tonic clonic seizures since the age of 20 years. At the age of 32 years, she underwent surgery for premature subcapsular cataract. In 1999, she was diagnosed to have hypothyroidism and started on L-thyroxine. Since 2000, she developed generalized anasarca with ascites and pleural effusion. She did not have diarrhea or steatorrhea. She also developed multiple patches of vitiligo. She reported to our hospital emergency room in 2001 with complaints of easy fatigability, day-time somnolence, cold intolerance, secondary amenorrhea, fever and altered sensorium. She was stable hemodynamically but had hypothermia.

Investigations: Hemoglobin 10.8 g/dL, macrocytosis, normal bilirubin and transaminases, alkaline phosphatase 75 IU/L, serum total protein 47 g/L (albumin 18), serum calcium 1.57 mmol/L (normal 2.2-2.6; ionized calcium 0.72 mmol/L), serum phosphate 2.7 mmol/L (normal 1.0-1.4), serum folate 10.7 ng/mL (normal 3.5-16.1), serum B12 101.8 pmol/L (normal 148-443), serum iron 13.4 mmo1/L (normal 9-27) and total iron binding capacity was 69.2mmo1/L (normal 45-66). D-xylose excretion in urine was 0.49 g over 5 hours following a 5 g load (normal >1 g/5g/5h). Twenty-four hour fecal fat excretion was 0.93 g. Upper gastro-intestinal endoscopy showed thickened duodenal folds with multiple whitish spots and white tipped villi. Duodenal mucosal biopsy showed a normal crypt:villous ratio and dilated lacteals in the lamina propria suggestive of lymphangiectasia. 99mTechenitium human serum albumin scans showed evidence of protein-losing enteropathy. Secondary causes of intestinal lymphangiectasia were excluded by a normal transit of radiotracer on 99mTechenitium HSA lymphoscintigraphy, a normal barium meal follow through and absence of any peripheral, mediastinal or abdominal lymphadenopathy.

Thyroid function tests revealed free T4 of 16 pmol/L (normal 13-23), thyroid-stimulating hormone 13.57 mU/mL (normal 0.27-4.2) while the patient was receiving 100 mg of L-thyroxine daily. Serum leutinizing hormone was 2.6 IU/L (normal 0.5-15.0), serum follicle stimulating hormone 5.4 IU/L (normal 0.2-10), serum prolactin 25 ng/mL (normal 0-18.8). Serum cortisol measured at 1800 h was 380 nmol/L (normal for evening level 70-345).

She had manifestations of hypoparathyroidism, hypothyroidism, pernicious anemia and secondary amenorrhea. In addition she had protein-losing enteropathy due to intestinal lymphangiectasia. She was treated with thyroxine, calcium, vitamin D, and vitamin B12 supplementation, human albumin, and medium chain triglyceride-based diet. Her anasarca improved on human albumin supplementation and medium chain triglyceride diet. After follow up of a period of about 18 months, she died because of overwhelming sepsis.

Case 2

A 33-year-old man had swelling of face and extremities, recurrent syncope and constipation since childhood. He was diagnosed as hypothyroidism and treated with thyroxine. He had features of myxedema, postural hypotension, anemia, hyperpigmentation of the buccal mucosa, dystrophic and dry skin, enamel hypoplasia and short stature.

