Alpha 1-antitrypsin Clearance Research Articles

The p24-family and COPII subunit SEC24C facilitate the clearance of alpha1-antitrypsin Z from the endoplasmic reticulum to lysosomes.

A subpopulation of the alpha-1-antitrypsin misfolding Z mutant (ATZ) is cleared from the endoplasmic reticulum (ER) via an ER-to-lysosome-associated degradation (ERLAD) pathway. Here, we report that the COPII subunit SEC24C and the p24-family of proteins facilitate the clearance of ATZ via ERLAD. In addition to the previously reported ERLAD components calnexin and FAM134B, we discovered that ATZ coimmunoprecipitates with the p24-family members TMP21 and TMED9. This contrasts with wild type alpha1-antitrypsin, which did not coimmunoprecipitate with FAM134B, calnexin or the p24-family members. Live-cell imaging revealed that ATZ and the p24-family members traffic together from the ER to lysosomes. Using chemical inhibitors to block ER exit or autophagy, we demonstrated that p24-family members and ATZ co-accumulate at SEC24C marked ER-exit sites or in ER-derived compartments, respectively. Furthermore, depletion of SEC24C, TMP21, or TMED9 inhibited lysosomal trafficking of ATZ and resulted in the increase of intracellular ATZ levels. Conversely, overexpression of these p24-family members resulted in the reduction of ATZ levels. Intriguingly, the p24-family members coimmunoprecipitate with ATZ, FAM134B, and SEC24C. Thus, we propose a model in which the p24-family functions in an adaptor complex linking SEC24C with the ERLAD machinery for the clearance of ATZ.

A Case of Primary Intestinal Lymphangiectasia Successfully Controlled with a Denver Peritoneovenous Shunt for Refractory Ascites.

A 53-year-old man presented with abdominal symptoms and a fever for 6 months and ascites and lower body edema for 2 months before visiting our clinic. Heart failure, renal failure, inferior vena cava or portal vein obstruction, cirrhosis, and malignancy were suspected, but none were present. We also suspected protein-leakage gastroenteropathy based on the elevated alpha-1 antitrypsin clearance (224 mL/day). Based on the double-balloon endoscopy findings, we diagnosed the patient with primary intestinal lymphangiectasia. Since the patient's ascites were not satisfactorily controlled medically, a Denver peritoneovenous shunt was placed. As a result, the ascites volume was successfully controlled over an extended period.

Exudative enteropathy in neonates: A case report

The term exudative gastroenteropathy is used to describe an entity characterized by excessive loss of plasma proteins in the gastrointestinal tract. This digestive exudation can be caused either by an obstacle to intestinal lymphatic drainage or by an alteration of the epithelial barrier. The clinical picture is often associated with chronic diarrhea and an edematous syndrome. Lymphedema, infectious complications secondary to lymphopenia or hypogammaglobulinemia, and thromboembolic complications may also be observed. Diagnosis is based on the measurement of fecal alpha-1 antitrypsin clearance. Sometimes primary in the context of Waldmann disease (primary intestinal lymphangiectasis) but more often secondary. It requires an endoscopic and morphological workup to confirm the origin of the protein leak, to evaluate its extent and cause. In addition to etiological treatment, management is based on a hyperprotein and hypolipid diet with medium-chain triglyceride supplementation. We report the case of an exudative enteropathy in a newborn.

