The association between Crohn's disease and desmoid tumors: A novel case and review of the literature

Desmoids are rare tumors resulting from the proliferation of fibroblasts. They occur in association with familial adenomatous polyposis (FAP), but they may also occur in the post-traumatic peri-partum or post-abdominal surgery setting, and a few present spontaneously. Presenting features of desmoids are protean and largely relate to the anatomical area of involvement.We describe a 50 year old male not known to have Crohn's disease and without FAP who presented with multiple desmoids. Investigation of post-operative diarrhea confirmed a diagnosis of Crohn's disease. This is the first report of a male patient, who had never undergone prior abdominal surgery, presenting with Crohn's disease and abdominal desmoid tumors. The reasons why Crohn's disease and desmoids may be associated are explored, focusing particularly on alternations in the fibrogenic cytokine TGF-β now known to be involved in the pathogenesis of both diseases.     

Fibromuscular dysplasia mimicking Crohn's disease over a period of 23 years

Rare diseases with similar clinical presentation as more frequent gastrointestinal disorders might be challenging in the diagnostic and therapeutic management. In this case we report on a 47-year-old woman who was thought to suffer from Crohn's disease. Symptoms, macroscopic and histological aspects of the gastrointestinal tract, treatment response and clinical course had encouraged the wrong diagnosis over a period of 23 years. After the patient died in the context of a sudden clinical deterioration, fibromuscular dysplasia of the aorta was finally unmasked by post-mortem examination as underlying cause of all symptoms attributed to Crohn's disease. Re-evaluation of former diagnostic procedures revealed subtle aspects of fibromuscular dysplasia, even in biopsy samples from 23 years ago. This first case report of fibromuscular dysplasia of the aorta documents a rare pitfall in the diagnostic workup of a frequent clinical presentation in gastroenterology.     

Maladie de Crohn métastatique ombilicale : une localisation exceptionnelle

IntroductionCutaneous manifestations of Crohn's disease are frequent and include metastatic lesions. These are separated from the digestive tract and affect particularly the limbs and major folds. Umbilical involvement is exceptional.Case reportA 93-year-old woman followed for 6 years for Crohn's disease, in remission on infliximab, 5 mg/kg every 8 weeks, consulted for a fissured and painful omphalitis. Histology revealed epithelioid granulomas without necrosis in the dermis, leading to the diagnosis of umbilical cutaneous metastasis of Crohn's disease. Infliximab intensification every 6 weeks led to a positive outcome.ConclusionWe report a unique case of umbilical metastatic localization of Crohn's disease occurring during treatment with anti-TNF alpha. The diagnosis was based on skin biopsy and histology which found epithelioid granulomas without caseous necrosis.     

Recurrent posterior scleritis and orbital myositis as extra-intestinal manifestations of Crohn's disease: Case report and systematic literature review

BackgroundOcular episcleritis and uveitis are well-recognised extra-intestinal manifestations of Crohn's disease. Orbital myositis is rare: to our knowledge it has been associated with Crohn's disease in thirteen cases. Posterior scleritis, orbital myositis and Crohn's disease have been reported as coexisting in only two cases.Methods and resultsWe describe a third case, that of a 31-year old female with Crohn's colitis for 8 years, complicated by enteropathic arthritis and pyoderma gangrenosum. She presented with intense and intractable periorbital pain, particularly at night and worse on eye movements. B-scan ultrasonography confirmed posterior scleritis and treatment with high dose oral steroids (up to 60 mg prednisolone) was initially effective, but subsequently failed to control the inflammation. There was only a partial response to infliximab. Five months after presentation, diplopia developed, with failure of abduction of the left eye. MRI scan of the orbits confirmed orbital myositis involving the left lateral and medial rectus muscles. Pulsed intravenous methylprednisolone and six cycles of intravenous cyclophosphamide over a three month period resulted in complete resolution of inflammatory symptoms.ConclusionsThis case highlights a rare combination of ocular abnormality secondary to Crohn's disease and reports successful resolution with aggressive immunosuppressive therapy.     

