Frequency analysis of NOD2 gene mutations in Korean patients with Crohn's disease]

BACKGROUND/AIMS: Several studies from Western populations have recently shown that three mutations in NOD2 gene (C2104T, G2722C, and 3020insC) are associated with susceptibility to Crohn's disease (CD). However, three mutations were shown not to be associated with CD in Japanese and Chinese population. Here, we have analyzed the frequency of three NOD2 mutations in Korean patients to determine whether the NOD2 mutations are associated with susceptibility to CD in Korean population. METHODS: Blood samples were obtained from 128 patients with CD, 47 patients with ulcerative colitis, 19 Behcet's colitis, and 200 healthy controls. DNA in the region of three NOD2 mutations was sequenced by single base extension method, and the frequency of mutations were analyzed. RESULTS: Among the subjects in our study groups, including patients with CD, ulcerative colitis, Behcet's colitis, and healthy controls, none had NOD2 mutations. CONCLUSIONS: Our results indicate that although three NOD2 mutations are associated with susceptibility to CD in Western populations, these might be rare and may not be associated with susceptibility to CD in Korean patients.     

Life-threatening acute lower gastrointestinal bleeding in patients with Crohn's disease]

OBJECTIVE: We aimed at evaluating the frequency of acute severe bleeding in CD and its potential association to some risk factors, including clinical features of CD, environmental factors, and genetic alterations. MATERIAL AND METHODS: 174 consecutive patients with CD (103 female (59%) and 71 men (41%), with a mean age of 37 years) were included. We analyzed all major acute lower gastrointestinal (GI) hemorrhage related to CD. Potential risk factors like smoking, site of disease, and presence of gene mutations in CARD15, TLR-4, and CD14 were also analyzed. RESULTS: Three patients (1.7%) suffered from severe acute lower GI bleeding. All patients required surgery to resolve their hemorrhage, and this indication represented 3.4% of all surgical procedures related to CD. All three patients were young ( < 25 years) and suffered ileal CD with inflammatory pattern (L1-B1 in the Vienna Classification). No relationship was found between acute bleeding and any of the potential risk factors evaluated. CONCLUSIONS:Acute severe GI bleeding is a rare, but severe complication in CD patients, and presents mainly in patients with inflammatory ileal disease. An association of endoscopy and arteriography is necessary for diagnosis. Urgent surgery is usually required in these patients.     

Crohn's disease involving the proximal stomach

We report an unusual case of Crohn's disease of the esophagus and stomach. Unlike previously described cases, the disease in this patient affected the fundus and body while sparing the antrum of the stomach, and produced a mass effect simulating malignancy.     

A model of quality of life in the patients with Crohn's disease]

PURPOSE: To identify the integrated impact of psychological, social, and clinical factors onto the quality of life (QOL) in the patients with Crohn's disease. SUBJECTS AND METHODS: Two hundred twenty two out-patients participated in a cross-sectional questionnaire survey in which health-related QOL (SF36), disease-specific symptoms, psychological adaptation and social support were measured. Multi-variable regression models were used to test the impact of clinical, psychological, and social factors on the patient's QOL and symptom reports. RESULTS: The patient's symptoms and health-related QOL were significantly associated not only with disease activities, but also with the patient's psychological adaptation and the quality of social support. CONCLUSION: The results strongly suggest that a psychoeducational intervention may be useful in combination with a clinical intervention to improve the patient's QOL.     

Crohn's disease of esophagus,stomach and duodenum

Crohn's disease with involvement of the esophagus, stomach and duodenum has a prevalence of 0.5% to 4% in symptomatic adult patients, but some studies have shown that these results may be underestimated, since upper gastrointestinal endoscopy is not performed routinely in the initial evaluation of the disease in adult patients, as it is in the pediatric population. In general, involvement of the upper gastrointestinal tract in Crohn's disease occurs concomitantly with involvement of the lower gastrointestinal tract. The diagnosis depends on clinical,endoscopic, histological and radiological evaluation. The presence of aphthoid ulcers, longitudinal ulcers, bamboo-joint-like appearance, stenoses and fistulas are endoscopic findings suggestive of the disease, and it is important to exclude the presence of Helicobacter pylori infection. The primary histological findings,which facilitate the diagnosis, are the presence of a chronic inflammatory process with a predominance of lymphoplasmacytic cells and active focal gastritis. The presence of epithelioid granuloma, although less frequent, is highly suggestive of the disease in the absence of chronic granulomatous disease. Treatment should include the use of proton pump inhibitors associated with corticosteroids,immunomodulators and biological therapy according to the severity of the disease.     

