Lymphangiectasia

Intestinal lymphangiectasia associated with recurrence of histiocytosis X.

2012-02-16T07:27:00.001-08:00

Intestinal lymphangiectasia associated with recurrence of histiocytosis X.

Sept 2011

Hui CK.

Source

Centre for Alimentary Studies, 5/F Century Square, 1 D'Aguilar Street, Central, Hong Kong SAR, China. bckhui@gmail.com

Abstract

K e y w o r d s : h i s t i o c y t o s i s X , i n t e s t i n a l

lymphangiectasia, secondary cause

Intestinal lymphangiectasia may occur as a primary congenital disorder or a secondary disorder. Secondarylymphangiectasia could be associated with diseases such as abdominal carcinoma, retroperitoneal fibrosis or chronic pancreatitis. This is the first reported case of intestinal lymphangiectasia associated with recurrent histiocytosis X. This case report illustrates the need for more prospective, well-designed studies to determine the natural history and outcome of intestinal lymphangiectasia in the duodenum. Hopefully, these studies will also help clinicians identify which group of patients with intestinal lymphangiectasia in the duodenum is more likely to have a secondary cause.

SMJ

Primary intestinal lymphangiectasia diagnosed by capsule endoscopy and double balloon enteroscopy.

2012-02-12T12:01:00.000-08:00

Primary intestinal lymphangiectasia diagnosed by capsule endoscopy and double balloon enteroscopy.

Nov 2011

Oh TG, Chung JW, Kim HM, Han SJ, Lee JS, Park JY, Song SY.

Source

Tak Geun Oh, Joo Won Chung, Hee Man Kim, Jung Yeob Park, Si Young Song, Division of Gastroenterology, Department of Internal Medicine, Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 120-752, South Korea.

Abstract

Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lymphatics and the development of protein-losing enteropathy. Patients with PIL develop hypoalbuminemia, hypocalcemia, lymphopenia and hypogammaglobulinemia, and present with bilateral lower limb edema, fatigue, abdominal pain and diarrhea. Endoscopy reveals diffusely elongated, circumferential and polypoid mucosae covered with whitish enlarged villi, all of which indicate intestinal lymphangiectasia. Diagnosis is confirmed by characteristic tissue pathology, which includes dilated intestinal lymphatics with diffusely swollen mucosa and enlarged villi. The prevalence of PIL has increased since the introduction of capsule endoscopy. The etiology and prevalence of PIL remain unknown. Some studies have reported that several genes and regulatory molecules for lymphangiogenesis are related to PIL. We report the case of a patient with PIL involving the entire small bowel that was confirmed by capsule endoscopy and double-balloon enteroscopy-guided tissue pathology who carried a deletion on chromosome 4q25. The relationship between this deletion on chromosome 4 and PIL remains to be investigated.

PubMedCentral

Lymphangiectasia of the vulva, treatment with CO 2 laser.

2012-02-09T06:23:00.000-08:00

Lymphangiectasia of the vulva, treatment with CO 2 laser.

Jan. 2012

Myriam Ben Hamida, Dora Baccouche, Nadia El Fekih, Becima Fazaa, Ridha Kamoun
Department of Dermatology, Charles Nicolle Hospital of Tunis, University of Medicine, Tunis El Manar, Tunisie,

Correspondence Address:
Myriam Ben Hamida
Service de Dermatologie,Hôpital Charles Nicolle, Bureau Entrées Boulevard du 9 Avril 1006, BAB SOUIKA TUNIS, Tunisie

Sir,

Lymphangiectasia is a pathological dilatation of lymphatic vessels. Vulvar presentation is uncommon and may be misdiagnosed as genital warts, molluscum contagiosum, or tuberculosis verrucosa cutis. We present here the first case reported of vulval lymphangiectasia associated with a benign pelvic tumor.

A 55-year-old woman, presented with vulvar itching associated with condyloma-like lesions, starting 2 years ago. There was a medical history of hypertension and dyslipidemia under treatment. There were no histories of sexually transmitted disease, filariasis, tuberculosis, trauma, Crohn's disease, pelvic surgery, or irradiation therapy. The clinical examination revealed a diffuse induration with verrucous appearance of both labia major, with overlying papulovesicular lesions [Figure 1]. There was no inguinal lymphadenopathy. Histological examination revealed, the presence in the papillary dermis, of multiple dilated lymphatic vessels, lined by a thin wall comprising of endothelial cells with valves. Acanthosis was also present in the epidermis [Figure 2]. The diagnosis of vulval lymphangiectasia was proposed. An extensive search for an etiology of this disease in our patient was initiated. The searches for tuberculosis and for a sexually transmitted disease (especially Chlamydia serology) were negative. Abdominopelvic ultrasound revealed a large polymyomatous uterus, with multiple interstitial myomas measuring from 2 to 8 cm of diameter. A pelvic magnetic resonance imaging (MRI) was performed and confirmed the presence of large myomas, without deep pelvic extension of lymphangioma. Because there were no other obvious causes, we considered that this benign pelvic tumor was the cause of the impaired lymph flow inducing lymphangiectasia. Surgical treatment represented by total hysterectomy was performed. For her vulval lymphangiectasia, a noninvasive therapy with CO ₂ -laser vaporization was indicated. The continuous wave CO ₂ laser was used in defocused mode with a 2-mm spot size. The patient had two laser sessions at 4 weeks interval, with a power of 10 W. The evolution was favorable with a good cosmetic result and no signs of recurrence after 15-month follow-up We report here an original case of vulval lymphangiectasia caused by a large polymyomatous uterus. Lymphangiectasia is also called acquired lymphangioma circumscriptum (LC) or secondary lymphangiomas. Requena and Sangueza ^[1] consider that this disorder results from obstruction of previously normal lymphatics, unlike congenital LC in which dilated superficial lymphatics are a consequence of transmitted pressure from a congenital malformation of deep dermal lymphatics.

Clinical and histological findings of lymphangiectasia and congenital LC of the vulva are very similar. However, history of congenital or early onset of the disease and the presence on histological examination of deeper lymphatic abnormalities in the reticular dermis and subcutaneous are suggestive of LC. ^[2]

For our patient, the late onset of the disease and the absence of deep lymphatic extension on histological examination and on pelvic MRI were suggestive of lymphangiectasia of the vulva.

In the literature, vulval lymphangiectasia occurred after a carcinoma of the cervix uteri managed with surgery or with radiation therapy. Other predisposing conditions reported were urogenital tuberculosis, Crohn's disease, recurrent bacterial infections, or radical pelvic surgery of non-gynecologic tumors. ^[3] In all these cases, lymphangiectasia was induced by obstruction of previous normal lymphatics. To the best of our knowledge, it is the first case of vulval lymphangiectasia associated with a benign pelvic tumor. We propose that these large myomas were probably the cause of the impaired lymph flow inducing lymphangiectasia.

There is no consensus about the treatment of lymphangiectasia. Treatment must provide a good cosmetic result, prevent recurrence, and protect from infections. The traditional treatment, surgical removal, is an effective treatment but rapid relapses often occur. Other treatment options include laser vaporization, sclerotherapy, cryotherapy, and electrocoagulation. Several reports have been published of successful CO ₂ laser ablation of lymphangiectasia, and it represents the main alternative to surgery. ^[2] The CO ₂ laser is described as effective in both LC and lymphangiectasia; however, focal recurrence are more frequently described in LC, which may reflect the persistence of deeper lymphatic abnormalities not destroyed by laser. ^[2] CO ₂ laser ablation is generally well tolerated but some authors noted pain and the development of vulva keloid. In our patient, a conservative treatment with CO ₂ -laser therapy was indicated. This treatment was well tolerated with a good cosmetic result and no recurrence after a follow-up of 15 months.

Malignant transformation of congenital LC has been reported in some cases from the literature. Cases of lymphangiosarcoma were described on sites of LC previously treated with extensive X-ray therapy. ^[4]

Cases of squamous-cell carcinoma have also been reported. ^[5] These complications have never been reported with lymphangiectasia; nevertheless, a close follow-up of patients with vulval lymphangiectasia is advisable.

Full text with Diagnostic Images

IJDVL

Cytomegalovirus-associated protein-losing enteropathy resulting from lymphangiectasia in an immunocompetent child.

2009-10-20T04:56:00.000-07:00

Cytomegalovirus-associated protein-losing enteropathy resulting from

lymphangiectasia in an immunocompetent child.

Jpn J Infect Dis. 2009 May

Hoshina T, Kusuhara K, Saito M, Hara T, Mtsuura S, Yano T, Aoki T, Hara T.

Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. hoshina@pediatr.med.kyushu-u.ac.jp

An immunocompetent 8-year-old boy with cytomegalovirus (CMV)-associated transient protein-losing enteropathy (PLE) is described. Colonoscopic examination revealed lymphoid hyperplasia of the terminal ileum. Histological examination of the biopsied specimens showed marked dilation of the lymphatic vessels. Primary CMV infection was demonstrated by serological test and polymerase chain reaction. The child had complete resolution of the disease without antiviral treatment. The present case suggests the etiologic role of CMV infection in PLE resulting from intestinal lymphangiectasia in childhood.

NIH

P13K 1-phosphatidylinositol 3-kinase definition and studies

2009-10-12T12:58:00.000-07:00

P13K 1-phosphatidylinositol 3-kinase definition

<cell biology> An enzyme that catalyses the conversion of phosphatidylinositol to phosphatidylinositol 3-phosphate. This is the first committed step in the biosynthesis of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. This pathway is thought to play a critical role in DNA repair, v(d)j recombination and cell cyle checkpoints.37.

Chemical name: ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase

Registry number: EC 2.7.1.137

Online Medical Dictionary

Additional studies on its role:

Effects of Tyroserleutide on Gene Expression of Calmodulin and P13K in Hepatocellular Carcinoma

Oncogenic P13K Deregulates Transcription and Translation

A role for phosphoinositol-3-kinase (P13K) in the stimulation of hepatic taurocholate uptake by cyclic AMP

Laminin-332 promotes the invasion of oesophageal squamous cell carcinoma via P13K activation

Patent application title: THIAZOLOPYRIMIDINE P13K INHIBITOR COMPOUNDS AND METHODS OF USE

Expression Status and Mutational Analysis of the PTEN and P13K Subunit Genes in Ovarian Granulosa Cell Tumors

High D-glucose alters PI3K and Akt signaling and leads to endothelial cell migration,

proliferation and angiogenesis dysfunction

Organ-specific lymphangiectasia, arrested lymphatic sprouting, and maturation defects P13K gene

2009-10-12T12:44:00.000-07:00

Organ-specific lymphangiectasia, arrested lymphatic sprouting, and maturation defects resulting from gene-targeting of the PI3K regulatory isoforms p85, p55, and p50

Dev Dyn. 2009 Oct

Mouta-Bellum C, Kirov A, Miceli-Libby L, Mancini ML, Petrova TV, Liaw L, Prudovsky I,Thorpe PE, Miura N, Cantley LC, Alitalo K, Fruman DA, Vary CP.

Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine, USA.

email: Calvin P.H. Vary (varyc@mmc.org)

The phosphoinositide 3-kinase (PI3K) family has multiple vascular functions, but the specific regulatory isoform supporting lymphangiogenesis remains unidentified. Here, we report that deletion of the Pik3r1 gene, encoding the regulatory subunits p85alpha, p55alpha, and p50alpha impairs lymphatic sprouting and maturation, and causes abnormal lymphatic morphology, without major impact on blood vessels. Pik3r1 deletion had the most severe consequences among gut and diaphragm lymphatics, which share the retroperitoneal anlage, initially suggesting that the Pik3r1 role in this vasculature is anlage-dependent. However, whereas lymphatic sprouting toward the diaphragm was arrested, lymphatics invaded the gut, where remodeling and valve formation were impaired. Thus, cell-origin fails to explain the phenotype. Only the gut showed lymphangiectasia, lymphatic up-regulation of the transforming growth factor-beta co-receptor endoglin, and reduced levels of mature vascular endothelial growth factor-C protein. Our data suggest that Pik3r1 isoforms are required for distinct steps of embryonic lymphangiogenesis in different organ microenvironments, whereas they are largely dispensable for hemangiogenesis.

Wiley InterScience

Reversal of protein-losing enteropathy after heart transplantation in young patients.

2009-10-12T12:40:00.000-07:00

Reversal of protein-losing enteropathy after heart transplantation in young patients

Rev Esp Cardiol. 2009 August

Soriano JR, Grima EZ, Vives MA, Sáez AO, Dolz LM, Bonet LA, Pérez MA, Sanz AS.

Servicio de Cardiología, Hospital Universitario La Fe, Valencia, Spain. ximo@ipeuropa.com

Protein-losing enteropathy is a rare but life-threatening complication that occurs in some patients who develop intestinal lymphangiectasis secondary to increased systemic venous pressure. Although different forms of treatment have been tried, with varying results, the majority were reported to be unsuccessful. The aim of this study was to demonstrate that heart transplantation may be an appropriate therapeutic option for patients who do not respond to medical treatment. At our center, we performed heart transplantations in three patients with this condition. The mean follow-up period was 11+/-2 months. No patient died and the enteropathy regressed in all three.

