Differential diagnosis of Crohn’s disease and intestinal tuberculosis based on ATR-FTIR spectroscopy combined with machine learning

BACKGROUND Crohn’s disease(CD)is often misdiagnosed as intestinal tuberculosis(ITB).However,the treatment and prognosis of these two diseases are dramatically different.Therefore,it is important to develop a method to identify CD and ITB with high accuracy,specificity,and speed.AIM To develop a method to identify CD and ITB with high accuracy,specificity,and speed.METHODS A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB.Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis.RESULTS The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm^(-1) and 1234 cm^(-1) bands,and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy,specificity,and sensitivity of 91.84%,92.59%,and 90.90%,respectively,for the differential diagnosis of CD and ITB.CONCLUSION Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level,and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.

Diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients:A mini review for clinicians

Among critically ill patients,severe pulmonary and extrapulmonary tuberculosis has high morbidity and mortality.Yet,it is a diagnostic challenge given its nonspecific clinical symptoms and signs in early stages of the disease.In addition,management of severe pulmonary and extrapulmonary tuberculosis is complicated given the high risk of drug-drug interactions,drug-disease interactions,and adverse drug reactions.To help clinicians acquire an up-to-date approach to severe tuberculosis,this paper will provide a narrative review of contemporary diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients.

Diagnosis of intestinal tuberculosis using a monoclonal antibody to Mycobacterium tuberculosis

AIM:To investigate the utility of immunohistochemical(IHC) staining with an antibody to Mycobacterium tuberculosis(M.tuberculosis) for the diagnosis of intestinal tuberculosis(TB).METHODS:We retrospectively identified 10 patients(4 males and 6 females;mean age = 65.1 ± 13.6 years) with intestinal TB.Clinical characteristics,including age,gender,underlying disease,and symptoms were obtained.Chest radiograph and laboratory tests,including sputum Ziehl-Neelsen(ZN) staining,M.tuberculosis culture,and sputum polymerase chain reaction(PCR) for tubercle bacilli DNA,as well as Tuberculin skin test(TST) and QuantiFERON-TB gold test(QFT),were examined.Colonoscopic records recorded on the basis of Sato's classification were also reviewed,in addition to data from intestinal biopsies examined for histopathological findings,including hematoxylin and eosin staining,and ZN staining,as well as M.tuberculosis culture,and PCR for tubercle bacilli DNA.For the present study,archived formalin-fixed paraffin-embedded(FFPE) intestinal tissue samples were immunohistochemically stained using a commercially available species-specific monoclonal antibody to the 38-kDa antigen of the M.tuberculosis complex.These sections were also stained with the pan-macrophage marker CD68 antibody.RESULTS:From the clinical data,we found that no patients were immunocompromised,and that the main symptoms were diarrhea and weight loss.Three patients displayed active pulmonary TB,six patients(60%) had a positive TST,and 4 patients(40%) had a positive QFT.Colonoscopic findings revealed that all patients had type 1 findings(linear ulcers in a circumferential arrangement or linear ulcers arranged circumferentially with mucosa showing multiple nodules),all of which were located in the right hemicolon and/or terminal ileum.Seven patients(70%) had concomitant healed lesions in the ileocecal area.No acid-fast bacilli were detected with ZN staining of the intestinal tissue samples,and both M.tuberculosis culture and PCR for tubercle bacilli DNA were negative in all samples.The histopathological data revealed that tuberculous granulomas were present in 4 cases(40%).IHC staining in archived FFPE samples with anti-M.tuberculosis monoclonal antibody revealed positive findings in 4 patients(40%);the same patients in which granulomas were detected by hematoxylin and eosin staining.M.tuberculosis antigens were found to be mostly intracellular,granular in pattern,and primarily located in the CD68 + macrophages of the granulomas.CONCLUSION:IHC staining with a monoclonal antibody to M.tuberculosis may be an efficient and simple diagnostic tool in addition to classic examination methods for the diagnosis of intestinal TB.

