Severe Perianal Disease Research Articles

Role of ileal diversion in pediatric inflammatory bowel disease.

Surgical intervention is often indicated in pediatric inflammatory bowel disease (IBD) for medically refractory disease or complications of severe disease. Specifically, surgical intervention via ileal diversion allows for fecal flow to be redirected away from diseased distal bowel and through an ileostomy. It is utilized in patients who have medically refractory colitis, severe perianal disease, or irreversible bowel damage. In patients with ulcerative colitis, it is primarily performed during a restorative proctocolectomy with ileal pouch anal anastomosis to protect the high-risk anastomoses. In the setting of Crohn's disease, ileal diversion reduces the exposure of diseased distal intestine to pro-inflammatory stool. During perioperative planning, it is crucial for the gastroenterologist to partner early with a multidisciplinary team including surgeons, nutritionists, wound ostomy care nurses, psychologists, and social workers. Patients should be assessed for malnutrition and should be optimized nutritionally with enteral or parenteral nutrition. As they are associated with increased risk of postoperative complications, corticosteroids should be significantly reduced or completely discontinued preoperatively. Though ileal diversion may reduce the complications associated with anastomosis, serious postoperative complications can include diversion colitis and high-output fistulae. This review aims to provide an overview of the role of ileal diversion in the treatment of pediatric IBD to pediatric gastroenterologists to inform their medical decision-making and discussions with patients and families.

P232 Common variable immunodeficiency-associated enteropathy in consecutive patients from a tertiary hospital

Abstract Background Common variable immunodeficiency (CVID) patients may develop intestinal inflammatory involvement in 9-20% of cases, although its diagnosis, management and prognosis are not well established. Methods We performed a transversal study with retrospective data collection. We reviewed all clinical records from consecutive adult CVID patients followed in Gregorio Marañón Hospital (Spain) from January 1st 1990 to January 1st 2023. A diagnosis of CVID-associated enteropathy (CVID-E) was established if patchy intestinal inflammation (Crohn-like pattern) or colonic inflammation (ulcerative colitis-like pattern) was demonstrated, or villous atrophy was observed in duodenal biopsies (celiac-like pattern) or inflammatory infiltrate was observed in colonic biopsies (microscopic colitis-like pattern). Differences between CVID-E patients and the rest of the CVID cohort were evaluated using chi-square and T student methods, when appropriate. Results 89 patients with confirmed CVID following ESID criteria were included. Patients’ characteristics are summarised in Table 1. All patients were receiving intravenous or subcutaneous Igs and reached an Ig G trough level >1000 mg/dL. CVID-E was diagnosed in 26 patients (29,2%), at a median of 6,4 years after CVID diagnosis. Surprisingly, 10 patients (38,5%) were diagnosed with CVID-E before or at the same time of CVID diagnosis. 5 patients were dead (19,2%), and the causes of death were gastric cancer (1 patient), liver complications (1), infectious complications (1), enteropathy (1) and unknown cause (1). 73,1% suffered from GI infections (Giardia lamblia, Campylobacter jejuni and Clostridioides difficile were the most frequent agents). The most frequent pattern of the disease was Crohn-like disease (Figure 1). Although exclusive celiac-like pattern was found in only 3 patients, 5 Crohn-like, 4 UC-like and 2 microscopic colitis-like pattern patients also presented duodenal atrophy. Unexpectedly, 46,2% of CVID-E patients suffered from concomitant liver involvement. Eight patients received corticosteroids, 2 azathioprine and 1 patient received infliximab and subsequent ustekinumab. One patient needed subtotal colectomy, another ileal resection and another patient received a terminal colostomy due to severe perianal disease. CVID-E patients presented statistically more frequent liver involvement, more GI infections, and a tendency towards more GI cancer. Conclusion CVID-E is frequent among CVID patients. These patients suffer from more GI infections, liver involvement and probably more GI cancer. Screening of levels of Igs at diagnosis of IBD and celiac disease is advisable as CVID diagnosis can occur at the same time or even after enteropathy diagnosis.