Cardiologia

Lighthouse Lymphedema Network

2009-09-29T04:48:00.000-07:00

I wanted to make a special announcement that the Lighthouse Lymphedema Network
is now on Facebook.

You can join by going to: Lighthouse Facebook

There is also an area where you can post and participate.

AND - don't forget our upcoming program in October.

see the details for that at:

Lighthouse Lymphedema Network

**yes, I'm on it too :-)**

Pat

Clinical significance of duodenal lymphangiectasia incidentally found during routine upper gastrointestinal endoscopy.

2009-09-21T22:35:00.000-07:00

Clinical significance of duodenal lymphangiectasia incidentally found during routine upper gastrointestinal endoscopy.

Endoscopy. 2009 Jun

Kim JH, Bak YT, Kim JS, Seol SY, Shin BK, Kim HK.
Department of Gastroenterology, Korea University Guro Hospital, Seoul, Korea.

BACKGROUND AND STUDY AIM: Although duodenal lymphangiectasia in individuals without clinical evidence of malabsorption has been reported, the prevalence and clinical significance in this situation are not yet known. The aim of this study was to evaluate the prevalence and clinical significance of incidentally found duodenal lymphangiectasia.

PATIENTS AND METHODS: A retrospective review of medical records was undertaken for consecutive patients who had undergone diagnostic upper endoscopy between January 2005 and June 2006. A prospective study was then performed in consecutive individuals undergoing routine upper endoscopy for health examination between July 2006 to October 2006.

Endoscopic features of duodenal lymphangiectasia were classified into three types: (1) multiple scattered pinpoint white spots; (2) diffuse prominent villi with whitish-discolored tips; and (3) focal small whitish macule or nodule. The histologic grade of duodenal lymphangiectasia was classified according to the depth and severity of lymphatic duct dilatations. Prevalence and clinical data of incidentally found duodenal lymphangiectasia were evaluated in the retrospective and prospective studies.

RESULTS: Among 1866 retrospective cases, duodenal lymphangiectasia was endoscopically suspected in 59 cases (3.2%), and histologically confirmed in 35 cases (1.9%). No clinical evidence of malabsorption was noted in the duodenal lymphangiectasia cases. The "scattered pinpoint white spots" type was the most frequently found endoscopic feature (40.0%). Duodenal lymphangiectasia was persistent in seven of 10 individuals who underwent repeat endoscopy after a median of 12 months. Among 134 prospective cases, duodenal lymphangiectasia was histologically confirmed in 12 cases (8.9%). There was no significant clinical difference between groups with and without duodenal lymphangiectasia. Lymphatic duct dilatation was histologically more severe in the "focal small whitish macule or nodule" type than in the other types.

CONCLUSION: Duodenal lymphangiectasia without clinical evidence of malabsorption is not extremely rare among cases undergoing routine upper gastrointestinal endoscopy.

eThieme Journal

Very late onset small intestinal B cell lymphoma associated with primary intestinal lymphangiectasia and diffuse cutaneous warts.

2009-09-17T04:44:00.000-07:00

Very late onset small intestinal B cell lymphoma associated with primary intestinal lymphangiectasia and diffuse cutaneous warts.

Gut. 2000 Aug

Bouhnik Y, Etienney I, Nemeth J, Thevenot T, Lavergne-Slove A, Matuchansky C.
Department of Gastroenterology and Hepatology, Hôpital Lariboisière, Paris, France. yoram.bouhnik@lrb.ap-hop-paris.fr

As only a handful of lymphoma cases have been reported in conjunction with primary intestinal lymphangiectasia, it is not yet clear if this association is merely fortuitous or related to primary intestinal lymphangiectasia induced immune deficiency. We report on two female patients, 50 and 58 years old, who developed small intestinal high grade B cell lymphoma a long time (45 and 40 years, respectively) after the initial clinical manifestations of primary intestinal lymphangiectasia. They presented with a longstanding history of fluctuating protein losing enteropathy, multiple cutaneous plane warts, and markedly dilated mucosal and submucosal lymphatic channels in duodenal biopsies. One had a large ulcerated tumour of the proximal ileum and the other diffuse ileal infiltration. In both, histological examination showed centroblastic high grade B cell lymphoma associated with duodenojejuno-ileal mucosal and submucosal lymphangiectasia. They were subsequently successfully treated with surgery and postoperative chemotherapy (AVmCP: adriamycin, cyclophosphamide, Vm26, and prednisolone), and chemotherapy alone (PACOB: adriamycin, cyclophosphamide, vincristine, bleomycine, and prednisolone), respectively. A three year follow up in both cases showed persistent diffuse lymphangiectasia without evidence of lymphoma. The present findings support the hypothesis that primary intestinal lymphangiectasia is associated with lymphoma development.

Gut Online

Protein-losing enteropathy in a case of nodal follicular lymphoma without a gastrointestinal mucosal lesion.

2009-09-17T04:38:00.000-07:00

Protein-losing enteropathy in a case of nodal follicular lymphoma without a gastrointestinal mucosal lesion.
Intern Med. 2008
Kaneko H, Yamashita M, Ohshiro M, Ohkawara Y, Matsumoto Y, Nomura K, Horiike S, Yokota S, Taniwaki M.
Department of Hematology, Aiseikai-Yamashina Hospital, Kyoto. hp@aiseikaihp.or.jp

Protein-losing enteropathy (PLE) is characterized by gastrointestinal loss of serum protein. It is usually caused by hypersecretion from a tumor, ulcer, or long standing lymphangiectasia. However, we report a 47-year-old man of peritoneal nodal follicular lymphoma who developed PLE with none of them. Oozing of whitish fluid from duodenal bulbar mucosa was endoscopically seen, resulting in continuous loss of protein. Chemotherapy was effective and PLE was rapidly diminished. Nodal lymphoma lesion was considered to disturb lymphatic flow and to regurgitate it to duodenal mucosa. To our knowledge, this is the second report of a lymphoma patient presenting PLE without a gastrointestinal mucosal lesion.

Internal Medicine

Georgia Lymphedema Education and Awareness Program

2009-09-11T04:42:00.000-07:00

11th Annual Lymphedema Education & Awareness Program

An educational and awareness conference for patients, caregivers and professionals!

Where?

Piedmont Hospital

Piedmont Hospital

Richard H. Rich Auditorium

1968 Peachtree Road, NW, Building 77

Atlanta, Georgia

When?

Saturday, October 18, 20087:30 am - 5:30 pm

Program includes

What to expect of tissue after radiation?

What is the physiology response of radiation?

What does radiation do to the lymph nodes? - Peter Rossi, MD

How does vascular flow affect the lymphatics? - Ken Harper, MD

Expectations of surgery. - Christopher Hart, MD, FACSThe Lymphatic System, Wound Care,

Infections and Treatment - Paula Stewart, MDParent Networking

Aquatic Exercises

The Connection of obesity and increased swelling in people with lymphedema and lipedema.and more.

Additional information and registration form - Home website - Lighthouse Lymphedema Network

See you there - Pat

Lympangiectasia of the vulva accompanying congenital lymphedema

2009-06-08T06:51:00.000-07:00

Lympangiectasia of the vulva accompanying congenital lymphedema
April 2009

M Ihsan Okur1, Rüştü Köse2, A Mustafa Yıldırım1, Bengü Çobanoğlu3

Dermatology Online Journal 15 (4): 13 1. Assistant Professor, Department of Plastic and Reconstructive Surgery, Fırat Medical Center, Firat (Euphrates) University, Elazig, Turkey2. Assistant Professor, Department of Plastic and Reconstructive Surgery, Harran University Medical Center, Şanlıurfa, Turkey. rkose@harran.edu.tr3.
Assistant Professor, Department of Pathology

Abstract

Lymphangiectasia is a benign condition with multiple dilated lymph vessels in the dermis. Vulvar localization is rare and mostly depends on disturbing the lymphatic flow. We present a patient with vulvar lesions and ipsilateral congenital lower extremity lymphedema. Surgical excision eliminated the lymphangiectasia and improved the appearance of the edematous vulva.

Introduction

Vulvar lymphangiectasia is not usually seen as a result of congenital lymphedema. Lymphangioma circumscriptum, a subtype of lymphangioma, is mainly a congenital malformation that presents in infancy but may be seen at any age. An acquired lesion, especially one related to the obstruction of lymphatic circulation, is defined as lymphangiectasis; however it is histologically indistinguishable from lymphangioma circumscriptum.
Lymphangiectasia of the vulva is a rare disease and usually reported following surgery and radiotherapy, performed because of a genital malignant tumor [1]. Long-standing Crohn disease with fistulae and tuberculosis lymphadenitis are the other associated conditions [1, 2, 3, 4]. Primary lymphedema is an unusual cause of vulvar lymphangiectasia. We present a case of vulvar lymphangiectasia with ipsilateral congenital lower extremity lymphedema.

Case Report

A 27-year-old woman was referred for treatment of a skin lesion on her right labium majus. The plaque had appeared initially at the age of 19. Sometimes vesicles arose on the surface from which clear and occasionally bloody fluid oozed. She underwent a few bouts of vulvar cellulitis. Four years prior, she had been seen in another dermatology clinic and was given the clinical diagnosis of "infected lymphangioma of the vulva," which was treated with antibiotics. Congenital lympedema along the entire right leg was noted. The lymphedema (Fig. 1) was apparent soon after birth and she regularly used a pressure garment. Genital examination revealed a red and skin-colored plaque with shining, clustered papules on the right labium majus and ipsilateral vulvar edema (Fig. 2). This edema deformed the appearance of the vulva, which was the main complaint of the patient. The growth was excised, including the edematous subcutaneous tissue, under general anesthesia. A negative pressure drain was placed and tissues were sutured.

The histopathological examination of the excised tissue showed many thin-wall lumenal structures with irregular size and shape, lined by a monolayer of endothelium in the upper dermis (Fig. 3). Postoperative recovery was uneventful and the surgical wound healed well.

After the surgery, the symmetry of the vulva was improved. Although a thin scar remained along the labium majus, the aesthetic outcome was good (Fig. 4) and the patient was satisfied. The patient was followed up for 31 months. Recurrence and infection were not observed during this period.

Comment

Vulvar lymphangiectasia is mainly associated with obstruction of the lymphatic flow. The lesions typically arise approximately 7-15 years after lymph node dissection and radiotherapy of the genitalia [1, 5, 6, 7, 8]. De novo acquired lesions without lymphatic disturbance are less frequently seen. In some cases, lymphangiectasia appears following lymphedema of the vulva or lower extremity [3, 4, 5, 6, 9]. However, the condition may arise without adjacent lymphedema [3].

Although deep lymphangiomas are seen in primary lymphedema cases, reports detailing subsequent lymphangiectasia of vulva are very few [2, 10]. Buckley and Barnes report a 35-year-old patient who had lymphedema since the age of 14 and underwent two cellulitis attacks. Thereafter, lymphangiectasia on the vulva appeared in the same year [10]. Another patient with late onset lymphedema in the right leg also presented with lymphangiectasia on the labium majus [2]. The lesions emerged three years after the lymphedema.

The mechanism behind development of the vulvar lymphangiectasia in our patient accompanied by congenital lymphedema is probably similar. A 13-year-old boy has been described who presented exhibited scrotal lymphangiectasia with congenital contralateral leg lymphedema [11].

He also experienced recurrent scrotal infections after the lymphangiectasia appeared. Our patient had congenital lymphedema and suffered episodes of cellulitis before and after the vulvar lymphangiectasia appeared.

Lymphangiectasia may be actually expected in primary lymphedema patients because lymphatic obstruction is an important etiologic factor in its etiology. The cause of the higher rate in acquired lymphatic damage may be because of the rapidly increasing pressure when there is a sudden blockage of the superficial lymphatic system. In addition, recurrent cellulitis further damages lymphatic vessels, increases lymphatic pressure, and induces formation of lymphangiectasia in lymphedema patients.

Lymphangiectasia on the vulva can be easily misdiagnosed, especially as viral warts [1-5, 7, 8, 12]. Oozing vesicules or papules and recurrent infections should bring into mind the possibility of lymphangiectasia.

Excisional surgery and carbon dioxide laser are two major treatment modalities in addition to cryotherapy, electrocoagulation, and sclerosing agent injection [13]. Whereas carbon dioxide laser only vaporizes the lesion superficially, it may seal the underlying lymph vessels and diminish recurrence [9, 14]. The laser therapy can be repeated if any recurrences occur. Delayed wound healing, scars, and even keloid formation may be seen after laser therapy [1, 14]. Excisional surgery eliminates the abnormal subcutaneous lymph vessels and cisterns, and corrects of the aesthetic appearance of the edematous vulva. It is the only plausible choice in the therapy of advanced disease [13].