Disease course and efficacy of medical therapy in stricturing paediatric Crohn's disease

BackgroundStricturing is the most common complicated phenotype in paediatric Crohn's disease, but only few studies have described its course, while data on the outcome of medical treatment are scanty.AimTo retrospectively describes the course of paediatric stricturing Crohn's disease and assess clinical and imaging response to medical therapy.Patients and methodsThirty-six patients with stricturing Crohn's disease were identified by our department database. Paediatric Crohn's disease activity index, need of surgery and magnetic resonance were evaluated as outcomes at 6, 12, 18 and 24 months after detection of stenosis.ResultsStrictures were ileal, ileocolonic and colonic in 61%, 28% and 11% of patients. Thirteen (36%) had stricturing disease at the diagnosis of Crohn's disease, while 64% developed it at the follow-up. At baseline, 89% had medical treatment, while 11% surgery. At 6, 12, 18, and 24 months, 53%, 50%, 42%, and 35% had complete response to medical treatment, respectively. Overall, 44% were unresponsive to medical therapy and required surgery at the follow-up. Responders and non-responders significantly differed for inflammatory imaging findings at the stenosis detection.ConclusionsA stricturing phenotype is not uncommon at the diagnosis of Crohn's disease in children. Medical therapy seems poorly effective in avoiding intestinal resection. Magnetic resonance imaging is valuable in identifying patients who will benefit from medical therapy.     

Methotrexate-induced pneumonitis in a patient with Crohn's disease

Pulmonary toxicity is a well recognised but infrequent adverse event of treatment with methotrexate. The vast majority of cases have occurred in patients with rheumatoid arthritis; here we present the case of a 44-year old woman with ileo-colonic Crohn's disease who developed methotrexate pneumonitis. The patient had a 10 year history of Crohn's disease and, in the last 18 months, she was treated with oral methotrexate because of steroid-dependency and intolerance to thiopurines. She was admitted to the hospital because of acute dyspnoea, non-productive cough and fever. High-resolution CT scan showed diffuse bilateral areas of ground-glass opacity, and pulmonary function tests disclosed a mild obstructive pattern with a decrease in carbon monoxide diffusing capacity. Blood cultures for pathogenic bacteria or fungi were negative as well as serologic tests against major pneumotropic agents. Methotrexate-induced lung injury was considered: the drug was discontinued and the patient received a steroid course with rapid symptomatic improvement. After 4 weeks pulmonary function tests and high-resolution chest CT scan were normal. To our knowledge this is the second reported case of methotrexate-induced pneumonitis occurring in a patient with Crohn's disease. A definite diagnosis has been made not invasively according to clinical, laboratory and radiological criteria and excluding any infectious aetiology of the pulmonary findings.     

Oral Crohn's disease: Is it a separable disease from orofacial granulomatosis? A review

Symptomatic oral Crohn's disease is comparatively rare. The relationship between orofacial granulomatosis, (where there is granulomatous inflammation and ulceration of the mouth in the absence of gastrointestinal disease) and true oral Crohn's disease is discussed along with the plethora of clinical oral disease presentations associated with both disorders and the differential diagnosis of oral ulceration in patients presenting to a gastroenterological clinic. Specific oral syndromes are outlined including the association between oral manifestations in Crohn's disease and the pattern of intestinal disease and their relationship to other recorded extraintestinal manifestations. The histological and immunological features of oral biopsies are considered as well as the principles of management of symptomatic oral disease. At present, it is suggested that both orofacial granulomatosis and oral Crohn's disease appear to be distinct clinical disorders.     

