Cyclosporin-responsive enteropathy and protracted diarrhea

We describe a child bom to unrelated parents who developed severe protracted secretory type diarrhea associated with subtotal villus atrophy and intestinal inflammation at the age of 19 months. No infectious, metabolic, or anatomical basis for this condition was identified and the child required total parenteral nutrition for a period of 18 months despite trials of special enteral formulas, steroids, and anti-inflammatory agents. This refractory “enteropathy” responded dramatically to the introduction of cyclosporin, with cessation of the secretory diarrhea, recovery from the enteropathy, and cessation of parenteral nutrition. The symptoms relapsed when cyclosporin was briefly discontinued and improved following reintroduction of this drug. This experience suggests a role for immune factors in the pathogenesis of the enteropathy in this case and that a trial of cyclosporin is worthy of consideration in similar cases. © 1990 Raven Press, Ltd., New York.

Effectiveness of rescue antiretroviral therapy including intravenously administered zidovudine and foscarnet in a child with HIV-1 enteropathy.

Case Reports

Serological markers for coeliac disease:changes with time and relationship to enteropathy

Antigliadin antibodies (AGA) may be present in healthy adults. One previous study has reported that IgA-AGA detected by population screening may become negative after a 6-year follow-up period.

Gliadin antibody detection in gluten enteropathy

Circulating antigliadin antibody has been described in patients with gluten enteropathy although the prevalence varies in different studies. It has been suggested that the investigation for antigliadin antibody might be useful as a screening test. The object of the present study was to evaluate two different techniques for assaying these antibodies - an indirect immunofluorescent method and an enzyme-linked immunosorbent assay (ELISA). Antibodies were assayed in the sera of 102 patients in whom jejunal biopsies were also obtained. The specificity of both tests was greater than 95%, and the correlation between the presence of antibody and histology was significant (p <0.005), though the sensitivity of each test was less than 70%.

Thoracic Duct Decompression for Protein-Losing Enteropathy in Failing Fontan Circulation

An infrequent but devastating late complication of Fontan circulation is protein-losing enteropathy (PLE), which results from unbalanced lymphatic homeostasis. Surgical decompression of the thoracic duct by redirecting its drainage to the pulmonary venous atrium has been introduced recently as a possible treatment. This report describes a single-institution experience with this innovative procedure in 2 patients with failing Fontan circulation with PLE refractory to optimized medical therapy.

Anti-tumour necrosis factor-α therapy for severe enteropathy in patients with common variable immunodeficiency (CVID)

We present three common variable immunodeficiency (CVID) patients with
severe inflammatory bowel disease of unknown aetiology, resistant to steroid
treatment, treated with infliximab.After exclusion of any infection, infliximab
was given at a dose of 5 mg/kg every 4 weeks for a 3 month induction followed
by every 4–8 weeks depending on clinical response. Two of these patients had
predominantly small bowel disease; they both showed clinical response to
infliximab with weight gain and improvement of quality of life scores. The
third patient had large bowel involvement with profuse watery diarrhea; this
patient improved dramatically within 48 hours of having infliximab
treatment. All three patients have been maintained on infliximab treatment
for between 5 and 53 months (mean 37 months) with no evidence of increased
susceptibility to infections in the patients with small bowel disease, although
the third patient developed two urinary tract infections and a herpes zoster
infection following therapy. This is the first small case series to show that
infliximab is a useful addition to current therapy in this rare group of patients
with potentially life threatening enteritis.

Lawsonia intracellularis proliferative enteropathy in a filly

Proliferative enteropathy (PE) caused by the obligate intracellular bacterium Lawsonia intracellularis is a disease of high economic impact in swine worldwide. In most other species the disease occurs as a sporadic infection. This paper reports a PE caused by L. intracellularis in a 9-month-old Pura Raza Española filly with a history of profuse diarrhoea. Pathological lesions consisted of a severe proliferative enteritis associated with argyrophilic bacteria in the apical cytoplasm of proliferating crypt epithelium. Characteristic PCR products confirmed the presumptive diagnosis of L. intracellularis infection. To our knowledge this is the first report of PE in a horse in Europe caused by L. intracellularis.