S2704 A New Protein Losing Enteropathy: Autoimmune Cryptolytic Enterocolitis

Introduction: Protein losing enteropathy (PLE) can be classified into erosive, non-erosive, and increased interstitial pressure PLE. Presenting signs are often chronic non-bloody diarrhea, anasarca, abdominal pain, and weight loss. We present a complex case of a PLE presentation with a novel diagnosis. Case Description/Methods: A 30-year-old woman with a history of migraines presented with severe abdominal pain and chronic diarrhea. She was on long-term combined estrogen-progestin oral contraceptive pills (OCP) and chronic high dose non-steroidal anti-inflammatory (NSAID) medications. She was exposed to mycoplasma pneumoniae one month prior to presentation, without other infectious exposures. Laboratory tests were notable for hemoglobin 6 g/dL, albumin 0.5 g/dL, stool pathogen PCR negative, and fecal calprotectin >3000µg/g. Extensive infectious work up only revealed Mycoplasma IgM+. Inflammatory markers and alpha-1 anti-trypsin clearance were elevated, and she was found to have warm autoimmune hemolytic anemia. CT angiography excluded ischemia and vasculitis (autoimmune serologies were negative), revealing diffuse enterocolitis, confirmed on magnetic resonance enterography with ileal ulcers. Endoscopic evaluation revealed diffuse superficial ulcerations terminal ileum and colon with diffuse mucosal sloughing. Histopathology revealed diffusely injured crypts with crypt drop-out and minimal inflammation, without any findings to suggest infection, inflammatory bowel disease (IBD) or autoimmune enteritis (Figure). Normal B-cell switching studies excluded common variable immunodeficiency (CVID). Due to profound anasarca and inability to tolerate oral intake, albumin infusions and total parenteral nutrition were started. There was minimal response to systemic or topical steroids. Diarrhea was mildly improved with albumin repletion, and she was empirically started on vedolizumab. Discussion: Given the absence of classic IBD findings, negative infectious and immunological testing, we present the first case of autoimmune cryptolytic enterocolitis, a histopathologic diagnosis of unclear etiology and pathogenesis. The patient has responded to vedolizumab infusions as an empiric treatment for an IBD-like entity. Nevertheless, supporting the autoimmune component of this entity, is a possible concomitant potential pathway of molecular mimicry in the setting of post-mycoplasma infection along with chronic high dose NSAID and OCP exposure.Figure 1.: Terminal Ileum and Sigmoid Colon with Diffuse Crypt Dropout.

Fontan protein-losing enteropathy is associated with advanced liver disease and a proinflammatory intestinal and systemic state.

Protein-losing enteropathy (PLE) after Fontan surgery carries significant morbimortality. Its pathophysiology and association with other Fontan complications are poorly understood. Our aims were to examine whether Fontan-PLE is associated with greater liver damage and to assess the presence of systemic and intestinal inflammation. Fontan patients with PLE and Fontan controls without PLE matched for age and Fontan surgery procedure were included. Data were prospectively compiled on blood and stool tests, liver imaging, elastography, cardiac-MRI and cardiac catheterization. Twenty-nine Fontan patients were enrolled (14 with PLE and 15 controls without PLE). Patients with PLE had more advanced liver disease estimated by non-invasive methods: blunt liver margins on ultrasonography (71.4% vs 26.7%, P=.027), greater median liver stiffness (25.4 vs 14.5kPa, P=.003) and higher FIB-4 (P=.016). Portal hypertension-related signs were more common in patients with PLE including ascites (P=.035), larger spleen size (P=.005), oesophageal varices/splanchnic collateral shunts (P=.03), higher liver stiffness-spleen size-to-platelet ratio risk score (P<.001) and lower platelet count (P=.01). Systemic proinflammatory cytokines (TNF-α, interleukin-6), biomarkers of intestinal permeability (intestinal fatty-acid binding protein) and faecal calprotectin concentrations were also significantly increased in Fontan-PLE (P<.05). Faecal calprotectin directly correlated with alpha-1 antitrypsin clearance and inversely with cardiac index, total serum proteins and body mass index. Fontan-PLE is associated with advanced liver disease and increased markers of systemic inflammation and intestinal permeability. Faecal calprotectin is elevated and correlates with Fontan-PLE severity. Liver assessment is mandatory in all Fontan patients, and especially in those with PLE.

A case of protein-losing gastroenteropathy caused by systemic AA amyloidosis secondary to undifferentiated carcinoma of unknown primary origin.