The association of Haptoglobin polymorphism with Crohn's disease in Israel

ObjectivesHaptoglobin is a α²-sialoglycoprotein with hemoglobin binding capacity. Functional differences between the Hp phenotypes with the Hp 1-1 protein being a superior anti-inflammatory to the Hp 2-2 protein have been identified. The aim of our study was to investigate the possible role of Hp polymorphism in the susceptibility to Crohn's disease and its clinical course.MethodsHp phenotypes were determined for 382 Israeli CD patients and 3243 healthy controls. Phenotypic data for all Crohn's disease patients were carefully characterized. Analysis was preformed to evaluate the association between Hp polymorphism and Crohn's disease.ResultsThe frequency of Haptoglobin 1-1 was lower in Crohn's disease patients than in healthy individuals (6.28% vs. 9.28%, P = 0.057). There was no association between Haptoglobin phenotypes and disease location, behavior or extra-intestinal manifestations. No association was found between the Haptoglobin polymorphism and the frequency of the three Crohn's disease associated NOD2 mutations examined.ConclusionsWe found a borderline significant decrease of the Haptoglobin 1-1 phenotype in Israeli Crohn's disease patients compared to healthy controls. Our findings may support the importance of inflammation in Crohn's disease pathogenesis and the protective function of Haptoglobin 1-1 in the susceptibility for Crohn's disease.     

Cyclophosphamide therapy in Sweet's syndrome complicating refractory Crohn's disease — Efficacy and mechanism of action

BackgroundSweet's syndrome is a rare extraintestinal manifestation of Crohn's disease that is usually treated by corticosteroids. Cyclophosphamide therapy has been shown to be effective in steroid-refractory Crohn's disease with extraintestinal manifestations. The mechanism of action remains obscure. Here, we report about a case of steroid-refractory Sweet's syndrome accompanying Crohn's colitis treated by cyclophosphamide.MethodsAt baseline and two weeks after initiating cyclophosphamide pulse therapy, clinical symptoms were evaluated and apoptosis in mononuclear cells of the colon mucosa was quantified via immunofluorescence TUNEL-labeling. Ongoing clinical follow-up lasts for more than three years.ResultsCyclophosphamide pulse therapy resulted in complete resolution of luminal activity and extraintestinal manifestations. TUNEL-marked CD4⁺, CD8⁺ and CD68⁺ cells in intestinal biopsies showed a 338% increase as compared to baseline.ConclusionsCyclophosphamide therapy was highly effective in steroid-refractory Crohn's colitis accompanied by Sweet's syndrome for induction of remission. Furthermore, apoptosis of mononuclear cells in the colon mucosa, including CD68⁺ macrophages as well as CD4⁺ and CD8⁺ cells, appears to be a component of the anti-inflammatory effect of cyclophosphamide in Crohn's disease.     

Limited granulomatosis with polyangiitis in an adolescent with Crohn's disease on infliximab therapy: cause or coincidence?

Pulmonary involvement in Crohn's disease (CD) may precede the development of intestinal inflammation, but in most cases occurs during the course of treatment, either as an extra‐intestinal manifestation, because of secondary infections, or as a side effect of the therapy itself. This case highlights the differential diagnosis and work up for multiple pulmonary nodules that developed in a patient with CD who had been in remission on infliximab therapy. Even though infectious causes, such as Mycobacteria and Fungi, account for majority of these cases, the possibility of non‐infectious conditions such as autoimmune disorders should also be considered.     

Oral inflammatory changes as an initial manifestation of Crohn's disease antedating abdominal diagnosis

The case of a 14-year-old boy who had oral ulcers with histologic proof of granulomatous disease nine months before the diagnosis of intestinal Crohn's disease is presented. Additional extraintestinal manifestations of this case were cheilitis, anal fissures, and “metastatic” disease to the umbilicus. The diagnosis was established after the onset of abdominal symptoms. All manifestations responded rapidly to systemic prednisone, sulfasalazine, and metronidazole.     

Abcès cutanés aseptiques récidivants atypiques révélateurs d’une maladie de Crohn

Introduction

We report here a case of chronic inflammatory bowel disease revealed by multiple large cutaneous aseptic distal necrotic ulcers.