From immunology to artificial intelligence: revolutionizing latent tuberculosis infection diagnosis with machine learning

Latent tuberculosis infection(LTBI)has become a major source of active tuberculosis(ATB).Although the tuberculin skin test and interferon-gamma release assay can be used to diagnose LTBI,these methods can only differentiate infected individuals from healthy ones but cannot discriminate between LTBI and ATB.Thus,the diagnosis of LTBI faces many challenges,such as the lack of effective biomarkers from Mycobacterium tuberculosis(MTB)for distinguishing LTBI,the low diagnostic efficacy of biomarkers derived from the human host,and the absence of a gold standard to differentiate between LTBI and ATB.Sputum culture,as the gold standard for diagnosing tuberculosis,is time-consuming and cannot distinguish between ATB and LTBI.In this article,we review the pathogenesis of MTB and the immune mechanisms of the host in LTBI,including the innate and adaptive immune responses,multiple immune evasion mechanisms of MTB,and epigenetic regulation.Based on this knowledge,we summarize the current status and challenges in diagnosing LTBI and present the application of machine learning(ML)in LTBI diagnosis,as well as the advantages and limitations of ML in this context.Finally,we discuss the future development directions of ML applied to LTBI diagnosis.

Primary extrapulmonary tuberculosis diagnosis warrants extraprecautious pulmonary tuberculosis exclusion workup

This editorial article takes an opportunity to apprehend the diagnostic challenges of primary gastrointestinal tuberculosis(an uncommon extrapulmonary tuberculosis condition)utilizing the recently published case report of a young male with prolonged gastrointestinal symptoms and weight loss who received intermittent anti-tubercular treatment and underwent operative interventions to relieve gastric outlet obstruction.The diagnosis chiefly relied on high-end examinations,like computed tomography scans and histopathological evaluation of postoperatively resected bowel tissue,which wasn't preceded by an all-inclusive stepwise primary pulmonary tuberculosis exclusion approach that usually begins with a detailed tuberculosis-pertinent history acquisition.Given the geographic locations where the patient had been(and/or treated),pivotal consideration of tuberculosis-associated endemicities in those regions,like human immunodeficiency virus(HIV)infection,might have improved the case description.The obtainment of HIV-relevant histories,like intravenous drug use and sexual practice,are good places to start.The sputum bacteriology also seems imperative to rule out atypical Mycobacterium species infection because of its clinico-radiohistopathological resemblance with pulmonary Mycobacterium tuberculosis.Altogether,this editorial aims to underscore that primary extrapulmonary tuberculosis diagnosis should comprise an elaborative,comprehensive,systematic,and stepwise primary pulmonary Mycobacterium tuberculosis exclusion workup.

Histopathology and TB-PCR kit analysis in differentiating the diagnosis of intestinal tuberculosis and Crohn’s disease

