A 40-Year-Old Man with a 7-Year History of Polyarthritis and a Late Diagnosis of Whipple Disease: A Journey to Resolve the Mystery.

BACKGROUND Whipple disease (WD) is rare, with an incidence of only a few patients per million. It is caused by infection with the gram-positive bacterium Tropheryma whipplei, and presents with symptoms that include joint pain, fever, diarrhea, and weight loss. This report is of a 40-year-old man with a 7-year history of polyarthritis and a late diagnosis of Whipple disease. The atypical nature of his symptoms led to misdirection and misdiagnosis for years. CASE REPORT A middle-aged white man with seronegative migratory polyarticular arthritis underwent 7 years of treatment with steroids, disease-modifying anti-rheumatic drugs (DMARDs), and a TNF (tumor necrosis factor)-alpha inhibitor, all without any clinical improvement. Throughout this period, he had persistent loose stools and iron-deficiency anemia. Extensive diagnostic investigations for various possibilities yielded negative results. However, after 7 years, he began displaying clinical signs of malabsorption. This prompted further evaluation, including an upper-gastrointestinal endoscopy and biopsy, which revealed the presence of PAS (periodic acid-Schiff)-positive Treponema whipplei, which led to the diagnosis of WD. Following initiation of appropriate treatment, the patient experienced complete resolution of symptoms. Retrospectively, all the pieces of this puzzle fell into place, providing a comprehensive understanding of the prolonged medical challenge the patient faced. CONCLUSIONS This case illuminates the diagnostic challenge faced when dealing with migratory polyarticular inflammatory arthritis and fever. This report has highlighted that Whipple disease can be associated with multiple symptoms and signs, which can result in a delay in diagnosis. However, once the diagnosis is confirmed, antibiotic treatment is effective.

Burden of Anxiety, Depression and Perceived Stress in Patients with Inflammatory Bowel Disease: A Cohort Study from North India.

BACKGROUND: Patients with Inflammatory bowel disease (IBD) are susceptible to psychiatric co-morbidities. We aimed to ascertain the burden of anxiety, depression, and perceived stress in patients with IBD from north India. METHODS: Consenting adult patients with an established diagnosis of IBD were enrolled. The enrolled patients filled the Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS) questionnaires. The patient and disease characteristics were analyzed to determine the correlations and predictors of psychiatric comorbidities. RESULTS: A total of 318 patients (255 UC, 63 CD; mean age 40.13 ± 12.06 years, 168 [52.8%] males; mean partial Mayo score 2.10 ± 2.35; and mean HBI 2.77 ± 2.13) were enrolled. The prevalence of anxiety, depression and moderate to high perceived stress was 14%, 12%, and 41%, respectively. Females had higher mean perceived stress, anxiety and depression scores compared to males. The partial Mayo score (PMS) correlated poorly with anxiety (ρ = 0.083, p = 0.187), depression (ρ = 0.123, p = 0.49) and perceived stress (ρ = 0.169; p = 0.007). The Harvey Bradshaw index (HBI) correlated fairly with anxiety (ρ = 0.336, p = 0.007) and poorly with depression (ρ = 0.287, p = 0.022) and perceived stress (ρ = 0.20; p = 0.117). Younger age (OR 0.93, 95% CI 0.90-0.97; p = 0.001) and hand-grip strength (OR 4.63, 95% CI 1.88-11.42; p = 0.001) predicted anxiety in patients with UC while rural area of residence (OR 4.75, 95% CI 1.03-21.98; p = 0.046) and HBI (OR 1.60, 95% CI 1.12-2.29; p = 0.009) were significant predictors of anxiety in patients with CD. CONCLUSION: Psychiatric comorbidities are common in patients with IBD, with higher prevalence in females. Young adults with UC and sarcopenia; and individuals with active CD living in rural areas are at an increased risk of anxiety.

Colonic Lipoma: A Rare Cause of Intussusception.

The most common and challenging chief complaint in the emergency department is abdominal pain. Intussusception, although rare in adults, is an important etiology to consider. The diagnosis is often delayed because of the nonspecific symptoms, especially in adults. This case highlights a rare case of intussusception in a middle-aged male with a colonic lipoma as a leading point. Endo-loop was applied to the colonic lipoma, leading to the resolution of intussusception. Therefore, this can be an effective alternative to surgery in select cases.