Case report

A 44-year-old male presented with high fever at 40 °C associated with multiple necrotic abcesses located on the distal part of his limbs. They were treated successfully by debridment and dressings associated with antibiotics allowing complete healing after 1 month. Six months later, the patient relapsed on his left hand with a short episode of diarrhoea. A total coloscopy revealed a Crohn's disease. Systemic corticotherapy and azathioprine were administered and complete remission was obtained with a 1-year follow-up.

Conclusion

Skin manifestations that this patient presented were atypical because of their number, size, and location, exclusively distally on the limbs. This report illustrates an unusual presentation of Crohn's disease with multiple necrotic ulcers only located on the patient extremities.     

Active Crohn's disease is associated with low vitamin D levels

Background and aimsCrohn's disease prevalence increases with increasing latitude. Because most vitamin D comes from sunlight exposure and murine models of intestinal inflammation have demonstrated beneficial effects of 1,25-(OH)₂ vitamin D treatment, we hypothesised that Crohn's disease activity is associated with low vitamin D levels.MethodsIn a cross-sectional study of 182 CD patients and 62 healthy controls, we measured serum 25-OH vitamin D. Stratified analysis was used to compare 25-OH vitamin D levels with Crohn's disease activity index, C-reactive protein, smoking status, intake of oral vitamin D supplements and seasonal variation in CD patients and healthy controls.ResultsSerum 25-OH vitamin D was inversely associated with disease activity: Median 25-OH vitamin D levels of Crohn's disease in remission, mildly, and moderately active diseases evaluated by Crohn's disease activity index were 64, 49, and 21 nmol/l (p < 0.01) and by CRP 68, 76, and 35 nmol/l (p < 0.05), respectively. Patients who took oral vitamin D supplementation had lower Crohn's disease activity index (p < 0.05) and C-reactive protein (p = 0.07) than non-users. Crohn's disease patients who smoked had lower vitamin D levels (51 nmol/l) than patients who did not smoke (76 nmol/l), p < 0.01. Overall, Crohn's disease patients did not differ from healthy controls regarding 25-OH vitamin D levels.ConclusionsActive Crohn's disease was associated with low serum 25-OH vitamin D. Patients who smoked had lower 25-OH vitamin D levels than patients who did not smoke, independently of disease activity.     

Accuracy and cost of diagnostic strategies for patients with suspected Crohn's disease

ObjectiveTo evaluate accuracy and cost of non-invasive diagnostic strategies including magnetic resonance imaging, intestinal ultrasonography, ileocolonoscopy and video-capsule endoscopy in suspected Crohn's disease.MethodsA decision-analytic model was used to assess the costs in low (25%), intermediate (50%) or high (75%) pre-test probability of Crohn's disease. Based on the published accuracy of diagnostic modalities and Bayes' rule, we calculated post-test probability of Crohn's disease using different strategies, starting from ileocolonoscopy, ultrasonography or magnetic resonance. Each strategy was considered successful when post-test probability was > 95% or < 5%.ResultsWith low pre-test probability, only ileocolonoscopy as the first investigation could exclude or confirm Crohn's disease while a normal ultrasonography may exclude Crohn's disease. With high pre-test probability, ileocolonoscopy or ultrasonography as the first test may confirm Crohn's disease, but at least 3 negative tests are required to exclude Crohn's disease.The cost to diagnose one patient was cheapest utilising an ultrasonography-based strategy both in low (ultrasonography €1076; ileocolonoscopy €2005; magnetic resonance €4515) and high pre-test probability of Crohn's disease (ultrasonography €321; ileocolonoscopy €712; magnetic resonance €1412).ConclusionThe accuracy and cost of these strategies depend on pre-test probability of Crohn's disease and vary according to the first test used. Ileocolonoscopy plus ultrasonography is the most accurate and less expensive initial diagnostic strategy.     

