Duodenal intraepithelial lymphocytosis in Helicobacter pylori gastritis: comparison before and after treatment.

Our aims were to assess performance of duodenal intraepithelial lymphocyte counting for diagnosis of Helicobacter pylori (H. pylori) gastritis, and effects of eradication therapy on intraepithelial lymphocytosis. Paired duodenal and gastric biopsies from subjects with a pathologic diagnosis of H. pylori gastritis were reviewed. Higher duodenal intraepithelial lymphocyte counts were observed in 40 subjects with H. pylori gastritis (26 ± 5 per villus) than 52 subjects negative for H. pylori (12 ± 2 per villus). After successful eradication therapy, duodenal lymphocytes were indistinguishable from H. pylori-negative subjects, whereas they remained elevated after failed eradication therapy. This study confirms previous reports of increased duodenal intraepithelial lymphocytes in patients with concurrent Helicobacter pylori gastritis. Intraepithelial lymphocyte counts of > 15 per villus or > 10 per 100 enterocytes were predictive of infection. Duodenal lymphocytosis decreases significantly after successful eradication therapy but remains elevated when treatment fails.

The coeliac stomach: A review of the literature.

Beyond the small intestine, coeliac disease (CeD) may affect other gastrointestinal tracts, including the stomach. However, various studies have reported conflicting results regarding the association between CeD and gastric manifestations. The aim of this study was to analyze the existing literature on gastric involvement in CeD. A literature search was conducted in bibliographic databases of Embase, PubMed, Scopus, and Web of Science. Studies reporting the association between CeD and gastric disorders were examined in detail and are fully described in the review. Both in children and adults, a strong correlation between lymphocytic gastritis and CeD was found at CeD diagnosis, and lymphocytic gastritis seemed to improve on a gluten-free diet. Most of the literature described a lower risk of gastritis related to Helicobacter pylori infection in CeD subjects compared to controls. However, due to the discordance among studies in terms of study design and population, a clear association could not be determined. Finally, the relationship between CeD and reflux or dyspepsia has yet to be defined, as well as the association between CeD and autoimmune gastritis. CeD appears to be a multiform entity associated with different gastric disorders with a different degree of relationship. Thus, gastric biopsies should be routinely taken during upper endoscopy in CeD patients.

Borrelia lusitaniae Infection Mimicking Headache, Neurologic Deficits, and Cerebrospinal Fluid Lymphocytosis.

Headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL) is a rare headache syndrome included in the Classification of Headache of the International Headache Society as a "headache attributed to non-infectious inflammatory intracranial disease." We report one 15-year-old patient with clinical history and cerebrospinal fluid findings compatible with the diagnosis of HaNDL in whom Borrelia lusitaniae was identified in cerebrospinal fluid by polymerase chain reaction.

Propionibacterium acnes overabundance and natural killer group 2 member D system activation in corpus-dominant lymphocytic gastritis.

Corpus-dominant lymphocytic gastritis (LyG) is characterized by CD8+ T-cell infiltration of the stomach epithelium by a so far uncharacterized mechanism. Although Helicobacter pylori is typically undetectable in LyG, patients respond to H. pylori antibiotic eradication therapy, suggesting a non-H. pylori microbial trigger for the disease. Comparative microbiota analysis of specimens from LyG, H. pylori gastritis and healthy controls precluded involvement of H. pylori in LyG but identified Propionibacterium acnes as a possible disease trigger. In addition, the natural killer group 2 member D (NKG2D) system and the proinflammatory cytokine interleukin (IL)-15 are significantly upregulated in the gastric mucosa of LyG patients, and gastric epithelial cells respond to microbe-derived stimuli, including live P. acnes and the microbial products short-chain fatty acids, with induction of NKG2D ligands. In contrast, H. pylori infection does not activate or even repress NKG2D ligands. Together, our findings identify P. acnes as a possible causative agent for LyG, which is dependent on the NKG2D system and IL-15 activation. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Helicobacter pylori in celiac disease and in duodenal intraepithelial lymphocytosis: Active protagonist or innocent bystander?