AIM: To compare the histopathologic features of intestinal tuberculosis (ITB) and Crohn’s disease (CD) and to identify whether polymerase chain reaction for Mycobacterium tuberculosis (TB-PCR) would be helpful for differential diagnosis between ITB and CD.METHODS: We selected 97 patients with established diagnoses (55 cases of ITB and 42 cases of CD) who underwent colonoscopic biopsies.Microscopic features of ITB and CD were reviewed,and eight pathologic parameters were evaluated.Nine cases of acid fast bacilli culture-positive specimens and 10 normal colonic tissue specimens were evaluated as the positive and negative control of the TB-PCR test,respectively.PCR assays were done using two commercial kits: kit <A> detected IS6110 and MPB64,and kit <B> detected IS6110 only;a manual in-house PCR method was also performed on formalin-fi xed,paraffi n-embedded colonoscopic biopsy specimens.RESULTS: Statistically significant differences were noted between ITB and CD with regard histopathologic criteria: size of granulomas (P = 0.000),giant cells (P = 0.015),caseation necrosis (P = 0.003),confluent granulomas (P = 0.001),discrete granulomas (P = 0.000),and granulomas with lymphoid cuffs (P = 0.037).However,29 cases (52.7%) of ITB showed less than fi ve kinds of pathologic parameters,resulting in confusion with CD.The sensitivities and specificities of the TB-PCR test by kit <A>,kit <B>,and the in-house PCR method were 88.9% and 100%,88.9% and 100%,and 66.7% and 100% in positive and negative controls,respectively.The PCR test done on endoscopic biopsy specimens of ITB and CD were signifi cantly different with kit <A> (P = 0.000) and kit <B> (P = 0.000).The sensitivities and specifi cities of TB-PCR were 45.5% and 88.1%,36.4% and 100%,and 5.8% and 100%,for kit <A> and kit <B> and inhouse PCR method on endoscopic biopsy specimens.Among the 29 cases of histopathologically confusing CD,10 cases assayed using kit <A> and 6 cases assayed using kit <B> were TB-PCR positive.A combination of histologic fi ndings and TB-PCR testing led to an increase of diagnostic sensitivity and the increase (from 47.3% to 58.2) was statistically signifi cant with kit <B> (P = 0.000).CONCLUSION: The TB-PCR test combined with histopathologic factors appears to be a helpful technique in formulating the differential diagnosis of ITB and CD in endoscopic biopsy samples.

Routine diagnosis of intestinal tuberculosis and Crohn's disease in Southern India

AIM:To investigate whether routinely measured clinical variables could aid in differentiating intestinal tuberculosis(ITB)from Crohn’s disease(CD).METHODS:ITB and CD patients were prospectively included at four South Indian medical centres from October 2009 to July 2012.Routine investigations included case history,physical examination,blood biochemistry,ileocolonoscopy and histopathological examination of biopsies.Patients were followed-up after 2 and 6 mo of treatment.The diagnosis of ITB or CD was re-evaluated after 2 mo of antituberculous chemotherapy or immune suppressive therapy respectively,based on improvement in signs,symptoms and laboratory variables.This study was considered to be an exploratory analysis.Clinical,endoscopic and histopathological features recorded at the time of inclusion were subject to univariate analyses.Disease variables with sufficient number of recordings and P<0.05 were entered into logistic regression models,adjusted for known confounders.Finally,we calculated the odds ratios with respective confidence intervals for variables associated with either ITB or CD.RESULTS:This study included 38 ITB and 37 CD patients.Overall,ITB patients had the lowest body mass index(19.6 vs 22.7,P=0.01)and more commonly reported weight loss(73%vs 38%,P<0.01),watery diarrhoea(64%vs 33%,P=0.01)and rural domicile(58%vs 35%,P<0.05).Endoscopy typically showed mucosal nodularity(17/31 vs 2/37,P<0.01)and histopathology more frequently showed granulomas(10/30vs 2/35,P<0.01).The CD patients more frequently reported malaise(87%vs 64%,P=0.03),nausea(84%vs 56%,P=0.01),pain in the right lower abdominal quadrant on examination(90%vs 54%,P<0.01)and urban domicile(65%vs 42%,P<0.05).In CD,endoscopy typically showed involvement of multiple intestinal segments(27/37 vs 9/31,P<0.01).Using logistic regression analysis we found weight loss and nodularity of the mucosa were independently associated with ITB,with adjusted odds ratios of 8.6(95%CI:2.1-35.6)and 18.9(95%CI:3.5-102.8)respectively.Right lower abdominal quadrant pain on examination and involvement of≥3 intestinal segments were independently associated with CD with adjusted odds ratios of 10.1(95%CI:2.0-51.3)and 5.9(95%CI:1.7-20.6),respectively.CONCLUSION:Weight loss and mucosal nodularity were associated with ITB.Abdominal pain and excessive intestinal involvement were associated with CD.ITB and CD were equally common.