Anti-CD20-Triggered Crohn’s-Like Disease with Severe Perianal Involvement in a Patient with Multiple Sclerosis: Case Report, Review of the Literature, and Potential Therapeutic Approach

This case report describes a 38-year-old female patient with a 3-year history of multiple sclerosis who developed rituximab-induced pancolitis, possibly representing a new onset of inflammatory bowel disease. The patient presented with bloody diarrhea, epigastric pain, fever, and general malaise. Laboratory testing revealed elevated acute inflammation markers, and endoscopy showed deep ulcerations and severe perianal disease. The patient was treated effectively with corticosteroids. Monthly doses of ustekinumab have been administered during follow-up due to perianal disease that has remitted. Rituximab was discontinued and ozanimod was initiated with clinical and analytical stability to date.

New Perianal Sepsis Risk Score Predicts Outcome of Elderly Patients with Perianal Abscesses.

Antibiotic therapy following surgical perianal abscess drainage is debated, but may be necessary for high-risk patients. Frailty has been shown to increase the risk of unfavorable outcomes in elderly surgical patients. This study aims to identify high-risk patients by retrospectively analyzing a single-center cohort and using a pretherapeutic score to predict the need for postoperative antibiotics and extended nursing care following perianal abscess drainage surgery. The perianal sepsis risk score was developed through univariable and multivariable analysis. Internal validation was assessed using the area under receiver-operating characteristic curve. Elderly, especially frail patients exhibited more severe perianal disease, higher frequency of antibiotic therapy, longer hospitalization, poorer clinical outcomes. Multivariable analysis revealed that scores in the 5-item modified frailty index, severity of local infection, and preoperative laboratory markers of infection independently predicted the need for prolonged hospitalization and anti-infective therapy after abscess drainage surgery. These factors were combined into the perianal sepsis risk score, which demonstrated better predictive accuracy for prolonged hospitalization and antibiotic therapy compared with chronological age or frailty status alone. Geriatric assessments are becoming increasingly important in clinical practice. The perianal sepsis risk score identifies high-risk patients before surgery, enabling early initiation of antibiotic therapy and allocation of additional nursing resources.

Predicting complications in pediatric Crohn's disease patients followed in CEDATA-GPGE registry.

Complications of Crohn's disease (CD) often impair patients' quality of life. It is necessary to predict and prevent these complications (surgery, stricturing [B2]/penetrating [B3] disease behavior, perianal disease, growth retardation and hospitalization). Our study investigated previously suggested and additional predictors by analyzing data of the CEDATA-GPGE registry. Pediatric patients (< 18 years) diagnosed with CD with follow up data in the registry were included in the study. Potential risk factors for the selected complications were evaluated by performing Kaplan-Meier survival curves and cox regression models. For the complication surgery, the potential risk factors older age, B3 disease, severe perianal disease and initial therapy with corticosteroids at the time of diagnosis were identified. Older age, initial therapy with corticosteroids, low weight-for-age, anemia and emesis predict B2 disease. Low weight-for-age and severe perianal disease were risk factors for B3 disease. Low weight-for-age, growth retardation, older age, nutritional therapy, and extraintestinal manifestations (EIM) of the skin were identified as risk factors for growth retardation during the disease course. High disease activity and treatment with biologicals were predictors for hospitalization. As risk factors for perianal disease, the factors male sex, corticosteroids, B3 disease, a positive family history and EIM of liver and skin were identified. We confirmed previously suggested predictors of CD course and identified new ones in one of the largest registries of pediatric CD patients. This may help to better stratify patients' according to their individual risk profile and choose appropriate treatment strategies.

Biallelic TLR4 deficiency in humans

Toll-like receptors (TLRs) mediate functions for host defense and inflammatory responses. TLR4 recognizes LPS, a component of gram-negative bacteria as well as host-derived endogenous ligands such as S100A8 and S100A9 proteins. We sought to report phenotype and cellular function of individuals with complete TLR4 deficiency. We performed genome sequencing and investigated exome and genome sequencing databases. Cellular responses were studied on primary monocytes, macrophages, and neutrophils, as well as cell lines using flow cytometry, reporter, and cytokine assays. We identified 2 individuals in a family of Qatari origin carrying a homozygous stop codon variant p.Q188X in TLR4 presenting with a variable phenotype (asymptomatic and inflammatory bowel disease consistent with severe perianal Crohn disease). Athird individual with homozygous p.Y794X was identified in a population database. In contrast to hypomorphic polymorphisms p.D299G and p.T399I, the variants p.Q188X and p.Y794X completely abrogated LPS-induced cytokine responses whereas TLR2 response was normal. TLR4 deficiency causes a neutrophil CD62L shedding defect, whereas antimicrobial activity toward intracellular Salmonella was intact. Biallelic TLR4 deficiency in humans causes an inborn error of immunity in responding to LPS. This complements the spectrum of known primary immunodeficiencies, in particular myeloid differentiation primary response 88 (MYD88) or the IL-1 receptor-associated kinase 4 (IRAK4) deficiency that are downstream of TLR4 and TLR2 signaling.

