Diagnosing and Monitoring Celiac Patients with Selective IgA Deficiency: Still an Open Issue.

Although, the association between celiac disease (CD) and selective immunoglobulin A deficiency (SIgAD) has been known for more than fifty years, the procedures for diagnosing and monitoring patients with both conditions are still far from definitive. When serological markers were introduced as pre-bioptic investigations, it was immediately clear that searching for specific IgA antibodies without checking total serum IgA could lead to a failure in diagnosing IgA-deficient CD patients, while specific IgG antibodies could be useful as additional tests, because they are frequently found in the serum of affected patients. Nonetheless, until recently the diagnosis of CD in IgA-deficient patients was based on the few, fragmentary and often contradictory data available in literature. The introduction of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines in 2012 provided the current criteria for diagnosing CD in IgA-deficient patients, although some issues remained open, such as the selection of patients who should undergo specific IgG antibody testing and the choice of the most reliable IgG-based test for both diagnosis and follow-up. A real-life study recently assessed the impact of the 2012 ESPGHAN guidelines in diagnosing and monitoring CD in SIgAD patients, highlighting several pitfalls that can lead to operational uncertainties and difficulties in patient management. In the present report, the evolution of diagnostic tools and criteria for CD in SIgAD patients has been critically assessed, both strengths and open issues have been highlighted, and future perspectives for improving the current diagnostic protocols have been suggested.

One-step immunochromatographic visual assay for anti-transglutaminase detection in organ culture system: An easy and prompt method to simplify the in vitro diagnosis of celiac disease.

BACKGROUND: Anti-tissue transglutaminase (anti-tTG) and endomysium antibodies (EMA) are detectable in duodenal culture media of celiac disease (CD) patients. To improve the management of this organ culture system, we evaluated the anti-tTG occurrence by immunochromatographic assay (ICA). METHODS: A total of 103 CD patients and 41 disease controls underwent duodenal biopsy for the organ culture. In culture supernatants, IgA anti-tTG were tested by both enzyme-linked immunosorbent assay (ELISA) and ICA, IgA EMA were searched by indirect immunofluorescence analysis (iIFA). RESULTS: Endomysium antibodies and anti-tTG measured by ELISA were positive in culture media of all CD patients, while anti-tTG detected by ICA were positive in culture media of 87/103 CD patients. Anti-tTG ICA scores significantly correlated with anti-tTG ELISA values (r=.71, P<.0001). Sensitivity, specificity and diagnostic accuracy of anti-tTG detected by ICA were 84.5%, 100% and 88.9%, respectively. CONCLUSIONS: Using ICA, anti-tTG are detectable in duodenal culture media of most CD patients and the intensity of indicative lines depends on the anti-tTG concentration. Sensitivity and diagnostic accuracy achieved with ICA are lower than those obtained with ELISA but, given that the first is a more easy and prompt method, data suggest the possibility of utilizing it in the in vitro diagnosis of CD.

Are Second Trimester Apparent Diffusion Coefficient Values of the Short Uterine Cervix Associated with Impending Preterm Delivery?