Temporal trends in the misdiagnosis rates between Crohn's disease and intestinal tuberculosis

AIM To investigate the temporal trends in the misdiagnosis rate between Crohn's disease(CD) and intestinal tuberculosis(ITB) in South Korea. METHODS We retrospectively reviewed the medical records of patients managed for CD or ITB at Asan Medical Center, a tertiary referral hospital, Seoul, Korea between 1996 and 2014. The temporal trends in the misdiagnosis rates between the two diseases were analyzed. The demographic and clinical characteristics were compared between CD patients who were initially misdiagnosed as ITB(final CD group) and vice versa(final ITB group). Final diagnostic criteria for ITB and medication for CD before definite diagnosis of TB were also analyzed in final ITB group.RESULTS In total, 2760 patients were managed for CD and 772 patients for ITB between 1996 and 2014. As well, 494 of the 2760 CD patients(17.9%) were initially misdiagnosed as ITB and 83 of the 772 ITB patients(10.8%) as CD. The temporal trend in misdiagnosing CD as ITB showed a decrease(OR = 0.89, 95%CI: 0.87-0.91, P < 0.001), whereas the temporal trend in misdiagnosing ITB as CD showed an increase(OR = 1.06, 95%CI: 1.01-1.11, P = 0.013). Age at diagnosis, presenting symptoms, and proportion of patients with active/past perianal fistula and active/inactive pulmonary tuberculosis(TB) were significantly different between final CD group and final ITB group. Forty patients(48.2%) in final ITB group were diagnosed by favorable response to empirical anti-TB treatment. Seventeen patients(20.5%) in final ITB group had inappropriately received corticosteroids and/or thiopurines due to misdiagnosis as CD. However, there were no mortalities in both groups. CONCLUSION Cases of CD misdiagnosed as ITB have been decreasing, whereas cases of ITB misdiagnosed as CD have been increasing over the past two decades.

Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis

Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB).Methods This study was conducted at the Shanghai Public Health Clinical Center.A total of 115patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,Gene Xpert MTB/RIF(Xpert),and histopathological examination.These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS).Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),respectively.Based on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),respectively.Histopathological examination showed the highest sensitivity but lowest specificity.Further,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%.Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB.Compared with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower specificity.The combination of histopathology with Xpert showed the best performance characteristics.

Gastrointestinal tuberculosis:Diagnostic approaches for this uncommon pathology

A case report entitled“Primary gastroduodenal tuberculosis presenting as gastric outlet obstruction”recently published in the World Journal of Clinical Cases presented a rare cause of gastric outlet obstruction and highlighted the atypical manner in which gastrointestinal tuberculosis(TB)can present.The literature with regards to this rare pathology is limited to case reports and case series with the largest being published using data from between 2003 and 2013.However,since then the diagnostic tools available have significantly changed with more modern and increasingly accurate tests now available.This editorial reviews the current state of the art with regards to diagnosis in gastrointestinal TB.

Intestinal tuberculosis with small bowel stricture and hemorrhage as the predominant manifestation: Three case reports

BACKGROUND Intestinal tuberculosis is a chronic disease caused by Mycobacterium tuberculosis that mainly affects the ileum and cecum.Small bowel tuberculosis,characterized by predominant involvement of the small intestine,is an extremely rare condition with highly atypical clinical presentations,making diagnosis even more challenging.CASE SUMMARY We report three cases of small intestinal tuberculosis,two of the patients pre-sented primarily with abdominal pain,and one presented with gastrointestinal bleeding.All patients underwent blood tests and imaging examinations.Small bowel endoscopy(SBE)revealed that the main lesions in these patients were in-testinal stenosis or gastrointestinal bleeding caused by small intestinal ulcers.One patient ultimately underwent surgical treatment.Following a complex diagnostic process and comprehensive analysis,all patients were confirmed to have small intestinal tuberculosis and received standard antituberculosis treatment,leading to an improvement in their condition.CONCLUSION Patients with SBTs present with nonspecific symptoms such as abdominal pain,weight loss,and occasional gastrointestinal bleeding.Accurate diagnosis requires a thorough evaluation of clinical symptoms and various tests to avoid misdiagno-sis and complications.