DermatologyOnline

Lymphangiectasias of the skin: victims of confusing nomenclature

2009-06-08T06:48:00.000-07:00

Lymphangiectasias of the skin: victims of confusing nomenclature
Clin Exp Dermatol. 2009 May
Verma SB.
Nirvana Skin Clinic, Vadodara, Gujarat, India.

Summary Lymphangiectasias are known by a variety of names, in the dermatology literature, including lymphangiectasis, acquired lymphangiomas, secondary lymphangiomas and acquired lymphangioma circumscriptum, which has led to confusion. The condition itself, especially in the genital region, is difficult to diagnose. This article attempts to resolve the issues of the confusing nomenclature and reviews the condition, which can arise under a variety of clinical circumstances. The relevant anatomical and histological details are described, with relevant clinical illustrations, to facilitate understanding of the aetiopathogenesis of this enigmatic condition. The available medical and non-medical treatments are discussed.

WileyInterScience

Primary mesenteric angiosarcoma in a child with associated lymphangiectasia: a case report.

2009-05-19T06:39:00.000-07:00

Primary mesenteric angiosarcoma in a child with associated lymphangiectasia: a case report.
Pediatr Dev Pathol. 2008 Nov-Dec

Castro EC, Galambos C, Shaw PH, Ranganathan S.
Department of Pediatric Pathology and Division of Pediatric Hematology/Oncology, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213, USA.

Angiosarcomas are rare tumors in children, usually occurring in soft tissue and liver. By contrast, angiosarcoma in adults usually occurs in the extremities in conjunction with lymphedema. Mesenteric angiosarcoma has only rarely been reported. When angiosarcomas arise in this location, they usually represent a 2nd malignancy following Hodgkin's lymphoma. We report a child who presented to the emergency room with an acute abdomen and underwent emergency surgery for a mesenteric angiosarcoma with associated lymphangiectasia of the bowel and mesentery. A brief review of the literature and the nomenclature of these unusual tumors are discussed.

Pediatric and Developmental Pathology

Evidence for Medium Chain Triglycerides in the Treatment of Primary Intestinal Lymphangiectasia.

2009-05-19T06:28:00.000-07:00

Evidence for Medium Chain Triglycerides in the Treatment of Primary Intestinal Lymphangiectasia.

Eur J Pediatr Surg. 2009 May 15
Desai AP, Guvenc BH, Carachi R.
1Department of Pediatric Surgery, King's College Hospital, London.

Primary intestinal lymphangiectasia is an uncommon congenital anomaly. It is an intrinsic abnormality of the intestinal lymphatics system. Over the years, various treatment options such as diuretics, albumin transfusions and a medium chain triglycerides (MCT) diet as well as surgical options such as resection of isolated segments and peritoneal-venous shunts have been used. An MCT diet, which is a low fat, high protein diet, is increasingly used in the management of this anomaly. AIM: The aim was to review the evidence for medium chain triglycerides as a therapeutic option in patients with primary intestinal lymphangiectasia.

MATERIAL AND METHODS: A literature search was performed and individual case details were extracted. We found 55 cases, of which 3 were from our own institute. The cases were divided in 2 groups: Group A (n=27) consisted of patients treated with MCT, and Group B (n=28) consisted patients not treated with MCT. Cases were analysed for symptomatic response to MCT as well as mortality.

RESULTS: 17 of 27 cases (63%) treated with MCT had complete resolution of symptoms while only 10 of 28 (35.7%) patients in group B showed complete resolution. Mortality for Group A was 1 out of 27 (3.7%), while mortality in group B was 5 of 28 (17.85%) patients.

CONCLUSION: We conclude that, although an MCT diet is not completely curative in all cases, it does improve the symptoms of primary intestinal lymphangiectasia and reduces mortality. Hence it is a valid option in the paediatric age group.

PMID: 19449286 [PubMed - as supplied by publisher]

A case of lymphangioleiomyomatosis associated with protein-losing gastroenteropathy lymphangiectasia

2008-12-30T08:31:00.000-08:00

A case of lymphangioleiomyomatosis associated with protein-losing gastroenteropathy - lymphangiectasia

Nippon Shokakibyo Gakkai Zasshi. 2008 Dec

Kinoshita A, Odagi I, Aoki Y, Hirohama K, Ishiguro H, Nikami T, Tamaki S, Searashi Y, Sudou S, Hokari A, Ishikawa T, Negishi M, Nishino H, Tajiri H, Ikegami M.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine.

A 29-year-old woman was referred to our hospital for the intensive examination of leg edema and hypoproteinemia. CT scan of showed multiple thin-walled cysts in both lungs, suggesting lymphangioleiomyomatosis. CT scan of the abdomen, lymphoscintigraphy showed enlarged abdominal lymph nodes. Protein loss from the gastrointestinal tract was documented by measurement of the clearance of alpha-1 antitrypsin from the plasma using a 72h stool collection and (99m)Tc human serum albumin scintigraphy. We thought that secondary lymphangiectasia with lymphangioleiomyomatosis caused protein-losing gastroenteropathy. Dietary therapy resulted in symptomatic improvement.

Stage Journal Archive

Lymphatic obstruction and protein-losing enteropathy (lymphangiectasia) in patients with congenital heart disease.

2008-11-22T02:47:00.000-08:00

Lymphatic obstruction and protein-losing enteropathy (lymphangiectasia) in patients with congenital heart disease.

Congenit Heart Dis. 2008 Jul

Meadows J, Gauvreau K, Jenkins K.
Department of Cardiology, Children's Hospital, Boston, MA, USA. jeffery.meadows@ucsf.edu

OBJECTIVE: Protein-losing enteropathy (PLE) is a known complication of surgical procedures for congenital heart disease. The pathogenesis and pathophysiology of PLE remain poorly understood. However, lymphatic insufficiency appears central to the disease process. We sought to investigate the role of lymphatic obstruction and central venous catheter-related central venous thrombosis in patients with congenital heart disease and PLE.

DESIGN: A case-control study design was constructed consisting of patients with congenital heart disease and PLE and 2:1 matched controls having undergone the same definitive surgical procedure. Obstruction to lymphatic return was considered present if the thoracic duct was ligated, or if there was complete central venous obstruction at the usual site of thoracic duct drainage.

RESULTS: Obstruction to lymphatic return was identified in 4 of 16 cases (25%) and 1 of 32 controls (4%), P = .06. There was no association between PLE and central venous catheter use or duration, and no discriminating characteristics between cases and controls with respect to anatomy, pre-Fontan hemodynamic variables, operative or perioperative factors, or hemodynamic variables at the time of PLE diagnosis. Mortality for patients with PLE was 25% compared with 9% in controls (P = not significant). Long-term resolution of PLE was obtained in six patients (38%).

CONCLUSION: There is a high prevalence of apparent lymphatic obstruction in patients with congenital heart disease and PLE, suggesting that physical lymphatic obstruction may play an important, and previously unrecognized role in the development of PLE in patients with complex congenital heart disease.

PMID: 18715461 [PubMed - indexed for MEDLINE]

A case of Hennekam syndrome presenting with massive pericardial effusion.]

2008-11-12T05:28:00.000-08:00

A case of Hennekam syndrome (lymphangiectasia) presenting with massive pericardial effusion.
Turk Kardiyol Dern Ars. 2008 Jul
Nişli K, Oner N, Kayserili H, Ertuğrul T.
Department of Pediatrics, Istanbul Medicine Faculty of Istanbul University, Istanbul, Turkey. kemalnisli@yahoo.com.

Hennekam syndrome is an autosomal recessive disease characterized by intestinal lymphangiectasia accompanied by severe lymphedema of the limbs, genitalia, and face, and learning difficulties. A 38-month-old boy was admitted with breathing difficulty. He had facial abnormalities and preputial hyperplasia consistent with Hennekam syndrome. Lymphangiography showed lymphedema in the left eye and right foot. Teleradiography showed cardiomegaly and echocardiography showed massive pericardial effusion. He first underwent pericardiocentesis for the removal of pericardial effusion, but pericardial tube drainage was required upon recurrence of effusion. On the fifth day, the drain was removed because of significant decrease in the drainage.

Full Text Article PDF

Computed tomographic scan in the diagnosis of bilateral renal lymphangiectasia.

2008-11-04T05:45:00.000-08:00

Computed tomographic scan in the diagnosis of bilateral renal lymphangiectasia.
Saudi J Kidney Dis Transpl. 2008 Nov

Rastogi R, Rastogi V.
Yash Diagnostic Center, Yash Hospital and Research Center, Civil Lines, Kanth Road, Moradabad (UP), India. eesharastogi@gmail.com.

Renal lymphangiectasia is a rarely reported disorder of lymphatic malformation. Although benign, it may lead to hypertension and renal failure in undetected or undiagnosed cases. Adult polycystic kidney disease is a close mimic. We herewith present a rare case of bilateral renal lymphangiectasia that was strongly suspected on Computed tomographic (CT) scan and confirmed by aspiration cytology. Awareness about this condition will result in early diagnosis, early treatment and reduced morbidity.

PMID: 18974588 [PubMed - in process]

Lymphangiectasia of small intestine presenting as intussusception.

2008-10-26T10:13:00.000-07:00

Lymphangiectasia of small intestine presenting as intussusception.
Indian J Pathol Microbiol. 2008 Jul-Sep

Katoch P, Bhardwaj S.
Department of Pathology, Government Medical College, Jammu, Jammu and Kashmir, India. pervezkatoch@rediffmail.com.

Intussusception is defined as telescoping of a segment of gastrointestinal tract into an adjacent one. In small children, it is the commonest cause of intestinal obstruction. More than 90% of childhood intussusceptions are idiopathic. We report a rare case of localized small intestinal lymphangiectasia, presenting as intussusception in a 6-month-old male child. The child presented with features of acute intestinal obstruction for which he was later operated. The gross examination of excised ileocecal mass revealed intussusception. Histopathologic examination revealed lymphangiectasia of small intestine, which acted as a lead point for ileocecal intussusception. Postoperative period was uneventful.

Pathology and Microbiology

Survival in primary congenital pulmonary lymphangiectasia with hydrops fetalis

2008-10-26T10:09:00.000-07:00

Survival in primary congenital pulmonary lymphangiectasia with hydrops fetalis

Fetal Diagn Ther. 2008

Laje P, Wilson RD, Guttenberg M, Liechty KW.
Department of General Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. laje@email.chop.edu

The recent advances in neonatal and pediatric intensive care have changed the outcome of patients with congenital pulmonary lymphangiectasia of different types, including those cases with early neonatal symptoms. However, the patients who present the most severe form of the disease, manifested by in utero hydrops (including those treated by in utero thoracoamniotic shunting to relieve the mediastinal compression), have had an unvaryingly fatal ending in all published reports, with most cases dying before birth, and the few born alive dying during the first days of life. We present a patient with primary congenital pulmonary lymphangiectasia complicated by hydrops fetalis, who was treated in utero, survived the neonatal period after intensive medical and surgical support, and was discharged home at the age of 2 months. She is currently 6 months old, and has minimal signs or symptoms of chronic lung disease. The different aspects of the management of congenital pulmonary lymphangiectasia are discussed in this report, together with a review of the literature. Copyright 2008 S. Karger AG, Basel.

Karger

Segmental dilatation of the ileum accompanying hypoproteinemia

2008-08-04T01:37:00.000-07:00

Segmental dilatation of the ileum accompanying hypoproteinemia

J Pediatr Surg. 2008 Jul
Elemen L, Inanc D, Oz F, Erdogan E.
Department of Pediatric Surgery, Istanbul German Hospital, Istanbul, Turkey. elemenlevent@hotmail.com

PURPOSE: Segmental intestinal dilatation (SID) is a rare pathologic finding, which causes intestinal obstruction in newborn period and gastrointestinal bleeding, anemia, abdominal pain, malabsorption, and growth failure in older children. We present a case of SID causing hypoproteinemia.

PATIENT: A 10-year-old girl presented with recurrent abdominal distension since she was 8.5 months old. She was diagnosed to have protein-losing intestinal lymphangiectasia. Result of physical examination was normal except moderate growth retardation. Her blood workup showed depletion in total protein, albumin, and globulin levels. Gastrointestinal series revealed a dilated segment of small intestine, and Tc(99m)-pertechnetate scintigraphy detected ectopic activity in abdomen. The patient was taken to operation with the presumptive diagnosis of intestinal duplication. A dilated segment of ileum was encountered, and segmental resection and anastomosis were performed.

RESULTS: Patient was discharged on the postoperative fourth day and remains well. Histopathologic examination of the specimen revealed SID.

DISCUSSION: Segmental intestinal dilatation is an uncommon congenital anomaly. Most of the cases were operated on in newborn period because of intestinal obstruction, and their diagnoses were made perioperatively; the others were diagnosed in older ages during the investigation of nonspecific symptoms. The index patient is the second case of SID having hypoproteinemia in the literature. Gastrointestinal series suggested the diagnosis, and segmental resection and anastomosis were the adequate treatments.