Purpose To prospectively determine whether the apparent diffusion coefficient (ADC) of the cervix is associated with preterm delivery in asymptomatic patients with a sonographic cervical length of 15 mm or less and positive fetal fibronectin test results between 23 and 28 weeks of gestation. Materials and Methods The institutional review board approved this prospective hypotheses-generating study. A total of 30 pregnant women (mean gestational age, 26 weeks) with a sonographic short cervix (≤15 mm) underwent pelvic 1.5-T magnetic resonance (MR) imaging. Oblique sagittal diffusion-weighted images were obtained with b values of 0, 400, and 800 sec/mm(2). ADC values at MR imaging of the subglandular and stromal cervix and the difference between both were correlated to the interval to delivery. Receiver operating characteristic curve analysis was performed to obtain sensitivity and specificity of ADC values in association with delivery within 7 days. Results Eight (27%) of 30 patients delivered within 6 or 7 days after MR imaging (impending delivery group), and 22 (73%) of 30 patients delivered between 18 and 89 days after imaging (mean, 55 days) (late delivery group). Mean subglandular ADC and mean ADC difference were higher (P < .001) in patients with impending delivery than in those with late delivery ([2406.3 ± 166.0] × 10(-6) mm(2)/sec vs [1708.9 ± 108.1] × 10(-6) mm(2)/sec and [657.3 ± 129.9] × 10(-6) mm(2)/sec vs [69.2 ± 70.2] × 10(-6) mm(2)/sec, respectively). Subglandular ADC inversely correlated with the interval between MR imaging and delivery (r = -0.75). Receiver operating characteristic curve analysis of subglandular ADC revealed 100% sensitivity (95% confidence interval: 63.1, 100) and 100% specificity (95% confidence interval: 84.6, 100) in association with impending delivery with a 1921 × 10(-6) mm(2)/sec threshold. Stromal ADC and sonographic cervical length showed no difference between groups (P = .072 and P = .511, respectively). Conclusion Cervical subglandular ADC at MR imaging is associated with impending preterm birth in patients with a short sonographic cervix. (©) RSNA, 2016.

Diagnosis of Small-Bowel Diseases: Prospective Comparison of Multi-Detector Row CT Enterography with MR Enterography.

PURPOSE: To prospectively compare the accuracies of computed tomographic (CT) enterography and magnetic resonance (MR) enterography for the detection and characterization of small-bowel diseases. MATERIALS AND METHODS: The institutional review board approved the study protocol, and informed consent was obtained from all participants. From June 2009 to July 2013, 150 consecutive patients (81 men and 69 women; mean age, 38.8 years; range, 18-74 years), who were suspected of having a small-bowel disease on the basis of clinical findings and whose previous upper and lower gastrointestinal endoscopy findings were normal, underwent CT and MR enterography. Two independent readers reviewed CT and MR enterographic images for the presence of small-bowel diseases, for differentiating between inflammatory and noninflammatory diseases, and for extraenteric complications. The histopathologic findings of surgical (n = 23) and endoscopic (n = 32) biopsy specimens were used as the reference standard; the results of video-capsule endoscopy (n = 36) and clinical follow-up (n = 59) were used only to confirm the absence of small-bowel disease. RESULTS: MR and CT enterography were successfully performed in all 150 patients. Overall sensitivity, specificity, and accuracy, respectively, in identifying patients with small-bowel lesions were 75.9% (41 of 54), 94.8% (91 of 96), and 88.0% (132 of 150) for CT enterography and 92.6% (50 of 54), 99.0% (95 of 96), and 96.7% (145 of 150) for MR enterography. The sensitivity of MR enterography was significantly higher than that of CT enterography for the detection of both overall small-bowel diseases (P = .0159) and neoplastic diseases (P = .0412) but not for the detection of inflammatory diseases (P > .99) or noninflammatory and nonneoplastic diseases (P = .6171). CONCLUSION: MR enterography is more accurate than CT enterography in the detection of small-bowel diseases; MR enterography was more accurate in detecting neoplastic diseases in particular.

Intestinal, Systemic, and Oral Gluten-related Alterations in Patients With Nonceliac Gluten Sensitivity.