Esophageal tuberculosis complicated with intestinal tuberculosis: A case report

BACKGROUND Although the overall incidence of tuberculosis in underdeveloped areas has increased in recent years, esophageal tuberculosis(ET) is still rare. Intestinal tuberculosis(ITB) is relatively more common, but there are few reports of ET complicated with ITB. We report a case of secondary ET complicated with ITB in a previously healthy patient.CASE SUMMARY A 27-year-old female was hospitalized for progressive dysphagia, retrosternal pain, acid regurgitation, belching, heartburn, and nausea. Upper gastrointestinal endoscopy showed a mid-esophageal ulcerative hyperplastic lesion. Endoscopic ultrasonography showed a homogeneous hypoechoic lesion, with adjacent enlarged lymph nodes. Biopsy histopathology showed inflammatory exudation,exfoliated epithelial cells and interstitial granulation tissue proliferation.Colonoscopy revealed a rat-bite ulcer in the terminal ileum and a superficial ulcer in the ascending colon, near the ileocecal region. The ileum lesion biopsy showed focal granulomas with caseous necrosis. Polymerase chain reaction for Mycobacterium tuberculosis was positive in the esophageal and ileum lesion biopsies. The T-cell spot tuberculosis test was also positive. The patient was diagnosed with secondary ET infiltrated by mediastinal lymphadenopathy and complicated with ITB, possibly from the Mycobacterium tuberculosis-infected esophageal lesion. After 2 mo of anti-tuberculosis therapy, her symptoms improved significantly, and upper gastrointestinal endoscopy showed healing ulcers.CONCLUSION When dysphagia or odynophagia occurs in patients at high-risk for tuberculosis,ET should be considered.

Diagnosis of abdominal tuberculosis:Experience from 11 cases and review of the literature

AIM:To analyze the experience within our hospital and to review the literature so as to establish the best means of diagnosis of abdominal tuberculosis. METHODS:The records of 11 patients (4 males,7 females, mean age 39 years,range 18-65 years) diagnosed with abdominal tuberculosis in Harran University Hospital between January 1996 and October 2003 were analyzed retrospectively and the literature was reviewed. RESULTS:Ascites was present in all cases.Other common findings were weight loss (81%),weakness (81%),abdominal mass (72%),abdominal pain (72%),abdominal distension (63%),anorexia (45%) and night sweat (36%).The average hemoglobin was 8.2 g/dL and the average FAR was 50 mm/h (range 30-125).Elevated levels of cancer antigen CA-125 were determined in four patients.Abdominal ultrasound showed abnormalities in all cases:ascites in all,tuboovarian mass in five,omental thickening in 3,and enlarged lymph nodes (mesenteric,para-aortic) in 2.CT scans showed ascites in all,pelvic mass in 5,retroperitoneal lymphadenopathy in 4,mesenteric stranding in 4,omental stranding in 3, bowel wall thickening in 2 and mesenteric lymphadenopathy in 2.Only one patient had a chest radiograph suggestive of a new TB lesion.Two had a positive family history of pulmonary TB.None had acid-fast bacilli (AFB) in the sputum and the tuberculin test was positive in only two.Laparotomy was performed in 6 cases,laparoscopy in 4 and ultrasound- guided fine needle aspiration in 2.In those patients subjected to operation,the findings were multiple diffuse involvement of the visceral and parietal peritoneum,white ‘miliary nodules’or plaques,enlarged lymph nodes,ascites, ‘violin string’fibrinous strands,and omental thickening. Biopsy specimens showed granulomas,while ascitic fluid showed numerous lymphocytes.Both were negative for acid-fast bacilli by staining.PCR of ascitic fluid was positive for Mycobactenum tuberculosis ( M.tuberculosis) in all cases. CONCLUSION:Abdominal TB should be considered in all cases with ascites.Our experience suggests that PCR of ascitic fluid obtained by ultrasound-guided fine needle aspiration is a reliable method for its diagnosis and should at least be attempted before surgical intervention.