We report the case of a 61-year-old woman with Kartagener syndrome who presented with a 3-month history of chronic watery diarrhoea and severe hypoalbuminaemia. Histopathological examination of duodenum and large intestine biopsies showed amyloid A (AA) amyloid deposition. Scintigraphy and alpha-1 anti-trypsin clearance evaluations revealed protein-losing gastroenteropathy. Computed tomography with contrast and positron emission tomography showed a pelvic mass with multiple para-aortic lymph node enlargement. We suspected protein-losing gastroenteropathy secondary to AA amyloid produced related to malignant tumours. Following tumour resection, histopathological examination of the lesion revealed undifferentiated carcinoma of unknown origin. Postoperatively, the patient’s nutritional condition improved. There has been no recurrence of protein-losing gastroenteropathy 6 months postoperatively. This is the first report of protein-losing gastroenteropathy and AA amyloidosis secondary to undifferentiated carcinoma. Early recognition and intervention could increase the likelihood of amyloidosis remission.

Gastro-entéropathies exsudatives

Protein-losing enteropathy is a rare syndrome of gastrointestinal protein loss. The primary causes can be classified into lymphatic leakage due to increased interstitial pressure and increased leakage of protein-rich fluids due to erosive or non-erosive gastrointestinal disorders. The diagnosis of protein-losing enteropathy should be considered in patients with chronic diarrhea and peripheral oedema. The diagnosis of protein-losing enteropathy is most commonly based on the determination of fecal alpha-1 antitrypsin clearance. Most protein-losing enteropathy cases are the result of either lymphatic obstruction or a variety of gastrointestinal disorders and cardiac diseases, while primary intestinal lymphangiectasia (Waldmann's disease) is less common. Treatment of protein-losing enteropathy targets the underlying disease but also includes dietary modification, such as high-protein and low-fat diet along with medium-chain triglyceride supplementation.

A Rare Cause of Diarrhea and Weight Loss

Purpose: A 70-year-old man presented with a five-month history of abdominal pain, low-grade fever, fatigue, anorexia, diarrhea and a 30-pound weight loss. The initial evaluation included EGD and ileocolonoscopy, with random biopsies showing an increase in colonic intraepithelial lymphocytes and mild plasmacytosis. An abdominal CAT scan showed two separate segments of small bowel circumferential thickening. Infectious etiologies were excluded and a presumptive diagnosis of Crohn's disease was rendered. He was empirically treated with steroids with partial improvement. Several weeks later, he presented with continued symptoms, as well as diffuse edema consistent with anasarca. A repeat evaluation was negative for celiac disease, stool culture, ova and parasite, C. difficile, mycobacterium tuberculosis, HIV, and fecal fat. Laboratory showed a hemoglobin 11.1 g/dL, platelet 131 X 10ˆ9/L, BUN 32.3 mg/dL, creatinine 1.2 mg/dL, albumin 1.9 g/dL, prealbumin 29.9 mg/dL, and increased serum-feces alpha-1 antitrypsin clearance 53 (<27). These findings suggested a protein-losing enteropathy, which prompted a deep enteroscopy. Retrograde deep enteroscopy showed diffuse edema, erythema and shallow ulcerations in the distal ileum up to 80 cm from the ileocecal valve. Terminal ileum histology showed a dense, small, mature-appearing lymphocytic infiltrate expanding the lamina propria, extending into the submucosa with blunted villi without significant intraepithelial lymphocytosis. The immunophenotype was positive for CD3, CD5, CD7, CD56 and T-cell gene rearrangement, and negative for CD4, CD8, and Tdt. Enteropathy-associated T-cell lymphoma (EATL) was diagnosed. The patient was started on cyclophosphamide, etoposide, vincristine and prednisone alternating with pralatrexate. Unfortunately, he developed bacteremia, septic shock and expired six weeks later. EATL is an uncommon gastrointestinal T cell lymphoma and is strongly associated with celiac disease. Patients typically present with abdominal pain, systemic B symptoms, fatigue or anorexia. The small intestine was the most commonly involved site at diagnosis (90%), followed by the large intestine (16%) with frequent involvement of mesenteric (35%) and para-aortic or iliac lymph nodes (11%). Clinical, radiologic and endoscopic manifestations of EATL can mimic Crohn's disease, as demonstrated in this case. The development of a protein-losing enteropathy in this case broadened the differential leading to the final diagnosis. Deep enteroscopy is an important endoscopic tool to obtain tissue for the proper diagnosis of EATL, especially when suggested by other imaging modalities, such as abdominal CT scan.