Evaluation of gastrointestinal permeability and mucosal absorptive capacity in dogs with chronic enteropathy

OBJECTIVE: To assess intestinal mucosal function by measuring permeability and absorptive capacity in dogs with chronic enteropathy (CE) before and after treatment and to determine whether those variables were correlated with clinical disease activity or histologic scoring of intestinal biopsy specimens. ANIMALS: 29 dogs with CE. PROCEDURE: Dogs were designated as having dietresponsive CE or CE requiring glucorticoid treatment. Severity of clinical signs was assessed by calculating the canine inflammatory bowel disease activity index (CIBDAI). Histologic severity of intestinal infiltration was assessed before and after 4 weeks of treatment in the diet-responsive group and before and after 10 weeks of treatment in the glucocorticoid group. Gastrointestinal permeability and mucosal absorptive capacity were assessed by use of intragastric administration of a solution containing lactulose, rhamnose, xylose, 3-O-methylglucose, and sucrose. Urine was collected 6 hours after administration of the sugar solution to determine urinary lactulose-to-rhamnose (L:R), xylose-to-methylglucose (X:M), and sucrose-to-methylglucose (S:M) ratios. RESULTS: Median CIBDAI scores decreased significantly in both groups of dogs after treatment. However, the median histologic grade of intestinal biopsy specimens did not change with treatment in either group. There were no significant differences in L:R, X:M, or S:M ratios after treatment in either group and no significant correlations between L:R, X:M, or S:M ratios and CIBDAI or histologic scores. CONCLUSIONS AND CLINICAL RELEVANCE: Results of tests for intestinal permeability and mucosal absorptive capacity were not useful indicators of clinical disease activity as assessed by the CIBDAI or the sever ity of infiltration as indicated by histologic evaluation.

Transmembrane tumor necrosis factor alpha is required for enteropathy and is sufficient to promote parasite expulsion in gastrointestinal helminth infection

To study the specific role of transmembrane tumor necrosis factor (tmTNF) in protective and pathological responses against the gastrointestinal helminth Trichinella spiralis, we compared the immune responses of TNF-alpha/lymphotoxin alpha (LTalpha)(-/-) mice expressing noncleavable transgenic tmTNF to those of TNF-alpha/LTalpha(-/-) and wild-type mice. The susceptibility of TNF-alpha/LTalpha(-/-) mice to T. spiralis infection was associated with impaired induction of a protective Th2 response and the lack of mucosal mastocytosis. Although tmTNF-expressing transgenic (tmTNF-tg) mice also had a reduced Th2 response, the mast cell response was greater than that observed in TNF-alpha/LTalpha(-/-) mice and was sufficient to induce the expulsion of the parasite. T. spiralis infection of tmTNF-tg mice resulted in significant intestinal pathology characterized by villus atrophy and crypt hyperplasia comparable to that induced following the infection of wild-type mice, while pathology in TNF-alpha/LTalpha(-/-) mice was significantly reduced. Our data thus indicate a role for tmTNF in host defense against gastrointestinal helminths and in the accompanying enteropathy. Furthermore, they also demonstrate that TNF-alpha is required for the induction of Th2 immune responses related to infection with gastrointestinal helminth parasites.

Apoptotic enteropathy caused by antimetabolites and TNF-α antagonists.

AIMS To investigate whether drugs others than mycophenolic acid and ipilimumab might cause graft-versus-host-like apoptotic enteropathy, the clinicopathological findings in four patients were examined who had developed watery diarrhoea and apoptotic enteropathy (three cases from colon and one case from ileal pouch) after intake of antimetabolites (methotrexate and capecitabine) and/or tumour necrosis factor-α inhibitors (etanercept and infliximab). METHODS The clinical charts, endoscopy reports and intestinal biopsies from all endoscopies were reviewed for all patients. Biopsies were evaluated semiquantitatively for apoptosis of basal crypts, dilated damaged crypts, defined as cystically dilated crypts with flattened degenerated epithelium containing apoptotic debris and few neutrophils, and mucosal architecture. Further, the presence of intraepithelial lymphocytes, chronic inflammatory cells in the lamina propria and mucosal ulcerations was recorded and immunohistochemical analysis for human cytomegalovirus and herpes simplex virus was performed. RESULTS Endoscopic examination revealed normal mucosa in two patients, whereas the other two showed focal ulcerations. Histological changes included increased apoptosis of basal crypts, the presence of dilated damaged crypts and architecture distortion. In all cases, a temporal association between drug intake and/or dose increase, and onset of diarrhoea, was observed, and no convincing evidence of other potentially underlying causes of colitis/enteritis was found, including infections. CONCLUSIONS Pathologists should be aware of the expanding spectrum of drugs that can cause apoptotic enteropathy, including antimetabolites and tumour necrosis factor-α inhibitors.