Diagnosis of Crohn's disease in India where tuberculosis is widely prevalent

AIM:To define the parameters that positively predict diagnosis of Crohn's disease (CD) and differentiate it from gastrointestinal tuberculosis (GITB). METHODS:This prospective study over 3 years was carried out in the consecutive Indian patients with definite diagnosis of CD and equal numbers of patients with definite diagnosis of GITB. Demographic, clinical, laboratory, morphological and histological features were noted in all the patients. Serological tests such as p-ANCA, c-ANCA, IgA ASCA and IgG ASCA, were performed. Endoscopic biopsy and/or surgical tissue specimens were subjected to smear and culture for acid-fast bacilli (AFB) and tissue polymerase chain reaction for tuberculosis (TB PCR). Diagnosis of CD and GITB was based on the standard criteria. Data were analyzed using univariate Chi-square test and multiple logistic regression (MLR). RESULTS:The study is comprised of 26 patients with CD (age 36.6 ± 8.6 year, male:female, 16:10) and 26 patients with GITB (age 37.2 ± 9.6 year, male:female, 15:11). The following clinical variables between the two groups (CD vs TB) were significant in univariate analysis:duration of symptoms (58.1 ± 9.8 vs 7.2 ± 3.4 mo), diarrhoea (69.2% vs 34.6%), bleeding per rectum (30.7% vs 3.8%), fever (23.1% vs 69.2%), ascites (7.7% vs 34.6%) and extra-intestinal manifestations of inflammatory bowel disease (61.5% vs 23.1%). Of these, all except ascites and extra-colonic manifestations were found statistically significant by MLR. Accuracy of predicting CD was 84.62% based on the fever, bleeding P/R, diarrhoea and duration of symptoms while it was 63.4% when histology was reported as inflammatory bowel disease and 42.3% when there was recurrence of disease after surgery. Accuracy of predicting GITB was 73.1% when there was co-existing pulmonary lesions and/or abdominal lymphadenopathy;75% when tuberculosis was reported in histology;63.4% when granuloma was found in histology;82.6% when TB PCR was positive;and 61.5% when smear and/ or culture was positive for AFB. Serological test was not useful in differentiation of CD from GITB. Positivity rates for CD and GITB were:p-ANCA-3.8% and 3.8%, c-ANCA-3.8% and 0%, IgA ASCA-38.4% and 23.1%, and IgG ASCA-38.4% and 42.3%, respectively. CONCLUSION:Simple clinical parameters like fever, bleeding P/R, diarrhoea and duration of symptoms have the highest accuracy in differentiating CD from GITB.

Delayed diagnosis and comprehensive treatment of cutaneous tuberculosis:A case report

BACKGROUND Tuberculosis(TB)is a widespread infectious disease,with an incidence that is increasing worldwide.Cutaneous TB(CTB)occurs rarely,accounting for less than 1%of all TB cases.Due to the clinical presentation and diagnostic difficulties,CTB is often clinically neglected and misdiagnosed.CASE SUMMARY A 32-year-old man underwent several debridement surgeries and skin flap transplantation after trauma.The wound remained unhealed,accompanied by sinus formation.According to empirical judgment,T-cell spot of TB test,and bacterial culture of pyogenic fluids,he was diagnosed with CTB due to infection with exogenous Mycobacterium tuberculosis.A comprehensive anti-TB regimen that included isoniazid,rifampicin,ethambutol,and pyrazinamide was applied.The sinus was filled with a hydrophilic fiber-containing silver dressing,and woundprotecting sponges were applied to part of the wound.The wound healed after 40 d.No ulceration was found within 2 mo after discharge;further follow-up will be conducted.CONCLUSION A non-healing wound may be caused by TB infection.Comprehensive treatment of CTB is effective.

Immune thrombocytopenic purpura induced by intestinal tuberculosis in a liver transplant recipient

A variety of clinical manifestations are associated directly or indirectly with tuberculosis. Among them, haematological abnormalities can be found in both the pulmonary and extrapulmonary forms of the disease. We report a case of immune thrombocytopenic purpura(ITP) associated with intestinal tuberculosis in a liver transplant recipient. The initial management of thrombocytopenia, with steroids and intravenous immunoglobulin, was not successful, and the lack oftuberculosis symptoms hampered a proper diagnostic evaluation. After the diagnosis of intestinal tuberculosis and the initiation of specific treatment, a progressive increase in the platelet count was observed. The mechanism of ITP associated with tuberculosis has not yet been well elucidated, but this condition should be considered in cases of ITP that are unresponsive to steroids and intravenous immunoglobulin, especially in immunocompromised patients and those from endemic areas.

Evaluation of Xpert MTB/RIF Ultra for Diagnosis of Extrapulmonary Tuberculosis: A Retrospective Analysis in a Low-Tuberculosis Prevalence Setting

Background: Extrapulmonary tuberculosis (EPTB) remains difficult to diagnose because the clinical specimens to be examined are often paucibacillary and obtained with difficulty from inaccessible sites. An updated Xpert® MTB/RIF Ultra (Ultra) test has been designed and licensed to improve sensitivity in the detection of Mycobacterium tuberculosis complex. The aim of the present study is to evaluate the performance of Ultra assay for the clinical diagnosis of EPTB in a low tuberculosis prevalence country. Methods: A retrospective analysis was performed at “A. O dei Colli” of Naples on consecutive extrapulmonary specimens for EPTB across a three-year period. All different types of extrapulmonary specimens were tested for EPTB by smear microscopy, culture and Ultra assay in accordance with relevant guidelines. Results: A total of 606 EPTB samples, 561 culture negative EPTB and 45 culture positive EPTB were included. Using culture as reference standard, the overall sensitivities and specificities of Ultra assay were 95.6% (95% CI 84.8 - 99.5) and 97.5% (95% CI 95.8 - 98.6) respectively. Sensitivity and specificity of Ultra for individual category of specimens were also performed. Conclusion: In a low-tuberculosis prevalence setting, Ultra assay confirms to have a good performance in the diagnosis of EPTB for all different extrapulmonary samples.

Differentiating Crohn's disease from intestinal tuberculosis

Differentiating Crohn's disease(CD) and intestinal tuberculosis(ITB) has remained a dilemma for most of the clinicians in the developing world, which are endemic for ITB, and where the disease burden of inflammatory bowel disease is on the rise. Although, there are certain clinical(diarrhea/hematochezia/perianal disease common in CD; fever/night sweats common in ITB), endoscopic(longitudinal/aphthous ulcers common in CD; transverse ulcers/patulous ileocaecal valve common in ITB), histologic(caseating/confluent/large granuloma common in ITB; microgranuloma common in CD), microbiologic(positive stain/culture for acid fast-bacillus in ITB), radiologic(long segment involvement/comb sign/skip lesions common in CD; necrotic lymph node/contiguous ileocaecal involvement common in ITB), and serologic differences between CD and ITB, the only exclusive features are caseation necrosis on biopsy, positive smear for acid-fast bacillus(AFB) and/or AFB culture, and necrotic lymph node on cross-sectional imaging in ITB. However,these exclusive features are limited by poor sensitivity, and this has led to the development of multiple multi-parametric predictive models. These models are also limited by complex formulae, small sample size and lack of validation across other populations. Several new parameters have come up including the latest Bayesian meta-analysis, enumeration of peripheral blood T-regulatory cells, and updated computed tomography based predictive score. However, therapeutic anti-tubercular therapy(ATT) trial, and subsequent clinical and endoscopic response to ATT is still required in a significant proportion of patients to establish the diagnosis. Therapeutic ATT trial is associated with a delay in the diagnosis of CD, and there is a need for better modalities for improved differentiation and reduction in the need for ATT trial.

