Crohn's Ileitis Research Articles

A Case of Pulmonary Carcinoid Tumor in a Patient on Adalimumab for Crohnʼs Disease

Purpose: We report a unique case of pulmonary carcinoid tumor associated with adalimumab therapy for Crohn's disease. Methods: Adalimumab is a fully human monoclonal antibody against tumor necrosis factor alpha (TNFα). TNFα is a protein synthesized by activated macrophages and T cells. It is approved for the treatment of Crohn's disease and its' safety is established by clinical trials. However serious side effects can occur. Patients on TNFα inhibitors are at risk for injection reactions, serious infections and can develop malignancy. There is an FDA warning regarding risk of B-cell lymphomas and other tumors. Results: 63 year old female with fisutlizing, structuring Crohn's colitis and ileitis diagnosed at age 18, required multiple bowel resections and ileocolonic anastomosis. Presented with recurrent peri-anal fistulas and was started on adalimumab 10-11 months ago. Recently had developed a peri-rectal fistula and abscess requiring drainage. Previous smoker. No family history of Inflammatory Bowel Disease (IBD) or colorectal cancer. Physical exam notable for a non-tender, non-distended abdomen and rectal exam revealing non-tender peri-anal excoriations and a draining sinus fistula tract. Abdominal CT done for follow up of perirectal abcess had incidental finding of pulmonary nodules. This was a new finding; a chest CT then showed a 2cm RUL lung mass and multiple bibasilar sub-centimeter pulmonary nodules. Prior chest x-rays upon close inspection did not reveal the mass. Bronchoscopy with bronchiolar lavage and transbronchial biopsy was inconclusive. Whole body PET scan was remarkable for the right upper lung bronchial nodular density with low level FDG activity. Surgery performed a thoracotomy and wedge resection for diagnosis and cure. Pathology review confirmed a typical carcinoid tumor with pathologic stage of pT1a pN0. Adalimumab was stopped and she was placed on antibiotics for her fistulas along with prednisone taper. Patient later underwent an uncomplicated right lung wedge resection with curative intent and has since been doing well. She denies rectal pain or discharge and has 1-2 formed bowel movements daily. Post operatively she was placed on methotrexate for Crohn's maintenance therapy. Conclusion: Studies have demonstrated the clinical association of biologic therapy and Non-hodgekin's lymphomas. The action of TNFα antagonists has been shown in laboratory models to possibly potentiate tumor growth. Pulmonary carcinoid is a slow growing neuroendocrine tumor, but in this case appears to have developed in conjunction with adalimumab therapy. To our knowledge this is the first case of primary pulmonary carcinoid to be associated with adalimumab.

Ileocecal Strictureplasty for Crohn’s Disease: Long‐Term Results and Comparison with Ileocecal Resection

The aim of the present study was to evaluate strictureplasty as the first choice for surgical treatment for Crohn's terminal ileitis. Between 1996 and 2000 we performed Finney-shaped ileocecal strictureplasty (ICS), doubling up the diseased terminal ileum, in 14 patients affected by Crohn's disease (group A). We compared the postoperative and long-term outcomes of these patients with those of 14 similar patients who underwent ileocecal resection with ileocolonic anastomosis during the same period (group B). No postoperative morbidity or mortality was recorded in group A, whereas two patients of group B had a pelvic hematoma and cholestatic hepatopathy, respectively. The mean hospital stay after surgery was 9.9days (range 7-13days) in group A and 7.4days (range 6-10days) in group B. After a median follow-up of 120months (range 103-147months), five patients of group A had a symptomatic recurrence: A stricture at the site of the ICS was present in four of them, but only one required surgery; symptoms were controlled by medical therapy in the other three. The fifth symptomatic patient was reoperated for multiple jejunoileal recurrence of the disease above the ICS. Group B patients have been followed for a mean of 108months (range 90-140months). Four of the patients had a preanastomotic recurrence, with subocclusive symptoms and mild malnutrition treated with medical therapy. Our results indicate that there are no significant differences between ICS and resection in terms of outcome and clinical relapse of Crohn's terminal ileitis.