Benefits of Routine Screening for Renal Cell Carcinoma of Native Kidney in Renal Transplant Recipients.

BACKGROUND: Renal-cell carcinoma (RCC) is the most common solid organ cancer in kidney transplantation recipients (KTRs). BACKGROUND: Analyze the incidence, prognosis, and evolution of primitive kidney RCC in KTRs at our institution. MATERIAL AND METHODS: Observational descriptive retrospective study in which all KTRs from January 2000 to December 2022 were included. We performed an annual abdominal ultrasound in all KTRs. Demographic and clinical data were collected. The surgical approach, location, size, histologic type, and tumor grade were analyzed. We assessed the coexistence of risk factors. We reported the appearance of tumors in other locations, changes in immunosuppressants (IS) after the diagnosis, and survival and recurrence rates observed during follow-up. RESULTS: Eighteen RCCs of native kidneys were diagnosed with an incidence in our population of 1.08%. The majority were men (77.8%), with a mean age of 59.9 years. The pathologic analysis revealed 11 clear cell carcinomas, 6 papillary carcinomas, and 1 chromophobe cell carcinoma. The median tumor size was 2.7 cm. TNM stage was T1aN0M0 in 15 cases. Laparoscopy was performed to remove the tumor in most cases. All our patients underwent changes in IS therapy, with conversion to mammalian target of rapamycin inhibitors when possible and reduction of IS in all of them. After a mean follow-up of 78.6 months, survival was 100% without tumor recurrence. Seven of the patients were diagnosed with a new tumor in another location. CONCLUSION: In our experience, annual abdominal ultrasound in KTRs may be an option for the early detection of RCC in native kidneys.

Management of Perianal Fistulizing Crohn's Disease.

Perianal fistulizing Crohn's disease (CD) represents a severe phenotype of CD that is associated with significant morbidity and reduction in quality of life. Perianal fistulizing CD is caused by a complex interplay of genetic predisposition, immune dysregulation, gut dysbiosis, and various unknown physiological and mechanical factors. A multidisciplinary approach is hence required for optimal management . A detailed anatomical description and classification of perianal fistula, including comprehensive clinical, endoscopic, and radiological diagnostic workup, is an important prerequisite to treatment. For simple perianal fistulas, use of antibiotics and immunomodulators, with or without fistulotomy, are appropriate measures. The medical management of complex perianal fistula, on the other hand, requires adequate control of infection before initiation of therapy with immunomodulators. In active complex perianal fistula, anti-tumor necrosis factors remain the most accepted therapy, with concomitant use of antibiotics or immunomodulators enhancing the efficacy. For patients refractory to anti-tumor necrosis factors, treatment with anti-integrins, anti-interleukins, and small molecules is being evaluated. Mesenchymal stem cells, hyperbaric oxygen therapy, and exclusive enteral nutrition have also been investigated as adjunct therapies. Despite the expansion of the medical armamentarium, a large proportion of the patients require surgical interventions. In this review, we provide an up-to-date overview of the pathophysiology, clinical presentation, diagnosis, and medical management of perianal fistulizing CD. A brief overview of the surgical management of perianal fistulizing CD is also provided.

With advances in the therapeutic armamentarium, revisiting the strategies employed to treat the perianal fistulizing Crohn's disease is essential. In the current review, we discuss the pathophysiology, classification, and management of the perianal fistulizing Crohn's disease.

Lenvatinib-Induced Tumor Lysis Syndrome in Advanced Hepatocellular Carcinoma.

This case report describes a 48-year-old man with hepatocellular carcinoma who developed tumor lysis syndrome (TLS) after 7 days of starting lenvatinib therapy. The patient was hospitalized and received appropriate interventions, including aggressive hydration, allopurinol, rasburicase, and electrolyte management. The patient's condition improved, and he was eventually discharged from the hospital. This case highlights the potential risk of TLS in patients with hepatocellular carcinoma receiving lenvatinib therapy, even after a short duration, and emphasizes the importance of early recognition and management of TLS to prevent serious complications.