Crohn's disease associated with IgA nephropathy]

Crohn's disease is a condition of chronic inflammation potentially involving any location of the alimentary tract from mouth to anus. Numerous extraintestinal manifestations can also be present. Urologic complications of inflammatory bowel disease are seen in up to 25% of patients, but renal parenchymal disease has been rarely reported. IgA nephropathy is recognized worldwide as a most common form of primary glomerulonephritis. Clinical manifestations vary, ranging from microscopic hematuria to nephrotic syndrome. Recently, IgA nephropathy associated with systemic diseases has been reported. We describe a case of a 22 year-old man with Crohn's disease associated with IgA nephropathy. At the age of 8 years, microscopic hematuria appeared. After fourteen years, he presented with melena, mild fever, recurrent oral ulcer, microscopic hematuria and proteinuria. Colonoscopic examination revealed characteristic features of Crohn's disease such as multiple ulcers. Microscopic findings showed superficial ulceration with small noncaseating granulomas. Renal biopsy revealed IgA nephropathy. The patient was treated with oral prednisolone, olsalazine, and metronidazole followed by maintenance therapy with sulfasalazine and azathioprine resulting in clinical improvement of Crohn's disease and IgA nephropathy.     

Gastrostomy placement in patients with Crohn's disease

Crohn's disease often involves the stomach, yet a permanent enterocutaneous fistula does not usually occur, after a percutaneous endoscopic gastrostomy is removed from a patient with Crohn's disease. This is because the factors that are related to the non-closure of a fistula are absent or have been treated (distal bowel obstruction, abdominal sepsis, undernutrition, poor gastric blood supply or abnormal serum levels of C-reactive protein and albumin). Gastric involvement in patients with Crohn's disease is common. Enterocutaneous fistulas from the stomach are rare. Percutaneous endoscopic gastrostomy (PEG) insertion and subsequent removal rarely cause problems in patients with Crohn's disease. Endoscopic removal of a PEG is advised in patients with Crohn's disease. Steroids may delay gastric adhesion to the anterior abdominal wall.     

Mycophenolate mofetil in patients with Crohn's disease

Objective: Intolerance to azathioprine is a rare but important problem in treating chronically active Crohn's disease. We performed this study to evaluate mycophenolate mofetil as an alternative immunosuppressive therapy for patients with Crohn's disease who did not tolerate azathioprine.
Methods: Four patients with highly active perianal Crohn's disease and two patients with chronically active, steroid-dependent Crohn's disease were included. All patients consumed 2 g/day of mycophenolate mofetil for a median of 8 months (range, 6–12 months). Disease activity was measured by the Perianal Crohn's Disease Activity Index in patients with perianal disease and by the Crohn's Disease Activity Index in patients with chronically active Crohn's disease.
Results: Azathioprine-induced side effects disappeared after the drug was discontinued. All patients improved during treatment with mycophenolate mofetil, as shown by a remarkable reduction in the respective clinical scores. Five patients showed no side effects during treatment with mycophenolate mofetil. After 4 months' treatment one patient developed diarrhea that was probably not due to mycophenolate mofetil.
Conclusions: Mycophenolate mofetil could be an alternative therapy to azathioprine in patients with Crohn's disease.     

Narcotic use in patients with Crohn's disease

OBJECTIVES: Despite advances in treatment for Crohn's disease (CD), some patients suffer from chronic pain. We sought to characterize the prevalence of narcotic use and contributing factors in CD patients at a referral center. METHODS: A retrospective analysis of 291 CD patients followed over a 5-yr period was performed. Clinical status was evaluated with the Harvey-Bradshaw index (HBI) of disease activity and the short inflammatory bowel disease questionnaire (SIBDQ). RESULTS: Narcotic use was identified in 13.1% of patients. Narcotic users were more likely to be female, 72%versus 49% (p= 0.01), had higher rates of disability, 15.4%versus 3.6% (p= 0.001), and a longer duration of disease, 17.0 versus 12.9 yr (p= 0.03). In addition, they took more medications 6.97 versus 4.7 (p < 0.001) and had a higher prevalence of neuropsychiatric drug use, 37%versus 19% (p= 0.01). CD patients receiving narcotics had worse disease activity (HBI 9.1 vs 5.0, p < 0.001) and diminished quality of life (SIBDQ 44.2 vs 51.6 (p= 0.04)). However, logistic regression analysis found that active disease [HBI score of > or = 4 (OR 3.9)], polypharmacy [use of > or = 5 drugs (OR 5.5)], and smoking (OR 2.8) were associated with narcotic use. CONCLUSIONS: Narcotic use may be an indicator of more severe disease since it is associated with increased disease activity and decreased quality of life. Factors correlating with narcotic use include smoking and PP. Our data emphasize the need for further work to characterize chronic pain in CD patients.     