BACKGROUND AND OBJECTIVE: Helicobacter pylori (H. pylori) infection influences duodenal inflammation. Consequently, in celiac disease and in duodenal intraepithelial lymphocytosis, the bacterium could affect the clinical-histological manifestations. The aim of this work was to evaluate the prevalence and the potential role of H. pylori infection in celiac disease and duodenal intraepithelial lymphocytosis. METHODS: H. pylori status was reviewed in 154 patients with celiac disease or duodenal intraepithelial lymphocytosis and in a control population. This retrospective study was performed at Molinette hospital, university of Torino, Italy. RESULTS: H. pylori prevalence was 36% in celiac disease patients, 19% in case of duodenal intraepithelial lymphocytosis and 41% in controls (P<0.05 vs. duodenal intraepithelial lymphocytosis). H. pylori prevalence was not significantly different between celiac disease patients with or without iron deficiency anemia (22% vs. 39%) and it was higher in patients with milder duodenal lesions: 50% in Marsh-Oberhuber classification type 1-2 vs. 33% in type 3. Celiac disease patients had a mean intraepithelial lymphocytes count greater than that of duodenal intraepithelial lymphocytosis patients (52 vs. 44 intraepithelial lymphocytes per 100 epithelial cells). Both in celiac disease and in duodenal intraepithelial lymphocytosis patients, H. pylori infection was associated with an increase in intraepithelial lymphocytes count, but this difference was not significant. CONCLUSION: H. pylori prevalence was similar in celiac disease patients and in controls and higher in patients with milder duodenal lesions. There was no association between H. pylori infection and duodenal intraepithelial lymphocytosis.

Iron deficiency anemia due to lymphocytic gastritis with Helicobacter pylori infection in childhood: case report.

Lymphocytic gastritis (LG) is a chronic inflammatory process of poorly understood pathogenesis. We report the case of a 12-year-old premenstrual girl with refractory iron deficiency anemia in which the oral iron absorption challenge suggested iron malabsorption. Laboratory studies ruled out celiac disease and autoimmune gastritis, and carbon-13 urea breath test for Helicobacter pylori was also negative. Upper endoscopy with gastric body and antral mucosa biopsies revealed a LG with focal intestinal metaplasia and H. pylori infection. H. pylori eradication was undertaken with success and 3 months later her hematologic parameters normalized. Histologic reevaluation showed disappearance of LG. This case shows that investigation of malabsorption disease in the presence of refractory iron deficiency anemia can lead to the diagnosis of important gastric diseases, even in the absence of gastrointestinal symptoms. This nonceliac child was diagnosed with a severe histopathologic pattern of LG, with potential risk of malignant transformation, which was completely reverted with adequate H. pylori eradication treatment.

Hypersensitivity pneumonitis induced by Shiitake mushroom spores.

Hypersensitivity pneumonitis (HP) is a pulmonary granulomatosis involving an immunoallergic mechanism caused by chronic inhalation of antigens, most frequently organic substances, as well as chemicals. We report the first European case of hypersensitivity pneumonitis due to the inhalation of Shiitake mushroom spores. A 37-year-old French Caucasian man with a one-month history of persistent dry cough, shortness of breath and loss of weight was admitted to our hospital on December 2010. Anamnesis showed he was involved in mushroom production beginning in the summer of 2010. His temperature on admission was 36.6°C and he had a normal blood pressure (135/90 mmHg). Bilateral fine crackles were audible in the base of both lungs. Pulmonary function tests showed a mild restrictive pattern with decreased DLco and a PaO(2) of 65 mmHg, Chest CT scan revealed reticulo-nodular shadows, slight ground glass opacities, liner atelectasis, and subpleural opacities in both lung fields. Bronchoscopy was normal but cytological examination of BAL revealed a predominant lymphocytosis (55%). Serum precipitins to the Shiitake mushroom spores were positive (3 precipitins arcs with high intensity) and as a result we advised the patient to cease his mushroom production activities. The diagnosis of hypersensitivity pneumonitis due to inhalation of Shiitake mushroom spores was established as a result of the improvement of all of his clinical symptoms, i.e., cough, weight loss, bilateral fine crackles, mild restrictive pattern of pulmonary function, and reticulo-nodular shadows on chest CT, once exposure was eliminated. Recent interest in exotic mushrooms varieties, e.g., Shiitake, in developed countries because of their possible medicinal properties might increase the potential risk of HP among mushrooms workers. Therefore, healthcare professionals have to take this new potential respiratory disease into account.

Parsonage-Turner syndrome revealing Lyme borreliosis.