P52: A virtual multidisciplinary clinic service for the diagnosis and treatment of severe perianal skin disease in hidradenitis suppurativa and Crohn disease

P52: A virtual multidisciplinary clinic service for the diagnosis and treatment of severe perianal skin disease in hidradenitis suppurativa and Crohn disease

S0798 Long-Term Outcomes of the Excluded Rectum in Crohn’s Disease – Results From the CAPER (Consortium to Assess Prognosis of the Excluded Rectum) Study

INTRODUCTION: Despite significant progress made in the treatment of Crohn’s disease (CD) there is still a need for fecal diversion in many refractory patients. The long-term outcome of the retained rectum following this surgery is still not fully understood. We reviewed our experience at two large New York City (NYC) Health Systems. METHODS: A database of all CD patients followed at our health systems was searched for all CD between 1990-2014 who underwent diversionary surgery and who had retained excluded rectums for at least 6 months post-operatively. Medical records were reviewed for baseline characteristics, indications for diversion, and outcomes of excluded rectums. Cases from The Mount Sinai Hospital previously reported1 were not included in this study. RESULTS: Among 78 new CD patients identified in our databases, 27 patients met our inclusion criteria. Baseline characteristics are listed in Table 1. Indications for rectal exclusion and fecal diversion were severe perianal disease in 11/27(41%), acute/refractory disease in 9/27(33.3%), internal fistulas in 6/27(22%) and bowel stricture 1/27(3.6%). Primary outcomes are detailed in Figure 1. 12/27(44%) patients underwent completion proctocolectomy. All were symptomatic except for one who underwent elective completion proctocolectomy. Hence, 15/27(56%) still had retained rectums at the time of last follow-up; 6/15(40%) had been reconnected while 9/15(60%) remained excluded. Out of 6/15 patients who had been reconnected, 3(50%) were symptom-free and 3(50%) continued to have problems. Among the 9/15 with continued rectal exclusion, 3(33%) were asymptomatic and 9(67%) experienced ongoing troubles. On intent-to-treat basis, among the 27 new cases added since our prior report, 6 retained their rectums without further problems(22%), while 21(78%) either ultimately lost their rectums or remained symptomatic with retained rectums (reconnected/excluded). These results are strikingly similar to those observed in our prior report of 81 patients.1 CONCLUSION: While many factors enter the decision whether to remove or retain an excluded rectum beyond 6 months in cases of CD, it could be helpful for patients and clinicians alike to know that in our 2 reported series from NYC, only about one-quarter of patients in long-term follow-up maintained their rectums in situ without ongoing symptoms.Table 1.: Baseline characteristics of all included patientsFigure 1.: Primary outcomes for all patients who underwent diversionary surgery and who had retained excluded rectums for at least 6 months post-operatively.

Stoma formation for Crohn’s disease in the post‐biologic era, Ma et al.

Up to one-third of patients with Crohn’s disease will require major abdominal surgery over the first 5 years of their disease and most Crohn’s patients will have a Crohn’s related operation at some time in their lifetime 1. Nonetheless, as surgeons we notice a trend towards less referrals for operations for Crohn’s disease, where the patients tend to present later and often in a poorer condition. It has been suggested that this change in surgical practice is due to the introduction of biologic medications for Crohn’s disease in the first half of the 2000s. However, despite the increasing use of novel biologic agents, counterintuitively the incidence of Crohn’s disease related surgery does not appear to be reducing 2. A recent large population based cohort study from Alberta, Canada, showed a decrease in emergency surgery but an increase in elective surgery 3. This might explain why surgeons get the sense that the burden for Crohn’s related surgery is less. One could expect that more elective surgery is related to earlier referral, a better condition of the patient at the time of surgery and therefore less stoma formation. In this month’s Editor’s choice study, Ma et al., from the same Canadian group, are looking at trends in stoma formation after the introduction of biologics in management of Crohn’s disease 4. In order to assess the need for stoma creation in the biological era, the authors queried an administrative population database from their area, serving 1.4 million inhabitants. They identified 545 patients who underwent bowel resection and stoma formation for Crohn’s disease between 2002 and 2011. They found a time based reduction in stoma rates from 2.30 stomas per 100 person-years to 1.51 stomas per 100 person-years. The number of emergency and temporary stomas decreased over time, whereas the number of elective permanent stomas remained stable. Except for severe perianal fistulising disease, elective stoma formation for Crohn’s disease becomes necessary where primary anastomosis is technically impossible or if there is a high risk for anastomotic breakdown. Unfortunately, this study was not able to identify the reason the stoma was indicated 4. Well-known risk factors for anastomotic complications in Crohn’s patients include recurrent clinical episodes, steroid use, and malnutrition 5. Nowadays, gastroenterologists have a wide range of medical therapies available to avoid intestinal resection. This might cause a delay to progress to surgery, which may result in a progressively more complex disease phenotype at the time of surgery. If this delay occurs, the patient’s condition deteriorates, and this forces the surgeon to elect for a stoma to avoid an anastomotic complication. The study by Ma et al. reminds us of the importance of appropriate and timely surgery, especially in the biologic era. Therefore, the IBD surgeon should be involved in the management of the Crohn’s patient from the first onset of the disease, as a member of an IBD multidisciplinary team.