Investigations: Hemoglobin 6.6 g/dL, and mean corpuscular volume 114 fl, serum bilirubin 1.3 mg/dL, ALT 10 IU/L, AST 52 IU/L, alkaline phosphatase 84 IU/L. Serum total protein 62 g/L (albumin 33 g/L), serum calcium 1.7 mmol/L, serum phosphate 1.7mmol/L. The anti-parietal cell antibody was positive; antinuclear antibody, anti-smooth muscle antibody, anti-liver-kidney-microsomal antibody, and anti-thyroid peroxidase antibody were negative. TSH 46 mU/mL, serum free T3 3.5 pmol/L, serum free T4 12.2 pmol/L. Basal morning cortisol at 8 AM was 690 nmol/L (normal 140-690), which rose to 772 nmol/L after 250 mg of adrenocorticotrophic hormone stimulation. Serum parathyroid hormone (PTH) level was 59.2 pg/mL (normal 16-46) with serum calcium 1.7 mmol/L. Serum follicle stimulating hormone was 13.5 IU/L, serum leutinizing hormone 13.5 IU/L, serum prolactin 27.1 mg/L and serum testosterone was 6 ng/mL (normal 3-10).UGI endoscopy revealed atrophic gastritis, esophageal candidiasis (smears showed fungal hyphae), thickened duodenal folds and multiple whitish nodular lesions with white tops in between and over the mucosal folds suggestive of intestinal lymphangiectasia. The jejunal biopsy showed dilation of lymphatic channels in the lamina propria and mild increase in the chronic inflammatory cells. The secondary causes of intestinal lymphangiectasia were excluded.

In summary, he had primary hypothyroidism, hypo-parathyroidism, macrocytic anemia, esophageal candidiasis and ectodermal dystrophy which suggested a diagnosis of APS type I. In addition, he had primary intestinal lymphangiectasia. He was treated with thyroxine, hydrocortisone, calcium, parenteral B12. His symptoms improved and hemoglobin rose to 9 g. He lost to follow up after 9 months.

Autoimmune polyglandular syndrome (APS) type I is comprised of a broad spectrum of diseases including chronic muco-cutaneous candidiasis, hypoparathyroidism hypothyroidism and type 1 diabetes mellitus. Patients with this syndrome and their families may have other non-endocrine manifestations, including ectodermal dystrophy, pernicious anemia, chronic atrophic gastritis, autoimmune hepatitis, vitiligo, alopecia, asplenia, cholelithiasis and keratoconjunctivitis.

Intestinal lymphangiectasia by virtue of loss of lymphocytes, immunoglobulins and albumin in the intestine may complicate the natural history of APS type I. Primary intestinal lymphangiectasia is mostly congenital and may be associated with lymphatic ductal abnormalities at other sites and organs. Secondary intestinal lymphangiectasia on the other hand occurs mostly due to inflammatory diseases of the small bowel, mesenteric tuberculosis, lymphoma, Whipple's disease, Crohn's disease, retroperitoneal fibrosis, and constrictive pericarditis.It has also been reported in systemic autoimmune diseases such as systemic lupus erythematosus and progressive systemic sclerosis. Although the exact pathogenesis of intestinal lymphangiectasia in SLE and PSS is not known, immunological injury has been suggested.Acquired hypospenism, enamel hypoplasia and nail dystrophy which are seen in patients with APS type I, have also been reported in patients with primary intestinal lymphangiectasia.

It is therefore, conceivable that these APS and intestinal lymphangiectasia share a similar etiology and/or pathogenetic mechanism; intestinal lymphangiectasia may be responsible for gastrointestinal manifestations in patients with APS type I.

Indian Journal of Gastroenterology

Adult Cardiac Cystic Lymphangiectasia of the Right Atrium

Adult Cardiac Cystic Lymphangiectasia of the Right Atrium

Echocardiography. 2008 Apr 17

Matarieh A, Harinstein ME, Salanitri J, Maganti K.
Department of Medicine, Division of Cardiology, Northwestern University, Feinberg, School of Medicine, Chicago, Illinois, USA.

Cardiac lympangiectasia is a rare pathological dilation of the lymphatic channels of the heart. Diagnosis is made by pathology; however, there remains no definitive diagnostic study. There are reports of cardiac cystic lymphangiectasias in children. A case of right atrial lymphangiectasia, initially identified by echocardiography, is presented here. This is the first report of such a mass.

PubMed

Acquired cutaneous lymphangiectasia with mesothelial cells reflux in a patient with cirrhotic ascites.

Acquired cutaneous lymphangiectasia with mesothelial cells reflux in a patient with cirrhotic ascites.