High Alpha-1 Antitrypsin Clearance Predicts Severity of Gut Graft Versus Host Disease (GVHD) In Children

AbstractAbstract 1242The clinical evaluation and management of gut GVHD is a significant challenge in pediatric hematopoietic stem cell transplantation (HSCT). It is often difficult to obtain pathological evidence to confirm the GVHD diagnosis and/or determine response to treatment. The severity of the disease itself may not just be related to the associated classic symptoms. Our objective herein was to prospectively study the effect of gut GVHD on protein losing enteropathy (PLE) as measured by alpha-1 antitrypsin clearance (AATC) in stools. Thirteen patients who were diagnosed with gut GVHD by clinical criteria were recruited; 5 patients were excluded as 4 had gut GVHD ruled out by biopsy and 1 was unable to complete study due to stool collection issues. Therefore, 8 patients; 6 males and 2 females, were studied. The median age was 9.5 years (range 6–17). Diagnoses included ALL (4), AML (2), Lymphoma (1) and Adrenoleukodystrophy (1). Donor types were; 7 unrelated (BM n=4 and cord n=3) one matched related BM donor. All patients received cyclosporine for GVHD prophylaxis, in addition 4 patients also received methotrexate and 3 others received prednisone as the second agent. All patients had negative stool EM for viruses and cultures for C.difficile on their first collection. Two 24 hour stool collections were taken from each patient at a mean of 8.5d (range 7–13d) apart. Patients' gut GVHD staging is summarized in Table 1.Table 1:Summary of Stage gut GVHD and PLEPatientsAATC Median(range)normal = <22Stool outputml/kg/d Median(range)Stage of gutGVHD (n=)# with PLECollection #1831 (3-339)28 (10-109)Stg 1 (2)4/8Stg 2 (3)Stg 3 (1)Stg 4 (2)Collection #2856 (8-561)19 (0-85)Stg 1 (0)5/8Stg 2 (0)Stg 3 (3)Stg 4 (1)At the time of 1st collection, 6 patients had ≥ stage II gut GVHD and at 2nd collection 4 patients had ≥stage II gut GVHD and 4 collections were of non-diarrheal stool. A total of 7 stool collections were taken at a diagnosis of ≥stage III gut GVHD. Mean alpha-1 antitrypsin clearance (AATC) from all 16 collections was 143 mls/day (range 3–561), levels >22 mls/day indicate the diagnosis of protein-losing enteropathy (PLE). Nine of the collections (56%) showed PLE with a mean AATC of 247mls/day (range 31–561). Six out of the 7 samples from patients with ≥stage III gut GVHD were positive for PLE. Five collections with stool volumes >30 ml/kg/day were positive for PLE. Stool volumes were significantly higher on second collection (Wilcoxon signed ranks test, p = 0.003) consistent with the second stool collections being significantly more likely to have an elevated AATC, therefore more severe PLE over time (p<0.001). We conclude that a highly significant positive correlation exists between the severity of PLE and the stage of gut GVHD, particularly obvious in patients with stage 3–4 GVHD (ANOVA, p=0.015). See Table 2.Table 2:Stage of gut GVHD and AATCStage ofGVHDNumber ofcollectionsMeanAATCStd.Deviation0426.0020.801217.0019.802384.67136.2934171.50176.2143406.33134.32When patients were grouped as stage 0–2 GVHD vs. stage 3–4 GVHD, those with stage 3–4 GVHD had significantly higher AATC values (p =0.02). Despite the small number of patients recruited, this study emphasizes the need to consider PLE as a useful aspect of the clinical picture. We suggest that in order to see a response to therapy and therefore a decrease in AATC, clinicians should not repeat stool collections before 2 weeks from the initiation of therapy. In light of the significant morbidity and mortality associated with grade 3 and 4 gut GVHD, and as an important therapeutic decision for these patients, one may consider escalating GVHD therapy if a patient's AATC is rising. Disclosures:No relevant conflicts of interest to declare.

