Falsely elevated anti-tissue transglutaminase antibodies in patients with immunoproliferative small intestinal diseases: A case series.

Immunoproliferative small intestinal disease (IPSID) is an uncommon disease of the small intestine. There is a similarity in the clinical presentations of enteropathic diseases, including celiac disease, tropical sprue, IPSID, and Whipple's disease. A differentiation between them is based on the use of a highly specific serological test for celiac disease and specific histological characteristics. We found that IgA-anti-tissue transglutaminase antibody (IgA-tTG Ab) is falsely elevated in a subset of patients with IPSID. The levels of IgA-tTG Ab fall with the treatment of IPSID. The healthcare professional should be aware of the conditions that lead to a false-positive anti-tTG Ab. Intestinal mucosal biopsies even in the presence of anti-tTG Ab should be done in endemic regions as they provide an opportunity for making a diagnosis of alternative and uncommon diseases before the diagnosis of celiac disease.

Immunoproliferative Small Intestinal Disease Diagnosed by Double-balloon Endoscopy with Biopsy Sampling.

We herein report an 80-year-old man diagnosed with immunoproliferative small intestine disease (IPSID) via small bowel endoscopy with a biopsy. He developed persistent diarrhea and subsequently presented with hypoproteinemia and moderate anemia. Transanal double-balloon endoscopy showed prominent villous edema in the middle and lower ileum, while a histological examination showed high lymphocyte/plasma cell infiltration in the mucosal layer. Furthermore, an immunostaining analysis showed that Cluster of differentiation (CD) 3 and CD20 were partially positive, while CD138 was diffusely positive. Immunoglobulin A positivity was also observed. He was diagnosed with IPSID and received a nutritional agent and minocycline. After three months, the patients' symptoms improved.

Immunoproliferative Small Intestinal Disease in a Liver Transplant Recipient: A Case Report and Literature Review.

Immunoproliferative small intestinal disease is an extranodal marginal zone B-cell lymphoma that arises from mucosa-associated lymphoid tissue and is associated with defective α heavy chain protein secretion. We present a case of an 18-year-old male patient admitted with diarrhea and weight loss who had previously received a liver transplant at the age of 19 months to treat biliary atresia. He underwent a thorough investigation and was diagnosed with immunoproliferative small intestinal disease lymphoma. The patient was switched from tacrolimus to everolimus and commenced on doxycycline treatment for 6 months and achieved long-term remission. Currently, 7 years after diagnosis, he is asymptomatic without evidence of histological relapse. This is the first case of immunoproliferative small intestinal disease described in a liver transplant recipient.

Heavy Chain Disease of the Small Bowel.

PURPOSE OF REVIEW: The purpose of this review is to discuss current knowledge and recent findings regarding pathogenesis, outcome, and treatment for heavy chain disease (HCD) involving the small bowel, focusing on alpha HCD or immunoproliferative small intestinal disease (IPSID), the HCD subtype typically affecting the small bowel. RECENT FINDINGS: A link between Campylobacter jejuni infection and IPSID has been established, but there is controversy as to the role played by this organism in disease pathogenesis. While cytogenetic abnormalities involving various immunoglobulin loci and PAX5 have been reported, these have been described in rare, single cases, limiting their ability to shed further light on disease pathogenesis. IPSID is typically regarded as a pre-lymphomatous condition with eventual progression to frank lymphoma; however, recent reports of longstanding non-progressive cases have expanded its clinical spectrum. IPSID is an uncommon disorder affecting the small intestine. This review focuses on current knowledge and novel insight regarding its pathogenesis, outcome, and treatment, with an emphasis on future directions.

Prevalence and Characteristics of Duodenal Villous Atrophy in Renal Transplant Patients Presenting With Persistent Diarrhea in a Developing Country.