BACKGROUND: Nonceliac gluten sensitivity (NCGS) is an emergent condition, the framework of which is yet unclear, whereas the diagnosis is suggested only by gluten-dependent symptoms after excluding wheat allergy and celiac disease (CD). Our goal was to highlight intestinal, systemic, and oral alterations to clarify the NCGS pathogenesis and identify new diagnostic tools. STUDY: A total of 60 NCGS patients, 20 untreated CD, 20 treated CD, and 20 healthy volunteers were recruited. The differential diagnosis among gluten-related disorders was performed by serological, allergy, and histologic tools. NCGS patients were also subjected to antigliadin antibody (AGA) detection and HLA typing. All participants underwent an oral mucosa patch test for gluten (GOMPT), whereas an oral provocation test (OPT) for gluten was performed in 26 NCGS patients. RESULTS: About 6/60 (10%) NCGS patients showed IgG AGA-positive results, whereas 45/60 (75%) patients carried HLA-DQ2 and/or HLA-DQ8 genes. GOMPT showed positive results in 45/60 (75%) NCGS patients, 3/20 (15%) untreated CD patients, 5/20 (25%) treated CD patients, and in no healthy volunteers. No significant difference was found between the severity of symptoms reported by NCGS patients subjected to OPT with gluten-containing croissants and those who underwent OPT with gluten-free croissants. CONCLUSIONS: GOMPT seems to be a specific tool for NCGS diagnosis, although further investigations are needed to overcome limits due to the small population studied and to contextualize GOMPT false-positive results.

Weaknesses of histological analysis in celiac disease diagnosis: new possible scenarios.

INTRODUCTION: Celiac disease (CD) is an autoimmune disorder triggered by the ingestion of gluten. Serology and organ culture system can support CD diagnosis, despite histology being the gold standard. AIM: We wanted to test the uniformity of application of Marsh-Oberhuber criteria by five different histologists. We also compared histological and serological data with cultural results to consider new possible strategies in CD diagnosis. METHODS: We studied 114 patients, who were divided in two groups. Group A was composed of 66 patients on a gluten-containing diet, with gluten-related signs and symptoms, showing positive serological anti-endomysial antibodies (EMA) and anti-tissue transglutaminase (anti- tTG). Group B was composed of 48 disease-control patients, presenting serological EMA and anti-tTG negative results. All patients studied underwent esophagogastroduodenoscopy with duodenal biopsy and duodenal mucosa organ culture. All histological samples were evaluated by five different histologists according to an appropriate questionnaire following Marsh-Oberhuber classification. Cohen κ inter-test was used for evaluating the agreement between histologists regarding group A. RESULTS: Strength of agreement was fair/moderate for villous:crypt ratio, moderate/good for villous height and crypt depth, and poor for intraepithelial lymphocytosis. Patients belonging to group A presented positive serological as well as cultural results in 100% of cases. None of the patients belonging to group B presented serological or cultural positive results. DISCUSSION: Our study stresses the limits of histological interpretation due to the lack of uniformity in the use of Marsh-Oberhuber classification. These findings could cast doubt on the role of histology as CD gold standard and could open a debate on the most appropriate CD diagnostic procedure.

Colonic involvement in celiac disease and possible implications of the sigmoid mucosa organ culture in its diagnosis.

PURPOSE: Celiac disease (CD), a systemic autoimmune disorder that typically involves duodenal mucosa, can also affect other intestinal areas. Duodenal and oral mucosa organ culture has already been demonstrated as a reliable procedure to identify CD. The present study investigated gluten-dependent immunological activation of colonic mucosa in CD patients. We took advantage of the numerous colonoscopies performed for various clinical conditions or only for defensive medicine. METHODS: Forty-four patients with gastrointestinal symptoms or in need of colorectal cancer screening were divided into patients with serum anti-endomysium (EMA) and anti-tissue transglutaminase (anti-tTG) antibody positive results (Group A), patients with serum antibody negative results (Group B), and patients with inflammatory bowel disease (IBD) (Group C). The autoantibodies EMA and anti-tTG were evaluated in supernatants of cultured sigmoid and duodenal biopsies from patients on a gluten-containing diet. RESULTS: In Group A, EMA and anti-tTG resulted positive in all duodenal culture supernatants. In sigmoid culture supernatants, EMA and anti-tTG were detected in 12/16 (75 %) and 13/16 (81.3 %) patients, respectively. In Group B, none of the 17 patients showed EMA and anti-tTG positive results in both duodenal and sigmoid cultures. In Group C, all 11 patients presented EMA negative results in sigmoid cultures. Only in one patient, anti-tTG were detectable in the sigmoid culture supernatant, as expected in cases of IBD. CONCLUSIONS: Data confirm that the gluten-dependent immunological activation affects more intestinal tracts with different degrees of involvement, suggesting that the organ culture of colonic biopsies could represent a new tool to opportunistically detect CD.