Protein-Losing Enteropathy: Case Illustrations and Clinical Review

Protein-losing enteropathy (PLE) is a rare syndrome of gastrointestinal protein loss that may complicate a variety of diseases. The primary causes can be divided into erosive gastrointestinal disorders, nonerosive gastrointestinal disorders, and disorders involving increased central venous pressure or mesenteric lymphatic obstruction. The diagnosis of PLE should be considered in patients with hypoproteinemia after other causes, such as malnutrition, proteinuria, and impaired protein synthesis due to cirrhosis, have been excluded. The diagnosis of PLE is most commonly based on the determination of fecal alpha-1 antitrypsin clearance. Treatment of PLE targets the underlying disease but also includes dietary modification, supportive care, and maintenance of nutritional status. In this article, cases illustrating a variety of clinical presentations and etiologies of PLE are presented, and its diagnostic approach and treatment are reviewed.

Protein Losing Enteropathy in Severe Atopic Dermatitis in an Exclusively Breast‐Fed Infant

We first report a case of protein losing enteropathy in severe atopic dermatitis in an exclusively breast-fed 5-month-old infant. Protein losing enteropathy was confirmed by fecal alpha1-antitrypsin clearance test and imaged successfully by 99mTc-human serum albumin scintigraphy. The present case highlights that protein losing enteropathy in severe infantile atopic dermatitis is being a topic of concern and also an issue even in exclusive breast feeding patients.

Non-invasive techniques for assessing postoperative recurrence in Crohn's disease

Postoperative recurrence after ileo-colonic resection is a feature of Crohn's Disease (CD), almost 73% of patients show endoscopic recurrence at 1 year and 90% at 3 years. After surgical resection for CD, symptoms may be related to the surgical resection itself. Moreover, the development of an early severe endoscopic recurrence within 1 year represents a risk factor for early clinical recurrence. On the basis of these observations, the early detection and assessment of asymptomatic endoscopic recurrence may allow a timely and appropriate treatment of CD patients after ileo-colonic resection. At this purpose, conventional colonoscopy with ileoscopy currently represents the gold standard for assessing CD recurrence, graded according to the Rutgeerts' score. Lesions compatible with CD recurrence can be also detected by conventional radiology, including small bowel follow through and enema, both associated with a high radiation exposure. Due to the ineluctable course of CD after resection, and to the need of a proper follow up for assessing CD recurrence, several alternative, non invasive techniques have been searched in order to assess the post-operative recurrence, including: faecal alpha 1-antitrypsin clearance, faecal calprotectin, 99Tc-HMPAO scintigraphy, virtual colonoscopy, ultrasonography and, more recently, wireless capsule endoscopy (WCE) and Small Intestine Contrast Ultrasonography (SICUS). Among these, current evidences suggest that in experienced hands, ultrasound examination by SICUS represents a non-invasive technique useful for assessing recurrence in CD patients under regular follow up after surgery. The same findings are suggested for WCE, although the impact risk related to the recurrence or to the surgical anastomosis itself limits the use of this non-invasive technique for assessing CD recurrence after surgery.

Primary intestinal lymphangiectasia (Waldmann's disease)

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 α1-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.