Am J Dermatopathol. 2008 Apr

Tomasini C, Butera AC, Pippione M.
Section of Dermatology, II Clinic, Department of Medical Sciences and Human Oncology, University of Turin, Turin, Italy. ctomasini@molinette.piemonte.it

A previously undescribed case of acquired cutaneous lymphangiectasias on the abdomen in a patient with cirrhotic ascites where peritoneal mesothelial cells refluxed in the skin is discussed. A 56-year-old man previously submitted to liver transplantation presented with vesiculobullous lesions on the developed as his cirrhotic ascites progressed. Histology showed dilated lymphatic channels in the upper dermis lined by a single, discontinuous layer of flattened, monomorphous endothelial cells with endoluminal papillary projections. In the deep reticular dermis, we observed irregular thin- often jagged-walled vascular channels lined by a single layer of bland endothelial cells, dissecting the collagen bundles. Vessels in the lumen were medium to large bizarre-shaped polygonal cells with abundant eosinophilic cytoplasm and hyperchromatic and irregular nuclei, arranged in small clusters or as solitary units, focally in close contact with the endothelial lining or free floating within vessel cavities. Immunohistochemistry indicated atypical intraluminal cells to be positive for calretinin, a specific marker for mesothelial cells. Pathophysiologic mechanisms and problems of differential diagnosis of this unique clinicopathologic entity are discussed.

Lippincott, Williams & Wilkins

Embryonic development and malformation of lymphatic vessels.

Embryonic development and malformation of lymphatic vessels.

Novartis Found Symp. 2007

Wilting J, Buttler K, Rössler J, Norgall S, Schweigerer L, Weich HA, Papoutsi M.
Department of Pediatrics 1, Georg-August-University, Goettingen, Germany.

In the human, malformations of lymphatic vessels can be observed as lymphangiectasia, lymphangioma and lymphangiomatosis, with a prevalence of 1.2-2.8 per thousand. Their aetiology is unknown and a causal therapy does not exist. We investigated the origin of lymphatic endothelial cells (LECs) in avian and murine embryos, and compared the molecular profile of LECs from normal and malformed lymphatics of children. In avian embryos, Prox1+ lymphangioblasts are located in the confluence of the cranial and caudal cardinal veins, where the jugular lymph sac (JLS) forms. Cell lineage studies show that the JLS is of venous origin. In contrast, the lymphatics of the dermis are derived from mesenchymal lymphangioblasts located in the dermatomes, suggesting a dual origin of LECs in avian embryos. The same may hold true for murine embryos, where Lyve1+ LEC precursors are found in the cardinal veins, and in the mesenchyme. The mesenchymal cells express the pan-leukocyte marker CD45, indicating a cell type with lymphendothelial and leukocyte characteristics. In the human, such cells might give rise to Kaposi's sarcoma. Microarray analyses of LECs from lymphangiomas of children show a large number of regulated genes, such as VEGFR3. Our studies show that lymphvasculogenesis and lymphangiogenesis occur simultaneously in the embryo, and suggest a function for VEGFR3 in lymphangiomas.

PMID: 18300425 [PubMed - in process]

Primary intestinal lymphangiectasia (Waldmann's disease).

Primary intestinal lymphangiectasia (Waldmann's disease).

Feb 2008 Orphanet J Rare Dis.

Vignes S, Bellanger J.

ABSTRACT:

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 alpha-1 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.

Orphanet

Successful resection of localized intestinal lymphangiectasia post-Fontan: role of (99m)technetium-dextran scintigraphy

Successful resection of localized intestinal lymphangiectasia post-Fontan: role of (99m)technetium-dextran scintigraphy

Pediatrics. 2003 Sep

Connor FL, Angelides S, Gibson M, Larden DW, Roman MR, Jones O, Currie BG, Day AS, Bohane TD.
Department of Gastroenterology, Sydney Children's Hospital, NSW, Australia.