Clinical and magnetic resonance imaging spectrum of complex perianal fistulizing Crohn's disease: A cohort study from northern India.

BACKGROUND: Fistulizing perianal Crohn's disease (CD) is a debilitating condition associated with significant morbidity and reduction in the quality of life. Magnetic resonance imaging (MRI) of the pelvis is the preferred imaging modality for the comprehensive assessment of the perianal fistula. There is a paucity of data from India on the MRI spectrum of complex perianal fistula in CD. METHODS: A single-centre cross-sectional analysis of patients with fistulizing perianal CD, who underwent pelvic MRI between January 2020 and December 2021, was performed. The clinical (age, sex, disease duration, disease location and behavior, disease activity [Perianal Disease Activity Index, PDAI] and treatment received) and radiological (number and location of fistulae, extensions, number and location of internal and external openings, fistula activity, presence or absence of perianal abscess and associated proctitis) characteristics of complex perianal fistula (defined according to the American Gastroenterological Association classification) were recorded. RESULTS: Of total 175 patients with CD who attended the gastroenterology clinic during the study period, 27 (15.42%) (mean age 42±15.5 years, 62.96% females and median disease duration four years) had complex perianal fistula and were included in the analysis. The mean PDAI was 5.48±2.53. The median Van Assche Index was 17 (interquartile range [IQR] 13-19). A majority (96.29%) of the fistulae were trans-sphincteric and four (14.81%) fistulae extended into the supralevator space. All fistulae were active on MRI. Concomitant perianal abscess and proctitis were seen in 59.26% (n=16) and 62.96% (n=17) of patients, respectively. Combination therapy with biologics and antibiotics/immune-suppressants were the most commonly prescribed medical therapy. Six (22.22%) patients underwent combined medical and surgical (non-cutting seton, fistulectomy, fecal diversion) treatment. CONCLUSION: The cumulative risk of the development of fistulizing perianal CD in a northern Indian cohort was similar to the western populations. Complex perianal fistulae were predominantly trans-sphincteric and commoner in females. MRI evaluation is pivotal for the delineation of fistula anatomy, assessment of disease extent and activity and the evaluation of concomitant perianal abscess and other complications.

Fibrolamellar hepatocellular carcinoma presenting as cholestatic jaundice: An unusual presentation of a rare disease.

Fibrolamellar hepatocellular carcinoma is a rare primary hepatic tumor that usually occurs in youth. The common presenting features are vague abdominal pain, nausea, vomiting and weight loss. We present a case report of a young male who presented with cholestatic jaundice and on evaluation was diagnosed to have fibrolamellar hepatocellular carcinoma. He underwent successful surgical resection of the tumor. In young individuals presenting with unexplained cholestasis, fibrolamellar hepatocellular carcinoma should be considered.

Low prevalence of primary sclerosing cholangitis in patients with inflammatory bowel disease in India.

BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) represents the most common hepatobiliary extraintestinal manifestation of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). Limited data exist on PSC in patients with IBD from India. We aimed to assess the prevalence and disease spectrum of PSC in Indian patients with IBD. METHODS: Database of IBD patients at 5 tertiary care IBD centers in India were analyzed retrospectively. Data were extracted and the prevalence of PSC-IBD was calculated. RESULTS: Forty-eight patients out of 12,216 patients with IBD (9,231 UC, 2,939 CD, and 46 IBD unclassified) were identified to have PSC, resulting in a prevalence of 0.39%. The UC to CD ratio was 7:1. Male sex and pancolitis (UC) or colonic CD were more commonly associated with PSC-IBD. The diagnosis of IBD preceded the diagnosis of PSC in most of the patients. Majority of the patients were symptomatic for liver disease at diagnosis. Eight patients (16.66%) developed cirrhosis, 5 patients (10.41%), all UC, developed malignancies (3 colorectal cancer [6.25%] and 2 cholangiocarcinoma [4.16%]), and 3 patients died (2 decompensated liver disease [4.16%] and 1 cholangiocarcinoma [2.08%]) on follow-up. None of the patients mandated surgical therapy for IBD. CONCLUSIONS: Concomitant PSC in patients with IBD is uncommon in India and is associated with lower rates of development of malignancies.