Œdèmes et entéropathie exsudative compliquant une péricardite chronique constrictive associée à un anévrisme de l’aorte ascendante

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

Intermediate outcomes after serial transverse enteroplasty in children with short bowel syndrome

Background Serial transverse enteroplasty (STEP) is a novel intestinal lengthening procedure introduced in 2003. To date, no human studies exist that report objective assessment of intestinal absorptive capacity. The aim of this study was to report intermediate outcomes in patients who have received the STEP at our institution using clinical and biochemical assessment of intestinal function. Methods All 14 patients who received the STEP since May 2003 were reviewed. Clinical (weight gain, enteral tolerance, stool frequency) and biochemical (citrulline levels, d-xylose absorption, alpha-1 antitrypsin clearance, and fecal fat content) outcomes were performed pre-STEP and post-STEP at 1, 6, and 12 months, respectively. Data are presented as means with standard deviation. Paired t tests were used to compare post-STEP outcomes with pre-STEP values ( P < .05 was significant). Three patients had a STEP as a newborn and are analyzed separately. Main Results There were 14 patients (3 females; mean age, 24.8 months; range, 1 day-14 years). Serial transverse enteroplasty resulted in a mean increase in length of dilated bowel segment of 94% ± 30% and increase in total small bowel length of 49% ± 42% with mean application of 16 ± 9 cartridges and cost of Can$2878.51 ± 1406.22. Patients demonstrated improvement in both clinical parameters, as well as intestinal absorptive function. Complications included 2 patients with staple line leak and 1 patient with gastrointestinal bleeding from staple line ulcers. Three patients died (2 from liver failure and 1 from sepsis and congenital heart disease). Two patients received liver-intestinal transplants at 4 and 5 months post-STEP. Mean follow-up was 23 ± 9 months, with 7 patients followed more than 2 years. Of 8 patients with post-STEP follow-up of more than 1 year, 7 have weaned from parenteral nutrition. Conclusion Clinical and objective biochemical outcomes of intestinal function after the STEP procedure show promise after intermediate follow-up.

Hypogammaglobulinaemia secondary to cow‐milk allergy in children under 2 years of age

Symptomatic hypogammaglobulinaemia in children younger than 2 years of age was studied to rule out a primary immunodeficiency. Thirty-four patients were referred to the Immunology Service to study the hypogammaglobulinaemia-associated clinical picture. Food allergy was documented in 10 patients by personal and familial history, presence of specific immunoglobulin E (IgE) and elevated total serum IgE levels. Coeliac disease and human immunodeficiency virus infection were also ruled out. Protein loss through stools was assessed by clearance of alpha1-antitrypsin (AAT). Serum immunoglobulin levels were determined by nephelometry and functional antibodies were studied by enzyme-linked immunosorbent assay. The cellular immune response was assessed by in vitro lymphocyte proliferation in response to mitogens and cell subsets were analysed by flow cytometry. In five patients of the 10 patients we suspected a protein loss through the mucosa. Four of these five patients showed an increased AAT and the other showed an extensive cutaneous lesion. Immunological studies revealed normal antibody function, in vitro lymphoproliferative responses and cell numbers in four of the 5 patients. One patient showed abnormally low numbers of CD4(+) T cells as well as a defective proliferative response to mitogens. After diagnosis of cow milk allergy, milk was replaced with infant milk formula containing hydrolysed proteins. Recovery of immunoglobulin values and clinical resolution were achieved. Hypogammaglobulinaemia during early childhood in some children may be secondary to cow milk allergy, and immunoglobulins and cells may leak through the inflamed mucosa. Resolution of symptoms as well as normalization of immunoglobulin values may be easily achieved by avoidance of the offending allergen.