Corticosteroid-sparing treatments in patients with Crohn's disease

Conventional corticosteroid therapy effectively induces remission of Crohn's disease (CD) across a range of disease severity. However, alternative treatments are needed for patients with disease unresponsive to corticosteroids, patients requiring maintenance therapy (for which corticosteroids are ineffective), corticosteroid-dependent patients, and patients with corticosteroid-related toxicities. Thus, corticosteroid-sparing effects are an important clinical endpoint for treatments of CD. Budesonide offers comparable efficacy with less short-term toxicity than conventional corticosteroids (prednisone, prednisolone); this agent has also demonstrated short-term remission maintenance efficacy, while potentially enabling withdrawal of more toxic corticosteroids in corticosteroid-dependent patients. However, budesonide has not shown long-term maintenance benefit in clinical studies, and the risk for and implications of budesonide dependency need further evaluation. The immunomodulators, azathioprine and 6-mercaptopurine, are most effective for maintenance of remission in quiescent disease, but may be useful in conjunction with other therapies in inducing remission in active CD; methotrexate may be considered an alternative because of its efficacy in inducing and maintaining remission. In clinical trials, treatment with azathioprine/6-methotrexate has enabled corticosteroid withdrawal in 55% of patients, and methotrexate, in 39% of patients with corticosteroid-dependent CD, while maintaining clinical response. Monitoring for infrequent hematological or hepatic toxicity is recommended during use of these immunomodulators. Infliximab is effective for induction and maintenance of remission in patients with refractory CD participating in randomized placebo-controlled studies and, in open-label experience, has enabled corticosteroid withdrawal in approximately three quarters of patients. This biological agent is generally well tolerated. Infusion reactions are the most commonly occurring side effects; such reactions may require adjustment of infusion rate and/or treatment with an antihistamine or acetaminophen. The investigational biological agent CDP-571 has also shown corticosteroid-sparing efficacy in patients with CD. In conclusion, recent research has helped identify corticosteroid-sparing treatments that can provide benefit in patients with corticosteroid-dependent and/or corticosteroid-refractory CD or patients at risk for corticosteroid-induced toxicities.     

A case of Crohn's disease with broncho-bronchiolitis]

A 41-year old man was hospitalized for abdominal pain and melena. Two years before, he had contracted Crohn's disease, which was brought into remission by using mesalazine and oral corticosteroids. When Crohn's disease appeared to flare up again, the dose of corticosteroids was increased. Afterwards, when a gradual decrease in this dose was initiated, melena developed once again, along with a dry cough. Chest radiography revealed diffuse patchy shadows. A significant increase of lymphocytes was observed in the bronchoalveolar lavage fluid. Mesalazine was suspended and steroid pulse therapy was initiated in combination with azathioprine. Although the symptoms were alleviated and the patchy shadows disappeared, the bronchiectatic shadows remained. A broncho-bronchiolitis associated with Crohn's disease was finally diagnosed despite the need for a differential diagnosis of mesalazine-induced disease due to the long-term administration of mesalazine before the onset of the pulmonary lesion. Also, the pathological findings were inconsistent with many other reported cases, the onset of the pulmonary lesion coincided with the flare-up of an intestinal disease, and the pulmonary shadows remained long after the suspension of mesalazine.     

Bone disease in vitamin D-deficient patients with Crohn's disease

Vitamin D deficiency is frequently observed in patients with Crohn's disease and may be associated with an increased risk of development of metabolic bone disease. To estimate the incidence of metabolic bone disease by noninvasive methods, 31 patients (17–75 years old) with Crohn's disease and low 25-hydroxy vitamin D (25-OHD) levels in winter were investigated in the following summer by measuring the bone mineral content (BMC) of the distal radius by single photon absorptiometry and the cortical area ratio (CAR) calculated from radiographs of the right hand and by x-ray of the lumbar spine. Forty-five percent of the patients showed signs of metabolic bone disease. BMC and CAR correlated with 25-OHD serum levels (P<0.05), especially in men. Furthermore, the amount of sun exposure has an influence not only on 25-OHD serum levels both in summer and in winter (P=0.0006), but also on the BMC (P=0.07). Consequently, vitamin D deficiency is of major importance for the development of metabolic bone disease in patients with Crohn's disease. Vitamin D deficiency can be prevented by increasing sun exposure and long-term vitamin D supplementation.