OBJECTIVES: Persistent diarrhea is a common complication after solid-organ transplant, including kidney transplant. Data on duodenal villous atrophy as a cause of persistent diarrhea in renal transplant recipients are scarce. MATERIALS AND METHODS: We conducted a prospective analysis of 207 patients who received renal transplants from 2009 to 2012 with persistent diarrhea and who underwent upper gastrointestinal endoscopy and duodenal biopsies. Duodenal biopsies were examined for duodenal villous atrophy. Age, sex, transplant duration, and drugs were compared between patients with and without duodenal villous atrophy. After exclusion of known causes of duodenal villous atrophy, a 3-month course of antibiotics was given and outcomes were analyzed. RESULTS: Of 207 renal transplant recipients, 104 patients (49.8%) displayed duodenal villous atrophy. Of these, 92 (88.5%) were male patients. The mean age of patients with duodenal villous atrophy was 34.9 ± 10.3 years. The mean onset of persistent diarrhea in DVA-positive patients posttransplant was 2.16 ± 0.8 years. Celiac disease serology was positive in 18 (17.3) patients. Giardiasis was demonstrated in 11 patients (10.7%), whereas immunoproliferative small intestinal disease was shown in 7 patients (6.8%). The remaining 68 patients (65.38%) received antibiotics, with 50 recipients (74.6%) showing complete response, although 13 of these patients (26%) relapsed. Among the remaining 18 patients (26.47%), 9 (50%) had other causes and 9 (50%) had no cause found. Isoniazid prophylaxis showed statistically significant negative association with duodenal villous atrophy. CONCLUSIONS: Duodenal villous atrophy is highly prevalent in renal transplant recipients irrespective of age, sex, and posttransplant duration. We found tropical sprue, giardiasis, immunoproliferative small intestinal disease, and celiac disease to be important causes of duodenal villous atrophy. Therefore, duodenal biopsy is recommended in renal transplant recipients with persistent diarrhea.

Management of the marginal zone lymphomas.

Marginal zone lymphomas (MZL) represent around 8 % of all non-Hodgkin lymphomas. During the last decades a number of studies have addressed the mechanisms underlying the disease development. Extranodal MZL lymphoma usually arises in mucosal sites where lymphocytes are not normally present from a background of either autoimmune processes, such as Hashimoto thyroiditis or Sjögren syndrome or chronic infectious conditions. In the context of a persistent antigenic stimulation, successive genetic abnormalities can progressively hit a B-cell clone among the reactive B-cells of the chronic inflammatory tissue and give rise to a MALT lymphoma. The best evidence of an etiopathogenetic link is available for the association between Helicobacter pylori-positive gastritis and gastric MALT lymphoma. Indeed, a successful eradication of this micro-organism with antibiotics can be followed by gastric MALT lymphoma regression in more than 2/3 of cases. Other microbial agents have been implicated in the pathogenesis of MZL arising in the skin (Borrelia burgdorferi), in the ocular adnexa (Chlamydophila psittaci), and in the small intestine (Campylobacter jejuni). The prevalence of hepatitis C virus (HCV) has also been reported higher in MZL patients (particularly of the splenic type) than in the control population, suggesting a possible causative role of the virus. In non-gastric MALT lymphoma and in splenic MZL the role of the antimicrobial therapy is, however, less clear. This review summarizes the recent advances in Marginal Zone Lymphomas, addressing the critical points in their diagnosis, staging and clinical management.

Campylobacter coli cultured from the stools of a patient with immunoproliferative small intestinal disease.

Campylobacter has been associated with immunoproliferative small intestinal disease (IPSID), on the basis of 16S rDNA sequencing, in situ hybridization, and immunohistochemistry. Here, for the first time, we have cultured Campylobacter from the stools of a patient with IPSID. Phenotypic analysis and whole genome sequencing identified Campylobacter coli. PCR on a IPSID tissue biopsy sample was positive for Campylobacter coli and negative for Campylobacter jejuni. These findings further support a causative role for Campylobacter in the development of IPSID.

[Primary small intestinal lymphoma: epidemiological, histological and therapeutic transition in Tunisia]. / Transition épidémiologique, histologique et thérapeutique des lymphomes primitifs du grêle (LPG) en Tunisie.