MR imaging in the evaluation of placental abruption: correlation with sonographic findings.

PURPOSE: To evaluate the accuracy of magnetic resonance (MR) imaging and color Doppler ultrasonography (US) in the diagnosis of abruption, to assess the accuracy of the different MR imaging sequences in the visualization of clots, and to evaluate the correlation between MR imaging findings and clinical outcome. MATERIALS AND METHODS: This study protocol was approved by the institutional review board, and written informed consent was obtained from all patients. Between March 2008 and June 2010, 60 consecutive patients (mean gestational age, 30.7 weeks [range, 27-38 weeks]; mean age, 29 years [range, 20-38 years]) who were referred for US and MR imaging owing to a putative diagnosis of abruption were assessed. Multiplanar half-Fourier rapid acquisition with relaxation enhancement, true fast imaging with steady-state precession, three-dimensional T1-weighted gradient-echo MR imaging, and sagittal diffusion-weighted MR imaging were performed. Two radiologists independently reviewed each case, resolving by consensus any diagnostic discrepancy. During a second imaging analysis, the same readers randomly and independently assessed the single sequences. The signal intensity of hematoma was correlated with clinical outcome. The reference standard for abruption was the presence of clots and/or fibrin at inspection of the placenta after delivery. The diagnostic efficacy of US and MR imaging was calculated with 95% confidence intervals. Interobserver agreement was assessed by using the Cohen κ test. RESULTS: The performance of US and MR imaging was calculated in 39 patients who gave birth less than 10 days after MR imaging; these women were considered to have an adequate reference standard. Abruption was found at delivery in 19 patients. Abruption was identified in 10 of the 19 patients (52%) with US and in all 19 (100%) with MR imaging (P = .002), with an interobserver agreement of 0.949. Diffusion- and T1-weighted sequences helped identify 19 (100%) and 18 (95%) of the 19 abruptions, respectively; interrater agreement was very good for all sequences (κ = 0.892-1.0). Hematomas classified as hyperacute or acute worsened to abruption grade II, with the mother being symptomatic or the fetus distressed. CONCLUSION: MR imaging can accurately depict placental abruption, with excellent interobserver agreement, and should be considered after negative US findings in the presence of late pregnancy bleeding if the diagnosis of abruption would change management.

Celiac disease: evaluation with dynamic contrast-enhanced MR imaging.

PURPOSE: To prospectively determine mural perfusion dynamics in patients with untreated celiac disease by using dynamic contrast material-enhanced magnetic resonance (MR) imaging and to compare these dynamics with those in a control population and in patients with celiac disease treated with a gluten-free diet. MATERIALS AND METHODS: Institutional review board approval and informed consent from all participants were obtained. Sixty consecutive patients with untreated celiac disease, 45 patients with celiac disease treated with a gluten-free diet for at least 1 year, and 30 control subjects were enrolled in this study. Dynamic contrast-enhanced MR imaging was performed by using a 1.5-T MR unit. For each MR imaging examination, maximum enhancement, slope of enhancement, and time-signal intensity curves were calculated at the level of the descending duodenal wall. Duodenal wall thickness was also evaluated. Statistical evaluation was performed by using one-way analysis of variance, and the results were confirmed by using the Bartlett test for equal variances and complemented by using Bonferroni multiple comparison, linear correlation, and the Student t test for paired data. RESULTS: Mean maximum enhancement of the duodenal wall was significantly higher in patients with untreated celiac disease (229.1 +/- 46.4 [standard deviation]) than in patients with treated celiac disease (109.8 +/- 27.8) and control subjects (94.7 +/- 17.9) (P < .001 for each comparison). All 60 untreated patients showed a curve characterized by fast enhancement and washout (type 4), while all 45 treated patients and the 30 control subjects showed a curve characterized by slow constant enhancement (type 2). Mean duodenal wall thickness was not significantly different between untreated patients (2.2 mm +/- 0.4), treated patients (2.0 mm +/- 0.3), and control subjects (2.0 mm +/- 0.4) (one-way analysis of variance, P = .4177; Bartlett test, P = .6951). CONCLUSION: The results of this study suggest that dynamic evaluation of the bowel wall by using contrast-enhanced MR imaging can be an effective and reproducible way to show the inflammation state in celiac disease.