Elsevier/ScienceDirect

Pregnancy and Intestinal Lymphangiectasia (Waldmann disease)

2008-07-13T03:21:00.000-07:00

Pregnancy and Intestinal Lymphangiectasia (Waldmann disease)

Clin Ter. 2008 May-Jun

Tourlakis D, Hatziveis K, Spiliopoulos E.
Obstetric, Gynecologic Clinic St. Andrews hospital, Patra, Greece.

We present a case of a woman with intestinal lymphangiectasia and pregnancy. She had been treated with albumin transfusions beginning from the age of 2 years. No major complications were caused to the pregnancy. During pregnancy she was given albumin transfusions at regular intervals, while measuring total proteins, albumin and calcium concentrations in the serum. Due to the increasing needs in proteins as the pregnancy went on, the interval between each transfusion went decreasing. Finally, at 39 weeks of gestation she gave birth by cesarean section due to placenta previa to a healthy female fetus. A worsening of hypoproteinemia and edema was noted during puerperium and lactation. Weaning improved her clinical status. The baby was followed by pediatricians and found her in good health. Summing up, normal pregnancy is compatible with the condition. A strict maternal and fetal care during pregnancy and puerperium is recommended. Clin Ter 2008; 159(3):173-174.

PubMed

HGF and MET Mututations involving lymphangiectasia

2008-06-27T02:25:00.000-07:00

HGF and MET Mutations in Primary and Secondary Lymphedema.
Lymphat Res Biol. 2008
inegold DN, Schacht V, Kimak MA, Lawrence EC, Foeldi E, Karlsson JM, Baty CJ, Ferrell RE.

Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania., Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania., DNF, CJB, and REF contributed equally to this work.

Abstract Background: Lymphedema is the abnormal accumulation of protein-rich fluid in the interstitial space. Primary lymphedema is a rare genetic condition with both autosomal dominant and autosomal recessive modes of inheritance.

Three genes, FLT4 (VEGFR3), FOXC2, and SOX18 cause varying forms of primary lymphedema. In industrialized countries, secondary lymphedema is usually associated with cancer therapy and/or trauma. Recent observations suggested that hepatocyte growth factor/high affinity hepatocyte growth factor receptor (HGF/MET) were new candidate lymphedema genes.

Methods and Results: The coding exons and flanking regions of HGF and MET were directly sequenced in 145 lymphedema probands, 59 unrelated women with secondary lymphedema following treatment for breast cancer, 21 individual patients with lymphedema and intestinal lymphangiectasia, and at least 159 unrelated ethnic matched control individuals. Mutations leading to truncation or missense changes in evolutionarily conserved residues of HGF and MET were identified. These mutations were not polymorphic in control individuals.

Conclusions:The identification of HGF/MET mutations in primary lymphedema, lymphedema/lymphangiectasia, and breast cancer-associated secondary lymphedema suggests that the HGF/MET pathway is causal or alters susceptibility for a broad range of lymphedema phenotypes. The HGF/MET pathway provides a new target for the prevention and/or treatment of lymphedema.

Mary Ann Liebert

Congenital Lymphedema-lymphangiectasia Associated With Scrotal Angiokeratoma (Fordyce Type) and Hearing Impairment.

2008-06-10T08:18:00.000-07:00

Congenital Lymphedema-lymphangiectasia Associated With Scrotal Angiokeratoma (Fordyce Type) and Hearing Impairment.

J Clin Gastroenterol. 2008 May

Pavone P, Lucenti C, Fraggetta F, Micali G, Incorpora G, Ruggieri M.
Departments of *Paediatrics §Dermatology, University of Catania †Department of Paediatrics, AUSL 3, Caltagirone ‡Pathology Unit, AUSL 3, Cannizzaro Hospital ∥Institute of Neurological Science, National Research Council, Catania, Italy.

Congenital lymphangiectasia-lymphedema is a rare disorder that presents with edema of the lower half of the body, the face, hands, and scrotum, or with protein-losing enteropathy owing to structural anomalies in the endothelium of the lymphatic system. We describe a biopsy-proven case of severe lymphangiectasia-lymphedema in a 16-year-old boy who was born to consanguineous parents and who, in addition, had mild (20 to 40 dB), early onset, sensorineural deafness and skin abnormalities, consisting of angiokeratomas of the face, hands, and feet, and also a large, localized angiokeratoma of the scrotum and the penis (Fordyce type). Both of the proband's parents had profound (>80 dB), congenital, mixed conductive/sensorineural, nonsyndromic deafness to low-mid frequencies. To the best of our knowledge, this constellation of lymphatic, skin, hearing, and systemic abnormalities seen in the proband has not been previously reported.

PubMed

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

2008-05-14T03:58:00.000-07:00

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

2008-04-22T06:55:00.000-07:00

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.

2008-03-27T10:38:00.000-07:00

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.

2008-03-01T20:13:00.000-08:00

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).

2008-02-26T18:20:00.000-08:00

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

2008-02-03T06:38:00.000-08:00

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.

2008-01-19T06:02:00.000-08:00

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

Probiotic Escherichia coli Nissle 1917 Inhibits Leaky Gut by Enhancing Mucosal Integrity

2007-12-24T05:06:00.000-08:00

Probiotic Escherichia coli Nissle 1917 Inhibits Leaky Gut by Enhancing Mucosal Integrity

PLoS ONE. 2007 Dec

Ukena SN, Singh A, Dringenberg U, Engelhardt R, Seidler U, Hansen W, Bleich A, Bruder D, Franzke A, Rogler G, Suerbaum S, Buer J, Gunzer F, Westendorf AM.

Department of Mucosal Immunity, Helmholtz Centre for Infection Research, Braunschweig, Germany.

Abstract

Background

Probiotics are proposed to positively modulate the intestinal epithelial barrier formed by intestinal epithelial cells (IECs) and intercellular junctions. Disruption of this border alters paracellular permeability and is a key mechanism for the development of enteric infections and inflammatory bowel diseases (IBDs).

Methodology and Principal Findings

To study the in vivo effect of probiotic Escherichia coli Nissle 1917 (EcN) on the stabilization of the intestinal barrier under healthy conditions, germfree mice were colonized with EcN or K12 E. coli strain MG1655. IECs were isolated and analyzed for gene and protein expression of the tight junction molecules ZO-1 and ZO-2. Then, in order to analyze beneficial effects of EcN under inflammatory conditions, the probiotic was orally administered to BALB/c mice with acute dextran sodium sulfate (DSS) induced colitis. Colonization of gnotobiotic mice with EcN resulted in an up-regulation of ZO-1 in IECs at both mRNA and protein levels. EcN administration to DSS-treated mice reduced the loss of body weight and colon shortening. In addition, infiltration of the colon with leukocytes was ameliorated in EcN inoculated mice. Acute DSS colitis did not result in an anion secretory defect, but abrogated the sodium absorptive function of the mucosa. Additionally, intestinal barrier function was severely affected as evidenced by a strong increase in the mucosal uptake of Evans blue in vivo. Concomitant administration of EcN to DSS treated animals resulted in a significant protection against intestinal barrier dysfunction and IECs isolated from these mice exhibited a more pronounced expression of ZO-1.

Conclusion and SignificanceThis study convincingly demonstrates that probiotic EcN is able to mediate up-regulation of ZO-1 expression in murine IECs and confer protection from the DSS colitis-associated increase in mucosal permeability to luminal substances.

Introduction

The epithelial layer of the gastrointestinal tract serves as one of the primary interfaces with the outside world. The mucosal surface of the intestinal epithelium is in constant contact with abundant populations of microbes and their metabolites. The intestinal barrier formed by the epithelial cells and the junctional complex, consisting of tight junctions (TJ), adherens junctions, gap junctions and desmosomes, excludes the majority of these microbes and their metabolites from access to the subepithelial cells. Its effectiveness and stability are ensured by the junctional complex [1]. Compromising the integrity of this barrier can promote manifestation of enteric infections and is a key feature of IBDs like Crohn's disease (CD) and ulcerative colitis (UC). Intestinal permeability was also found to be increased in HIV infection [2], and diarrhea is one of the most predominant symptoms of HIV-infected patients. The diarrhea of these patients is mainly due to infections with enteropathogens. However, in a number of HIV patients with gastrointestinal complaints no enteropathogen can be identified [3], [4]. The role of a ‘leaky gut’ in the pathogenesis of gastrointestinal diseases is increasingly recognized. Consequently, reduction of the increased permeability is an interesting target for improvement of the clinical status of gastrointestinal diseases. Tight junctions are intricate macromolecular protein structures located at the most apical regions of the junctional complex, sealing the spaces between the IECs. The first junction-associated protein identified was zonula occludens 1 (ZO-1), with a molecular mass between ~210–225 kDa [5]. This molecule constitutes the structural link between the cytoskeleton and the tight junction by binding to both actin filaments and the TJ protein occludin [6]. Reorganization of TJ proteins like ZO-1, triggered by cytokines produced secondary to the inflammatory processes in IBDs, results in increased intestinal permeability [7], [8]. ZO-2 is another TJ associated protein that forms a complex together with ZO-1 [9] and has recently been shown to be up-regulated by EcN in vitro [10].

Probiotics are defined as live microorganisms which, when administered in adequate amounts, confer health benefits to the host [11]. The use of such microorganisms as novel therapeutic agents and as an alternative to standard medication in gastrointestinal diseases is promising, although their mechanism of action is still under investigation. EcN has evolved into one of the best characterized probiotics, and its therapeutic efficacy and safety have convincingly been proven [12]–[16]. A potential mechanism by which probiotics may exhibit their beneficial activities is modulation of the epithelial barrier function [17], [18]. This hypothesis is also supported by a recent study demonstrating that probiotic Streptococcus thermophilus and Lactobacillus acidophilus can prevent invasion of enteroinvasive E. coli and enhance intestinal epithelial barrier function by amplifying phosphorylation of occludin and ZO-1 in vitro [19].

Driven by mounting evidence affirming the beneficial effects of probiotics on the intestinal epithelial barrier and the already well-documented therapeutic efficacy of EcN, we set out to investigate the impact of EcN on the intestinal epithelial barrier function in vivo.

Materials and Methods

Mice

All mice used in this study were 6–8 weeks old females. Conventional BALB/c mice were obtained from Harlan (Borchen, Germany). Gnotobiotic BALB/c mice were obtained from colonies maintained germfree at the Central Animal Facility of Hannover Medical School, as described previously [20]. The animal experiments reported here were conducted in accordance with the German Animal Welfare Law and with the European Communities Council Directive 86/609/EEC for the protection of animals used for experimental purposes. All experiments were approved by the local institutional animal care and research advisory committee and authorized by the district authority of Braunschweig and Hannover.

Bacterial colonization of gnotobiotic BALB/c mice

EcN or E. coli MG1655 was freshly grown to an OD600=1 (~0.8–1.2×109 CFU/ml) from an overnight culture diluted 1:500 in LB media [21]. Bacteria were collected by centrifugation (1 ml, 3 min at 1000×g). The resulting pellet was redissolved in 200 µl sterile PBS and administered by oral gavage. Application was repeated two days later. After 6 days of colonization, fecal CFU were determined by plate count from pooled stool samples and were calculated per gram feces. The animals grew comparable numbers of both bacterial strains in all experiments averaging 5.8×109 CFU/g feces with EcN and 5.1×109 CFU/g feces with E. coli MG1655. Feces of mice that had received PBS remained sterile.

Induction of colitis

Acute colitis was induced in BALB/c mice by addition of 4–6% dextran sodium sulfate (DSS) (MP Biomedicals, Eschwege, Germany) to drinking water for a period of 8 days, according to a protocol recently described by Grabig et al. [22]. Animals were separated into the following groups: Group I was treated orally with PBS two times a day. Group II received drinking water with 4–6% DSS and was treated orally with PBS twice daily. Group III also received drinking water with 4–6% DSS and was given 1.5–2×108 CFU (Mutaflor mite, Ardeypharm, Germany) EcN twice daily by oral application (DSS+EcN) (Figure 1). Colitis induction indicated by weight loss of the mice was monitored by comparing the body weight upon DSS treatment to the initial body weight of the respective animals.

Isolation of IECs

IECs were isolated as described elsewhere [23]. Briefly, the small and/or large intestine were isolated, rinsed with PBS and opened longitudinally. Mucus was removed by treatment with DTT for 15 min at 37°C on a shaker. Having washed the mucosa in PBS, it was placed in HBSS/1.5 mM EDTA and tumbled for 10 min at 37°C. The supernatant was collected and the remaining mucosa was vortexed in PBS. This supernatant was also collected. Pooled IECs were centrifuged with HBSS/PBS; the pellet was resuspended in FACS buffer (PBS+2% FCS+2 mM EDTA) and stained with anti-CD45 APC antibody (BD Biosciences, Heidelberg, Germany) to deplete hematopoietic cells [24]. IECs were sorted with a MoFlow cell sorter (Cytomation, Fort Collins, CO, USA).