INTRODUCTION: Primary small intestinal lymphoma (PSIL) is the second Non-Hodgkin lymphoma (NHL) of the digestive tract (after gastric NHL). PURPOSE: To evaluate during the past 28 years the epidemiological, anatomoclinical and therapeutic changes of PSIL in Tunisia through an acquired experience of more than a quarter of a century. METHODS: Our retrospective study included patients with histologically confirmed small intestinal lymphoma from 1981 to 2008 in Tunisia at Salah Azaiz Institute. The cohort of 210 patients was divided into two groups: A group from 1981 to 1992 (152 patients) and B group from 1993 to 2008 (58 patients). We analysed the epidemiological, anatomoclinical, histological, and therapeutic characteristics. RESULTS: We observed a significant decrease in the annual incidence of PSIL but also a significant transition of diffuse immunoproliferative small intestinal disease (IPSID) also known as "Mediterranean" PSIL, which were progressively replaced by "Western" lymphomas. Laparotomy with or without a debulking surgery, largely performed in group A, has disappeared at the cost of a primary chemotherapy (p < 0.001). Five-year actuarial global and relapse free survivals were respectively 60.5 and 57.3%. CONCLUSION: PSIL in Tunisia were subjected to a triple transition: epidemiological, histological and therapeutic.

[Intestinal non-Hodgkin lymphoma: "immunoproliferative small intestinal disease"]. / Lymphomes malins non hodgkiniens de l'intestin grêle de type "immunoproliferative small intestinal disease".

Immunoproliferative small intestinal disease (IPSID), also known as alpha chain disease, is a rare disease. In the recent WHO classification of hematopoietic and lymphoid tissue, IPSID is considered as a variant of extranodal mucosa-associated lymphoid tissue (MALT) lymphoma. Campylobacter jejuni is a specific pathogen, found to be related to IPSID. Diagnosis is based on histology and immunochemistry (± fluorescent in situ hybridization), with presence of many variable levels of abnormal immunoglobulin in the serum, identified to be truncated alpha-heavy chains. Early-stage disease is treated by antibiotics (tetracyclines). Chemotherapy is recommended up front for patients with advanced disease at presentation or refractory to antibiotics. The chemotherapy schedule used is the CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) regimen.

Immunoproliferative small intestinal disease (IPSID).

This study describes the frequency, demographics, clinical presentation, endoscopic findings, histopathological features, treatment and outcome of 'Immunoproliferative small intestinal disease' (IPSID). Archives contained a total of 27 cases of IPSID diagnosed and treated over an 18-year period. A M: F ratio of 2.4:1 was seen with a mean and median ages of 28.7 and 25 years. Most patients (68.8%) presented with abdominal pain and diarrhoea. In the majority (62.5%), duodenum was the primary site of involvement. Endoscopy showed polypoidal, raised or flat lesions. Biopsy findings included blunting or flattening of villi with dense plasma cell infiltrate and lymphoepithelial lesions. Twenty-four cases were categorized as stage A and B (benign and intermediate) and three were categorized as stage C (malignant, diffuse large B-cell lymphoma with plasmacytoid features). Stage A and B patients responded well to antibiotic treatment (tetracycline) with regression of the lesions while for stage C patients standard CHOP chemotherapy was administered.

Regression of immunoproliferative small intestinal disease after eradication of Helicobacter pylori.

A 20-year-old male presented with low-grade fever, abdominal pain, anorexia, and weight loss of 4-month duration. On examination, he was emaciated. Barium meal follow-through examination showed extensive nodularity and thickening of duodenal and jejunal folds. Contrast-enhanced computed tomography of the abdomen revealed extensive proximal small-bowel thickening with mesenteric lymphadenopathy. Upper gastrointestinal endoscopy and enteroscopy revealed thickening of folds with multiple small superficial ulceration involving antrum, duodenum, and jejunum. The duodenal and jejunal biopsy was suggestive of immunoproliferative small intestinal disease, stage 0 (Salem) or stage A (Galian). Antral biopsy showed presence of Helicobacter pylori infection. He underwent H. pylori eradication following which he had significant clinical improvement; repeat evaluation at 6 months showed dramatic improvement in his clinical, radiological, and histological parameters.

Nonsecretory variant of immunoproliferative small intestinal disease: a case report with pathologic, immunophenotypic, and molecular findings.