Evaluation of Nutritional Characteristics Reveals Similar Prevalence of Malnutrition in Patients with Ulcerative Colitis and Crohn's Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with an increased risk of malnutrition and sarcopenia. AIMS: To evaluate the nutritional status of patients with IBD and determine the threshold values of different parameters of nutritional assessment to identify malnutrition. METHODS: This was a single-centre cross-sectional analysis of adult patients with IBD [ulcerative colitis (UC) and Crohn's disease (CD)] who underwent anthropometry [body mass index (BMI), mid upper arm circumference (MUAC) and triceps-fold thickness (TSF)], body composition analysis and assessment for sarcopenia [hand-grip strength and skeletal muscle index (SMI) at L3 vertebral level)]. Age- and gender-matched healthy adults served as controls. Malnutrition was defined according to the European Society of Clinical Nutrition and Metabolism (ESPEN) criteria. RESULTS: A total of 406 patients [336 (82.76%) UC and 70 (17.24%) CD; mean age 40.56 ± 13.67 years; 215 (52.95%) males] with IBD and 100 healthy controls (mean age 38.69 ± 10.90 years; 56 (56%) males) were enrolled. The mean BMI, MUAC, TSF thickness, fat and lean mass, hand-grip strength, and SMI at L3 vertebral level were lower in patients with IBD compared to controls. The prevalence of malnutrition was similar in UC and CD [24.40% (n = 82) and 28.57% (n = 20), respectively (p = 0.46)]. Thresholds for fat mass in females (15.8 kg) and visceral fat index in males (0.26) were both sensitive and specific to detect malnutrition. The cutoff values of MUAC and TSF thickness to identify malnutrition were 23.25 cm and 25.25 cm, and 16.50 mm and 8.50 mm, in females and males, respectively. CONCLUSION: Malnutrition and sarcopenia were common in patients with IBD, with the prevalence being similar in patients with both UC and CD.

(Re)Appraising Remission in Ulcerative Colitis.

As the therapeutic targets in ulcerative colitis (UC) shift from control of symptoms to mucosal healing and prevention of disease complications like disability, colectomy, and cancer, the definition of remission has evolved. The current definition of clinical remission is variable and is determined by the clinical context in which it is being used. This results in skepticism and uncertainty about the true meaning of the term "clinical remission." In this review, the authors reexamine the definition of clinical remission and propose a novel approach to define remission in UC.

The current definition of clinical remission in ulcerative colitis (UC) is variable and is determined by the clinical context in which it is being used. In this review, the authors reexamine the definition of clinical remission in UC and propose a novel approach to define remission based on the parameter being assessed.

Clinical spectrum of elderly-onset inflammatory bowel disease in India.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is increasingly being recognized in elderly patients. Data on clinical spectrum of elderly-onset IBD patients is lacking from India. METHODS: A cross-sectional retrospective analysis of a prospectively maintained database of patients diagnosed with IBD was conducted at 2 centers in India. The clinical spectrum of elderly-onset IBD including demographic profile (age and sex), clinical presentation, disease characteristics (disease behavior and severity, extent of disease), and treatment were recorded and compared with adult-onset IBD. RESULTS: During the study period, 3,922 (3,172 ulcerative colitis [UC] and 750 Crohn's disease [CD]) patients with IBD were recorded in the database. A total of 186 patients (4.74%; 116 males [62.36%]) had elderly-onset IBD (69.35% UC and 30.64% CD). Diarrhea, blood in stools, nocturnal frequency and pain abdomen were the commonest presentations for UC, whereas pain abdomen, weight loss and diarrhea were the most frequent symptoms in CD. For both elderly onset UC and CD, majority of the patients had moderately severe disease. Left-sided colitis was the commonest disease location in UC. Isolated ileal disease and inflammatory behavior were the most common disease location and behavior, respectively in CD. 5-Aminosalicylates were the commonest prescribed drug for both elderly onset UC and CD. Thiopurines and biologics were used infrequently. Prevalence of colorectal cancer was higher in elderly onset IBD. CONCLUSIONS: Elderly onset IBD is not uncommon in India. Both the elderly onset UC and CD were milder, with no significant differences in disease characteristics (disease extent, location and behavior) when compared to adult-onset IBD. Colorectal cancer was more common in elderly onset IBD.