Parsonage-Turner syndrome, also known as acute brachial neuritis or neuralgic amyotrophy, can be caused by various infectious agents. We report on four patients who experienced Parsonage-Turner syndrome as the first manifestation of Lyme disease. The clinical picture was typical, with acute shoulder pain followed rapidly by weakness and wasting of the shoulder girdle muscles. Electrophysiological testing showed denervation. A single patient reported erythema chronicum migrans after a tick bite. Examination of the cerebrospinal fluid showed lymphocytosis and protein elevation in 3 patients. Serological tests for Lyme disease were positive in the serum in all 4 patients and in the cerebrospinal fluid in 2 patients. Antibiotic therapy ensured a favorable outcome in all 4 cases. Two patients achieved a full recovery within 6 months. Parsonage-Turner syndrome should be added to the list of manifestations of neuroborreliosis. Serological tests for Lyme disease should be performed routinely in patients with Parsonage-Turner syndrome.

Intraepithelial lymphocytes in duodenum from Brazilian adolescents with type 1 diabetes. Influence of Helicobacter pylori.

BACKGROUND: An increased number of intraepithelial lymphocytes (IELs) can be the only histological feature in early stages of celiac disease (CD). This is also presented in duodenum of patients with Helicobacter pylori-associated gastritis and in autoimmune diseases. Because CD is frequently associated with type 1 diabetes mellitus, we analyzed the density of IELs in the distal duodenum of non-celiac diabetic patients associated or not with H.pylori infection. METHODS: IEL density and the presence of H.pylori were determined in biopsies of the distal duodenum and gastric antrum and body obtained from Brazilian diabetic adolescents who were negative for anti-human tissue transglutaminase and anti-endomysial. The results were compared with the histological findings of gastric and duodenal biopsies obtained from non-diabetic older children and adolescents. RESULTS: H.pylori was detected in 33.3% of diabetic patients and in 56.7% of the control group. No association was observed between the presence of H.pylori and an increased lymphocyte density in the distal duodenum in either group. Diabetic patients presented a duodenal IEL density similar to that of the control group. Lymphocytic gastritis was not identified in any of the biopsies analyzed. CONCLUSIONS: The density of IELs in the distal duodenum of diabetic adolescents did not differ from that observed in older children and adolescents without this autoimmune disease. H.pylori infection, which is frequent among adolescents from developing countries, did not modify lymphocyte density in the distal duodenum in the absence of lymphocytic gastritis.

Lymphocytic pleural effusion in acute melioidosis.

An endemic outbreak of melioidosis developed in southern Taiwan following a flood caused by a typhoon in July 2005. A total of 27 patients were diagnosed with the acute and indigenous form of pulmonary melioidosis. Parapneumonic pleural effusions were noted on chest X-rays in six patients. Thoracentesis was done in three patients and all revealed lymphocyte predominance in differential cell count. Burkholderia pseudomallei was isolated in the pleural effusion in one of them. All three patients survived after antibiotic treatment. Lymphocytic pleural effusion is generally seen in tuberculosis or malignancy. However, our findings suggest that melioidosis should be considered in the differential diagnosis of lymphocytic pleural effusion.

Expansion of TcRalphabeta+CD3+CD4-CD8- (CD4/CD8 double-negative) T lymphocytes in a case of staphylococcal toxic shock syndrome.

A 55-year-old woman presented with staphylococcal toxic shock syndrome (TSS). During the course of the disease a significant lymphocytosis appeared, and a high number of TcRalphabeta+CD3+CD4-CD8- (double-negative, DN) lymphocytes was observed both in bone marrow and in peripheral blood samples. Correction of the altered lymphocyte immunophenotype was observed only 6 weeks after recovery from TSS. The immunophenotype of circulating and bone marrow lymphocytes was also studied during a phase of an aspecific febrile episode observed 2 months after recovery, but no subset of DN lymphocytes was found. A small subset of DN lymphocytes can be found in normal bone marrow, liver, thymus, and skin. These cells show peculiar immune regulatory properties and can increase in certain autoimmune diseases. Our findings may represent a specific effect of lymphocyte stimulation by the staphylococcal exotoxin, which is the effector agent of TSS.

T cell costimulatory molecule function determines susceptibility to infection with Pneumocystis carinii in mice.