RNA isolation and expression analysis

To analyze ZO-1 and ZO-2 mRNA expression in murine IECs, total RNA was isolated using the RNeasy Minikit (Qiagen, Hilden, Germany) with on-column DNase digestion using the RNase-Free DNase set (Qiagen). Isolated mRNA was reverse transcribed with 200 U Superscript II® (Invitrogen, Karlsruhe, Germany), oligo dT- and random hexamer primers (Invitrogen). PCR was performed using the following primers: ribosomal protein 9 (RPS9) mouse (mm) sense primer CTG GAC GAG GGC AAG ATG AAG C, RPS9 mm anti-sense primer TGA CGT TGG CGG ATG AGC ACA; ZO-1 mm sense primer TTT TTG ACA GGG GGA GTG G, ZO-1 mm anti-sense primer TGC TGC AGA GGT CAA AGT TCA AG; ZO-2 mm sense primer CTA GAC CCC CAG AGC CCC AGA AA, ZO-2 mm anti-sense primer TCG CAG GAG TCC ACG CAT ACA AG. Quantitative real-time RT-PCR was done with the GeneAmp 5700 Sequence Detection System (Perkin Elmer, Rodgau-Jügesheim, Germany) using Brilliant SYBR Green QPCR Core Reagent Kit (Stratagene, Heidelberg, Germany). RPS9 served as control.

Western blot analysis

To examine the ZO-1 protein expression in IECs, lysates of sorted cells from colonized gnotobiotic mice were homogenized and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS–PAGE), followed by blotting the proteins on a PVDF membrane. After the blocking of unsaturated protein binding sites, the membrane was incubated with the primary antibody rabbit anti-ZO-1 (Zymed, South San Francisco, CA, USA) or rabbit anti-β actin (Sigma-Aldrich, Taufkirchen, Germany) and the secondary antibody goat anti-rabbit IgG (Dianova, Hamburg, Germany), respectively.

Electricphysiologic measurements

The colonic mucosa was mounted between two chambers with an exposed area of 0.625 cm2 and placed in an Ussing chamber. Parafilm “O” rings were used to minimize edge damage to the tissue where it was secured between the chamber halves. Tissues were bathed with HCO3− containing solutions on both sides which were gassed with 95% O2/5% CO2. The composition (in mM) was 108 NaCl, 22 NaHCO3, 3 KCl, 1.3 MgSO4, 2 CaCl2, 1.5 KH2PO4, at pH 7.4. The serosal bath contained (in mM) 8.9 glucose, 10 sodium pyruvate, 10−3 indomethacin, and 10−3 tetrodotoxin; the luminal bath contained 8.9 mannitol and 10−2 amiloride (to block potential amiloride-sensitive Na+ channels). Short-circuit current (Isc), potential difference (PD) and tissue resistance (R) were recorded using the Mussler 6-channel voltage clamp system (Mussler, Aachen, Germany). 22Na+ studies were performed during voltage clamp to zero PD. 74 kBq/ml 22Na+ was added to either the serosal or the mucosal solution after reaching stable electrical parameters. After stabilization (approximately 20–30 minutes after mounting), a 45-minute period of equilibration followed, then aliquots were taken in 15-minute intervals (two intervals for basal flux, two after forskolin, and two after luminal glucose). For the presented results, we used the values from the second basal flux period, the first period after forskolin, and the first period after glucose. There were no statistically significant differences between the values obtained in the first and second flux period after forskolin and after glucose. Radioactivity was determined in a liquid scintillation counter, and bidirectional flux rates for the respective substance were calculated. The values for Isc represent the average value of the 15-minute period.

Measurement of colonic epithelial permeability

Animals were maintained with free access to food and water. Induction of anesthesia was achieved by the administration of 10 µl/g intraperitoneal haloperidol/midazolam/fentanyl cocktail (haloperidol 12.5 mg/kg, fentanyl 0.325 mg/kg and midazolam 5 mg/kg body weight). The lower abdomen was opened by one small central incision, and a small polyethylene tube (PE100) with a distal flange was advanced to the proximal colon (immediately after the cecum), and secured by a ligature that served as inlet tube. A PE200 flanged tubing was inserted through the rectum and secured by ligature to allow for drainage through the rectum. The isolated colon segment with an intact blood supply was gently flushed and then perfused (Perfusor compact, BRAUN, Melsungen, Germany) at a rate of 30 ml/h with 150 mmol/l NaCl for 5 min, followed by perfusion with 1% Evans Blue in NaCl for 10 min. To wash-out the sticking dye in the mucus, the lumen was perfused with 6 mM acetylcysteine for 5 min followed by NaCl for 10 min. The animals were then sacrificed by cervical dislocation and the ligated colon was removed. The colon was rinsed once more with saline, its length was recorded and it was then placed in 5 ml N,N- dimethyl-formamide overnight to extract the Evans Blue. The dye concentration was measured spectrophotometrically at 620 nm (Hitachi U-2000 UV/VIS, Hitachi, Japan).

Immunofluorescence

Tissue sections were fixed with 4% paraformaldehyde, washed extensively and blocked with porcine serum. Subsequently, the sections were incubated with the primary antibody rabbit anti-ZO-1 (Zymed) followed by incubation with a Cy3 labeled secondary goat anti-rabbit IgG antibody (Jackson Immunoresearch, Cambridgeshire, UK). The sections were then dried, covered with gelatine and visualized by fluorescence microscopy.

Statistical analysis

Statistical analysis was performed with Origin 7.5 software (OriginLab, Northampton, MA, USA). For analysis of numeric values, the one-tailed analysis of variance and the Student's t-test were used. A p-value of <0.05>

Results

ZO-1 mRNA and protein expression are elevated in gnotobiotic mice colonized with EcN

In order to investigate the impact of a single bacterial species on host IEC gene expression, we established a model for colonization of gnotobiotic mice with EcN and E. coli MG1655. To further investigate the in vivo impact of EcN on the epithelial barrier, primary IECs from the intestine of gnotobiotic mice were isolated and sorted by FACS resulting in an IEC population with greater than 94% purity (Figure 2A). ZO-1 is a TJ protein which has been described to play an important role in the prevention of intestinal barrier disruption by probiotics. Therefore, we investigated whether EcN differentially regulates ZO-1 mRNA expression in vivo. As depicted in figure 2B colonization of gnotobiotic mice with EcN resulted in a specific up-regulation of ZO-1 mRNA in IECs (p<0.05).>Figure 3A). Comparison of ZO-1 staining along the surface of the crypts revealed only a slight increase of ZO-1 protein in IECs of mice colonized with EcN. To further analyze the up-regulated ZO-1 expression at protein level, isolated IECs were investigated by Western blotting. In comparison to IECs isolated from control mice and those colonized with E. coli MG1655, IECs from EcN treated animals showed a markedly elevated expression of ZO-1 protein (Figure 3B). Thus, we could clearly demonstrate that colonization of gnotobiotic mice with EcN specifically up-regulates ZO-1 expression at the mRNA as well as at the protein level. Due to the important functional role of ZO-1 in the junctional complex, these findings suggest that enhancement of the intestinal epithelial barrier function by EcN could at least in part be attributed to up-regulation of ZO-1. It has also been previously demonstrated that treatment of T84 cells with EcN leads to an up-regulation of ZO-2 in vitro [10]. In contrast to the data generated with the T84 cell line, analysis of ZO-2 mRNA expression in IECs isolated from gnotobiotic mice colonized with EcN or E. coli MG1655 did not result in an increase of ZO-2 mRNA levels (fold change <2)>Figure 2C).

Elevated ZO-1 expression after EcN treatment in experimental colitis

It has been shown that the impaired barrier function in IBD is associated with an altered TJ structure [7], [8], [25]–[28]. Recently it was demonstrated that EcN, used as a therapeutic for the treatment of ulcerative colitis, ameliorates acute colitis in mice [29]. These observations raised the question whether an alleviated acute colitis-as a consequence of EcN treatment-may be due to its effect on the epithelial barrier. To investigate this aspect acute colitis was induced in BALB/c mice by administration of 4–6% DSS in drinking water for a period of 8 days [22]. In addition, mice were given 1.5–2×108 CFU EcN or PBS orally two times a day. In contrast to untreated control mice of group I, mice exposed to DSS (group II) developed symptoms of acute colitis with diarrhea, rectal bleeding and wasting, loosing 10% of their initial body weight within 8 days (Figure 4A). Concomitant oral administration of EcN (group III) significantly ameliorated the severity of DSS-induced colitis and the loss of body weight was reduced (6%) (p<0.05).>Figure 4B). Colonic inflammation is correlated with strong infiltration of hematopoietic cells into the intestine. To further elaborate the beneficial effect of EcN in DSS treated mice, FACS analysis of hematopoietic cells in the colon was performed. Consistent with the reduction in loss of body weight and colon shortening, mice treated with DSS and EcN (group III) exhibited significantly lower leukocyte infiltrates in the colon in comparison to DSS treated mice (group II) (Figure 4C). To analyze whether the improved state of health after EcN treatment is accompanied with an increased ZO-1 expression, IECs were isolated from the colon of treated mice and analyzed for ZO-1 gene expression. IECs of mice treated with DSS and EcN showed elevated ZO-1 mRNA levels in comparison to DSS treated animals (p<0.05)>Figure 5). Although ZO-2 mRNA was not up-regulated by EcN under healthy conditions, a slight increase of ZO-2 mRNA could be detected in DSS mice treated with EcN (data not shown). These results further underline the beneficial effects of EcN on the intestinal barrier even under inflammatory conditions.

Electrolyte transport capacity and tissue resistance after EcN treatment in experimental colitis

In order to assess the electrolyte transport capacity and the tissue resistance (R) in acute DSS colitis, and the influence of EcN treatment on these parameters, the basal and forskolin-stimulated Isc, basal and forskolin-inhibited Na+ absorption, and the tissue-resistance R in isolated colonic mucosa of inflamed DSS treated mice (group II), DSS and EcN treated mice (group III), and healthy controls (group I) were studied. To ensure that any potential inflammation-related changes would be detected, the mucosa was neither stripped nor were the prostaglandin production or neural transmission inhibited. Interestingly, no difference was found in either the basal and forskolin-stimulated Isc (Figure 6A), or in the transmucosal electrical resistance (R) between the different groups (data not shown). This demonstrates that in acute DSS colitis, the anion secretory capacity, which originates from the cryptal region of the colonic epithelium, is not perturbed. On the other hand, net Na+ absorption was significantly decreased in colonic mucosa of DSS and EcN treated mice (group III), and reversed to Na+ leakage into the luminal fluid in the mucosa of DSS treated mice (group II) (Figure 6B). Since the transporters for Na+ absorption are expressed in the surface colonic enterocytes, this demonstrates severe alterations in surface cell electrolyte transport following treatment with EcN.

Reduction of colonic epithelial permeability after EcN treatment in experimental colitis

In order to address the question whether the pronounced ZO-1 expression in EcN treated mice (group III) impacts the permeability of the colonic epithelium for transport of luminal substances, the uptake of Evans Blue into the mucosa in anesthetized mice after a short-term luminal perfusion with the dye was measured. In comparison to untreated mice (group I), a strong increase of Evans Blue uptake into the colonic mucosa of DSS treated mice (group II), and a much lesser increase into the colonic mucosa of DSS and EcN treated mice (group III) was detected (Figure 7). This demonstrates that the concomitant application of EcN during colitis induction with DSS markedly ameliorates the leakiness of the colonic epithelium.

Discussion

The current study establishes that E. coli Nissle 1917 positively impacts the intestinal epithelial barrier in vivo in three different ways. First, EcN is capable of producing a specific up-regulation of ZO-1 expression in IECs of healthy gnotobiotic mice. When treated concomitantly with EcN, IECs of mice with DSS-induced colitis also exhibit a pronounced expression of ZO-1 mRNA. Finally, EcN provides protection against the DSS-mediated leakiness of the gut in our mouse model. Our data strongly suggest that one of the protective effects of EcN treatment on colitis prevention could be a modulation of tight junctional integrity which in turn leads to preserved intestinal barrier function against noxious or infectious agents.

Critical for the development of IBDs are imbalances in mucosal immunity as well as a disturbed function of the epithelial barrier, which leads to a marked infiltration of luminal microflora [30]. Moreover, in the majority of cases, gastrointestinal diseases develop from the disruption of the intestinal epithelial barrier by enteropathogenic bacteria that alter the cellular cytoskeleton [31], [32] or affect specific tight junction proteins like ZO-1 [33]. In the past years, probiotics have been shown to be effective in the treatment of mild to moderately active IBD [18] and to reduce inflammation in animal models of colitis [29], [34]–[36]. Three large clinical trials have investigated the therapeutic efficacy of EcN in maintaining remission of UC. EcN was reported to be as efficacious as standard medication in preventing the relapse of UC [12]–[14]. Although the mechanisms leading to relapses in the pathogenesis of IBDs have not yet been clarified, there is growing evidence that increased intestinal permeability plays a key role. This report is the first to demonstrate a direct influence of the therapeutic EcN on expression of the TJ associated molecule ZO-1 in vivo under healthy and inflammatory conditions. We demonstrate that EcN specifically up-regulates ZO-1 expression both at the mRNA and at the protein level in IECs of gnotobiotic mice. Very recently, Zyrek et al. described the up-regulation of ZO-2 after EcN exposure to the T84 cell line in vitro [10]. However, in this study analysis of IECs from gnotobiotic mice colonized with EcN did not reveal a differential ZO-2 mRNA expression in vivo following EcN treatment.