A case of Crohn's disease complicated by Adult Onset Still's Disease

Arthritis and arthralgia are the most common extra-intestinal manifestations of Inflammatory Bowel Disease (IBD), occurring in up to a third of patients. These may affect the peripheral or axial skeletal system and may or may not reflect disease activity. As a result, it is challenging to identify an alternative diagnosis to account for joint manifestations in the setting of IBD.We describe a case of a 30 year old woman with quiescent Crohn's colitis who presented with 2 weeks of fever, flitting arthralgia, a sore throat and a nocturnal rash on her thighs. She denied any gastrointestinal symptoms to suggest a flare up of IBD. Investigations revealed a neutrophilia and a markedly elevated serum ferritin. The patient met all four major and several minor Yamaguchi criteria for Adult Onset Still's Disease (AOSD). She was treated with corticosteroids and analgesia with resolution of her symptoms and normalisation of her biochemical markers.While joint manifestations are the most common extra-intestinal symptoms of Inflammatory Bowel Disease, atypical presentations should raise the concern of an additional diagnosis. This case represents a rare presentation of Crohn's disease complicated by AOSD.     

Surgical management of gluteal metastatic cutaneous Crohn's disease

Metastatic cutaneous Crohn's disease is a rare entity first described by McCallum et al. in 1976. It is diagnosed when histologically characteristic granulomata are seen at a site not contiguous with inflammatory disease in the gastrointestinal tract. We herein report presentation, diagnosis and management of a 28 year old lady with disabling, symptomatic cutaneous Crohn's of the buttocks and natal cleft refractory to Infliximab therapy. To the best of our knowledge only four other adult cases have been reported in the literature of metastatic cutaneous Crohn's disease of the buttock area distant from a flexure or area of skin apposition. The differential diagnosis in this case was Hidradenitis Suppurativa. A good cosmetic result and excellent symptom control were achieved with extensive debridement, wide local excision, vacuum assisted closure and delayed skin grafting.     

The prevalence of inflammatory bowel disease in an Israeli Arab population

AimsTo determine the prevalence of inflammatory bowel disease among the 1.5 million Arab residents in Israel who represent 20% of the total population.MethodsFamily physicians in all Arab towns and villages were contacted to obtain information on patients with inflammatory bowel disease. Relevant clinical data were retrieved and updated to December 31, 2009.ResultsInformation was obtained from 23/71 municipalities approached (representing 200,000 out of 1.5 million Arabs). There were 64 confirmed cases of Crohn's disease indicating a prevalence rate of 32/100,000. The rate of smoking within this cohort was lower than in the general population (1.5% vs. 40%; P < 0.001). There were 44 confirmed cases of ulcerative colitis with a prevalence rate of 22/100,000. The percentage of active smokers in this cohort was 18%. Clinical remission or mild activity was observed in 75% of patients in both cohorts at the time of the survey. Fourteen patients (21%) had undergone surgery for Crohn's disease, whereas none had undergone surgery for ulcerative colitis. Twenty-eight (42%) patients with Crohn's disease and 20 (45%) with ulcerative colitis were on maintenance therapy with 5-aminosalicylic acid. Only 18% with Crohn's disease and 6.8% with ulcerative colitis had received anti-tumor necrosis factor. The most prevalent extra-intestinal manifestations were perianal disease (18%) in Crohn's disease, and arthralgia or arthritis (6.8%) in ulcerative colitis.ConclusionsWe found a low prevalence rate of inflammatory bowel disease in the Israeli Arab population.     

