Redefining WILD syndrome: a primary lymphatic dysplasia with congenital multisegmental lymphoedema, cutaneous lymphovascular malformation, CD4 lymphopaenia and warts

BackgroundPrimary lymphoedema (PL) syndromes are increasingly recognised as presentations of complex genetic disease, with at least 20 identified causative genes. Recognition of clinical patterns is key to diagnosis, research and therapeutics. The defining criteria for one such clinical syndrome, ‘WILD syndrome’ (Warts, Immunodeficiency, Lymphoedema and anogenital Dysplasia), have previously depended on a single case report.Methods and resultsWe present 21 patients (including the first described case) with similar clinical and immunological phenotypes. All had PL affecting multiple segments, with systemic involvement (intestinal lymphangiectasia/pleural or pericardial effusions) in 70% (n=14/20). Most (n=20, 95%) had a distinctive cutaneous lymphovascular malformation on the upper anterior chest wall. Some (n=10, 48%) also had hyperpigmented lesions resembling epidermal naevi (but probably lymphatic in origin). Warts were common (n=17, 81%) and often refractory. In contrast to the previous case report, anogenital dysplasia was uncommon—only found in two further cases (total n=3, 14%). Low CD4 counts and CD4:CD8 ratios typified the syndrome (17 of 19, 89%), but monocyte counts were universally normal, unlike GATA2 deficiency.ConclusionWILD syndrome is a previously unrecognised, underdiagnosed generalised PL syndrome. Based on this case series, we redefine WILD as ‘Warts, Immunodeficiency, andLymphatic Dysplasia’ and suggest specific diagnostic criteria. The essential criterion is congenital multisegmental PL in a ‘mosaic’ distribution. The major diagnostic features are recurrent warts, cutaneous lymphovascular malformations, systemic involvement (lymphatic dysplasia), genital swelling and CD4 lymphopaenia with normal monocyte counts. The absence of family history suggests a sporadic condition, and the random distribution of swelling implicates mosaic postzygotic mutation as the cause.

A case of primary intestinal lymphangiectasia with non-Hodgkin lymphoma

Background Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy characterized by the loss of proteins, lymphocytes, and immunoglobulins into the intestinal lumen. Increasing evidence has demonstrated an association between PIL and lymphoma. Case presentation A 54-year-old man with a 20-year history of abdominal distension and bilateral lower limb edema was admitted. Laboratory investigations revealed lymphopenia, hypoalbuminemia, decreased triglyceride and cholesterol level. Colonoscopy showed multiple smooth pseudo polyps in the ileocecal valve and terminal ileum and histological examination showed conspicuous dilation of the lymphatic channels in the mucosa and submucosa. A diagnosis of PIL was made. Three years later colonoscopy of the patient showed an intraluminal proliferative mass in the ascending colon and biopsy examination confirmed a malignant non-Hodgkin lymphoma. Then the patient was been underwent chemotherapy, and his clinical condition is satisfactory. Conclusion Our report supports the hypothesis that PIL is associated with lymphoma development.

Protein-losing enteropathy caused by disseminated Mycobacterium avium complex infection in a patient receiving antiretroviral therapy: an autopsy case report

Background Disseminated Mycobacterium avium complex infection is an important indicator of acquired immunodeficiency syndrome (AIDS) in patients with advanced human immunodeficiency virus (HIV) infection. Effective antiretroviral therapy has dramatically reduced the incidence of and mortality due to HIV infection, although drug resistance and poor medication adherence continue to increase the risk of disseminated M. avium complex infection. However, gastrointestinal lesions in cases of disseminated M. avium complex infection resulting in protein-losing enteropathy have been rarely discussed. Therefore, we present a case of protein-losing enteropathy caused by disseminated M. avium complex infection in a patient undergoing antiretroviral therapy. Case presentation A 29-year-old man was diagnosed with AIDS 4 years ago and was admitted for a 10-month history of refractory diarrhea and fever. Despite receiving antiretroviral therapy, the viral load remained elevated due to poor medication adherence. The patient was diagnosed with disseminated M. avium complex infection and started on antimycobacterial drugs 2 years before admission. However, the infection remained uncontrolled. The previous hospitalization 1 year before admission was due to hypoalbuminemia and refractory diarrhea. Upper gastrointestinal endoscopy revealed a diagnosis of protein-losing enteropathy caused by intestinal lymphangiectasia, and treatment with intravenous antimycobacterial drugs did not resolve his intestinal lymphangiectasia. The patient inevitably died of sepsis. Conclusions Clinical remission is difficult to achieve in patients with AIDS and protein-losing enteropathy caused by disseminated M. avium complex infection due to limited options of parenteral antiretroviral drugs. This report highlights the importance of identifying alternative treatments (such as an injectable formulation) for patients who do not respond to antiretroviral therapy due to protein-losing enteropathy with disseminated M. avium complex infection.