We report a case of the nonsecretory variant of immunoproliferative small intestinal disease involving the distal small bowel and the mesenteric and retroperitoneal lymph nodes in a 19-year-old woman from Mexico. This variant extranodal marginal zone B-cell lymphoma appeared similar in the different sites of involvement, with more interspersed large cells and greater plasmacytic differentiation present in intestinal specimens. Characteristic lymphoepithelial lesions and follicular colonization were seen in intestinal and lymph node sections, respectively. The neoplastic B cells were cytoplasmic immunoglobulin (Ig) A heavy-chain restricted and lacked surface and cytoplasmic light-chain expression by flow cytometric analysis. Serum and urine protein electrophoresis/immunofixation revealed hypogammaglobulinemia with no paraprotein. Molecular studies showed absence of immunoglobulin heavy-chain (IgH) gene rearrangement, with a nonfunctional clonotypic rearrangement of the kappa light-chain gene. This case highlights the role for kappa light-chain gene evaluation in immunoproliferative small intestinal disease, because IgH gene rearrangement analysis is often negative.

Immunoproliferative small intestinal disease (IPSID): a model for mature B-cell neoplasms.

Immunoproliferative small intestinal disease (IPSID) was recently added to the growing list of infectious pathogen-associated human lymphomas. Molecular and immunohistochemical studies demonstrated an association with Campylobacter jejuni. IPSID is a variant of the B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), which involves mainly the proximal small intestine resulting in malabsorption, diarrhea, and abdominal pain. Geographically, IPSID is most prevalent in the Middle East and Africa. IPSID lymphomas reveal excessive plasma cell differentiation and produce truncated alpha heavy chain proteins lacking the light chains as well as the first constant domain. The corresponding mRNA lacks the variable heavy chain (V(H)) and the constant heavy chain 1 (C(H)1) sequences and contains deletions as well as insertions of unknown origin. The encoding gene sequence reveals a deletion of V region and parts of C(H)1 domain. Cytogenetic studies demonstrated clonal rearrangements involving predominantly the heavy and light chain genes, including t(9;14) translocation involving the PAX5 gene. Early-stage IPSID responds to antibiotics (30%-70% complete remission). Most untreated IPSID patients progress to lymphoplasmacytic and immunoblastic lymphoma invading the intestinal wall and mesenteric lymph nodes, and may metastasize to a distant organ. IPSID lymphoma shares clinical, morphologic, and molecular features with MALT lymphoma, lymphoplasmacytic lymphoma, and plasma cell neoplasms.

[Malabsorption syndrome. Rare differential diagnosis in a young patient]. / Malassimilationsyndrom. Seltene Differenzialdiagnose bei einer jungen Patientin.

In a young female patient originally coming from Albany, immunoproliferative small intestinal disease (IPSID) could be diagnosed as a cause for severe maladsorption. Considering clinical and histological criteria an early disease stage of IPSID could be diagnosed. Under the continuous treatment of doxycycline for more than 3 1/2 years, all disease manifestations like watery diarrhea, vomiting, pain in the upper abdomen and loss of weight disappeared. After discontinuation of the antibiotic therapy the patient reached a sustained response.

Immunoproliferative small intestinal disease associated with Campylobacter jejuni.

BACKGROUND: Immunoproliferative small intestinal disease (also known as alpha chain disease) is a form of lymphoma that arises in small intestinal mucosa-associated lymphoid tissue (MALT) and is associated with the expression of a monotypic truncated immunoglobulin alpha heavy chain without an associated light chain. Early-stage disease responds to antibiotics, suggesting a bacterial origin. We attempted to identify a causative agent. METHODS: We performed polymerase chain reaction (PCR), DNA sequencing, fluorescence in situ hybridization, and immunohistochemical studies on intestinal-biopsy specimens from a series of patients with immunoproliferative small intestinal disease. RESULTS: Analysis of frozen intestinal tissue obtained from an index patient with immunoproliferative small intestinal disease who had a dramatic response to antibiotics revealed the presence of Campylobacter jejuni. A follow-up retrospective analysis of archival intestinal-biopsy specimens disclosed campylobacter species in four of six additional patients with immunoproliferative small intestinal disease. CONCLUSIONS: These results indicate that campylobacter and immunoproliferative small intestinal disease are associated and that C. jejuni should be added to the growing list of human pathogens responsible for immunoproliferative states.

Malabsorption syndrome in a patient of Mediterranean origin; immunoproliferative small intestinal disease.

We describe a 30-year-old woman of Turkish descent presenting with abdominal pain and signs of malabsorption. The cause of her complaints turned out to be immunoproliferative small intestinal disease which is a very uncommon disorder in our geographical region. We discuss the differential diagnosis of this disease and the therapeutical options.