Role of Fecal Diversion in Complex Crohn's Disease.

Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract resulting in progressive tissue damage, which can result in strictures, fistulae, and abscesses formation. The triggering mechanism is thought to be in the fecal stream, and diversion of this fecal stream is sometimes required to control disease when all other avenues of medical and surgical management have been exhausted. Fecal diversion can be temporary or permanent with the indications being defunctioning a high-risk anastomosis, as a result of a surgical complication, for disease control, or due to severe colonic, rectal, or perianal disease. The incidence of ostomy formation in CD has increased epidemiologically over time. The primary indication for ostomy formation is severe perianal fistulizing disease. However, while 64% of patients have an early clinical response after diversion for refractory perianal CD, restoration of bowel continuity is attempted in only 35% of patients, and is successful in only 17%. The current review discusses the indications for ostomy creation in complex CD, strategies for procedure selection, and patient outcomes.

Impaired IL‐10 Receptor‐mediated Suppression in Monocyte From Patients With Crohn Disease

Interleukin-10 (IL-10) is an immunoregulatory cytokine that has a central role in suppressing proinflammatory responses. Patients with deleterious mutations in interleukin (IL)-10 or IL-10 receptor (IL-10R) genes develop severe colitis and perianal disease in the first months of life. Whether IL-10R expression and signaling in pediatric- or adult-onset Crohn disease (CD) are altered is unknown. The objective of this study was to characterize IL-10R expression and IL-10R-mediated suppression in patients with CD. Monocytes were sorted from peripheral blood mononuclear cells of patients with CD and control subjects. IL-10R expression was determined by flow cytometry. Monocytes were stimulated with lipopolysaccharide (LPS) for 3 hours in the presence of different concentrations of IL-10 to determine IL-10-mediated suppression of tumor necrosis factor α production. Signaling through the IL-10R was evaluated by quantifying STAT3 phosphorylation in response to IL-10 stimulation. Forty-two subjects were enrolled in this study: 19 with CD and 23 controls. Stimulation of monocytes with LPS markedly increased IL-10R expression in both groups but to a much lower extent in patients with CD. In addition, IL-10-mediated suppression of TNFα production upon LPS stimulation and IL-10-induced STAT3 phosphorylation were attenuated in patients with CD versus controls. Finally, LPS-stimulated monocytes from patients with CD secreted significantly lower quantities of IL-10, compared with control monocytes. IL-10R expression and signaling are decreased in monocytes from patients with CD. Additional studies are required to assess whether similar patterns occur in other innate immune cells, especially in the gut, and whether disease activity, medical therapy, and genetic factors modulate these findings.