In order to study functional consequences of DSS-mediated colitis and EcN treatment and also the potential significance of ZO-1 up-regulation for an enhancement of intestinal barrier function, we performed experiments aimed to assess transport and barrier function of the colonic epithelium of DSS-treated mice with and without application of EcN. To evaluate secretory and absorptive function of the colonic epithelium, we measured the basal and forskolin-stimulated Isc (which is an assessment of the electrogenic anion secretion, and its stimulation by an increase in intracellular cAMP levels), as well as net Na+ absorption before and after an increase in cAMP levels. Interestingly, after one week of DSS treatment, the acute colitis did not compromise the secretory function of the epithelium at all, but abolished the Na+ absorptive function completely. Na+ absorption is mediated by electroneutral (apical Na+/H+ exchangers NHE3 and possibly NHE2) and electrogenic (apical Na+ channel ENaC) pathways in the colon [37]. Na+ absorptive transporters are compromised during acute colitis, and this is one major reason for diarrhea during colonic inflammation [38].

Active fluid absorption is also dependent on intact tight junctions, otherwise a phenomenon called “leak flux diarrhea” occurs [39]–[41]. A cytokine-induced intestinal barrier dysfunction via a leak flux mechanism has recently been proposed by Schmitz et al. as potential cause for non-infectious diarrhea in HIV-infected patients, in addition to mucosal transformation with a consecutive malabsorptive mechanism [42]. When cholera toxin deletion mutants of Vibrio cholerae were given to healthy volunteers they still developed mild diarrhea [43]. Searching for the causative agent led to the detection of the ZOT, a toxin which causes a disruption of the tight junctions in isolated intestine [44]. Later studies revealed yet another agent from Vibrio cholerae, the HA/protease, that specifically interferes with the tight junction proteins occludin and ZO-1 resulting in barrier disruption [45], [46]. Thus, it became clear that the integrity of the tight junctions was necessary for the maintenance of an absorptive state of the gut epithelium. In addition, it was found that a disruption of the tight junctional complex allowed easier permeation of substances from the lumen [47]. Our experiments demonstrated a strongly elevated influx of Evans Blue into the colonic mucosa in the live mouse with DSS colitis which is indicative of increased gut permeability. Much less dye was bound to IECs of mice treated concomitantly with EcN. Combined with the absorptive Na+ flux in these animals, this is likely to explain the nearly normal appearance of the feces in the DSS plus EcN treated mice compared to the liquid stools of the mice with DSS colitis. It is feasible that the reduction of DSS-mediated downregulation of ZO-1 expression by EcN treatment is one reason for the enhanced barrier stability.

Several lines of evidence suggest that increased intestinal permeability has a central role in the pathogenesis of IBDs. For example, between 10–20% of presymptomatic CD patients have been shown to exhibit increased gut permeability [48], [49]. Alteration of TJ structure in UC for instance results in impaired barrier function [40]. Localization studies in mucosal biopsies of IBD patients have revealed disappearance of key TJ proteins from intercellular junctions [26], [50]. Probiotics have been shown to reduce the increased intestinal permeability in vitro [51] as well as in clinical trials [52]. Here we demonstrate for the first time that the substantially increased intestinal permeability of mice treated with DSS is significantly alleviated by simultaneous oral application of EcN. In addition, we observed an altered ZO-1 expression profile in IECs of mice with DSS-induced colitis. Recently, a study described the translocation of ZO-1 from the apical to the basolateral side in CD patients [53] indicating an alteration of ZO-1 under pathological conditions. Moreover, using a mouse colitis model, Resta-Lenert et al. have shown that the increase in intestinal permeability is associated with a decrease of occludin and ZO-1 phosphorylation [54].

However, administration of EcN in our mouse models not only diminished the clinical signs of colitis like colon shortening and weight loss, but also prevented an increase in intestinal permeability while concurrently minimizing the down-regulation of IEC ZO-1 expression. This indicates a considerable association between the severity of colitis, as evidenced by increased gut permeability, and altered ZO-1 mRNA expression levels. It can be speculated that the rise of ZO-1 expression results in a reduced intestinal permeability by an enhanced junctional complex or a reinforced interaction of the junctional complex with actin. This hypothesis is consistent with recently published data regarding the antrum mucosal protein (AMP)-18 that ameliorates DSS colitis in mice and also enhances accumulation of occludin and ZO-1 in TJ domains in vitro [55]. Since AMP peptide also prevented a fall in transepithelial resistance during disruption of actin filaments and stabilized the perijunctional actin during oxidant injury, it has been suggested that AMP-18 could protect the intestinal mucosal barrier by acting on specific TJ proteins and stabilizing perijunctional actin [55]. Using another murine colitis model, administration of n-3 polyunsaturated fatty acids resulted not only in reduced pathological scores but also an increase of ZO-1 protein expression [56].

The present study clearly demonstrates that EcN specifically up-regulates ZO-1 mRNA expression in IECs in vivo. Together with the influence of EcN on intestinal permeability and an enhanced ZO-1 expression under pathological conditions, it can be speculated that EcN augments mucosal barrier function. These in vivo results corroborate the in vitro findings from other groups by demonstrating that probiotic EcN plays an important role in the maintenance of intestinal barrier function. An improved barrier integrity elicited by EcN is an appealing explanation for the success of this probiotic in the therapy of UC and could be an important aspect in treating further human intestinal disorders, including HIV-associated diarrhea.

Acknowledgments

We thank further Lothar Gröbe for FACS sorting, Marco Metzger for performing immunohistochemistry and Silvia Prettin for technical support as well as Anna Smoczek and Ina Köhn for animal care. The authors also gratefully acknowledge Michael J. Schubert for critically reading the manuscript.

Footnotes

Competing Interests: The authors have declared that no competing interests exist.
Funding: Supported by grants from the Deutsche Forschungsgemeinschaft (SFB 621).

PLOS One

Immunohistochemical studies in a hydroptic fetus with pulmonary lymphangiectasia and trisomy 21.

2007-12-21T02:10:00.000-08:00

Immunohistochemical studies in a hydroptic fetus with pulmonary lymphangiectasia and trisomy 21.
Lymphology. 2007

Rutigliani M, Boccardo F, Campisi C, Bonioli E, Fulcheri E, Bellini C.
Department of Pathology (DICMI), University of Genoa, Gaslini Institute, Genova, Italy.

This case report presents a hydroptic trisomy 21 fetus affected by lymphatic dysplasia with no other malformations. Our studies using CD31, CD34, smooth muscle actin, desmin, and D2-40 antibodies immunohistochemistry confirm the diagnosis of severe pulmonary lymphangiectasia associated with lymphangiectasia ih the mediastinum and small bowel.

PMID: 18062612 [PubMed - in process]

Sucessful dietetic-therapy in primary intestinal lymphangiectasia and recurrent chylosa ascites: a case report

2007-12-15T03:32:00.000-08:00

Sucessful dietetic-therapy in primary intestinal lymphangiectasia and recurrent chylosa ascites: a case report
Nutr Hosp. 2007 Nov-Dec

Martín CC, García AF, Restrepo JM, Pérez AS.
Unidad de Nutrición Clínica y Dietética, Servicio de Endocrinología y Nutrición, Hospital Universitario Virgen Macarena, Sevilla, España. smaradigna@hotmail.com

OBJECTIVES: Primary intestinal lymphangiectasia is a lymphatic system's disorder, where lymphatic drainage is blockaged. Clinically it produces malabsorption, protein-losing enteropathy, hypogammaglobulin in blood, and several degrees of malnutrition. Its treatment is not easy and includes dietetic-therapy and drugs.

MATERIAL AND METHOD: A 35-year-old-woman case report is exposed. She has recurrent chylosa ascites, requiring several admissions and evacuatory paracentesis. After food-fat was replaced by medium-chain triacyl-glicerol-enriched diet, a clinical, analytical and anthropometric improvement was demonstrated.

CONCLUSSIONS: The major way of treatment in intestinal lymphangiectasia in this case is the employement of specific-diet and adaptaded-basic-food. It's difficult and high collaboration of the patient is required, being necessary medical revisions during the whole life, due to the not well known evolution of this long-standing disease.

PMID: 18051999 [PubMed - in process]

Lymphangiogenesis in Crohn’s disease: an immunohistochemical study using monoclonal antibody D2-40

2007-11-30T03:24:00.000-08:00

Lymphangiogenesis in Crohn’s disease: an immunohistochemical study using monoclonal antibody D2-40
F. Pedica1 , C. Ligorio1, P. Tonelli2, S. Bartolini3 and P. Baccarini1
(1)
Section of Pathology, Bellaria Hospital, University of Bologna, Via Altura 3, 40139 Bologna, Italy
(2)
General Surgery 1, Department of Medicine and General Surgery, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy
(3)

Unity of Oncology, Bellaria Hospital, Bologna, Italy
Received: 17 September 2007 Revised: 24 October 2007 Accepted: 26 October 2007 Published online: 27 November 2007

Abstract

Crohn’s disease (CD) is a chronic inflammatory bowel disorder of unknown etiology. An involvement of the intestinal lymphatic system has been suggested. Recently, monoclonal antibodies have become available to distinguish lymphatic vessels from blood vessels. The aim of the study was to examine the distribution of lymphatic vessels in ileal and colic walls of patients affected by CD and compare it with healthy controls and other inflammatory bowel diseases. Twenty-eight cases of CD, 13 cases of other inflammatory bowel diseases, and 10 normal ileal and colic walls were studied. Immunohistochemical staining was performed using the monoclonal antibody D2-40. Quantification of lymphatic vessels was performed by identifying four fields with high density of lymphatics and then counting the number of lymphatic vessels at high resolution. Lymphatic diameter was also evaluated by using an ocular micrometer. Lymphatic vessels showed the highest density in CD specimens. The median number of lymphatics was significantly higher both in ileal and colic samples of CD than the other inflammatory diseases as well as normal controls. Moreover, in patients with CD, diffuse lymphangiectasia was also observed. The present data suggest that lymphangiogenesis and lymphangiectasia probably play a role in the pathogenesis of CD.

Springer Link

Changes in regulatory molecules for lymphangiogenesis in intestinal lymphangiectasia with enteric protein loss.

2007-11-17T03:30:00.000-08:00

Changes in regulatory molecules for lymphangiogenesis in intestinal lymphangiectasia with enteric protein loss.

J Gastroenterol Hepatol. 2007 Nov 14

Hokari R, Kitagawa N, Watanabe C, Komoto S, Kurihara C, Okada Y, Kawaguchi A, Nagao S, Hibi T, Miura S.Department of Internal Medicine, National Defense Medical College, Saitama, Japan.

Background and Aim: Vascular endothelial growth factor receptor 3 (VEGFR3) and LYVE-1 are specifically expressed in the endothelium of the lymphatic systems. VEGF-C, D, FOXC2, Prox 1, and SOX18 are known to play central roles in lymphatic development. We investigated the expression of regulatory molecules for lymphangiogenesis in the duodenal mucosa of idiopathic intestinal lymphangiectasia.

Methods: Biopsy samples were obtained from duodenal biopsies in patients with intestinal lymphangiectasia complicated with protein-losing from white spot lesions in which lymphangiectasia was histologically confirmed. Immunohistochemical analysis for VEGFR3 and LYVE-1 was performed. mRNA expression of VEGF-C, VEGF-D, VEGFR3, and transcription factors was determined by the quantitative reverse transcription-polymerase chain reaction method.

Results: In the control mucosa, VEGFR3 was weakly expressed on the central lymphatic vessels in the lamina propria and LYVE-1 was expressed mainly on the lymphatic vessels in the submucosa. In intestinal lymphangiectasia, VEGFR3 and LYVE-1 expression levels were increased on the mucosal surface corresponding to widely dilated lymphatic vessels, while they were decreased in the deeper mucosa. mRNA expression study showed a significant increase in the expression level of VEGFR3 in lymphangiectasia, but the expression of VEGF-C and -D mRNA was significantly suppressed compared with that in controls despite the presence of lymphangiectasia. The mRNA expression levels of FOXC2 and SOX18 were also decreased, whereas Prox 1 was not altered.

Conclusions: There is an altered expression of regulatory molecules for lymphangiogenesis in the duodenal mucosa in these patients.

PMID: 18005011 [PubMed - as supplied by publisher]

Osteomalacia in a patient with primary intestinal lymphangiectasis (Waldmann's disease).

2007-11-15T16:13:00.000-08:00

Osteomalacia in a patient with primary intestinal lymphangiectasis (Waldmann's disease).

Joint Bone Spine. 2007 Aug 29
Sahli H, Ben Mbarek R, Elleuch M, Azzouz D, Meddeb N, Chéour E, Azzouz MM, Sellami S.
Rheumatology Department, La Rabta Hospital, 1007 Tunis, Tunisia.