Predictive value of epithelial gene expression profiles for response to infliximab in Crohnʼs disease‡

Infliximab (IFX) has become the mainstay of therapy of refractory Crohn's disease (CD). However, a subset of patients shows incomplete or no response to this agent. In this study we investigated whether we could identify a mucosal gene panel to predict (non)response to IFX in CD. Mucosal biopsies were obtained during endoscopy from 37 patients with active CD (19 Crohn's colitis [CDc] and 18 Crohn's ileitis [CDi]) before and after first IFX treatment. Response was defined based on endoscopic and histologic findings. Total RNA was analyzed with Affymetrix Human Genome U133 Plus 2.0 Arrays. Quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to confirm microarray data. At baseline, significant gene expression differences were found between CDc and CDi. For predicting response in CDc, comparative analysis of CDc pretreatment expression profiles identified 697 significant probe sets between CDc responders (n = 12) and CDc nonresponders (n = 7). Class prediction analysis of CDc top 20 and top 5 significant genes allowed complete separation between CDc responders and CDc nonresponders. The CDc top 5 genes were TNFAIP6, S100A8, IL11, G0S2, and S100A9. Only one patient with CDi completely healed the ileal mucosa. Even using less stringent response criteria, we could not identify a predictive gene panel for IFX responsiveness in CDi. This study identified a 100% accurate predictive gene signature for (non)response to IFX in CDc, whereas no such a predictive gene set could be identified for CDi.

Comparative analysis of E. Coli associated with Inflammatory Bowel Disease across species

Escherichia coli have been associated with IBD in people, dogs and mice. The purpose of this study was to determine if E. coli associated with IBD across species share common features that are pathoadaptive for IBD. E. coli was isolated from the inflamed intestinal mucosa of people with Crohn's ileitis (ICD, 25 strains), dogs with granulomatous colitis (GC, 35 strains) or lymphoplasmacytic colitis (LP, 7strains), and mice with ileitis (2 strains). E. coli from the non-inflamed ileum of people (39 strains: 14 non-IBD (NIBD), 9 colonic Crohn's (CCD), 16 ulcerative colitis, UC), and the colon of healthy dogs (34 strains) were included as controls. CD-associated E. coli LF82, murine IBD inducing E. coli NC101 and DH5-a were used as reference strains. E. coli were examined for serotype (O:H), phylogroup (A, B1, B2, D), multi locus sequence type (MLST-7), virulence genes (ratA, PmtI, colV, hcp, lpfA-141, lpfA-154 kpsMII, fyuA, iss, malX, typeII, typeIV, afaBC, focG, ibeA, papC, sfaDE, cnf1, Stx1 and eae), and their ability to invade Caco-2 cells. A wide variety of serotypes were present in E. coli isolated from inflamed and uninflamed mucosa. O - was the most common among human (19%) and dog (24%) strains. O25 was the second most common human O type (9%), whereas O4 and O83 were detected in 16% and 9% of dog strains respectively. E. coli from ICD, GC and NIBD were distributed among all four phylogroups. B1 was most frequent in ICD (36%), GC (34%) and murine ileitis (100%), whereas A was most common in NIBD (36%), and B2 in healthy dogs (44%), but these differences were not significant. In contrast, E. coli isolated from the non-inflamed ileum of UC were predominantly B2 and D (63% B2 and 19% D, P= 0.001). Phylogenetic analysis of MLST-7 sequences revealed E. coli strains clustered by phylogroup independent of disease association or species of origin. It is noteworthy that a well-defined cluster of B2 strains (bootstrap value of 100) isolated from GC, ICD, UC and CCD all shared serotype O25:H4. Virulence genes segregated by phylogroup rather than disease association or species of origin: ratA, colV, kpsMII, fyuA, malX, focG, ibeA, papC, sfa DE and cnf1 were more prevalent among B2 strains, while presence of lpfA was associated with phylogroup B1 (p<0.001). There was no significant effect of disease association, species of origin or phylogroup on the ability of E. coli to invade Caco-2 cells. However, the presence of lpfA was associated with Caco-2 cell invasion by human E. coli strains (P<0.05). We conclude that no single cluster of E. coli is associated with IBD in people, dogs and mice. We found no evidence to link B2 and D strains to ileal CD, or GC in dogs. In contrast, we found that E. coli of phylogroup B1 were frequently isolated from ICD, GC and murine ileitis, and the B1 associated gene encoding long polar fimbriae (lpfA-154) was associated with increased invasion of caco-2 cells.