The effects of modified versus unmodified wheat gluten administration in patients with celiac disease.

Celiac disease (CD) treatment requires a gluten-free diet (GFD), although alternative approaches have been proposed. Modification of gliadin peptides using microbial transglutaminase (mTG) inhibits their ability to induce immune response in vitro. Our aim was to evaluate the safety of mTG-modified wheat flour ingestion in CD patients. Twenty-one CD patients in remission were randomized to receive mTG-modified (n=11) or unmodified (n=10) wheat flour rusks, in double-blind fashion. Monthly, patients completed a symptom questionnaire. Serum anti-tTG, EMA and creatinine levels were monitored. At baseline and after 90days, serum anti-actin antibodies (AAA) were measured and upper endoscopy was performed. Data were analyzed by non-parametric tests. 7/11 patients eating modified rusks and 7/10 patients receiving unmodified rusks completed the study. At baseline, all patients showed negative serum anti-tTG and EMA results. At the end, 2/7 (28.6%) patients ingesting modified and 4/7 (57.1%) patients taking unmodified rusks presented positive serum anti-tTG and EMA results. Creatinine results were unmodified. Moreover, 1/7 (14.3%) patients ingesting modified and 4/7 (57.1%) patients taking unmodified rusks presented villous atrophy. In patients who received unmodified rusks, the AAA levels increased significantly and duodenal anti-tTG levels appeared higher than those measured in patients who ate modified rusks. Abdominal swelling, bloating and nausea were more severe in patients ingesting unmodified rusks than those taking modified rusks. Our results may support larger clinical trials to confirm the enzymatic treatment of wheat flour as an alternative to GFD. Clinicaltrials.gov registration no: NCT02472119.

Nickel-Related Intestinal Mucositis in IBS-Like Patients: Laser Doppler Perfusion Imaging and Oral Mucosa Patch Test in Use.

Nickel (Ni) is often the trigger of irritable bowel syndrome (IBS)-like gastrointestinal disorders: its ingestion may cause allergic contact mucositis, identifiable by means of oral mucosa patch test (omPT). OmPT effectiveness has been proven, but it is still an operator-dependent method. Laser Doppler perfusion imaging (LDPI) was tested to support omPT in Ni allergic contact mucositis diagnosis. Group A: 22 patients with intestinal/systemic symptoms related to the ingestion of Ni-containing foods. Group B: 12 asymptomatic volunteers. Ni-related symptoms and their severity were tested by a questionnaire. All patients underwent Ni omPT with clinical evaluation at baseline (T0), after 30 min (T1), after 2 h (T2), and after 24-48 h (T3). LDPI was performed to evaluate the mean mucosal perfusion at T0, T1, and T2. Statistical analysis was performed by ANOVA test and Bonferroni multiple-comparison test. All 22 Ni-sensitive patients (group A) presented oral mucosa hyperemia and/or edema at T2. Eight out of the same 22 patients presented a local delayed vesicular reaction at T3 (group A1), unlike the remaining 14 out of 22 patients (group A2). All 12 patients belonging to control group B did not show any alteration. The mean mucosal perfusion calculated with LDPI showed an increase in both subgroups A1 and A2. In group B, no significant perfusion variations were observed. LDPI may support omPT for diagnostic purposes in Ni allergic contact mucositis. This also applies to symptomatic Ni-sensitive patients without aphthous stomatitis after 24-48 h from omPT and that could risk to miss the diagnosis.