Covering the Cover

Covering the Cover

Variants in TRIM22 That Affect NOD2 Signaling Are Associated With Very-Early-Onset Inflammatory Bowel Disease

Severe forms of inflammatory bowel disease (IBD) that develop in very young children can be caused by variants in a single gene. We performed whole-exome sequence (WES) analysis to identify genetic factors that might cause granulomatous colitis and severe perianal disease, with recurrent bacterial and viral infections, in an infant of consanguineous parents. We performed targeted WES analysis of DNA collected from the patient and her parents. We validated our findings by a similar analysis of DNA from 150 patients with very-early-onset IBD not associated with known genetic factors analyzed in Toronto, Oxford, and Munich. We compared gene expression signatures in inflamed vs noninflamed intestinal and rectal tissues collected from patients with treatment-resistant Crohn's disease who participated in a trial of ustekinumab. We performed functional studies of identified variants in primary cells from patients and cell culture. We identified a homozygous variant in the tripartite motif containing 22 gene (TRIM22) of the patient, as well as in 2 patients with a disease similar phenotype. Functional studies showed that the variant disrupted the ability of TRIM22 to regulate nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-κB. Computational studies demonstrated a correlation between the TRIM22-NOD2 network and signaling pathways and genetic factors associated very early onset and adult-onset IBD. TRIM22 is also associated with antiviral and mycobacterial effectors and markers of inflammation, such as fecal calprotectin, C-reactive protein, and Crohn's disease activity index scores. In WES and targeted exome sequence analyses of an infant with severe IBD characterized by granulomatous colitis and severe perianal disease, we identified a homozygous variant of TRIM22 that affects the ability of its product to regulate NOD2. Combined computational and functional studies showed that the TRIM22-NOD2 network regulates antiviral and antibacterial signaling pathways that contribute to inflammation. Further study of this network could lead to new disease markers and therapeutic targets for patients with very early and adult-onset IBD.

The recurrence of severe perianal crohns disease in a vram flap reconstruction post disease excision – The clinical implications of extraneous crohns disease in flap reconstruction and options to consider

The recurrence of severe perianal crohns disease in a vram flap reconstruction post disease excision – The clinical implications of extraneous crohns disease in flap reconstruction and options to consider

Mucosal Healing With Thalidomide in Refractory Crohn’s Disease Patients Intolerant of Anti-TNF-α Drugs

Thalidomide is an oral immunomodulatory and anti-inflammatory drug with antitumor necrosis factor-α (TNF-α) activity. Several case reports and some clinical trials have demonstrated its efficacy in the treatment of refractory Crohn's disease (CD). We report the effect and tolerability of thalidomide in 3 patients with moderate-to-severe CD who were not responsive to anti-TNF-α therapies, and review the relevant literature. The first case is of a 28-year-old female affected by Crohn's colitis complicated by a severe fistulizing perianal disease; she was treated with infliximab, adalimumab, and certolizumab pegol, which were stopped because of intolerance. The second case is of a 39-year-old female with fistulizing ileocolitis complicated by severe arthralgias and perianal disease with loss of response to infliximab and intolerance of certolizumab pegol. The third case is of a 39-year-old male with gastric and ileocolonic CD refractory to immunosuppressors and intolerant of infliximab. All the 3 cases achieved complete clinical remission and endoscopic healing of mucosal lesions at a low dose of thalidomide (50 to 150 mg/d). In our CD patients who experienced loss of response or were unable to tolerate anti-TNF-α drugs, thalidomide was an effective and well-tolerated therapy for inducing and maintaining long-term remission.

Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease

Children and adolescents with Crohn’s disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohn’s and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.

IL-10 in humans: lessons from the gut, IL-10/IL-10 receptor deficiencies, and IL-10 polymorphisms.

Inflammatory bowel disease (IBD) represents a heterogeneous group of gastrointestinal disorders, where commensal gut flora provokes an either (a) insufficient or (b) uncontrolled immune response. This results either in a lack of or in excessive inflammation mainly manifesting as Crohn's disease or ulcerative colitis. IBD commonly presents in adolescence and adulthood and often follows a chronic relapsing course. Genetic and/or environmental factors contribute to the failure of gut immune homeostasis. Genome-wide association studies have identified over 160 susceptibility loci associated with IBD, including polymorphisms in interleukin-10 (IL-10). The anti-inflammatory cytokine IL-10 dampens intestinal inflammation and is therefore a good candidate gene for IBD. Polymorphisms in the IL-10 receptor are also associated with ulcerative colitis presenting in early childhood. Moreover, severe infantile enterocolitis resembling Crohn's disease, caused by loss-of-function mutations in IL-10 and IL-10 receptor, is characterised by a very early onset (usually within the first 3 months of life), unresponsiveness to standard treatment including immunosuppressive therapy, and severe perianal disease with abscesses and fistulas. In these patients, inflammation and polymorphic infiltrates are mainly confined to the colon with very little involvement of the small intestine. Ulceration and granulomas, bloody diarrhoea and failure to thrive also occur. Furthermore, patients may suffer from recurrent fever and respiratory infections. Individuals with IL-10 receptor mutations also experience cutaneous folliculitis and arthritis. Hematopoietic stem cell transplantation is currently the only curative therapy.

