1130-0108/2017/109/5/385-388 REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS REV ESP ENFERM DIG © Copyright 2017. SEPD y © ARÁN EDICIONES, S.L. 2017, Vol. 109, N.º 5, pp. 385-388 CASE REPORT Waldmann’s disease: a rare cause of protein losing enteropathy in an adult patient Cláudio Martins1, Alice Gagnaire2, Florian Rostain2 and Côme Lepage2 1Department of Gastroenterology. Centro Hospitalar de Setúbal. Hospital de São Bernardo. Setúbal, Portugal. 2Department of Hepatogastroenterology and Digestive Oncology. Centre Hospitalier Universitaire de Dijon. Dijon, France ABSTRACT formation or secondary obstruction of intestinal lymphatic drainage (1). As lymphatic fluid contains a lot of proteins, Primary intestinal lymphangiectasia or Waldmann’s disease fat and lymphocytes, leakage of lymph will cause hypo- is an uncommon cause of protein losing enteropathy with an proteinemia, lymphopenia and decreased serum levels of unknown etiology and is usually diagnosed during childhood. It is characterized by dilation and leakage of intestinal lymph vessels immunoglobulins (2). leading to hypoalbuminemia, hypogammaglobulinemia and Depending on the cause of the disease, it can be clas- lymphopenia. Differential diagnosis should include erosive and non- sified into primary or secondary. Primary intestinal erosive gastrointestinal disorders, conditions involving mesenteric lymphangiectasia (PIL) or Waldmann’s disease, original- lymphatic obstruction and cardiovascular disorders that increase ly described by Waldmann in 1961 (3), is a rare cause of central venous pressure. Since there are no accurate serological or radiological available tests, enteroscopy with histopathological PLE, whose prevalence and etiology are unknown. The examination based on intestinal biopsy specimens is currently the diagnosis is generally established before the third year of gold standard diagnostic modality of intestinal lymphangiectasia. life but can be rarely seen in adults (4). The gold-standard We report a rare case of a primary intestinal lymphangiectasia in diagnostic modality is enteroscopy with the respective his- a 60-year-old Caucasian female who presented with asymptomatic tological examination of the intestinal biopsy specimen. hypoalbuminemia and hypogammaglobulinemia. After the diagnosis of a protein losing enteropathy, the patient underwent The confirmation of the primary nature of disease requires an enteroscopy and biopsies were taken, whose histological the exclusion of secondary causes (4). Main differential examination confirmed dilated intestinal lymphatics with diagnosis includes congestive cardiac failure, constrictive broadened villi of the small bowel. Secondary causes of intestinal pericarditis, intestinal lymphoma, Crohn’s disease, intes- lymphangiectasia were excluded and the diagnosis of Waldmann’s disease was recorded. The patient was put on a high-protein and tinal tuberculosis, sarcoidosis, Whipple’s disease, human low-fat diet with medium-chain triglyceride supplementation with immunodeficiency virus (HIV)-related enteropathy, cyto- improvement. megalovirus (CMV)-related enteropathy or systemic scle- rosis. Key words: Protein losing enteropathy. Primary intestinal A low-fat diet associated with medium-chain tri- lymphangiectasia. Single-balloon enteroscopy. glycerides (MCT) supplementation is the cornerstone of PIL medical management (5). We report an uncommon case of PIL diagnosed in an INTRODUCTION adult asymptomatic female during etiological investigation of hypoproteinemia. Protein losing gastroenteropathies, characterized by an excessive loss of serum proteins into the gastrointesti- nal tract, are an important cause of hypoproteinemia, and CASE REPORT their diagnosis should be considered in patients when oth- er causes of hypoproteinemia have been excluded, such We present a 60-year-old Caucasian female that was as malnutrition, heavy proteinuria and impaired protein referred to our Department due to asymptomatic hypoal- synthesis due to liver diseases. A high fecal alpha-1-anti- buminemia and hypogammaglobulinemia. She reported a trypsin clearance suggests exudative enteropathy. medical history of hypothyroidism, hypercholesterolemia Intestinal lymphangiectasia is an uncommon cause of and gastroesophageal reflux disease under treatment with protein losing enteropathy (PLE) due to congenital mal- levothyroxine, simvastatin and omeprazole. There was no Received: 08-09-2016 Accepted: 01-12-2016 Martins C, Gagnaire A, Rostain F, Lepage C. Waldmann’s disease: a rare Correspondence: Cláudio Martins. Department of Gastroenterology. Centro cause of protein losing enteropathy in an adult patient. Rev Esp Enferm Dig Hospitalar de Setúbal. São Bernardo Hospital. Rua Camilo Castelo Branco. 2017;109(5):385-388. 