Loss of T cell number and function during HIV infection or secondary to pharmacologic immunosuppression renders individuals susceptible to opportunistic infections, including Pneumocystis carinii pneumonia. Because costimulatory receptors are critical for optimal T cell function, we hypothesized that these proteins would regulate susceptibility to opportunistic infections. We found that despite normal T cell numbers, mice deficient in the costimulatory molecules CD2 and CD28 spontaneously developed P. carinii pneumonia. In experiments using intratracheal injection of P. carinii organisms to induce infection, the loss of CD28 alone was sufficient to render mice susceptible to acute infection; however, the organism was eventually cleared. Examination of inflammatory responses to P. carinii revealed that mice deficient in both CD2 and CD28 accumulated CD8(+) T cells in their lungs in response to infection and demonstrated markedly reduced specific Ab titers. Analysis of cytokine profiles suggested that regulation of IL-10 and IL-15 may be important elements of the response to this pathogen. Thus, costimulatory molecule function is critical in determining the initial susceptibility to infection with P. carinii. Analysis of immunologic responses in these mice may provide important insights into the defects that render individuals susceptible to opportunistic infection, and provide opportunities for novel immunologically based therapies.

Natural killer-cell lymphocytosis and strongyloides infection.

We report a case of strongyloides infection in a 72-year-old man presenting with acute angio-oedema and urticaria. He was also found to have natural killer cell (NK) large granular lymphocytosis (LGL). We discuss the possible relationship between the strongyloides infection and the NK-LGL lymphocytosis.

Effects of Helicobacter pylori eradication on the natural history of lymphocytic gastritis.

BACKGROUND: Lymphocytic gastritis is characterised by an accumulation of lymphocytes in the surface epithelium of the stomach. Lymphocytic gastritis has been linked to coeliac disease and Helicobacter pylori infection. AIMS: To determine whether H pylori eradication leads to resolution of the lymphocytic infiltrate and clinical improvement in patients with lymphocytic gastritis, and to determine their HLA status. METHODS: The Leeds Dyspepsia Questionnaire (LDQ) was administered to 13 patients with lymphocytic gastritis. H pylori serology, (13)C urea breath test (UBT), and upper gastrointestinal endoscopy with sampling of the duodenum, antrum, and corpus were done in all cases and the HLA status was determined. Eleven patients had at least one positive test for H pylori. Patients with lymphocytic gastritis and H pylori infection were treated with a one week course of omeprazole, clarithromycin, and metronidazole. Gastric and duodenal intraepithelial lymphocyte (IEL) counts were performed, along with histological assessment of gastric and duodenal biopsies before and after H pylori eradication. RESULTS: Two months after treatment there was a significant reduction in gastric IEL counts in both antrum and corpus. There was no significant change in duodenal IEL counts before and after eradication. According to the Sydney grading there was significant improvement in corpus inflammation after eradication. The patients histologically H pylori positive before treatment became H pylori negative. Dyspepsia scores also improved significantly after treatment. CONCLUSIONS: H pylori eradication treatment in patients with lymphocytic gastritis causes significant improvement in the gastric IEL infiltrate, corpus inflammation, and dyspeptic symptoms. H pylori serology is frequently positive when histology and UBT are negative. Lymphocytic gastritis may represent a specific immune response to H pylori infection.

Lymphocytic gastritis and coeliac disease: evidence of a positive association.

AIMS: To investigate the prevalence of lymphocytic gastritis in patients with coeliac disease. METHODS: Gastric biopsies from 70 patients with coeliac disease were examined by light microscopy for the presence of lymphocytic gastritis, defined as 25 or more intraepithelial lymphocytes/100 gastric columnar epithelial cells. RESULTS: Lymphocytic gastritis was found in seven cases. Positive cases had a mean of 32.1 intraepithelial lymphocytes/100 columnar cells, compared with a mean of 13.9 in negative cases, and 5.15 in noncoeliac controls. No differences were found for age, sex, gastric corpus or antrum, or degree of inflammation in the gastric lamina propria. All intraepithelial lymphocytes were of T cell lineage. Cases not showing lymphocytic gastritis did however show significantly increased gastric intraepithelial lymphocytes compared with non-coeliac controls. Eighteen of 70 cases were positive for Helicobacter pylori, and four of seven cases of lymphocytic gastritis were H pylori positive; no significant difference was observed between H pylori positive and negative patients. Three cases had concomitant ulcerative enteritis, of which none showed lymphocytic gastritis, while five cases had concomitant enteropathy associated T cell lymphoma, of which one showed lymphocytic gastritis. CONCLUSIONS: Lymphocytic gastritis occurred in 10% of patients with coeliac disease. Cases without lymphocytic gastritis nevertheless showed increased gastric intraepithelial lymphocytes. Coeliac disease may on occasion be a diffuse lymphocytic enteropathy occurring in response to gluten. Lymphocytic gastritis outside coeliac disease may involve an immune response to luminal antigens, such as H pylori, not unlike the response to gluten in patients with coeliac disease.