Canine Intestinal Lymphangiectasia Concomitant with Renal Cell Carcinoma

The etiology of dilation of lymphatic vessels, termed as intestinal lymphangiectasia, remains unknown. In most cases, it occurs secondary to other pathologic conditions such as gastrointestinal neoplasms. However, only a few cases of canine intestinal lymphangiectasia concurrent with non-gastrointestinal neoplasms have been reported so far. Moreover, the correlation between intestinal lymphangiectasia and non-gastrointestinal neoplasms has not been discussed in any other literature. In this study, we report a rare case of intestinal lymphangiectasia concomitant with renal cell carcinoma in an 11 year old female mixed Maltese, suggesting that non-gastrointestinal neoplasms could be associated with the development of intestinal lymphangiectasia. On gross observation, the small intestine was irregularly swollen presenting an accordion like shape. Microscopic examination revealed prominent dilatation of the lymphatic vessels, especially, within the submucosa and muscularis layer. The lacteals within the villi were dilated and presented “club-shaped” tips. The carcinoma might trigger intestinal lymphangiectasia by compressing the main lymphatic vessels or the cisterna chyli, subsequently increasing the pressure of the lymphatic vessels in the gastrointestinal tract. Moreover, metastasis of the carcinoma to the gastrointestinal tract could induce intestinal lymphangiectasia. Thus, the occurrence of intestinal lymphangiectasia must be considered when an abdominal neoplasm is located around major lymphatic vessels.

Protein-losing Enteropathy Caused by Disseminated Mycobacterium Avium Complex Infection in a Patient Receiving Antiretroviral Therapy: An Autopsy Case Report

Background: Disseminated Mycobacterium avium complex infection is an important indicator of acquired immunodeficiency syndrome (AIDS) in patients with advanced human immunodeficiency virus (HIV) infection. Effective antiretroviral therapy has dramatically reduced the incidence and mortality of HIV, although drug resistance and poor medication adherence continue to increase the risk of disseminated M. avium complex infection. However, gastrointestinal lesions in cases of disseminated M. avium complex infection resulting in protein-losing enteropathy have been rarely discussed. Therefore, we report a case of protein-losing enteropathy caused by disseminated M. avium complex infection in a patient undergoing antiretroviral therapy.Case presentation: A 29-year-old male diagnosed with AIDS for four years and was admitted for a 10-month history of refractory diarrhea and fever. Despite receiving antiretroviral therapy, viral load remained elevated due to poor medication adherence. The patient was diagnosed with disseminated M. avium complex infection and started on antimycobacterial drugs two years prior to admission. However, it remained uncontrolled. Previous hospitalization a year before admission was due to hypoalbuminemia and refractory diarrhea. Upper gastrointestinal endoscopy revealed a diagnosis of protein-losing enteropathy caused by intestinal lymphangiectasia, and treatment with intravenous antimycobacterial drugs did not resolve his intestinal lymphangiectasia. The patient inevitably died of sepsis.Conclusions: Clinical remission is difficult to achieve in patients with AIDS and protein-losing enteropathy caused by disseminated M. avium complex infection due to its limited options for parenteral antiretroviral drugs.

Diagnosis and Individualized Nutritional Management of Primary Intestinal Lymphangiectasia in Children: A Clinical Conundrum

Background: Primary Intestinal Lymphangiectasia (PIL) is a rare congenital and digestive disease, which could present through a broad spectrum of clinical manifestations, diagnostic and treatment management. The aim of this study was to introduce the diagnosis and nutrition treatment of children with IL through the twelve years of experience. Methods: The patients diagnosed with PIL admitted to the Department of Gastroenterology and Nutrition in Xinhua Hospital from June, 2006 to September, 2017 were included in the study. Basic information and laboratory results were collected from the medical records. Results: Ten patients were found to have PIL. The mean age was 66 months at the time of diagnosis and 11 months at onset. The main clinical manifestations were diarrhea, edemas and abdominal distention. Marked dilatation of the intestinal lymphatic vessels was the characteristic of the endoscopic. All the patients presented with hypoproteinemia and hypoimmunoglobulinia. 6 of them were treated with parenteral nutrition, and 9 of them were treated with a low-LCT (long-chain triglycerides), high-protein diet supplemented with MCT(medium-chain triglycerides).The clinical symptoms of the patients have improved after the MCT diet therapy. Conclusion: PIL should be considered first when there are clinical manifestations of chronic diarrhea, edema and abdominal distention, and biochemical results indicated the hypoproteinemia and hypoimmunoglobulinia, and the general treatment is invalid. Gastroscopy and E-colonoscopy with biopsies are the preferred method of diagnosis. MCT diet is the cornerstone and longtime medical treatment, which can improve the nutritional status and promote the survival quality of patients with IL.Trial registration: This study was reviewed and approved by the Research Ethics Committee of Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University.