Keywords: Waldmann's disease; Primary intestinal lymphangiectasis; Intestinal malabsorption; Osteomalacia; Vitamin D

Primary intestinal lymphangiectasis (PIL), also known as Waldmann's disease, is a rare protein-losing enteropathy characterized by abnormal enlargement of the lymphatic ducts in the bowel wall. The symptoms usually start in early infancy. We report a case of osteomalacia in a 63-year-old patient with delayed-onset of PIL, for which she was on dietary treatment. She presented with a 3-year history of mechanical pain in the back and pelvis. Mild ascites and edema with functional impairment of the lower limbs were noted. The neurological evaluation was normal. Blood tests showed hypocalcemia, hypophosphatemia, alkaline phosphatase elevation, and evidence of intestinal malabsorption. Radiographs of the pelvis disclosed a fracture, Looser's zones in the iliopubic rami and left femoral neck, and a washed-out appearance of the vertebras. Dual-energy X-ray absorptiometry showed bone loss with T-score values of -1.2SD at the lumbar spine and -2.5SD at the femoral necks. A diagnosis of osteomalacia related to vitamin D deficiency was given. Serum 25-OH-vitamin D was 18.2ng/ml (normal, 20-40ng/ml) and serum parathyroid hormone was 620pg/ml (normal, 15-65pg/ml), suggesting secondary hyperparathyroidism. Intramuscular vitamin D was given, together with oral calcium and an adequate diet. At follow-up 8 months later, small improvements were noted in the symptoms and absorptiometry findings.

Elsevier

Edema and protein-losing enteropathy (lymphangiectasia) complicating chronic constrictive pericarditis associated with an ascending aortic aneurysm

2007-11-09T19:28:00.000-08:00

Edema and protein-losing enteropathy complicating chronic constrictive pericarditis associated with an ascending aortic aneurysm

**Here is an interesting abstract showing how swelling (ab edema) from pericarditis will trigger protein losing enteropathy (dilation of intestinal lymphatics/protein lose)**

Presse Med. 2007 Nov 5
Article in French]

Lesaffre F, Sandras R, Saade YA, Duval S, Metz D.Département de cardiologie et pathologies vasculaires, CHU de Reims, Hôpital Robert Debré, Avenue du Général Koenig, F-51100 Reims, France.

INTRODUCTION: Chronic constrictive pericarditis is suspected on clinical and echocardiographic grounds. Its treatment is surgical.

CASE: We report here the case of a 45-year-old man, admitted for edema characteristic of lymphatic obstruction. Examination revealed ascending aorta ectasia, associated with chronic constrictive pericarditis. Measurement of alpha-1 antitrypsin clearance confirmed protein-losing enteropathy. Total recovery followed pericardectomy and aneurysm resection.

DISCUSSION: The clinical edema in this case was due to several phenomena: protein-losing enteropathy from a functional lymphatic overload, induced by chronic constrictive pericarditis and by compression of the right atrium and vena cava by an aortic aneurysm. The hypoalbuminemia induced by protein loss may also magnify edema. An association between chronic constrictive pericarditis and ascending aortic aneurysm is uncommon. No cause for this association was found.

PMID: 17988828 [PubMed - as supplied by publisher]

Protein losing enteropathy (PLE) detected by Tc99m-labelled human serum albumin abdominal scintigraphy--case report

2007-10-27T09:23:00.000-07:00

Protein losing enteropathy (PLE) detected by Tc99m-labelled human serum albumin abdominal scintigraphy--case report

Przegl Lek. 2003

Hubalewska-Hoła A, Sowa-Staszczak A, Szczerbiński T, Lis G, Huszno B, Szybiński Z.
Katedra i Klinika Endokrynologii, Collegium Medicum, Uniwersytetu Jagiellońskiego w Krakowie. alahuh@endo.cm-uj.krakow.pl

Protein losing enteropathy (PLE) is a gastrointestinal disorder that is associated with excessive loss of plasma protein into the gut resulting from abnormal mucosal permeability. The disease is usually caused by inflammation. The loss of protein in PLE is a nonselective process affecting albumin, globulin and transferrin. Abdominal scintigraphy with human serum albumin marked by Tc99m seems to be an easy and sensitive method for diagnosing PLE. An 4-year-old girl was presented to an outside Pediatric Department due to hypoproteinemia and recurrent pneumonia which had caused several prior hospitalizations. The laboratory tests revealed hypoproteinemia, hypoalbuminemia, low level of IgG, sideropenia, and a decreased level of T lymphocytes. The loss of protein into the gut was confirmed by fecal clearance of alfa-1 antitrypsin. Only nonspecific inflammation was detected by biopsy of the small intestine. These clinical and laboratory findings, quickly decreasing IgG and albumin levels in spite of i.v. supplementation and the lack of proteinuria permitted PLE diagnosis. The abdominal scintigraphy was planned to assess and localise protein losing through GIT and for strategy of possible surgical treatment.

Abdominal dynamic scintigraphy was performed immediately after the injection of 300 MBq Tc99m human albumin. 90 images were taken within 180 minutes. Delayed abdominal images were obtained 6 and 24 hours after the tracer injection. Anterior abdominal scintigraphy showed pathological activity of Tc99m-albumin in small bowel in the upper left segment of the abdomen in the 40th minute after injection. Extensive accumulation of albumin was seen in the 160th minute. Delayed images, after 3 and 6 hours, revealed translocation of the tracer into the lower right abdominal segment. The further passage and tracer concentration was detected in ascendant and transverse colon.

Based on the laboratory tests and scintigraphic images the girl was suspected to have segmental lymphangiectasia of small intestine and was qualified for laparatomy and, possibly, for surgical resection of the pathologically changed bowel. However, diffuse pathological changes revealed in the guts during the operation, rendered the operation impossible. Tc99m-labelled human serum albumin scintigraphy may be considered the method-of-choice in the diagnosis of protein-losing enteropathy. However, in this test the assessment of the enteropathy dimension is difficult and surgical treatment should be planned with caution.

PMID: 15065343 [PubMed - indexed for MEDLINE]

Hypocalcaemic seizures: sign of intestinal disease lymphangiectasia?

2007-09-26T05:30:00.000-07:00

Hypocalcaemic seizures: sign of intestinal disease?

Acta Gastroenterol Belg. 2007 Apr-Jun

Van Biervliet S, Velde SV, Robberecht E, Van Winckel M.
Department of paediatric gastroenterology, Ghent University Hospital, Ghent, Belgium. Stephanie.vanbiervliet@ugent.be

We describe a baby admitted with convulsions, fever, low protein level and coagulation abnormalities where congenital intestinal lymphangiectasia was confirmed by endoscopy and histology. Treatment with a low fat diet, supplemented with medium chain triglycerides (MCT), resulted in a disappearance of the symptoms and normal growth. When confronted with seizure-like attacks, electrolyte disturbances and hypo-albuminemia one should consider the possibility of protein losing enteropathy.

PMID: 17715644 [PubMed - in process]

Clinico-pathological Characteristics of Congenital Pulmonary Lymphangiectasis: Report of Two Cases.

2007-09-12T18:24:00.000-07:00

Clinico-pathological Characteristics of Congenital Pulmonary Lymphangiectasis: Report of Two Cases.

J Korean Med Sci. 2007 Aug

Eom M, Choi YD, Kim YS, Cho MY, Jung SH, Lee HY.

Department of Forensic Medicine, Western District Office, National Institute of Scientific Investigation, Jangseong, Korea.

Department of Pathology, Wonju College of Medicine, Yonsei University, Wonju, Korea. soonheej@yonsei.ac.kr

Congenital pulmonary lymphangiectasis (CPL) is a rare, poorly documented disease, characterized by abnormal dilatation of pulmonary lymphatics without lymphatic proliferation. This disease is seen almost exclusively in infancy and early childhood. It can usually be divided into primary (congenital) and secondary forms. The primary form presents in neonates, and the patients mostly die due to the respiratory distress, shortly after birth. The authors experienced two cases of primary CPL in a 13-day-old male neonate and a one-day-old male neonate, showing prominent lymphatic dilatation in the septal, subpleural, and peri-bronchial tissue throughout both lungs. The latter case was associated with congenital cardiac anomaly including single ventricle. These are unique cases of CPL in Korea of which the diagnosis was established through post-mortem examination. Therefore, the authors report these two cases with primary CPL with a review of the literature.

Journal of Korean Medical Science

Renal lymphangiectasia.

2007-08-20T09:51:00.000-07:00

Renal lymphangiectasia.

Br J Radiol. 2007 Jun

Ashraf K, Raza SS, Ashraf O, Memon W, Memon A, Zubairi TA.
Cross-sectional Imaging Section, James Paget University Hospitals, Norfolk NP31 6LA, UK. kashif.ashraf@jpaget.nhs.uk

Renal lymphangiectasia is a benign disorder of renal lymphatics. Seldom observed, the pathophysiology is unclear. The clinical course may vary, and management alternatives range from percutaneous drainage in symptomatic cases to pharmacological substitutes in the form of anti-hypertensives and diuretics. We present a case of bilateral perinephric collections on imaging, which presented with gross ascites, abdominal pain and reversible hypertension. Ultrasound examination indicated ascites.

Computerized tomography revealed bilateral symmetrical large perinephric collections. This is consistent with the appearance of renal lymphangiectasis (enlarged kidneys with fluid collections seen to be abutting the surrounding structures) reported in the literature. Needle aspiration of the perinephric fluid was undertaken, and laboratory analysis was carried out, which revealed a protein level of 643 mg dl(-1) and a total leucocyte count of 50, of which 80% were lymphocytes.

Thereafter, a diagnosis of renal lymphangiectasia was made, and conservative treatment with diuretics and anti-hypertensives was initiated. Reassessment at subsequent follow up visits showed improvement in the patient's clinical condition.

British Journal of Radiology

Intestinal Lymphangiectasia With Protein-Losing Enteropathy in Waldenstrom Macroglobulinemia.

2007-07-22T04:27:00.000-07:00

Intestinal Lymphangiectasia With Protein-Losing Enteropathy in Waldenstrom Macroglobulinemia.

Medicine (Baltimore). 2007 Jul

Pratz KW, Dingli D, Smyrk TC, Lust JA.
From Department of Medical Oncology (KWP), Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland; Division of Hematology (DD, JAL), Department of Internal Medicine; and Department of Laboratory Medicine and Pathology (TCS), Mayo Clinic College of Medicine, Rochester, Minnesota.

Gastrointestinal complications of Waldenstrom macroglobulinemia (WM) are unusual but often treatable. We report a case of WM associated with significant gastrointestinal involvement manifest as chronic diarrhea with protein-losing enteropathy and recurrent venous thromboses. Small bowel biopsy was negative for amyloidosis but revealed intestinal lymphangiectasia with deposition of monoclonal IgM. The patient was treated with cyclophosphamide, vincristine, and prednisone with rapid and complete resolution of the peripheral edema and diarrhea. We follow the case report with a retrospective analysis of patients with WM and gastrointestinal symptoms seen at our institution, and review the available literature on this unusual association.

An increased awareness of the gastrointestinal manifestations of WM may help to explain and to treat the chronic, debilitating, and potentially life-threatening symptoms in patients with this lymphoproliferative disorder.

Lippincott, Williams & Wilkins

Clinical application and diagnostic yield of wireless capsule endoscopy in children

2007-07-15T04:30:00.000-07:00

Clinical application and diagnostic yield of wireless capsule endoscopy in children

J Laparoendosc Adv Surg Tech A. 2007 Jun

Antao B, Bishop J, Shawis R, Thomson M.
Pediatric Surgical Unit and Sheffield Children's Hospital, Sheffield, United Kingdom.

Objective:

The small bowel is anatomically difficult to examine and was investigated by invasive, indirect modalities, such as push enteroscopy and small bowel follow-through. The aim of this study was to assess the efficacy and clinical impact of wireless capsule endoscopy (WCE) in children.

Materials and Methods:

Over the last 3 years (2002-2005), 37 patients with suspected small-bowel disease were investigated with WCE at a median age of 11 years (range, 16 months-16 years). The indications for WCE was suspected Crohn's disease (CD) (18), obscure or occult gastrointestinal bleeding (7), polyposis syndromes (5), protein losing enteropathy (4), recurrent abdominal pain (2), and malabsorption syndrome (1). All patients had preceding upper gastrointestinal endoscopy (OGD), ileocolonoscopy, and 26 cases had a small bowel follow-through (SBFT). These results were compared with the findings on WCE.

Results:

Thirty-three (33) cases successfully completed the WCE through the small bowel. Four (4) patients were unable to swallow the capsule, 3 of which had to be placed in the duodenum endoscopically. In 3 patients, the capsule remained in the stomach and no small bowel images were obtained. The overall diagnostic yield was 85% (28/33 patients). The diagnostic findings included CD (13), source of gastrointestinal bleeding (7), polyposis syndromes (3), erosive enteropathy and patchy lymphangiectasia (4), and intussusception (1). WCE was found to be more sensitive for small bowel pathology than SBFT (20 vs. 6 [30% sensitivity, compared to WCE]) and endoscopic investigations (28 vs. 12 [43% sensitivity compared to WCE]). As a result of WCE findings, there was a positive alteration in the management in 28 of 33 (85%) cases.