Retractile Mesenteritis Presenting as Protein-Losing Gastroenteropathy

Retractile mesenteritis is a rare, idiopathic condition characterized by nonspecific inflammation of the mesenteric adipose tissue. The majority of patients present with abdominal pain and/or a palpable mass. In the present report, a 68-year-old man with peripheral edema and mild hypoalbuminemia is presented. Protein-losing gastro-enteropathy was confirmed with an abnormal stool alpha1-antitrypsin clearance test and retractile mesenteritis was diagnosed at laparoscopy. This rare condition may respond to therapy with corticosteroids, azathioprine, cyclophosphamide, colchicine, progesterone, tamoxifen or thalidomide. Gastroenterologists should consider the diagnosis of protein-losing enteropathy in patients who present with unexplained peripheral edema or hypoalbuminemia. The test of choice to confirm this diagnosis is the stool alpha1-antitrypsin clearance test.

A Case of Severe Protein-losing Enteropathy as a Late Complication of Pelvic Irradiation

Protein-losing enteropathy is the manifestation of a diverse set of disorders, and it is characterized by the excessive loss of plasma proteins into the affected portions of the gastrointestinal tract, and this results in hypoalbuminemia. We report here on a case of severe protein-losing enteropathy with the typical clinical features of hypoalbuminemia, dependent edema and increased alpha 1-antitrypsin (α1-AT) clearance, as measured by using 24hr stool testing. The associated disorder with the protein-losing enteropathy of our case was radiation enterocolitis and lymphatic obstruction that was due to radiation treatment and lymph node dissection in the remote past for the treatment of uterine cervical carcinoma. Our case suggests that chronic radiation enterocolitis can result in irreversible injury to the intestinal mucosa and a protein-losing enteropathy, which can bring about a very poor quality of life and even the loss of life.

A Systemic Lupus Erythematosus Patient with Protein Losing Enteropathy

Protein-losing enteropathy (PLE) is a rare manifestation of systemic lupus erythematosus (SLE), and it is an uncommon cause of hypoalbuminemia without proteinuria. We describe a case of an 11 year-old girl who had diarrhea and periorbital edema as the initial symptoms of SLE. PLE was diagnosed by 24-hour stool alpha-1 antitrypsin clearance and (99m)Tc-human serum albumin scintigraphy.

Fecal alpha 1-antitrypsin clearance as a marker of clinical relapse in patients with Crohn's disease of the distal ileum.

Crohn's disease (CD) shows a chronic relapsing course but no marker of relapse is currently available. However, fecal alpha 1-antitrypsin (alpha 1-AT) clearance (alpha 1-ATCl) is an indicator of protein loss and increases during active inflammation. We assessed the usefulness of fecal alpha 1-ATCl in predicting clinical relapse in patients with inactive ileal CD. In a prospective longitudinal study, 26 patients with inactive ileal CD (Crohn's disease activity index (CDAI) < 150) (18 males, mean age 43 +/- 10, range 23-58) were enrolled. Fecal alpha 1-ATCl and concentration, daily stool weight and serum alpha 1-AT were measured at baseline (visit 1), after 1 week (visit 2) and 3 weeks (visit 3) in 24/26 patients (two drop-outs) (short-term study). In six of these 26 patients, fecal alpha 1-ATCl was also measured every 3 months for 1 year (long-term study). All patients were clinically assessed every 3 months for 1 year and every 6 months for 2 years. Ten healthy volunteers were tested as controls. Serum and fecal alpha 1-AT concentration was quantified by radial immunodiffusion. The median fecal alpha 1-ATCl value at baseline was higher in inactive patients undergoing clinical relapse (CDAI > 200) in the next 6 months than in those remaining in remission at 6 months (P = 0.03). Fecal alpha 1-ATCl showed a 75% sensitivity, 85% specificity, 50% positive predictive value and 94% negative predictive value in predicting CD relapse in the next 6 months. In the long-term follow-up, fecal alpha 1-ATCl values increased at 12 months compared with both baseline and 6 month values (P = 0.005; P = 0.009). Fecal alpha 1-ATCl was higher in patients with raised C-reactive protein (P = 0.039). Results from our study suggest that fecal alpha 1-ATCl is an indicator of clinical relapse in patients with CD of the distal ileum under regular surveillance.