Extension of the celiac intestinal antibody (CIA) pattern through eight antibody assessments in fecal supernatants from patients with celiac disease.

BACKGROUND: Detection of anti-transglutaminase, anti-endomysium and anti-gliadin antibodies is commonly used to screen celiac disease patients. Besides that in serum, these antibodies are detectable in culture supernatants of oral, duodenal and colonic biopsy samples, saliva, gut lavage fluid samples, and fecal supernatants. Our aim was to extend the intestinal antibody pattern in fecal supernatants from patients with celiac disease. METHODS: The fecal supernatants obtained from 25 celiac disease patients and 12 healthy volunteers were used to determine IgA and IgG1 anti-endomysium by immunofluorescence analysis, IgA and IgG anti-transglutaminase, IgA and IgG anti-deamidated gliadin peptides, IgA/IgG anti-transglutaminase/deamidated gliadin peptides and IgA anti-actin by enzyme-linked immunosorbent assay. RESULTS: IgA anti-endomysium were found in 11 of 25 (44.0%) celiac disease patients and in none of healthy volunteers (p=0.0066). The levels of IgA anti-transglutaminase, IgA anti-deamidated gliadin peptides, IgA/IgG anti-transglutaminase/deamidated gliadin peptides and IgA anti-actin determined in celiac disease patients were significantly higher (p=0.0005, p=0.0018, p=0.0061 and p=0.0477, respectively) than those measured in healthy volunteers. The ROC curve analysis showed a diagnostic significance in IgA anti-transglutaminase (AUC=0.862, p<0.0001), IgA anti-deamidated gliadin peptides (AUC=0.822, p<0.0001) and IgA/IgG anti-transglutaminase/deamidated gliadin peptides (AUC=0.783, p=0.0003) fecal tests. CONCLUSIONS: Our data extend the intestinal antibody pattern detectable in fecal supernatants, thus increasing the knowledge in the humoral immunity of celiac disease. Further studies are needed to better evaluate the role of fecal antibody tests in identifying celiac disease patients.

Identification of a serum transglutaminase threshold value for the noninvasive diagnosis of symptomatic adult celiac disease patients: a retrospective study.

BACKGROUND: A celiac disease (CD) diagnosis is based on duodenal histology, with the exception of children showing anti-tissue transglutaminase (anti-tTG) serum levels exceeding ten times the cut-off. Our aim was to reproduce this simplified approach in adults, identifying an anti-tTG threshold value useful to diagnose CD without endoscopic procedures. METHODS: A total of 671 adult CD patients were subjected to blood sampling to determine anti-tTG serum levels, as well as to endoscopy with biopsy to perform duodenal histology. The anti-tTG serum levels/cut-off ratio was compared with the degree of duodenal lesions. RESULTS: Anti-tTG serum levels/cut-off ratio determined in patients with type IIIc was significantly higher than that measured in patients with type IIIb (p < 0.001), IIIa (p < 0.001), II (p < 0.05) and 0 (p < 0.001) of Marsh-Oberhuber histological classification. A significant correlation (r = 0.297, p < 0.0001) was found between the anti-tTG serum levels/cut-off ratio and the degree of duodenal lesions. The anti-tTG serum levels/cut-off ratio was classified as an accurate parameter (AUC = 0.715, p < 0.0001), with the best diagnostic performance obtained considering the threshold value >3.6 (sensitivity = 76.8 %, PPV = 97.2 %). CONCLUSIONS: The anti-tTG serum levels/cut-off ratio correlates with the degree of duodenal lesions and, if used with the threshold value >3.6, could avoid endoscopy with biopsy in about 75 % of seropositive adults waiting for CD diagnosis. However, since this procedure could also imply CD diagnosis in almost 3 % of seropositive patients with normal villous architecture, a consensus opinion is needed to suggest its use in the diagnosis of adult CD.