Conclusions:

WCE is a novel, noninvasive, and useful tool for the investigation of the small intestine in children. It is superior and more sensitive than other conventional endoscopic and radiologic investigations in the assessment of the small bowel. It can help in guiding surgical decisions and should be routinely integrated as a part of the diagnostic work-up of small bowel pathology.

Article

Renal-hepatic-pancreatic dysplasia syndrome (ivemark's syndrome) with lymphangiectasia

2007-07-06T04:17:00.000-07:00

Renal-hepatic-pancreatic dysplasia syndrome (ivemark's syndrome).
With lymphangiectasia as a complication

Diagn Pathol. 2007 Jul

Vankalakunti M, Gupta K, Kakkar N, Das A.

ABSTRACT
BACKGROUND: Renal-Hepatic-Pancreatic dysplasia syndrome described by Ivemark in 1959 constitutes a triad pancreatic fibrosis, renal dysplasia and hepatic dysgenesis.

CASE PRESENTATION: We describe two unrelated cases of Renal-hepatic-pancreatic dysplasia syndrome in stillborn babies. The characteristic microscopic features were present in both the cases. The second case illustrates the unique association lymphangiectasia with Renal-hepatic-pancreatic dysplasia syndrome. Both cases are unrelated and there is no history of any consanguineous marriage.

CONCLUSION: These two cases are unrelated and are rare. In the developmental research, the perinatal autopsy needs to be utilized as a major tool and an Ad hoc committee formation is required to formulate the approach towards syndromic diseases.

Diagnostic Pathology

Is double-balloon enteroscopy an accurate method to diagnose small-bowel disorders?

2007-06-30T23:02:00.000-07:00

Is double-balloon enteroscopy an accurate method to diagnose small-bowel disorders?

Surg Endosc. 2007 Jun 26

Safatle-Ribeiro AV, Kuga R, Ishida R, Furuya C, Ribeiro U, Cecconello I, Ishioka S, Sakai P. Gastroenterology, University of São Paulo, São Paulo, SP, Brazil, adrisafatleribeiro@terra.com.br.

Keywords: Enteroscopy - Double-balloon enteroscopy - Small intestine endoscopy

BACKGROUND AND STUDY AIMS: The aim of this study was to analyze the contribution of the double-balloon enteroscopy (DBE) for diagnosis of the small bowel disorders.

PATIENTS AND METHODS: Forty-four patients (20 women, 24 men; mean age 53.5 years-old, range 21-89 years) with chronic gastrointestinal bleeding, diarrhea, polyposis, weight-loss, Roux-en-Y surgery, and other indications underwent DBE.

RESULTS: Twenty patients had occult or obscure gastrointestinal bleeding. The source of bleeding was identified in 15/20 (75%): multiple angiodysplasias in four, arterial-venous malformation beyond the ligament of Treitz in two that could be treated with injection successfully. Other diagnoses included: duodenal adenocarcinoma, jejunal tuberculosis, erosions and ulcer of the jejunum. Of 24 patients with other indications, the diagnosis could be achieved in 18 of them (75%), including: two lymphomas, plasmocytoma, Gardner's syndrome, Peutz-Jeghers' syndrome, familial adenomatous polyposis, Behçet's disease, jejunal submucosal lesion, lymphangiectasia due to blastomycosis and unspecific chronic jejunitis. Of three cases with Roux-en-Y reconstruction, two underwent DBE in order to perform biopsies of the excluded duodenum. Additionally, two patients underwent DBE to exclude Crohn's disease and lymphoma of the small bowel. The mean length of small bowel examination was 240 +/- 50 cm during a single approach. The diagnostic yield was 75% (33/44 cases) and therapeutic yield was 63.6%. No major complications were observed, only minor complication such as sore throat in 4/44 (9.1%).

CONCLUSIONS: 1. DBE is a safe and and accurate method to diagnose small bowel disorders; 2. this method permits chromoscopy, biopsies and treatment of the lesions.

Springer Link

Congenital pulmonary lymphangiectasia in a newborn: a response to autologous blood therapy.

2007-06-24T05:29:00.000-07:00

Congenital pulmonary lymphangiectasia in a newborn: a response to autologous blood therapy.

Neonatology. 2007

Akcakus M, Koklu E, Bilgin M, Kurtoglu S, Altunay L, Canpolat M, Budak N.
Division of Neonatology, Department of Paediatrics, School of Medicine, Erciyes University, Kayseri, Turkey.

Author Contacts
Esad Koklu, MDDivision of Neonatology, Department of PaediatricsSchool of Medicine, Erciyes UniversityTR-38039 Kayseri (Turkey)Tel. +90 352 437 4937, Fax +90 352 437 5825, E-Mail esad@erciyes.edu.tr

Congenital pulmonary lymphangiectasia is a rare condition that may present antenatally with pleural effusions and hydrops, and the prognosis is reported to be very poor. Treatments for lymphangiectasia have included corticosteroids for patients with primary inflammatory conditions, dietary modifications, surgical resection for isolated lesions, octreotide, antiplasmin therapy and fibrin glue pleurodesis. However, there is no experience with pleurodesis by autologous blood therapy in the literature. We present a newborn with primary pulmonary lymphangiectasis who developed progressively profuse chylous pleural effusions after enteral full feeding from the 8th day of life and improved with pleurodesis by autologous blood therapy.

Karger

Acquired lymphangiectases and breast cancer

2007-06-18T10:53:00.000-07:00

Acquired lymphangiectases and breast cancer
Actas Dermosifiliogr. 2007 Jun

Valdés F, Peteiro C, Toribio J.
Unidad de Dermatología. Hospital da Costa. Burela, Lugo. Spain. Fernando.Valdes.Tascon@sergas.es.

Acquired lymphangiectases represent superficial lymphatic dilatations caused by a wide range of processes. Many cases reported in the literature develop in patients with upper limb lymphedema secondary to mastectomy, radiotherapy, keloids or scleroderma. Clinically they consist of traslucent vesicles in a chronic lymphedematous area. Histologically they are characterized by the presence of dilated spaces with flattened endotelial cells in the papillary dermis. All these cases have a good prognosis and there have not been any reports of malignant transformation. We describe a 67-year-old woman that showed multiple papules along her left upper limb associated with lymphedema. She had undergone a mastectomy followed by radiotherapy fourteen years before due to a breast cancer. Laboratory and radiological exams were within normal limits. The cutaneous lesions showed characteristic clinical and histological features of lymphangiectases and they progressively resolve in several weeks without any treatment.

Actos dermo-sifiliograficas

Chronic interstitial lung disease in children

2007-06-10T05:05:00.000-07:00

Chronic interstitial lung disease in children
J Pediatr (Rio J). 2007 May/June

Paiva MA, Amaral SM.

Hospital dos Servidores do Estado, Rio de Janeiro, RJ, Brazil. mariaaparecida.paiva@gmail.com.

OBJECTIVES: To describe clinical and diagnostic features and the results of therapeutic conduct in a group of pediatric patients with chronic interstitial lung disease.

METHODS: A retrospective study of 25 immunocompetent patients, aged 2 months to 17 years, with chronic interstitial lung disease, admitted to the Pediatric Pulmonary Section, Department of Pediatrics, Hospital dos Servidores do Estado, over a 20-year period (1984-2004). A routine protocol for persistent chronic pneumonias was used and the patients with interstitial lung disease were selected. Clinical, laboratory and imaging data were analyzed.

RESULTS: Twenty-five patients were diagnosed with chronic interstitial lung disease, 13 were aged less than 2 years and 17 were male. Diagnoses were made based on history, physical examination and routine tests in one case, based on more complex tests in three cases and based on the results of invasive tests in 21 cases (20 by lung biopsy and one by bronchoalveolar lavage). Except for one patient with pulmonary lymphangiectasia, the long-term treatment (1 to 7 years) consisted of corticosteroid, in six cases associated with hydroxychloroquine. Four patients required home oxygen therapy. The authors followed the patients in the outpatient department (6 a 8 visits/year). Patient outcome was: good (15); regular, with mild sequelae (4); and poor, with severe sequelae (3). One patient was lost in the follow-up period and two died.

CONCLUSIONS: Chronic interstitial lung diseases in children are a group of rare pulmonary disorders, but a relevant one because of the possible progression to pulmonary fibrosis. Early diagnosis and a long-term, specialized treatment and follow-up are important for the patient outcome. Pediatricians should be aware of these diseases because in many cases diagnosis and treatment are overlooked.

PMID: 17551654 [PubMed - as supplied by publisher]

Primary gastrointestinal lymphangiectasia presenting as cryptococcal meningitis.

2007-06-02T05:31:00.000-07:00

Primary gastrointestinal lymphangiectasia presenting as cryptococcal meningitis.
Ann Allergy Asthma Immunol. 2007 May

Cole SL, Ledford DK, Lockey RF, Daas A, Kooper J.
Department of Medicine, Division of Allergy and Immunology, University of South Florida College of Medicine, James A. Haley Veterans' Hospital, Tampa, Florida 33612, USA. scole@health.usf.edu

BACKGROUND: Opportunistic infections commonly occur in immunocompromised patients; however, it is unusual for an adult to present with a combined cellular and humoral immunodeficiency. Cryptococcal meningitis is a fatal condition if untreated and is usually found in patients with cellular immunodeficiency.

OBJECTIVE: To report the case of an adult patient with cryptococcal meningitis secondary to intestinal lymphangiectasia.

METHODS: A 59-year-old man was admitted to the hospital for disseminated cryptococcal meningitis and osteomyelitis. Laboratory evaluation, computed tomography, esophagogastroduodenoscopy, and biopsy were performed.

RESULTS: Laboratory evaluation revealed a lymphopenia, hypoalbuminemia, hypogammaglobulinemia, and negative human immunodeficiency virus test results by enzyme-linked immunosorbent assay and polymerase chain reaction. The complete blood cell count, urinalysis, serum and urine protein electrophoresis, and functional antibody responses to protein and polysaccharide antigens were normal. Results of computed tomography of the chest, abdomen, and pelvis were unremarkable. Multiple lymphangiectasias were visualized with esophagogastroduodenoscopy and confirmed by biopsy. The patient was treated with intravenous amphotericin B and flucytosine, and the meningitis resolved.

CONCLUSIONS: Based on a computerized search of the medical literature, this is the first description of cryptococcal meningitis secondary to intestinal lymphangiectasias. The combination of lymphopenia, hypogammaglobulinemia, and hypoalbuminemia should alert the clinician to the possibility of intestinal lymphangiectasias and the potential for immune dysfunction.

Recurrent hemolytic uremic syndrome associated with intestinal lymphangiectasia.

2007-05-27T09:41:00.000-07:00

Recurrent hemolytic uremic syndrome associated with intestinal lymphangiectasia.
J Nephrol. 2007 Mar-Apr
Kalman S,
Bakkaloglu S,
Dalgic B,
Ozkaya O,
Soylemezoglu O,
Buyan N.

Department of Pediatric Nephrology, Gazi University, Besevler, Ankara - Turkey.

A 17-year-old boy was admitted to the hospital twice in a year for 2 episodes of hemolytic uremic syndrome (HUS). During these 2 HUS episodes he had diarrhea, decreased serum complement, decreased total protein and decreased serum albumin concentrations. We suggest that protein-losing enteropathy and hypocomplementemia due to intestinal lymphangiectasia is may be a rare cause of atypical HUS.

PMID: 17514630 [PubMed - in process]

A primary intestinal lymphangiectasia patient diagnosed by capsule endoscopy and confirmed at surgery: A case report.

2007-05-19T20:19:00.000-07:00

A primary intestinal lymphangiectasia patient diagnosed by capsule endoscopy and confirmed at surgery: A case report.
World J Gastroenterol. 2007 Apr

Fang YH,
Zhang BL,
Wu JG,
Chen CX.
Department of gastroenterlogy, The First Affiliated Hospital of College of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. chcx@zj139.com.

Intestinal lymphangiectasia (IL) is a rare disease characterized by dilated lymphatic vessles in the intestinal wall and small bowel mesentery which induce loss of protein and lymphocytes into bowel lumen. Because it most often occurs in the intestine and cannot be detected by upper gastroendoscopy or colonoscopy, and the value of common image examinations such as X-ray and computerized tomography (CT) are limited, the diagnosis of IL is difficult, usually needing the help of surgery.

Capsule endoscopy is useful in diagnosing intestinal diseases, such as IL. We here report a case of IL in a female patient who was admitted for the complaint of recurrent edema accompanied with diarrhea and abdominal pain over the last twenty years, and aggravated ten days ago. She was diagnosed by M2A capsule endoscopy as a primary IL and confirmed by surgical and pathological examination.

World Journal of Gastroenterology