An Abscess in Crohnʼs Disease Identified by MR Enterography that Could Not be Diagnosed by CT Scan

Purpose: Crohn's disease can lead to penetrating complications in the gastrointestinal tract and result in abscess formation. Accurate identification of complications is important when selecting appropriate therapies. Methods: We report a patient with Crohn's disease with an abdominal abscess that was correctly identified with Magntetic Resonance Enterography (MRE), but not confirmed by CT scan. Results: A 27 year old man with known Crohn's disease was admitted to the hospital with abdominal pain, vomiting, and a fever. He was diagnosed with Crohn's ileitis one year prior to admission. At that time he reported abdominal pain and diarrhea and a CT scan revealed a markedly thickened, inflamed ileum with several enteroenteric and enterocolic fistulae and right hydronephrosis. A colonoscopy confirmed the diagnosis of Crohn's disease. His ureter was stented and he was treated with antibiotics and initiated on certolizumab. His symptoms resolved and he remained in remission for several months on certolizumab. He later developed recurrent abdominal pain with vomiting and a fever. He was admitted to the hospital and an MRE revealed dilated small bowel with a thickened, inflamed ileum and several fistulae. On initial review of the standard T2-weighted and enhanced fat-suppressed Tlweighted images, multiple fluid filled loops of small bowel were present in the right lower quadrant, and the confident distinction between intraenteric and extraenteric fluid was considered difficult by a MR trained radiologist with experience in MR enterography. However, diffusion-weighted images obtained as part of the MR enterography protocol clearly defined an extraluminal fluid collection with restricted diffusion, interpreted as abscess. Percutaneous drainage was attempted using CT-guidance to allow for an elective surgery at a later date. However, CT was unable to confidently delineate between the abscess and adjacent bowel loops, and the drainage procedure was aborted. The patient was taken for urgent surgery where the findings of the MRE were confirmed including a thickened, inflamed ileum with fistulae and a large abscess. The abscess was drained, the ileum was resected, and a temporary ileostomy was created. Conclusion: While traditional imaging with CT is often used to evaluate for complications of Crohn's disease, confident distinction between abscess and adjacent bowel loops can be difficult in the absence of excellent opacification of the bowel with enteric contrast material. Most CT enterography protocols utilize negative enteric contrast material to allow for better depiction of bowel wall enhancment. MRE with diffusion-weighted imaging provides an alternate imaging technique, without radiation, that may provide more accurate information in select cases. Disclosure: Dr Leyendecker: Speaker, Bracco Diagnostics; Speaker, Bayer Healthcare; Research grant, Bracco Diagnostics.

W1626 A NOD2-Mutant-Like Phenotype in Wild Type NOD2 Monocytes from Crohn's Disease Patients

E. coli strains that invade and replicate within cultured epithelial cells and macrophages are increasingly associated with Crohn's disease (CD). Knowledge of the bacterial factors conferring this pathogenic behavior is incomplete. We examined the ability of 47 ileal E. coli strains to invade caco-2 cells and replicate in J774 macrophages by their disease association (Crohn's ileitis, CD, 24 strains; normal ileum, NI, 23 strains), phylogroup (A, B1, B2, D), and virulence gene content (determined by microarray, subtractive hybridization and PCR). There was no effect (P>0.05) of disease association on the degree of invasion (median, log10 cfu/ml: CD 2.86, NI 2.6) or replication (median, %: CD 221, NI 315). The prevalence of E. coli strains with an adherent and invasive (AIEC) pathotype was similar in CD (13 of 23 strains) and NI (9 of 22 strains) (P>0.05). There was no effect of E.coli phylogroup on invasion or persistence (P>0.05). A screen for genes encoding virulence in E. coli (microarray of 22 E.coli strains: 11 CD, 11 NI), and genes present in AIEC but absent in commensal DH5 (subtractive hybridization of one AIEC strain from each phylogroup), identified ratA. Pmt,I colV, hcp, lpfA-141, lpfA-154 kpsMI,I fyuA, iss, malX, typeII, typeIV, afaBC, focG, ibeA, papC, sfaDE, cnf1, Stx1 and eae as putative virulence determinants. The presence or absence of these genes in 47 ileal E. coli strains was determined by PCR and related to invasion and persistence. The presence of lpfA-154, a gene encoding long polar fimbriae, was associated with increased invasion of caco-2 cells (P=0.02: median, log10 cfu/ml, lpfA+ 3.50, lpfA2.05). LpfA-154 was present in 15 of 22 (68%) AIEC strains. It's presence in ileal E. coli was influenced by phylogroup (present in 93% B1, 50% D and 15% A, but absent from B2 strains), but not by disease association (50% of CD vs. 33% of NI strains). DNA sequence analysis of lpfA-154, cloned from a B1 CD isolate, showed highest homology to E. coli E24377A (an ETEC strain) and Shigella boydii CDC3083-94. We conclude that a gene encoding long polar fimbriae (lpfA-154) is associated with increased invasion of caco-2 cells by ileal E. coli, and is common in E. coli with an AIEC pathotype. LpfA is involved in the adhesion of Salmonella to Peyer's patches, and may influence host-E. coli interactions in a CD susceptible individual.

W1625 The Ability of Crohn's Associated E. coli to Invade CACO-2 Cells Is Related to the Presence of a Gene Encoding Long Polar Fimbriae

E. coli strains that invade and replicate within cultured epithelial cells and macrophages are increasingly associated with Crohn's disease (CD). Knowledge of the bacterial factors conferring this pathogenic behavior is incomplete. We examined the ability of 47 ileal E. coli strains to invade caco-2 cells and replicate in J774 macrophages by their disease association (Crohn's ileitis, CD, 24 strains; normal ileum, NI, 23 strains), phylogroup (A, B1, B2, D), and virulence gene content (determined by microarray, subtractive hybridization and PCR). There was no effect (P>0.05) of disease association on the degree of invasion (median, log10 cfu/ml: CD 2.86, NI 2.6) or replication (median, %: CD 221, NI 315). The prevalence of E. coli strains with an adherent and invasive (AIEC) pathotype was similar in CD (13 of 23 strains) and NI (9 of 22 strains) (P>0.05). There was no effect of E.coli phylogroup on invasion or persistence (P>0.05). A screen for genes encoding virulence in E. coli (microarray of 22 E.coli strains: 11 CD, 11 NI), and genes present in AIEC but absent in commensal DH5 (subtractive hybridization of one AIEC strain from each phylogroup), identified ratA. Pmt,I colV, hcp, lpfA-141, lpfA-154 kpsMI,I fyuA, iss, malX, typeII, typeIV, afaBC, focG, ibeA, papC, sfaDE, cnf1, Stx1 and eae as putative virulence determinants. The presence or absence of these genes in 47 ileal E. coli strains was determined by PCR and related to invasion and persistence. The presence of lpfA-154, a gene encoding long polar fimbriae, was associated with increased invasion of caco-2 cells (P=0.02: median, log10 cfu/ml, lpfA+ 3.50, lpfA2.05). LpfA-154 was present in 15 of 22 (68%) AIEC strains. It's presence in ileal E. coli was influenced by phylogroup (present in 93% B1, 50% D and 15% A, but absent from B2 strains), but not by disease association (50% of CD vs. 33% of NI strains). DNA sequence analysis of lpfA-154, cloned from a B1 CD isolate, showed highest homology to E. coli E24377A (an ETEC strain) and Shigella boydii CDC3083-94. We conclude that a gene encoding long polar fimbriae (lpfA-154) is associated with increased invasion of caco-2 cells by ileal E. coli, and is common in E. coli with an AIEC pathotype. LpfA is involved in the adhesion of Salmonella to Peyer's patches, and may influence host-E. coli interactions in a CD susceptible individual.

S1684 Human Beta Defensin 3 Protein Accumulation Is Increased and Redirected in Crohn's Ileitis In Vivo and Modulates T Cell Responses In Vitro

S1684 Human Beta Defensin 3 Protein Accumulation Is Increased and Redirected in Crohn's Ileitis In Vivo and Modulates T Cell Responses In Vitro

TNF driven activation of invariant NKT cells favours regulation of combined gut and joint inflammation. (134.22)

Abstract Invariant natural killer T (iNKT) cells are a subset of glycolipid reactive T cells, implicated in the protection against microbial pathogens and immune regulation. While the pathways leading to iNKT cell activation in the context of infectious diseases have been uncovered, much less is known how iNKT cells become activated in the context of chronic inflammatory diseases. Here, we unveil a novel mode of iNKT cell activation which occurs during chronic TNF driven inflammation through generation of inflammatory dendritic cells. This in turn, leads to a spontaneous activation of iNKT cells by promoting CD1d mediated presentation of endogenous glycolipids. This mode of activation is capable of attenuating combined Crohn's like ileitis and joint inflammation occurring in TNFΔARE mice, and thus may represent a natural counter regulatory mechanism to dampen TNF driven inflammation.

Is Crohn’s Disease Associated With Appendectomy or Appendicitis?

To the Editor: In Kaplan and colleagues', of 16 case–control studies and 3 cohort studies entitled risk of developing Crohn's disease after an appendectomy: a meta-analysis (1), which appears to be strongly influenced by their recent population-based cohort study including 709,353 appendectomy patients without Crohn's disease (CD) and 1,655 appendectomy patients with CD (2), the authors reveal that the risk of CD was significantly increased during the first year following an appendectomy but decreased thereafter and reached baseline levels by 5 years after the operation. The authors mention that CD may rarely involve the appendix and precipitate appendicitis, referring to a study (3), and they speculate that the early increased risk of CD associated with appendectomy is probably attributable to a diagnostic bias. In other words, patients with incipient CD are more likely to undergo negative appendectomy because of right lower quadrant abdominal pain caused by Crohn's ileitis.

Increased expression of protease-activated receptor-2 in mucosal mast cells in Crohn's ileitis

Background and aims Activation of protease-activated receptor-2 (PAR-2) may stimulate various events of importance in inflammatory processes, including release of inflammatory mast cell mediators. PAR-2 is frequently up-regulated during inflammatory conditions, but it is not known if the expression is altered in Crohn's disease. The aim of the present study was to investigate the ileal mucosal PAR-2 expression in Crohn's ileitis, with particular emphasis on the expression in ileal mucosal mast cells. Methods Surgical specimens from the distal ileum were collected from patients with Crohn's ileitis and patients with colonic cancer as controls. The overall expression of PAR-2 was investigated by Western blot, and the presence of PAR-2 expressing mucosal mast cells by immunohistochemistry and cell counting. The effect of tumor necrosis factor-α (TNF-α) on the PAR-2 expression in a human mast cell line (HMC-1) was investigated by RT-PCR and immunocytochemistry. Results In Crohn's specimens, the fraction of PAR-2-expressing mucosal mast cells was increased about 2.5 times ( P < 0.001; n = 14) compared with specimens from control patients ( n = 6). No difference was found between inflamed ( n = 6) and uninflamed Crohn's specimens ( P > 0.05; n = 8). Exposure to TNF-α for 48 h up-regulated PAR-2 mRNA and protein expression in the HMC-1 cell line. Conclusion PAR-2 is up-regulated on ileal mucosal mast cells in Crohn's ileitis, possibly due to the action of inflammatory cytokines, such as TNF-α. This may contribute to perpetuating the inflammatory process in the intestinal mucosa in Crohn's ileitis.

Molecular diversity of Escherichia coli in the human gut: New ecological evidence supporting the role of adherent-invasive E. coli (AIEC) in Crohnʼs disease

Escherichia coli, particularly the adherent-invasive E. coli (AIEC) pathovar, has been increasingly implicated in the ethiopathogenesis of Crohn's disease (CD). We describe the richness, abundance, diversity, and pathogenic features of E. coli and AIEC strains that colonize the intestinal mucosa. Approximately 100 E. coli colonies per biopsy from 20 CD patients (18 biopsies from colon and 23 from ileum) and 28 healthy controls (C) (25, colon; 27, ileum) were isolated. Repetitive extragenic palindrome-polymerase chain reaction (Rep-PCR) and pulsed field gel electrophoresis (PFGE) were used to analyze the clonality of isolates. For AIEC identification, adhesion and invasion assays were performed over Intestine-407 cells, and the capacity to survive and replicate intracellularly was determined over macrophages J774. The serotypes, phylotypes, and genotypes (19 virulence genes) of strains were also investigated. Mucosa-associated E. coli richness (E. coli subtypes/patient: C = 2.0 +/- 1.0; CD = 2.1 +/- 1.3) and diversity (Shannon Index: H'(C): 2.1 +/- 0.6; H'(CD): 2.5 +/- 0.8) were similar between CD and C, but higher E. coli counts were characteristic of CD patients (P = 0.010), particularly those with Crohn's ileitis (P = 0.001). Host-specific pulsotypes shared virulence features of ExPEC at similar frequencies between CD and C, except for iucD, which was more prevalent in E. coli from controls (C: 75%, CD: 40%, P = 0.027). In contrast, greater AIEC prevalence (% subjects with AIEC: CD = 51.9%; C = 16.7%; P = 0.003), abundance (% AIEC/E. coli: CD = 3.8 +/- 5.0%; C = 1.5 +/- 3.8%; P = 0.039), and richness (number of AIEC subtypes: CD = 0.8 +/- 1.4; C = 0.2 +/- 0.4; P = 0.015) of E. coli strains belonging to the AIEC pathovar was observed for CD patients. AIEC subtypes showed a high variability of seropathotypes and pulsotypes, although the B2 phylogroup was the most prevalent (AIEC: 64%, non-AIEC: 38%, P = 0.044). New data about ecological parameters of AIEC reinforces the implication of AIEC in CD.

Perforated Meckel's diverticulitis complicating active Crohn's ileitis: a case report

IntroductionIn Crohn's disease, the extension of active terminal ileitis into a Meckel's diverticulum is possible, but usually has no impact on clinical decision-making. We describe an original surgical approach in a young woman presenting with a combination of perforated Meckel's diverticulitis and active Crohn's ileitis.Case presentationWe report the case of a 22-year-old woman with Crohn's disease, who was admitted for abdominal pain, fever and diarrhoea. CT scan demonstrated active inflammation of the terminal ileum, as well as a fluid collection in the right iliac fossa, suggesting intestinal perforation. Laparoscopy was performed and revealed, in addition to extensive ileitis, a 3 × 3 cm abscess in connection with perforated Meckel's diverticulitis. It was therefore possible to avoid ileocaecal resection by only performing Meckel's diverticulectomy; pathological examination of the surgical specimen revealed the presence of transmural inflammation with granulomas and perforation of the diverticulum at its extremity.ConclusionCrohn's disease of the ileum may be responsible for Meckel's diverticulitis and cause perforation which, in this case, proved to be a blessing in disguise and spared the patient an extensive small bowel resection.

Cytomegalovirus enteritis mimicking Crohn’s disease in a lupus nephritis patient: A case report

Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract has been reported in both immunocompetent and, more frequently, in immunocompromised patients. We describe a case of a 19-year-old male who developed CMV infection of the terminal ileum while receiving immunosuppression for lupus nephritis. This was a distinctly unusual site of infection which clinically mimicked Crohn's ileitis. We note that reports of terminal ileal CMV infection have been infrequent. Despite a complicated hospital course, ganciclovir therapy was effective in resolving his symptoms and normalizing his ileal mucosa. This report highlights the importance of accurate histological diagnosis and clinical follow-up of lupus patients with GI symptoms undergoing intense immunosuppression.