Antiendomysial antibodies in Berger's disease.

The finding of increased levels of immunoglobulin A (IgA) against food antigens in patients with IgA nephropathy prompted the hypothesis of an association between IgA nephropathy and celiac disease (CD). Attention was initially directed to antigliadin antibodies, then to IgA antiendomysial antibodies (IgA-EMA). IgG1-EMA have been found in patients with CD with IgA-EMA-negative results. The presence of IgA- and IgG1-EMA was investigated in 36 patients with IgA nephropathy, 15 patients with other primary glomerulonephritis, and 15 patients with lupus nephritis. IgA-EMA and IgG1-EMA were detected by indirect immunofluorescence analysis. At the time of renal biopsy, the following factors were evaluated: history of macroscopic hematuria, serum creatinine level, urinalysis, 24-hour proteinuria, blood pressure, and histological classification of IgA nephropathy. Sixteen of 36 patients with IgA nephropathy (44.4%) showed EMA positivity. Among patients with positive EMA, 12 patients (75%) were IgG1-EMA positive, 2 patients (12.5%) were IgA-EMA positive, and 2 patients (12.5%) were positive for both isotypes. No significant differences were observed between the two groups (EMA positive versus EMA negative) concerning age, serum creatinine level, macroscopic hematuria, blood pressure, 24-hour proteinuria, or degree of renal histological involvement. IgA- and IgG1-EMA were not detected in patients with other primary nephropathies or lupus nephritis. These results, based on the finding of IgG1-EMA, suggest a common pathogenetic pathway for CD and IgA nephropathy. On this basis, the presence of IgG1-EMA and/or IgA-EMA should be investigated in patients with IgA nephropathy. Furthermore, the role of a gluten-free diet in the natural history of IgA nephropathy, at least in EMA-positive patients, needs to be ascertained.

Celiac disease as a cause of chronic pelvic pain, dysmenorrhea, and deep dyspareunia.

BACKGROUND: Celiac disease may be subclinical and difficult to diagnose in adults. It has been associated with infertility and miscarriage but rarely with other gynecologic symptoms. CASE: A 43-year-old woman complaining of chronic abdominal and pelvic pain, deep dyspareunia, dysmenorrhea, diarrhea, and a 5-kg weight loss during the last 6 months was referred to our institution. Laboratory and clinical examinations were negative. At laparoscopy, numerous small leiomyomata were seen. A few filmy adhesions between the small bowel and the abdominal wall were lysed. With the exception of deep dyspareunia, all symptoms remitted after surgery, only to recur at 6 months of follow-up. A diagnostic work-up for celiac disease revealed the presence of antigliadin and antiendomysial antibodies. The diagnosis was confirmed at gastroduodenoscopy including biopsy. A gluten-free diet was prescribed, and the patient is now free of symptoms. CONCLUSION: Celiac disease should be considered in women presenting with unexplained chronic pelvic pain, dysmenorrhea, and deep dyspareunia.

Mutatis mutandis: are we diagnosing too many people with non-celiac gluten sensitivity? Multiple case report.

We report three patients presenting with gluten-related signs and symptoms. Since villous height/crypt depth ratio, intraepithelial lymphocyte count, and serum antibody tests were not diagnostic for celiac disease (CD), a diagnosis of non-celiac gluten sensitivity (NCGS) was suggested. On the other hand, antibodies suggestive for CD surprisingly showed positive results in the duodenal biopsy organ culture of all three cases. The reported cases suggest the precious potential role that organ culture systems may play in differentiating CD from NCGS. This method should be recommended when gluten-related disorders are suspected in order to reduce the inappropriate diagnosis of NCGS.

Peripheral blood lymphocyte typing as a useful tool to objectify the oral mucosa patch test in the diagnosis of allergic contact mucositis to nickel.