A Case Report of a Patient with Crohnʼs Disease Complicated by Pyoderma Gangrenosum Treated with Intravenous Immunoglobulin

Purpose: We report a case of a 45-year-old male with a history of ileal, fistualizing Crohn's disease. The patient was originally diagnosed with ulcerative colitis status post ileal-pouch anal anastomosis that was reversed. He later developed severe perianal disease and his disease process appeared consistent with Crohn's disease (CD). He had multiple ileostomies with multiple complications most significant of which was severe difficult to control peristomal pyoderma gangrenosum (PG). The patient initially was treated with infliximab (Remicade®), but experienced an infusion reaction. He was then switched to adalimumab (Humira®) with mild benefit, but continued to have severe PG. He was later treated with anakinra without significant effects. His PG remained severe and required long-term steroids. He was later treated with cyclosporine with mild improvement. This had to be stopped in the setting of renal failure. He was also treated with methotrexate, which significantly worsened his symptoms. He was switched to mycophenolate mofetil (CellCept) which was also stopped in the setting of renal failure. Eventually, the patient was started on intravenous immunoglobulin (IVIG) which resulted in dramatic improvement to his PG as well as his CD. One year later, the patient has been off of adalimumab, continuing treatment with only IVIG, on minimal dose of steroids and has been feeling very well with complete clearance of his PG. Pyoderma gangrenosum (PG) is a rare, inflammatory neutrophilic dermatosis of unknown etiology. It is the second more frequent and most debilitating cutaneous extra intestinal manifestation in inflammatory bowel disease (IBD) patients. It is commonly treated with immunosuppressants and systemic corticosteroids; however, patients have reported that long-term usage of these medications cause serious side effects. Although there are only a few studies available, a very effective and safe therapeutic alternative for PG has been high dose IVIG with minimal side effects. IVIG has also been used in patients with Crohn's disease with great response. With limited data about the use of IVIG in Crohn's patients, the exact dose and duration of treatment remain to be defined.

Early Administration of Azathioprine vs Conventional Management of Crohn's Disease: A Randomized Controlled Trial

Immunomodulator therapy is effective for patients with Crohn's disease (CD) but has not been shown to affect disease progression, presumably because it is given too late after diagnosis. We compared the efficacy of early treatment (within 6 months after diagnosis) with azathioprine versus conventional management of patients at high risk for disabling disease. We performed an open-label trial of adults with a diagnosis of CD for less than 6 months who were at risk for disabling disease. From July 2005 to November 2010, patients at 24 French centers were randomly assigned to treatment with azathioprine (2.5 mg ∙ kg(-1) ∙ day(-1), n = 65) or conventional management (azathioprine only in cases of corticosteroid dependency, chronic active disease with frequent flares, poor response to corticosteroids, or development of severe perianal disease) (n = 67). The primary end point was the proportion of trimesters spent in corticosteroid-free and anti-tumor necrosis factor (TNF)-free remission during the first 3 years after inclusion. During the 3-year follow-up period, 16 patients in the azathioprine group were switched to mercaptopurine or methotrexate therapy because of intolerance or poor efficacy. Forty-one patients in the conventional management group required immunosuppressant therapy (61%; median time to first prescription, 11 months). In the azathioprine group, a median 67% of trimesters were spent in remission (interquartile range, 11%-85%) compared with 56% in the conventional management group (interquartile range, 29%-73%) (P = .69). Among secondary outcomes, a higher cumulative proportion of patients in the azathioprine group were free of perianal surgery than in the conventional management group (96% ± 3% and 82% ± 6% at month 36, respectively; P = .036). The cumulative proportion of patients free of intestinal surgery and anti-TNF therapy did not differ between groups. Based on results from a clinical trial, administration of azathioprine within 6 months of diagnosis of CD was no more effective than conventional management in increasing time of clinical remission. Clinicaltrials.gov, Number NCT00546546.

Severe perianal disease degenerated to adenocarcinoma: Is close monitoring of long-term perianal disease necessary?

Severe perianal disease degenerated to adenocarcinoma: Is close monitoring of long-term perianal disease necessary?