Evaluation of serum biochemical marker concentrations and survival time in dogs with protein-losing enteropathy

OBJECTIVE: To evaluate serum concentrations of biochemical markers and survival time in dogs with protein-losing enteropathy (PLE). DESIGN: Prospective study. ANIMALS: 29 dogs with PLE and 18 dogs with food-responsive diarrhea (FRD). PROCEDURES: Data regarding serum concentrations of various biochemical markers at the initial evaluation were available for 18 of the 29 dogs with PLE and compared with findings for dogs with FRD. Correlations between biochemical marker concentrations and survival time (interval between time of initial evaluation and death or euthanasia) for dogs with PLE were evaluated. RESULTS: Serum C-reactive protein concentration was high in 13 of 18 dogs with PLE and in 2 of 18 dogs with FRD. Serum concentration of canine pancreatic lipase immunoreactivity was high in 3 dogs with PLE but within the reference interval in all dogs with FRD. Serum α1-proteinase inhibitor concentration was less than the lower reference limit in 9 dogs with PLE and 1 dog with FRD. Compared with findings in dogs with FRD, values of those 3 variables in dogs with PLE were significantly different. Serum calprotectin (measured by radioimmunoassay and ELISA) and S100A12 concentrations were high but did not differ significantly between groups. Seventeen of the 29 dogs with PLE were euthanized owing to this disease; median survival time was 67 days (range, 2 to 2,551 days). CONCLUSIONS AND CLINICAL RELEVANCE: Serum C-reactive protein, canine pancreatic lipase immunoreactivity, and α1-proteinase inhibitor concentrations differed significantly between dogs with PLE and FRD. Most initial biomarker concentrations were not predictive of survival time in dogs with PLE.

Environmental Enteropathy and Fibroblast Growth Factor 21 are associated with early childhood growth in Bangladesh

Thesis (Ph.D.)--University of Washington, 2016-06

Protein losing enteropathy in critically ill adult patients with burns: a preliminary report

Objective: Few data have been published regarding protein losing enteropathy in adult patients with burns. This study characterised the presence of protein-losing enteropathy in adults with burns and examined the relationship between the magnitude of bum size and the severity of protein loss. Methods: Twenty adult patients with burns (BSA 31+/-25%, range 2-80%) were studied. Fluid resuscitation was based on the Parkland's formula. Protein loss into the gastrointestinal tract was measured using faecal alpha(1)-antitrypsin (FA-1-AT) concentrations. Serial measurements of serum protein and albumin concentrations were performed. Results: Fourteen patients demonstrated elevations in FA-1-AT levels. The mean peak FA-1-AT level was 3.6+/-4.2 mg/g dry weight of stool. Two patients demonstrated elevated FA-1-AT excretion 1.5 months and 3 months after the bums. There was a good correlation between burn size and FA-1-AT excretion (R-2=0.40). Conclusions: Protein losing enteropathy was demonstrable in patients with major burns. The magnitude of this phenomenon appears to be proportional to the burns size.

Microbes, the gut and ankylosing spondylitis

It is increasingly clear that the interaction between host and microbiome profoundly affects health. There are 10 times more bacteria in and on our bodies than the total of our own cells, and the human intestine contains approximately 100 trillion bacteria. Interrogation of microbial communities by using classic microbiology techniques offers a very restricted view of these communities, allowing us to see only what we can grow in isolation. However, recent advances in sequencing technologies have greatly facilitated systematic and comprehensive studies of the role of the microbiome in human health and disease. Comprehensive understanding of our microbiome will enhance understanding of disease pathogenesis, which in turn may lead to rationally targeted therapy for a number of conditions, including autoimmunity.