Correlation between magnetic resonance enterography and ileo-colonoscopy for assessment of disease activity in terminal ileal Crohn's disease.

BACKGROUND: Magnetic resonance enterography (MRE) has emerged as a novel tool for the assessment of disease activity in Crohn's disease (CD). Real world data from Indian subcontinent on performance of MRE in terminal ileal CD are lacking. METHODS: Retrospective analysis of patients with terminal ileal CD who underwent both ileo-colonoscopy and MRE was performed. Ileo-colonoscopy was considered the gold standard for assessment of disease activity. On ileo-colonoscopy, a simple endoscopic score for Crohn's disease (SES-CD) ≥2 was considered active disease; presence of ulcers indicated severe disease. MRE scoring of the disease activity was performed using magnetic resonance index of activity (MARIA) and simplified MARIA (MARIAs). The measure of agreement between ileo-colonoscopy and MRE and comparison of MARIA and MARIAs for assessment of disease activity and sensitivity of MRE to detect mucosal ulcerations were calculated. RESULTS: Seventy patients with terminal ileal CD (mean age 40.74±15.56 years; 71.4% males [n=50]) were evaluated. The sensitivities of MARIA and MARIAs scores to detect active disease were 0.76 and 0.84, respectively. The area under the receiver operating characteristic curve (AUROC) for detecting severe disease was 0.836 (p<0.0001) for MARIA and 0.861 (p<0.0001) for MARIAs. For mild active disease, there was no agreement between SES-CD and MARIA or MARIAs; however, for severe disease, the agreement was fair and moderate for MARIA and MARIAs, respectively. MARIA and MARIAs were comparable for identification of active and severe disease (κ 0.759, p<0.0001 and κ 0.840, p<0.0001, respectively). MRE was 68.18% sensitive to detect mucosal ulcers. CONCLUSION: MRE is a reliable and sensitive tool for detection of endoscopically severe, but not mild, terminal ileal CD.

Vaccine breakthrough infection leads to distinct profiles of neutralizing antibody responses by SARS-CoV-2 variant.

Protective immunity against SARS-CoV-2 infection after COVID-19 vaccination may differ by variant. We enrolled vaccinated (n = 39) and unvaccinated (n = 11) individuals with acute, symptomatic SARS-CoV-2 Delta or Omicron infection and performed SARS-CoV-2 viral load quantification, whole-genome sequencing, and variant-specific antibody characterization at the time of acute illness and convalescence. Viral load at the time of infection was inversely correlated with antibody binding and neutralizing antibody responses. Across all variants tested, convalescent neutralization titers in unvaccinated individuals were markedly lower than in vaccinated individuals. Increases in antibody titers and neutralizing activity occurred at convalescence in a variant-specific manner. For example, among individuals infected with the Delta variant, neutralizing antibody responses were weakest against BA.2, whereas infection with Omicron BA.1 variant generated a broader response against all tested variants, including BA.2.

Machine learning guided structure function predictions enable in silico nanoparticle screening for polymeric gene delivery.