Nickel (Ni) exposure through the intestinal mucosa may cause a hypersensitivity reaction recently defined as allergic contact mucositis (ACM). This condition is identifiable by the oral mucosa patch test (omPT), a qualitative and subjective examination that requires clinical expertise. Our aim was to evaluate if a peripheral blood lymphocyte typing performed before and after the omPT for Ni may be able to objectify this examination for diagnostic purposes. Thirty patients with symptoms referable to the ingestion of Ni-rich foods were subjected to omPT for Ni. Before and after the omPT, each patient underwent blood sampling for the typing of total lymphocytes and their subsets (T, T helper or Th, T cytotoxic or Tc, B, natural killer or NK). Statistical analysis was performed by Student t test and receiver operating characteristic (ROC) curve analysis. According to the omPT outcomes, 18 patients were defined as Ni-sensitive and the remaining 12 as controls. In Ni-sensitive patients, the number of total, T, Th, Tc, and B lymphocytes/µL whole blood increased after the omPT (p<0.0001 for the first three, p=0.0004 and p=0.0001 for the last two lymphocyte types). No omPT-dependent lymphocyte increase was observed in controls. The post/pre omPT cell ratio, especially if calculated for Th lymphocytes, appears to be an effective index for diagnostic purposes (sensitivity=100%, specificity=83.3%, Youden index=0.833, area under curve (AUC)=0.926, p<0.0001). In conclusion, the peripheral blood lymphocyte typing with calculation of post/pre omPT cell ratio has the potential to support the omPT in diagnosing ACM, with the advantage of providing quantitative and objective data.

Immunological characterization of the allergic contact mucositis related to the ingestion of nickel-rich foods.

BACKGROUND: The ingestion of nickel (Ni)-rich foods may result in allergic contact mucositis (ACM), a not yet well defined condition identifiable by oral mucosa patch test (omPT). Our aim was to characterize immunologically the ACM taking advantage from the allergen exposure that occurs during the omPT for Ni. METHODS: Thirty-seven symptomatic patients underwent to omPT for Ni. Before and after omPT, serum and urine Ni concentrations were determined by mass spectrometry, the white blood cells were counted by hemochromocytometric assay, the peripheral lymphocyte typing was carried out by flow cytometry, total IgE and cytokine serum concentrations were measured by immunoenzymatic assays. The local lymphocyte typing was performed by immunohistochemistry only after omPT. RESULTS: According to the omPT outcomes, 25 patients were defined as Ni-sensitive and the remaining 12 as controls. After omPT, serum and urine Ni concentrations increased significantly in all patients, while a significant increment of circulating lymphocytes and neutrophils was highlighted, respectively, in Ni-sensitive and control patients. Consistently, the Th and Tc circulating lymphocytes, as well as the Th/Tc ratio increased significantly in Ni-sensitive patients after omPT. No noteworthy increment in serum concentrations of total IgE and selected cytokines was observed in any patient after omPT. The presence of CD3+, CD4+, and CD8+ cells was highlighted on the oral mucosa biopsy samples taken from Ni-sensitive patients after omPT. CONCLUSIONS: In patients with ACM, a local adaptive response with increased lymphocyte trafficking appears to be the most likely mechanism of reaction to Ni administered with the omPT.

Reactivity to dietary gluten: new insights into differential diagnosis among gluten­related gastrointestinal disorders.

The ingestion of dietary gluten sometimes may trigger allergic, autoimmune or nonallergic and nonautoimmune response. The typical gluten­related allergic disorder is the wheat allergy (WA). Celiac disease (CD) is a well­known gluten­related autoimmune condition. The clinical expression of a gluten­related nonallergic and nonautoimmune response is nonceliac gluten sensitivity (NCGS), an emerging condition whose framework is yet unclear and whose diagnosis is suggested only by demonstration of gluten­dependency in patient' symptoms after exclusion of WA and CD. This review discusses the current tools to identify patients suffering from WA, CD, and NCGS, as well as the most recent insights in the differential diagnosis among these gluten­related gastrointestinal disorders .