Effectiveness of interferon-gamma release assays for differentiating intestinal tuberculosis from Crohn's disease:A meta-analysis

AIM:To investigate the clinical usefulness of interferon-gamma release assays(IGRAs)in the differential diagnosis of intestinal tuberculosis(ITB)from Crohn’s disease(CD)by meta-analysis.METHODS:A systematic search of English language studies was performed.We searched the following databases:Medline,Embase,Web of Science and the Cochrane Library.The Standards for Reporting Diagnostic Accuracy initiative and Quality Assessment for Studies of Diagnostic Accuracy tool were used to assess the methodological quality of the studies.Sensitivity,specificity,and other measures of the accuracy of IGRAs in the differential diagnosis of ITB from CD were pooled and analyzed using random-effects models.Receiver operating characteristic curves were applied to summarize overall test performance.Two reviewers independently judged study eligibility while screening the citations.RESULTS:Five studies met the inclusion criteria.The average inter-rater agreement between the two reviewers for items in the quality checklist was 0.95.Analysis of IGRAs for the differential diagnosis of ITB from CD produced summary estimates as follows:sensitivity,0.74(95%CI:0.68-0.80);specificity,0.87(95%CI:0.82-0.90);positive likelihood ratio,5.98(95%CI:3.79-9.43);negative likelihood ratio,0.28(95%CI:0.18-0.43);and diagnostic odds ratio,26.21(95%CI:14.15-48.57).The area under the curve was 0.92.The evaluation of publication bias was not significant(P=0.235).CONCLUSION:Although IGRAs are not sensitive enough,they provide good specificity for the accurate diagnosis of ITB,which may be helpful in the differential diagnosis of ITB from CD.

Differences in clinical features of Crohn's disease and intestinal tuberculosis

AIM: To investigate the clinical features of Crohn's disease(CD) and intestinal tuberculosis(ITB) with a scoring system that we have developed.METHODS: A total of 25 CD and 40 ITB patients were prospectively enrolled from August 2011 to July 2012.Their characteristics and clinical features were recorded. Laboratory, endoscopic, histologic and radiographic features were determined. The features with a high specificity were selected to establish a scoring system. The features supporting CD scored +1, and those supporting ITB scored-1; each patient received a final total score. A receiver operating characteristic(ROC) curve was used to determine the best cut-off value for distinguishing CD from ITB.RESULTS: Based on a high specificity of differentiating between CD and ITB, 12 features, including longitudinal ulcers, nodular hyperplasia, cobblestone-like mucosa, intestinal diseases, intestinal fistula, the target sign, the comb sign, night sweats, the purified protein derivative test, the interferon-γ release assay(T-SPOT.TB), ring ulcers and ulcer scars, were selected for the scoring system. The results showed that the average total score of the CD group was 3.12 ± 1.740, the average total score of the ITB group was-2.58 ± 0.984, the best cutoff value for the ROC curve was-0.5, and the diagnostic area under the curve was 0.997, which was statistically significant(P < 0.001). The patients whose total scores were higher than-0.5 were diagnosed with CD; otherwise, patients were diagnosed with ITB. Overall, the diagnostic accuracy rate and misdiagnosis rate of this scoring system were 97% and 3%, respectively. CONCLUSION: Some clinical features are valuable for CD and ITB diagnosis. The described scoring system is key to differentiating between CD and ITB.