Developing highly efficient non-viral gene delivery reagents is still difficult for many hard-to-transfect cell types and, to date, has mostly been conducted via brute force screening routines. High throughput in silico methods of evaluating biomaterials can enable accelerated optimization and development of devices or therapeutics by exploring large chemical design spaces quickly and at low cost. This work reports application of state-of-the-art machine learning algorithms to a dataset of synthetic biodegradable polymers, poly(beta-amino ester)s (PBAEs), which have shown exciting promise for therapeutic gene delivery in vitro and in vivo. The data set includes polymer properties as inputs as well as polymeric nanoparticle transfection performance and nanoparticle toxicity in a range of cells as outputs. This data was used to train and evaluate several state-of-the-art machine learning algorithms for their ability to predict transfection and understand structure-function relationships. By developing an encoding scheme for vectorizing the structure of a PBAE polymer in a machine-readable format, we demonstrate that a random forest model can satisfactorily predict DNA transfection in vitro based on the chemical structure of the constituent PBAE polymer in a cell line dependent manner. Based on the model, we synthesized PBAE polymers and used them to form polymeric gene delivery nanoparticles that were predicted in silico to be successful. We validated the computational predictions in two cell lines in vitro, RAW 264.7 macrophages and Hep3B liver cancer cells, and found that the Spearman's R correlation between predicted and experimental transfection was 0.57 and 0.66 respectively. Thus, a computational approach that encoded chemical descriptors of polymers was able to demonstrate that in silico computational screening of polymeric nanomedicine compositions had utility in predicting de novo biological experiments. STATEMENT OF SIGNIFICANCE: Developing highly efficient non-viral gene delivery reagents is difficult for many hard-to-transfect cell types and, to date, has mostly been explored via brute force screening routines. High throughput in silico methods of evaluating biomaterials can enable accelerated optimization and development for therapeutic or biomanufacturing purposes by exploring large chemical design spaces quickly and at low cost. This work reports application of state-of-the-art machine learning algorithms to a large compiled PBAE DNA gene delivery nanoparticle dataset across many cell types to develop predictive models for transfection and nanoparticle cytotoxicity. We develop a novel computational pipeline to encode PBAE nanoparticles with chemical descriptors and demonstrate utility in a de novo experimental context.

Early fecal microbiome transfer after donor defecation determines response in patients with moderate to severe ulcerative colitis.

BACKGROUND: Fecal microbiome transfer (FMT) targeting gut microbiome dysbiosis is an emerging therapy for ulcerative colitis (UC). There is however no consensus on protocols for performing FMT in UC, especially in relation to time after donor feces defecation. METHODS: This is a single-center retrospective analysis of patients with moderate-severe UC (total Mayo Clinic score ≥6 and endoscopic Mayo Clinic subscore of ≥2) treated with FMT between September 2017 and December 2019 at Dayanand Medical College and Hospital, Ludhiana, India. Fresh fecal samples from unrelated healthy voluntary donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. Time interval between donor feces defecation and FMT procedure was recorded for each FMT session and the mean time of seven sessions was designated aika. Impact of aika on clinical response and safety of FMT was evaluated. RESULTS: During the study period, 123 adult patients (mean age 33.75±11.97 years, 61.8% [n=76] males) with moderate-severe UC (mean total Mayo Clinic and endoscopic Mayo Clinic scores 7.49±1.60 and 2.50±0.50, respectively) were treated with FMT. The mean aika was 2.29±0.75 h. The aika was smaller in patients who responded to FMT as compared to non-responders (2.13±0.75 h vs. 2.71±0.76 h, p=0.0002) as well as in patients achieving clinical remission (2.15±0.76 h vs. 2.42±0.76 h, p=0.05). There was no significant impact of aika on adverse effects except for the incidence of borborygmi after FMT, which was higher in patients with aika ≤2 h. CONCLUSION: Early FMT after donor feces defecation favorably impacts the clinical response rates in patients with active UC.

Endoscopy for assessment of mucosal healing in ulcerative colitis: time bound or response guided?

The timing of colonoscopy in patients with active ulcerative colitis (UC) lacks coherence. The published guidelines and recommendations advocate time-bound colonoscopy in patients with active UC to assess for mucosal healing. However, the practice of performing colonoscopies at fixed time frames lacks reasoning. The time to achieve mucosal healing in UC is not uniform across the patient populations and is influenced by the disease severity and efficacy and time to therapeutic response of the drugs being used. Additionally, with the availability of sensitive noninvasive inflammatory biomarkers such as fecal calprotectin, that parallel the disease activity and correlate with mucosal healing, the notion of performing colonoscopy at fixed intervals sounds unjustifiable. The authors express their view that a response-guided colonoscopy (driven by normalization of clinical symptoms and inflammatory biomarkers), rather than a time-bound colonoscopy, would be more logical, apart from being cost-effective and patient-friendly.

Use of thiopurines in inflammatory bowel disease: an update.

Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential.