Long-standing Crohn's Disease Research Articles

Cutaneous Rosai–Dorfman Disease of the Forearm: Case Report

Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease (RDD), is a rare non-neoplastic pathologic condition that frequently pursues a prolonged clinical course marked by exacerbations and remissions. Cutaneous RDD is even less common than cases involving lymph nodes. We present the case of a patient with long-standing Crohn's disease who developed cutaneous RDD in the forearm.

Dietary intakes and body composition in adult patients with long-standing Crohn's disease currently in remission

Dietary intakes and body composition in adult patients with long-standing Crohn's disease currently in remission

Increased uptake of non‐pathogenic E. coli via the follicle‐associated epithelium in longstanding ileal Crohn's disease

In Crohn's disease (CD), inflammation is driven by luminal commensal micro-organisms; however, mechanisms of early phases of inflammation need further clarification. The earliest observable lesions of recurrent CD are microscopic erosions at the specialized follicle-associated epithelium (FAE), which lines the Peyer's patches. Therefore, our aim was to investigate the mucosal barrier to non-pathogenic bacteria in FAE of CD. The FAE of macroscopically normal ileum from patients with longstanding CD, ulcerative colitis, and controls was studied in Ussing chambers regarding electrophysiology and permeability to 51Cr-EDTA, horseradish peroxidase, and non-pathogenic E. coli strains. Transepithelial passage routes and uptake into dendritic cells were studied by confocal and electron microscopy. FAE of CD showed increased numbers of adherent bacteria, after E. coli exposure in Ussing chambers, as well as spontaneously in non-exposed archival surgical tissues. Further, we found increased uptake of fluorescent E. coli K-12 and HB101 across FAE of CD, but not in ulcerative colitis. Microscopy demonstrated intercellular and transcellular uptake of E. coli in CD, but only transcellular in controls. FAE exposed to E. coli demonstrated changes in conductance and 51Cr-EDTA permeability, suggesting that bacteria affected the paracellular pathway in CD mucosa. Following bacterial uptake, CD mucosa also demonstrated an increased percentage of E. coli co-localizing with dendritic cells, and augmented tissue release of TNF-alpha. Our data present novel insights into the pathophysiology of CD by demonstrating a previously unrecognized defect of FAE barrier to bacteria in ileal CD, leading to increased load of commensal bacteria to the inductive sites of mucosal immunity.

Active Crohn Disease and Hypercalcemia Treated With Infliximab: Case Report and Literature Review

To report a case of 1,25-dihydroxyvitamin D-mediated hypercalcemia caused by active Crohn disease that improved with infliximab therapy. We present the clinical and laboratory findings and describe the clinical course of a patient who had hypercalcemia during Crohn disease exacerbations. The literature is reviewed regarding 1,25-dihydroxyvitamin D production in Crohn disease, and the 3 cases of hypercalcemia in individuals with Crohn disease reported in the literature are described. A 50-year-old man with long-standing Crohn disease treated with multiple bowel resections presented for take-down ileostomy. He was hypercalcemic and had suppressed parathyroid hormone and parathyroid hormone-related peptide levels. Histopathology of the resected ileostomy site and adjacent small bowel indicated active Crohn disease. Hypercalcemia promptly resolved after a few days of treatment with intravenous glucocorticoids. One month later, hypercalcemia recurred in the presence of an inappropriately high 1,25-dihydroxyvitamin D level and increased urinary calcium and serum angiotensin-converting enzyme levels. The serum and urinary calcium levels became normal with infliximab therapy. Three previous reports of hypercalcemia caused by active Crohn disease describe effective treatment with glucocorticoids. This is the first report of successful response to infliximab in this setting. Hypercalcemia mediated by 1,25-dihydroxyvitamin D in the setting of Crohn disease may respond to glucocorticoid-sparing immunomodulators.

Myocutaneous flaps and proctocolectomy in severe perianal Crohn’s disease—a single stage procedure

Complex perianal wounds can be extremely difficult to treat and primary closure of these defects can be a challenge even for experienced surgeons. So far, myocutaneous flaps for wound closure after removal of malignant tumors are a well-accepted option, but there are only a few reports focusing on the primary closure of the perineal wound after proctocolectomy for Crohn's disease. We describe our experience with wide excision of the diseased perineum using a combined abdominoperineal two-team approach. We performed proctocolectomy with permanent ileostomy in five patients with longstanding extensive Crohn's disease. All five patients had fistulizing perineal Crohn's disease combined with Crohn's colitis. Each patient received at least one flap for primary wound closure, either a rectus abdominis myocutaneous flap or a gracilis flap. Indication for surgical intervention included anal or bowel stenosis, septic condition, fecal incontinence, or a combination of these features. One patient had a simultaneous adenocarcinoma of the sigmoid colon. Five patients underwent a total of seven flaps. Three months after surgery, complete healing was achieved in all patients; one patient suffered recurrence in the region of his right thigh. Mean follow up was 19.6 months (range-12-43 months). Myocutaneous flaps are a promising therapeutic option in patients with chronic perianal disease. With the transposition of well-vascularized tissue into the perineal defect, complete healing and control of sepsis can be achieved in the majority of patients.

An unusual case of Crohn's disease with unresponsive pleural exudates. Is Crohn's disease finally a systemic immunological disorder?

Crohn's disease has been infrequently associated with various respiratory manifestations. Reports of pleural effusions in Crohn's disease are even sparser, but differential diagnosis is rich, with causes either associated with the disease or being independent. Processes directly or indirectly related to therapy, entities overlapping with Crohn's disease in pathogenesis and common causes of effusions should all be considered, under the guidance of laboratory testing and imaging. We report here an unusual case of bilateral pleural effusions unresponsive so far to medical therapy, in a patient with long-standing Crohn's disease and several features of autoimmunity. A short review of the literature is presented, the differential diagnosis is outlined and the systemic immunological profile of Crohn's disease is discussed.

Q Fever Community-Acquired Pneumonia in a Patient With Crohn’s Disease on Immunosuppressive Therapy

Community-acquired pneumonia (CAP) may be caused by typical or atypical pathogens. The three most common zoonotic atypical pathogens are Chlamydophila psittaci (psittacosis), Francisella tularensis (tularemia), and Coxiella burnetii (Q fever). Atypical CAPs are suggested by a distinctive pattern of extrapulmonary organ involvement. Zoonotic CAP may be differentiated from nonzoonotic CAP (Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionnaire's disease) by a recent zoonotic vector contact history. Zoonotic atypical CAP occurs sporadically, but not randomly, and require close association with the appropriate zoonotic vector to transmit the infection. CAP accompanied by the extrapulmonary finding of splenomegaly in a normal host limits differential diagnostic possibilities to Q fever and psittacosis. Splenomegaly does not occur with other typical or atypical CAP. Another common extrapulmonary finding occurs with some atypical pneumonias, that is, Q fever, psittacosis, and Legionnaire's disease is early mild/transient elevations of serum transaminases indicative of (hepatic) extrapulmonary organ involvement. The case presented is a middle-aged man with longstanding Crohn's disease who was further immunosuppressed by chronic prednisone therapy. The patient presented with CAP and extrapulmonary findings, that is, splenomegaly and increased serum transaminases. He denied recent contact with birds or animals. Because Crohn's disease and Q fever CAP may be accompanied by splenomegaly, the cause of his splenomegaly was a diagnostic dilemma. The patient was treated with levofloxacin. Serologic tests for atypical pathogens (Q fever, psittacosis, Legionnaire's disease, C. pneumoniae, and M. pneumoniae) were ordered. Enzyme-linked immunosorbent assay serology for Q fever was positive with elevated acute immunoglobulin-M (phase II) titers. Re-questioning of the patient revealed a recent exposure to a neighbor's parturient cat, providing the necessary zoonotic vector contact history for Q fever. The patient responded to levofloxacin, which resulted in resolution of the patient's symptoms, right lower lobe pneumonia, and splenomegaly. Because a prior abdominal computed tomography scan indicated no splenomegaly and his splenomegaly resolved with antimicrobial therapy, the splenomegaly was related to Q fever CAP.

Akute Pankreatitis und choledochobulbäre Fistel - eine seltene Komplikation bei Morbus Crohn

A 53-year-old man with long-standing Crohn's disease presented with recurrent abdominal pain and vomiting; lipase levels were elevated. At admission ultrasound demonstrated a swollen head of the pancreas, dilated pancreatic and intrahepatic bile ducts and peripancreatic fluid. At upper gastrointestinal endoscopy a 10 mm bleeding ulcer was identified, which histologically proved to be epitheloid cell-containing granulomas. A fistula connecting to the hepatocholedochal duct was identified at the floor of the ulcer. Helicobacter pylori was not demonstrated. After sphincterotomy of the papilla of Vater concrements were extracted and a stent was implanted into the common bile duct. Ultimately a total of five stents were consecutively implanted via the major papilla, closing the fistula. After three years all stents were removed and pancreatitis did not recur. The differential diagnosis of abdominal pain in patients with Crohn's disease is often difficult and should include fistulas of the upper gastrointestinal tract which may be treated endoscopically.

Nutritional supplementation with N-3 fatty acids and antioxidants in patients with Crohn's disease in remission: Effects on antioxidant status and fatty acid profile

In patients with Crohn's disease (CD), malnutrition is frequently observed and is generally accepted to be an important issue. The aim of this study was to investigate the effects of 3 months of supplementation with a liquid formula containing either antioxidants (AO) or n-3 fatty acids plus AO on the antioxidant status and fatty acid profile of plasma phospholipids and adipose tissue, respectively, in patients with long-standing CD currently in remission. In a randomized, double-blind placebo-controlled study, CD patients received either placebo, AO, or n-3 fatty acids plus AO for 3 months in addition to their regular diet. In all, 25/37 CD patients completed the study. AO status was assessed by blood biochemical parameters. A statistical per-protocol analysis was performed. Serum concentrations of selenium, vitamin C, and vitamin E, the activity of superoxide dismutase and total antioxidant status were significantly (p < 0.05) increased after AO supplementation. Furthermore, compared with controls, serum concentrations of β-carotene, selenium, and vitamin C and the activity of glutathione peroxidase (GPx) were significantly (p < 0.05) lower before supplemention; however, after AO supplementation these levels were not significantly different from controls (except for GPx). N-3 fatty acids plus AO supplementation significantly (p < 0.05) decreased the proportion of arachidonic acid, and increased the proportion of eicosapentanoic acid and docosahexanoic acid in both plasma phospholipids and adipose tissue. Supplementation with antioxidants improved antioxidant status in patients with CD in remission. In addition, supplementation with n-3 fatty acids plus antioxidants significantly changed the eicosanoid precursor profile, which may lead to the production of eicosanoids with attenuated proinflammatory activity. This study indicates that an immunomodulating formula containing n-3 fatty acids and/or AO may have the potential to play a role in the treatment of CD.

Primary and metastatic perineal adenocarcinoma: aetiology and management

Objective: Adenocarcinoma of the perineum is unusual. This series of nine patients highlights the challenges of management.Results: Six male and three female patients aged 29–85 years presented to a single unit, five were T4 and three were T3 tumours. Pain and swelling in the perineum and perianal tissues remote from the anal canal occurred in six patients whilst three patients had chronic perineal fistulae, two of whom had longstanding Crohn's disease. In eight patients a primary adenocarcinoma was identified. One patient with fistulating perineal Crohn's disease had multifocal mucinous adenocarcinoma without evidence of a gastrointestinal primary. Radical multimodality treatment including long course chemo‐radiotherapy (CRT) and radical abdominoperineal resection was used in seven patients, four of whom required perineal reconstruction with myocutaneous flaps. Two patients had CRT without surgery, (one unresectable and one refused surgery). Negative resection margins were achieved in six out of seven patients. All seven patients undergoing resection were well palliated with relief of pain and currently four patients remain free of disease with only one patient developing further perineal disease remote from the surgical resection site.Conclusion: Perineal adenocarcinoma may be associated with an occult colorectal primary or chronic fistulae. Lower GI endoscopy and biopsies of nonhealing mucous producing fistulae should be undertaken to establish the diagnosis. Radical surgery often achieves local disease control.

How Adherent to Treatment With Azathioprine Are Patients With Crohnʼs Disease in Long-term Remission?

Patients with longstanding quiescent Crohn's disease on azathioprine usually maintain an excellent quality of life but are also concerned about long-term safety. This may affect adherence to treatment. The aim of the present study was to assess the adherence to azathioprine in a cohort of patients with Crohn's disease in long-term remission. Thirty patients with Crohn's disease in remission on azathioprine for > or =48 months were enrolled in the study. All were asked to record the number of azathioprine tablets they consumed daily. Notes were kept every other month for 6 months. Adherence was defined as consumption of > or =80% of medication. Most patients (18/28, 74.3%) were not adherent to treatment. The mean (+/-SD) daily dose of azathioprine in adherent and nonadherent patients was 145 +/- 45 mg and 102 +/- 20 mg, respectively. However, there were no significant differences between the 2 groups in the mean IBDQ score and mean Crohn's Disease Activity Index (CDAI) score, both throughout the entire study and at each time point of the study. Male gender, single status, and consumption of >5 concomitant medications were associated with nonadherence. Most patients with Crohn's disease in longstanding remission had low self-reported adherence to azathioprine. Both male gender and single status were associated with nonadherence to azathioprine, whereas disease factors were not related to self-reported adherence. Patients considered nonadherent to treatment maintained disease remission and a quality of life similar to patients who were adherent to treatment.

Primary Coloduodenal Fistula in a Patient with Crohn's Disease

The posterior surface of the proximal transverse colon and the anterior surface of the descending duodenum are intimately related, predisposing to fistulization in this area. We herein describe a rare case of benign duodenocolic fistula secondary to Crohn's disease. We emphasize the clinical presentation with fecaloid vomiting, as well as the establishment of the diagnosis by endoscopy, which are both extremely rare. The presence of a colonic stricture supports the hypothesis that the disease started in the colon rather than in the duodenum, and mandates surgical rather than medical therapy. Our case illustrates the possibility of coloduodenal fistula in patients with long-standing Crohn's disease, which should be considered in patients presenting with fecaloid vomiting, abdominal pain, and weight loss.

Caecal cancer associated with longstanding Crohn's disease

in patients with ulcerative colitis; however, the risk of intestinal cancer in Crohn’s disease was uncertain until two recent meta-analyses suggested an association between Crohn’s disease and intestinal cancer. 2,3 Notably, there appears to be an increasing number of patients at risk of developing intestinal cancer because prevalence and incidence rates of Crohn’s disease in the general population have been increasing. Therefore, we should consider long-standing Crohn’s disease as a high-risk condition for development of intestinal cancer. However, newer therapies for Crohn’s disease, such as biological agents, may aff ect the natural history of the disease. Future prospective studies, taking new treatment strategies into account, will provide information about the risk of intestinal cancer in Crohn’s disease. In our case, the patient complained of bloody stools—haematochezia is rare as a clinical sign in right-sided Crohn’s disease and might be a sign of possible cancer, which should justify immediate endoscopic examination. Although mesalazine has cancer-preventive eff ects in ulcerative colitis, its benefi ts in our patient remain un– clear. 4,5 Further investigations are needed to assess its effi cacy in long-standing Crohn’s disease. Moreover, immunohistochemistry for products of the p53 tumour suppression gene might be helpful in diagnosing intestinal cancer associated with Crohn’s disease. There are many reports on an association between the p53 tumour suppressor gene and colorectal cancer in ulcerative colitis, but not in Crohn’s disease. Our case suggests that, as in colorectal cancer associated with ulcerative colitis, mutations of the p53 tumour suppressor gene might have an important role in the development of intestinal cancer in cases of longstanding Crohn’s disease.

Primary and metastatic perineal adenocarcinoma: aetiology and management

Objective: Adenocarcinoma of the perineum is unusual. This series of nine patients highlights the challenges of management. Method: Six male and three female patients aged 29–85 years presented to a single unit, five were T4 and three were T3 tumours. Results: Pain and swelling in the perineum and perianal tissues remote from the anal canal occurred in six patients whilst three patients had chronic perineal fistulae, two of whom had longstanding Crohn's disease. In eight patients a primary adenocarcinoma was identified. One patient with fistulating perineal Crohn's disease had multifocal mucinous adenocarcinoma without evidence of a gastrointestinal primary. Radical multimodality treatment including long course chemo-radiotherapy (CRT) and radical abdominoperineal resection was used in seven patients, four of whom required perineal reconstruction with myocutaneous flaps. Two patients had CRT without surgery (one unresectable and one refused surgery). Negative resection margins were achieved in six of seven patients. All seven patients undergoing resection were well palliated with relief of pain and currently four patients remain free of disease with only one patient developing further perineal disease remote from the surgical resection site. Conclusion: Perineal adenocarcinoma may be associated with an occult colorectal primary or chronic fistulae. Lower GI endoscopy and biopsies of non-healing mucous producing fistulae should be undertaken to establish the diagnosis. Radical surgery often achieves local disease control.

Life-Threatening Venous Thromboses in Two Pediatric Patients Receiving Infliximab for Treatement of Inflammatory Bowel Disease

Infliximab therapy is an effective treatment in many patients with IBD. A variety of thrombotic complications have been reported in patients receiving this therapy including pulmonary embolism, deep venous thrombosis of both the upper and lower extremities, Budd-Chiari Syndrome (BCS), and retinal vein thrombosis. We report two cases of thrombotic complications in pediatric patients with inflammatory bowel disease receiving infliximab therapy. The first patient, a 15 year old Caucasian female, was hospitalized with an exacerbation of her ulcerative colitis. Medical therapy included solumedrol and a 5-ASA product. She did not tolerate therapy with azathioprine and it was decided to administer infliximab prior to consideration for colectomy. Within less than 1 week of the initial dose, the patient developed significant diffuse abdominal pain. CT of the abdomen showed the heterogeneous enhancement of the liver with no opacification of the hepatic veins consistent with BCS. Doppler studies and transjugular venogram confirmed the diagnosis. Needle biopsy of the liver showed centrilobular sinusoidal dilation and hemorrhage with hepatocyte injury, consistent with BCS; no fibrosis was present supporting the acute presentation. The second patient was an 11 year old Caucasian female with longstanding Crohn's disease, also admitted to the hospital for an exacerbation of her disease. She also was on IV solumedrol and antibiotic therapy, but demonstrated no clinical improvement. Infliximab was administered and her diarrhea improved. Eleven days following initial infusion, however, the patient developed a severe headache, disorientation, slurred speech and twitching of the right eye. Head CT showed thrombosis of the left transverse and sigmoid dural venous sinuses with resultant venous infarction and parenchymal hemorrhage.Both patients had extensive hematologic evaluation and no underlying thrombophilia was diagnosed. The precise etiologies of venous thrombosis in these patients remains uncertain. The temporal relation of the occurrence of cerebral vascular thrombosis as well as the case of BCS each occuring within less than 2 weeks of the initial infliximab treatment raises concern for these representing possible medication-related complications. The purpose of this abstract is to increase awareness about venous thrombosis as a potential complication of infliximab therapy in patient's with IBD.

Exclusive enteral feeding as primary therapy for Crohn’s disease in Australian children and adolescents: A feasible and effective approach

Exclusive enteral feeding has been shown to be as efficacious as corticosteroids in inducing remission in children with Crohn's disease (CD), with additional nutritional benefits. The use of polymeric formulae provides superior palatability and acceptance over elemental feeds, but polymeric formulae have not been universally adopted. The present retrospective analysis of enteral feeding in children with Crohn's disease aims to demonstrate the short-term benefits of enteral feeding in children upon disease activity and nutrition parameters. The case records of children with CD managed with exclusive enteral nutrition (EEN) by a multidisciplinary team over a 2-year period were reviewed. Data relating to therapy, background disease details, and outcome were collated. Primary outcome measures established were weight change and disease activity (Pediatric Crohn's Disease Activity Index: PCDAI). Twenty-seven children received EEN with polymeric formulae. Fifteen children had newly diagnosed CD and 12 had known long-standing CD. Twenty-four children completed the prescribed period of EEN. Twelve of 15 (80%) newly diagnosed CD and seven of 12 (58%) with long-standing disease entered remission. Children with newly diagnosed CD responding to EEN took all feeds orally and gained an average of 4.7+/-3.5 kg with mean PCDAI decreasing from 37.1+/-10.8 to 6.7+/-5.1 after 8 weeks. In addition, four children continued supplementary polymeric formula (without other medical therapies) and all have maintained remission during an average follow-up period of 15.2 months. Exclusive enteral feeds induced remission in 80% of children with newly diagnosed CD (on intention-to-treat basis) when used as sole initial therapy while also improving nutritional status. All newly diagnosed children treated with EEN, who were able to establish feeds, achieved remission. In addition, remission may be prolonged with oral supplementary formula as sole ongoing treatment. Further study of the role(s) of enteral feeds and of longer-term benefits of enteral feeding in children with CD is now required.

Anorectal Carcinoma After Infliximab Therapy in Crohn's Disease: Report of a Case

Infliximab, monoclonal antibody against tumor necrosis factor alpha, is an effective agent in the therapy of Crohn's disease. Although therapy with infliximab is generally well tolerated, there is an obvious concern about the effect of this treatment on the incidence of cancer. We report a case of mucinous anorectal adenocarcinoma observed in a 39-year-old patient with long-standing Crohn's disease after therapy with two courses of infliximab. The carcinoma was discovered fortuitously after abdominoperineal resection. Despite clear margins, the tumor recurred in a few months and progressed during combination chemotherapy. Although there is currently no definitive proof of a causal link between infliximab therapy and cancer, the present observation and other reports in the literature should lead to a careful evaluation of the possibility of increased cancer risk in patients treated with this new agent.

Tumours of the anal canal

Summary Anal canal pathology, particularly infections and tumours, has recently come into prominence, mainly because of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome. This review provides a framework for diagnostic pathologists who may encounter anal canal tumours. A summary of embryology, anatomy and terminology is provided by way of background. Important points of distinction between the surgical, anatomic and histologic anal canal are highlighted. Squamous carcinomas and their precursor lesion, anal intra-epithelial neoplasia, are the most common primary epithelial abnormalities seen in the anal canal. In addition, there is a predilection for HIV-positive homosexual men with co-existent human papillomavirus (HPV) infection to develop squamous carcinomas. The more proximal the tumour is in the anal canal, the greater the association with basaloid morphology and HPV infection. Adenocarcinomas are uncommon and may arise from the anal transitional zone, anal glands or fistulous tracts, which may or may not be associated with long-standing Crohn's disease. The immunohistochemical profiles and separation from morphologically similar tumours are provided in this article. In addition, the role of new molecular markers is discussed in relation to tumour behaviour and therapeutic options.

Crohn’s Disease-Induced Non-Alcoholic Fatty Liver Disease (NAFLD) Sensitizes for Severe Acute Hepatitis B Infection and Liver Failure

Non-alcoholic fatty liver disease (NAFLD) commonly is associated with chronic inflammatory bowel disease (CIBD) and usually is considered to be stable and benign. However, NAFLD -- and in particular its subset, non-alcoholic steatohepatitis (NASH) -- may lead to progressive liver disease. Moreover, NAFLD sensitizes the liver to injury and increases the risk of developing acute-on-chronic liver failure following a "third hit". We here present one patient with NASH, as probably induced by long-standing Crohn's disease in the absence of ethanol consumption or abuse. The patient acquired an acute HBV infection and died from complications. As based on the clinical and histological findings, Crohn's disease appears to be a risk factor for developing NAFLD and thus to contribute to the progression into NASH. In conclusion, we suggest that Crohn's disease-related NAFLD may increase the vulnerability of the liver, which indicates that patients with a known history of CIBD merit special attention.

Reporting Ileocolonoscopy in Inflammatory Bowel Disease

Reporting Ileocolonoscopy in Inflammatory Bowel Disease