Key Words: intestinal lymphangiectasia • resection • Fontan procedure • 99mtechnetium-dextran • scintigraphy

Abbreviations: PLE, protein-losing enteropathy • 51Cr, chromium-51 • 125I, iodine-125 • 111In, indium-111 • 99mTc, technetium-99m • 131I, iodine-131 • 67Cu, copper-67

Intestinal lymphangiectasia is a well-recognized complication of the Fontan procedure, occurring in up to 24% of patients. Because of the loss of chylous fluid into the gut lumen, protein-losing enteropathy results as well as lymphopenia and hypogammaglobulinaemia. In some cases, dilated lymphatics in the intestinal serosa or mesentery also rupture, causing chylous ascites. Standard medical and cardiac surgical interventions are generally ineffective and the condition is frequently lethal.

We report a case of intractable and life-threatening chylous ascites and chylothorax in a 14-year-old girl, associated with intestinal lymphangiectasia and protein-losing enteropathy after a Fontan procedure for tricuspid atresia. The condition was refractory to all standard medical therapies, including dietary modifications, diuretics, corticosteroid therapy, albumin infusions, octreotide, heparin, bowel rest, and parenteral nutrition. Cardiac surgery to optimize her hemodynamic status was also ineffective and large volume pleural and ascitic fluid losses continued. Having exhausted all other therapeutic modalities, (99m)technetium-dextran scintigraphy was performed to assess the extent of intestinal protein loss and the potential for surgical intervention.

Scintigraphy suggested localized protein loss from the proximal jejunum and subsequent segmental resection was effective. Postoperatively, ascites and pleural effusions resolved, and there was no evidence of short bowel syndrome. Growth has accelerated and the patient has entered puberty. There is mild persistent intestinal protein loss requiring diuretic therapy. Ascites or pleural effusions are absent, and the patient remains well >2 years after surgery.

Intestinal lymphangiectasia post-Fontan procedures has traditionally been ascribed to hemodynamic factors such as raised systemic venous pressure, which would predispose to a generalized intestinal lesion. However, in this case, scintigraphy demonstrated a localized, surgically correctible lesion.

To our knowledge, this is the first reported case of the use of (99m)technetium-dextran scintigraphy for this indication and of successful partial small bowel resection in such a case.

Pediatrics

Chronic renal insufficiency in a boy with cystic renal lymphangiectasia: morphological findings and long-term follow-up.

Chronic renal insufficiency in a boy with cystic renal lymphangiectasia: morphological findings and long-term follow-up.
Clin Nephrol. 2007 Dec

Ueda S, Yanagida H, Sugimoto K, Fujita S, Yagi K, Okada M, Takemura T.
Dpartment of Pediatrics, Kinki University School of Medicine, Osaka-Sayama, Japan.

Cystic renal lymphangiectasia (CRL) is a rare malformation of lymphatics that can present in childhood and adulthood. Symptoms and radiologic features are relatively well defined, but clinical evolution and prognosis remain unclear. We treated a boy with CRL who developed chronic renal insufficiency. The first manifestation was abdominal swelling associated with an umbilical hernia noted incidentally at 1.6 years. Computed tomography with intravenous contrast administration demonstrated perirenal cysts with fluid collection, suggesting CRL.

Intractable ascites resisted pharmacologic treatments such as diuretics. After approximately 7 years, the ascites resolved spontaneously, but the perirenal cysts persisted. At 11 years, proteinuria was noted.

A renal biopsy specimen showed interstitial abnormalities consistent with CRL, glomeruli showed a focal segmental mesangial increase. Proteinuria persisted despite administration of an angiotensin-converting enzyme inhibitor, increasing as obesity and hypertension worsened. Renal function gradually declined in the ensuing years. Polycythemia coexisted with a normal serum erythropoietin concentration. A follow-up renal biopsy specimen disclosed glomerular enlargement together with focal segmental mesangial expansion, suggesting obesity-related glomerulopathy.

Our observation suggest that under some specific circumstances like our patient CRL may exacerbate. Management of complicating obesity and hypertension are likely to be important for maintaining normal renal function, especially in the diffuse bilateral type of CRL present in our patient.

PubMed