2910 Setúbal, Portugal DOI: 10.17235/reed.2017.4593/2016 e-mail: [email protected] 386 C. MARTINS ET AL. REV ESP ENFERM DIG history of diarrhea, limb swelling, abdominal pain, fever, vomiting, anorexia, weight loss, skin rash or urinary symp- toms. Physical examination was unremarkable. Initial laboratory tests showed no anemia (hemoglobin 13.6 g/dL), normal total white blood cells count (4.18 x 109/L) with normal lymphocytes (1,720/uL) and platelet count (200,000/uL); protein electrophoresis with hypo- proteinemia (4.6 g/dL), hypoalbuminemia (2.9 g/dL) and hypogammaglobulinemia (2.6 g/L); normal calcium lev- els, liver and kidney function tests. Further investigations showed no proteinuria and fecal alpha-1-antytripisin clear- ance was increased. These results were consistent with a PLE. In order to clarify the etiology of exsudative enteropathy, the patient underwent an upper gastrointestinal endoscopy with gastric and duodenal biopsies which were normal. Computed tomography (CT) scan enterography and mag- netic resonance imaging (MRI) enterography revealed dif- Fig. 2. Enteroscopy showing the jejunum covered by diffuse white spots fuse and regular thickening throughout the jejunum; there with a “snowflake” appearance. were no adenopathies (Fig. 1). A single-balloon enterosco- py was performed and scattered white spots with a “snow- flake” appearance overlying the jejunum were observed and low-fat diet with supplementation of medium chain (Fig. 2). These findings were consistent with diffuse intes- triglyceride with good response. tinal lymphangiectasia. Multiple biopsies were taken and the histopathological examination revealed broadened villi with dilated lymphatic channels in mucosa and submucosa. DISCUSSION To exclude secondary causes of intestinal lymphangi- ectasia an additional study was performed. Coprocultures, Intestinal lymphangiectasia, an uncommon but import- parasitological stool sample examination, serological test- ant cause of protein losing enteropathy, is characterized ing for HIV and CMV and interferon-gamma release assay by an impaired small intestinal lymph drainage associated were negative. Antinuclear antibodies, anti-double strand- with dilated lymphatic channels. It can be due to prima- ed DNA and immunoglobulin A (IgA) anti-tissue transglu- ry disorders of intestinal lymphatics or due to second- taminase were negative. Erythrocyte sedimentation rate ary causes. Regardless of the cause, the impaired flow and serum beta-2 microglobulin were normal. Immuno- and increased pressure in intestinal lymphatics lead to phenotypic analysis of peripheral blood revealed no atyp- decreased absorption of fat-soluble vitamins (A, D, E and ical cells. Transthoracic echocardiogram was normal. K), reduced recirculation of intestinal lymphocytes into the These findings were fully consistent with PIL (Wald- peripheral circulation and leakage of intestinal lymph into mann’s disease). The patient was put on a high-protein the intestinal lumen (6). PIL, first described in 1961 by Waldmann et al. (3), is a rare disorder whose prevalence and etiology are unknown. A B After 1961, as per available literature, less than 200 cases have been reported. It is mainly seen in pediatric patients, usually diagnosed before three years of age, with an equal incidence in both genders (4). Although most cases are sporadic, PIL has been reported in multiple siblings of several families, suggesting a genetic contribution. Fur- thermore, PIL can occur as an isolated disorder or as a part of a syndrome such as Von Recklinghausen, Turner, Noonan, Klippel-Trenaunay-Weber, Hennekan and yel- low-nail syndrome. In a retrospective analysis of 84 cases in 2010, the most common symptoms were limb edema, diarrhea, ascites and lymphedema, present in 78, 62, 41 and 22%, respective- ly (7). Other non-specific symptoms are fatigue, abdom- Fig. 1. Diffuse thickening through the jejunum seen on CT (A) and IRM inal pain, nausea, vomiting, weight loss, failure to thrive, enterography (B). iron deficiency anemia, obstructive ileus, steatorrhea and REV ESP ENFERM DIG 2017;109(5):385-388 2017, Vol. 109, N.º 5 WALDMANN’S DISEASE: A RARE CAUSE OF PROTEIN LOSING ENTEROPATHY IN AN ADULT PATIENT 387 fat-soluble vitamin deficiency (2). Due to leakage from the tract but may also be seen in the retroperitoneum and the ruptured lymph vessels, other major features are lymph- mediastinum. Recurrent and opportunistic infections are not openia, hypoalbuminemia and hypogammaglobulinemia. rare due to moderate or severe hypogammaglobulinemia and However, in a few cases, patients are asymptomatic and lymphopenia (e.g., Streptococcus G, meningitis, cryptococ- the diagnosis is made during etiological investigation of cus, cytomegalovirus) (9,10). hypoproteinemia (13). In our case,