Sterile Seroma after Surgical Drainage of Purulent Psoas Muscle Abscess in Crohnʼs Disease

Purpose: Introduction: Psoas muscle abscess can occur as a purulent complication of Crohn's Ileitis. We present a case of a sterile seroma of the psoas muscle occurring after surgical drainage of a chronic purulent psoas muscle abscess in Crohn's disease. Case: A 32 years old female underwent Ileal resection for Crohn's Ileitis and drainage of a chronic right psoas muscle abscess. Her psoas muscle abscess had been present for 3 years. She had previously refused surgical resection and drainage of her abscess and was therefore treated with prolonged course of antibiotics. She did not require immunosuppressant, immunomodulators, steroids or biologics postoperatively. 3 years after the resection she presented with right lower quadrant pain and a positive psoas sign. She was afebrile and had a normal white cell count. CT scan showed a 15 cm x 6 cm fluid collection in right psoas muscle at the site of her previous psoas muscle abscess. Colonoscopy with Ileoscopy showed no recurrence of Crohn's disease. Small bowel barium x-ray was negative for ileo-psoas fistula. CT guided aspiration showed a sterile fluid collection, with no organisms and sparse white cells. Multiple cultures were negative. She was treated with a prolonged course of percutaneous drainage and ultimately tetracycline injection to sclerose the remaining sinus tract. There has been no recurrence of her sterile seroma in 3 years. Discussion: Psoas muscle abscess is a known purulent complication of Crohn's ileitis. We describe a sterile seroma of the psoas muscle occurring 3 years after surgical drainage of a chronic purulent psoas muscle abscess. We speculate that the seroma developed in the dead space remaining in the psoas muscle after drainage of the chronic walled off abscess. Her sterile seroma was initially concerning for a recurrent purulent psoas muscle abscess. Gastroenterologists should be aware of the possible development of sterile seromas in such cases.

A Case of Adalimumab-Induced Psoriasis in Crohnʼs Disease with Literature Review

Results: A 29 y/o WF with 4 year history of Crohn's ileitis was treated with adalimumab for refractory disease. There was no past or family history of psoriasis. After 6 weeks of therapy, she developed a rash on her feet and palms. A skin biopsy demonstrated pustular psoriasis. Adalimumab was withdrawn and methotrexate begun with topical anti-psoriatic therapy. Tumor necrosis factor (TNF) inhibitors have been shown to paradoxically cause psoriasis (1). Cases of infliximab-induced psoriasis have also been described in patients with Crohn's disease (2). The mechanism by this class effect is poorly understood. It has been suggested that “psoriasis” may actually represent a form of cutaneous bacterial infection (keratoderma blenorrhagicum) or that the rheumatoid arthritis patients who developed psoriasis may have been misdiagnosed and actually had psoriatic arthritis (3). Harrison et al. (4) found an increased incidence of psoriasis in patients with rheumatoid arthritis treated with TNF inhibitors (1.04/1000 person years 95% CI 0.67/1.54) as compared to those treated with disease modifying anti-rheumatic drugs (0/1000 person years upper 97.5% CI 0.71). They also found a significantly higher incidence in adalimumab treated patients as opposed to those treated with infliximab and entanercept. Conclusion: TNF-induced psoriasis is a rare side effect which has been documented with entanercept, infliximab, and adalimumab. Defining this ill-defined mechanism may help us better understand the pathophysiology of the immune system and modify treatments in immune mediated diseases. 1. Matthews C, Rogers S, FitzGerald O. Development of new-onset psoriasis while on anti-TNF α treatment. Ann Rheum Dis 2006;65:1529–1530. 2. Sladden MJ, Clarke PJ, Wettenhall J. Infliximab-induced palmoplantar pustulosis in a patient with crohn's disease. Arch Dermatol 2007;143:1449. 3. Ritchlin C, Tausk F. A medical conundrum: onset of psoriasis in patients receiving anti-tumour necrosis factor agents. Ann Rheum Dis 2006;65:1541–1544. 4. Harrison MJ, Dixon WG, Watson KO, King Y, Graves R, Hyrich KC, et al. Rates of new-onset psoriasis in patients with rheumatoid arthritis receiving anti-TNF {alpha} therapy. Results from the british society for rheumatology Biologics register. Ann Rheum Dis 2008, April 2.

Expression of T cell receptors alpha beta and gamma delta in the ileal mucosa of patients with Crohn's disease and with spondylarthropathy.