Anti-TNF-α antibodies improve intestinal barrier function in Crohn's disease

Background and aimsIntestinal barrier function in Crohn's disease patients and their first degree healthy relatives is impaired. The increased intestinal permeability may result in an enhanced mucosal immune response and thereby aggravate intestinal inflammation. Humanised anti-TNF-α antibodies have been shown to be effective in the treatment of active Crohn's disease and in the treatment of entero-cutaneous fistula.The aim of the present study was to investigate the influence of anti-TNF-α antibody (infliximab) treatment on the intestinal barrier function of patients with active Crohn's disease.MethodsThe differential intestinal uptake of lactulose and mannitol was measured to quantify intestinal permeability in patients with long standing active Crohn's disease (n = 17) directly before and seven days after treatment with infliximab (5 mg/kg bodyweight). In parallel, intestinal permeability was studied in a healthy control group (n = 20). Serum samples were analysed with pulsed amperometric detection after separation on an anion exchange column.ResultsIntestinal permeability was significantly increased in all patients with Crohn's disease (L/M ratio 0.24 ± 0.17) prior to infliximab treatment compared to the control group (L/M ratio 0.01 ± 0.02; p-value < 1 × 10^− 7). Treatment of patients with infliximab resulted in a marked decrease of intestinal permeability as measured by L/M ratio from 0.24 ± 0.17 before to 0.02 ± 0.02 (p-value < 1 × 10^− 7) seven days after infliximab application.ConclusionsTreatment with anti-TNF-α antibodies improved impaired intestinal barrier function in patients with Crohn's disease. This effect may correlate to the well documented anti-inflammatory effect of TNF-α blockade in this intestinal disease.     

Expression and functional analysis of intestinal organic cation/l-carnitine transporter (OCTN) in Crohn's Disease

BackgroundThe IBD5 locus is a genetic risk factor for IBD, particularly Crohn's Disease, coding for the organic cation/carnitine transporters (OCTN1 and 2). Two variants of OCTN are associated with susceptibility to Crohn's Disease. Modified transport of carnitine in vitro has been reported for a polymorphism of OCTN1. The aim was to investigate the function of intestinal OCTNs in IBD in relation to genetic polymorphisms.MethodsIntestinal tissue was obtained from endoscopic biopsies and surgical resections from IBD patients (n = 33 and 14, resp.) and controls (n = 22 and 14, resp.). OCTN protein levels were measured in intestinal biopsies and carnitine transport was quantified in intestinal resections.ResultsOCTN1 protein levels were significantly higher in ileal versus colonic tissue (2.95% ± 0.4 vs 0.66% ± 0.2, resp.; p < 0.0002). OCTN1 expression was higher in Crohn's disease patients with mutant homozygous or heterozygous genotypes (0.6% ± 0.1 vs 3% ± 0.8, resp., p < 0.02). Carnitine transport was very rapid and Na+ dependent (10 s). It was not different comparing Crohn's Disease and control groups (0.45 ± 0.12 vs 0.51 ± 0.12 nM carnitine/mg prot/min, resp.). Carnitine transport tended to be higher in subjects with mutant homozygous and heterozygous OCTN1 and OCTN2 genotypes (0.19 vs 0.59 and 0.25 vs 0.6, respectively).ConclusionsThe present data reveal that OCTN protein levels appear to be similar in intestinal tissue from Crohn's Disease patients and controls. Overall, ileal carnitine transport appears to as well equal in Crohn's Disease and control groups. However, there was a trend towards higher carnitine transport in subjects with OCTN1 and OCTN2 mutations.     

Effectiveness of combined anticoagulant therapy for extending portal vein thrombosis in Crohn's disease

PURPOSE: Portal vein thrombosis is a rare complication of Crohn's disease, and its precise cause and appropriate treatment are not known. We describe a patient with extending portal vein thrombosis in Crohn's disease who was successfully treated with combined anticoagulant therapy. METHOD: Urokinase and tissue plasminogen activator were administered from a catheter inserted into the superior mesenteric artery, and heparin and a serine protease inhibitor also were given intravenously. RESULTS: On admission, thromboembolic occlusion was observed throughout the entire portal venous system in association with massive ascites and remarkable intestinal edema. After administration of combined anticoagulant therapy, thrombus rapidly decreased in size, and color Doppler ultrasonography showed a gradual increase in portal venous flow. The patient had no recurrence of symptoms while receiving warfarin after resolution of thrombus. CONCLUSION: This case report suggests that combined anticoagulant therapy is effective for patients with severe portal vein thrombosis in Crohn's disease and that color Doppler ultrasonography is useful for evaluation of portal venous flow.