Immunohistochemical detection of GM-CSF, IL-4 and IL-5 in a murine model of allergic bronchopulmonary aspergillosis.

BACKGROUND: Granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and IL-5 are important in tissue eosinophil accumulation and high IgE production in allergic inflammatory reaction. OBJECTIVE: We examine lung GM-CSF, IL-4 and IL-5 expression in a murine model of allergic bronchopulmonary aspergillosis (ABPA) characterized by eosinophil and lymphocyte lung infiltration and elevated serum IgE level. METHODS: C57BL/6 mice were intranasally treated three times a week for 1, 2 or 3 week(s) with Aspergillus fumigatus (Af) antigen or saline and were sacrificed on days 7, 14 and 21. Immunohistochemical analyses for GM-CSF, IL-4 and IL-5 were performed on lung sections. RESULTS: Af treatment induced a remarkable pulmonary eosinophil influx. Increased numbers of lung T lymphocytes and GM-CSF positive cells were observed on days 14 and 21. IL-4 and IL-5 positive cells were increased significantly only on day 14. Immunostained serial sections showed that most (> or = 98%) cytokine positive cells were CD3 positive. Few eosinophils (< 2% of cytokine positive cells) were immunoreactive for GM-CSF and IL-5. Significant correlations were found between the number of GM-CSF and IL-5 positive cells, and the number of eosinophils in Af-treated lung (r = 0.62, P < 0.05 and r = 0.52, P < 0.05 respectively), and between the number of IL-4 positive cells and the serum total IgE level (r = 0.64, P < 0.01). CONCLUSIONS: Our data suggest a role for T lymphocyte GM-CSF, IL-4 and IL-5 in Af-induced mouse pulmonary eosinophilia and increased serum IgE production and further support the importance of T helper (TH2) cells in the pathogenesis of ABPA.

Lymphocytic gastritis and Helicobacter pylori infection in gastric lymphoma.

Lymphocytic gastritis and primary gastric lymphoma are rare conditions with unknown aetiology. It has recently been suggested that Helicobacter pylori has a role in the pathogenesis of both of them. The occurrence of lymphocytic gastritis and H pylori was studied in a series of patients with primary gastric lymphoma. The cases of primary gastric lymphomas (n = 35) diagnosed in years 1970-1993 were identified. The specimens of 22 cases contained gastric mucosa sufficiently so that the number of intra-epithelial lymphocytes, severity of gastritis, and occurrence of H pylori could be studied. Lymphocytic gastritis was detected in seven of 22 patients (32%), and in most cases both in antral and body mucosa. Atrophy of the body glands was significantly more severe in lymphocytic gastritis patients. H pylori was detected in 13 of all 22 patients (59%); two of seven lymphocytic gastritis patients (29%), and 11 of 15 (73%) of patients without lymphocytic gastritis were H pylori positive. Patients with gastric lymphoma have significantly increased prevalence of lymphocytic gastritis. Rarity of H pylori in these patients might be connected with atrophic changes in body mucosa. Further studies are needed to show the significance of lymphocytic gastritis as a precursor of gastric lymphoma.

Epstein-Barr virus-associated lymphoproliferative disorder of granular lymphocytes presenting initially as cutaneous vasculitis.

Lymphoproliferative disorders of granular lymphocytes (LDGL) represent a family of diseases characterized by persistent granular lymphocytosis with variable prognosis. The Epstein-Barr virus (EBV) has been occasionally linked with the development of LDGL. However, cutaneous manifestations of LDGL have rarely been reported. One patient had cutaneous vasculitis for 10 years before a definite diagnosis of LDGL was made. Chronic EBV infection was documented serologically and EBV DNA was detected in the peripheral blood lymphocytes. EBV RNA was detected in the nuclei of infiltrating lymphoid cells expressing CD43 in a skin biopsy specimen. A cytogenetic study showed clonal chromosomal abnormalities. This is the first report of EBV-associated LDGL of natural killer cells with cutaneous manifestations.