The expression of the alpha beta and gamma delta heterodimer of the T cell receptor (TCR) was studied in normal human ileal mucosa or in ileal biopsies featuring Crohn's disease or acute and chronic spondylarthropathy-related gut inflammation. With an immunohistochemical technique we demonstrated that the increase of mucosal lymphocytes per mm mucosa in Crohn's disease and spondylarthropathy-related ileitis is exclusively due to expansion of the alpha beta + T cell compartment. In Crohn's disease and chronic ileitis observed in some spondylarthropathy patients the alpha beta + T cells were increased amongst intraepithelial lymphocytes (IEL). The lamina propria lymphocytes (LPL) were augmented in all studied inflammatory conditions. The gamma delta + T cells showed no changes in IEL or LPL and their proportions were not altered. They were evenly dispersed throughout the ileal mucosa and did not seem to participate in the inflammatory process. This study confirms that gamma delta T cells are a distinct subset in the intestinal mucosa. The increase in alpha beta + T cells suggests augmented mucosal antigen handling and involvement of the major histocompatibility complex in the pathogenesis of spondylarthropathy-related gut inflammation and Crohn's disease.

Altered expression of cell adhesion molecules in uninvolved gut in inflammatory bowel disease.

Adhesion of circulating cells to vascular endothelium occurs in the early phase of inflammation, and is mediated by specific cell adhesion molecules. Many such adhesion molecules are increased in inflamed regions of ulcerative colitis (UC) and Crohn's disease (CD) but there is limited knowledge of their expression in the uninvolved gut, adjacent to inflammation. We investigated immunohistochemically the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) on resected specimens taken at a distance of 2-4 cm from the inflamed area and without histological signs of inflammation. Compared with normal gut, we found (i) a significant increase of PECAM-1-positive vessels in the mucosa of uninvolved UC (149.0 +/- 24.1 vessels/mm2 (mean +/- s.d.); normal colon = 123.1 +/- 21.6; P = 0.004); (ii) a significant decrease of ICAM-1-positive vessels in uninvolved CD (111.9 +/- 22.6 vessels/mm2; normal ileum = 136.9 +/- 27.6; P = 0.04); and (iii) a moderate but statistically insignificant increase of LFA-1-positive cells in the mucosa of uninvolved UC and Crohn's ileitis. This altered expression of cell adhesion molecules may contribute to the early lesion in inflammatory bowel disease and provide new therapeutic opportunities.

Bovine glycomacropeptide ameliorates experimental rat ileitis by mechanisms involving downregulation of interleukin 17

Bovine glycomacropeptide (BGMP) is an inexpensive, non-toxic milk peptide with anti-inflammatory effects in rat experimental colitis but its mechanism of action is unclear. It is also unknown whether BGMP can ameliorate inflammation in proximal regions of the intestine. Our aim was therefore two-fold: first, to determine the anti-inflammatory activity of BGMP in the ileum; second, to characterise its mechanism of action. We used a model of ileitis induced by trinitrobenzenesulphonic acid in rats. Rats were treated orally with BGMP and its efficacy compared with that of oral 5-aminosalicylic acid or vehicle, starting 2 days before ileitis induction. BGMP pretreatment (500 mg kg(-1) day(-1)) resulted in marked reduction of inflammatory injury, as assessed by lower extension of necrosis and damage score, myeloperoxidase, alkaline phosphatase, inducible nitric oxide synthase, interleukin 1beta, tumour necrosis factor and interleukin 17. These effects were generally comparable to those of 5-aminosalicylic acid (200 mg kg(-1) day(-1)). Neither compound affected the production of interferon gamma, tumour necrosis factor and interleukin 2 by mesenteric lymph node cells isolated from animals with ileitis. The expression of Foxp3 was increased in ileitis and not reduced significantly by BGMP or aminosalicylate treatment. These results demonstrate that BGMP has anti-inflammatory activity in the ileum with similar efficacy to 5-aminosalicylic acid. The mechanism of action may involve Th17 and regulatory T cells and perhaps macrophages but probably not Th1 lymphocytes. Patients with Crohn's ileitis may benefit from treatment with BGMP.

This Month in Gastroenterology

This Month in Gastroenterology