Extraintestinal Manifestation Of Crohn's Disease Research Articles

Unusual Extra-intestinal Manifestations of Crohn Disease Complicated by Incidentally Diagnosed Pancreatic Neuroendocrine Tumor

Unusual Extra-intestinal Manifestations of Crohn Disease Complicated by Incidentally Diagnosed Pancreatic Neuroendocrine Tumor

Metronidazole for the treatment of cutaneous vulval Crohn disease: A systematic review.

Cutaneous vulval Crohn disease (VCD) is an under-recognised extra-intestinal manifestation of Crohn disease (CD) which is challenging to identify and treat. It causes significant oedema, painful deep fissures, and has potential to cause permanent disfiguring changes to vulval anatomy. There is no agreement on the best management for VCD. This systematic review evaluates the use of metronidazole for the treatment of VCD in women and children. We conducted a systematic review (PROSPERO CRD42021285033) of the use of metronidazole in clinically or histologically diagnosed non-contiguous VCD in patients of all ages and ethnicities. We recorded clinical improvement, reduction in flares, relapse and adverse events using a standardised form. 49 records (40 case reports and 9 case series) met inclusion criteria, comprising a total of 57 patients with an age range of 5-61years. The most reported presenting features in VCD were: oedema, erythema, ulcers/fissures and induration/thickening. Gastrointestinal CD was present in 33/57 (58%). Vulval biopsies were undertaken in 47/57 (83%). Daily doses ranged from 250 to 1500mg with treatment duration 8days to 18months. Improvement of any magnitude was observed in 40/57 (70%) cases. Relapse was described in 11/57 (19%) cases. No response/worsening was reported in 17/57 (30%) cases. Adverse events occurred in two patients. Metronidazole appears to be useful in managing VCD, either as a primary treatment or adjunctive therapy. However, the evidence is insufficient for firm conclusions to be drawn. Further studies including randomised controlled trials are recommended.

The risk of subsequent surgery following bowel resection for Crohn's disease in a national cohort of 19 207 patients.

Surgery is required for most patients with Crohn's disease (CD) and further surgery may be necessary if medical treatment fails to control disease activity. The aim of this study was to characterize the risk of, and factors associated with, further surgery following a first resection for Crohn's disease. Hospital Episode Statistics from England were examined to identify patients with CD and a first recorded bowel resection between 2007 and 2016. Multivariable logistic regression was used to examine risk factors for further resectional surgery within 5 years. Prevalence-adjusted surgical rates for index CD surgery over the study period were calculated. In total, 19 207 patients (median age 39 years, interquartile range 27-53 years; 55% women) with CD underwent a first recorded resection during the study period. 3141 (16%) underwent a further operation during the study period. The median time to further surgery was 2.4 (interquartile range 1.2-4.6) years. 3% of CD patients had further surgery within 1 year, 14% by 5 years and 23% by 10 years. Older age (≥58), index laparoscopic surgery and index elective surgery (adjusted OR 0.65, 95% CI 0.54-0.77; 0.77, 0.67-0.88; and 0.77, 0.69-0.85; respectively) were associated with a reduced risk of further surgery by 5 years. Prior surgery for perianal disease (1.60, 1.37-1.87), an extraintestinal manifestation of CD (1.51, 1.22-1.86) and index surgery in a high-volume centre for CD surgery (1.20, 1.02-1.40) were associated with an increased risk of further surgery by 5 years. A 25% relative and 0.3% absolute reduction in prevalence-adjusted index surgery rates for CD was observed over the study period. Further surgery following an index operation is common in CD. This risk was particularly seen in patients with perianal disease, extraintestinal manifestations and those who underwent index surgery in a high-volume centre.

Prevalence and Impact of Acute Pancreatitis on Hospitalization Outcomes in a Cohort of Patients With Crohn's Disease.

BackgroundFew studies evaluated the risk of acute pancreatitis (AP) in patients with Crohn’s disease (CD). It’s controversial if AP can be considered as an extraintestinal manifestation of CD. We studied this potential association in a retrospective cohort of patients with CD.MethodsWe draw our cohort from the Nationwide Readmission Databases 2016 - 2018. We used the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes to identify all adult patients admitted with a diagnosis of CD. Patient with a comorbid AP were identified. We analyzed the significant impact of AP on hospitalization outcomes. A multivariate regression analysis was used to identify factors associated with AP.ResultsWe included 214,622 patients discharged from an index hospitalization for CD, 1.1% had AP. AP was independently associated with higher odds of inpatient mortality (odds ratio (OR): 1.831; 95% confidence interval (CI): 1.345 - 2.492, P < 0.001), gallstone disease (OR: 4.047; 95% CI: 3.343 - 4.9, P < 0.001), nonalcoholic fatty liver disease (NAFLD) (OR: 3.568; 95% CI: 3.08 - 4.133, P < 0.001), and hypercalcemia (OR: 1.964; 95% CI: 1.302 - 2.965, P = 0.001). Thirty-day readmission analysis showed that CD patients with AP were more commonly to be readmitted for AP than for any other reason.ConclusionsIn our nationwide cohort of CD patients, there was a significant association between AP and worse hospitalization outcomes. Additionally, we found independent associations for having AP that may help identify patients at high risk.

Lacrimal Gland Enlargement as an Extraintestinal Manifestation of Crohn Disease: A Case Report

A 29-year-old woman was referred for a 3-month history of recurrent fever, abdominal pain, and diarrhea. Abdominal computed tomography (CT) scans revealed diffuse intestinal wall thickening involving the transverse colon. When her abdominal pain recurred 1 month later, she noticed bilateral upper eyelid edema with an “S-shaped” contour. Lacrimal gland CT scans revealed enlarged lacrimal glands. Crohn disease sometimes presents with extraintestinal symptoms including ocular complications. Dacryoadenitis is rarely associated with ocular complications. Enteroscopy revealed a noncaseating granuloma in the small intestine, and Crohn disease was diagnosed. We report the characteristics of dacryoadenitis resulting from Crohn disease and review published case reports.

P053 Interstitial Nephritis from IBD: Complicated Conclusions.

BACKGROUND: Kidney injury in IBD is challenging. Tubulointerstitial nephritis (TIN) is linked to aminosalicylates, but also described in drug-naïve patients, suggesting that TIN may be a direct manifestation of IBD. We describe three cases of TIN in IBD to illustrate the challenges in determining the etiology of the injury. Case #1: 58-year-old male with a horseshoe kidney deformity, uncontrolled hypertension, GERD and small bowel stricturing Crohn's disease (CD), previously on mercaptopurine and allopurinol, subsequently transitioned to adalimumab, maintaining clinical and radiologic remission. Two years later, he developed acute kidney injury in setting of high fevers and sweats, with negative infectious evaluation. Medications included adalimumab, PPI, valacyclovir and torsemide. Renal biopsy revealed TIN with dense, zonal and focal granulomatous features suggestive of drug-induced hypersensitivity, chronic infection, sarcoidosis or an extra-intestinal manifestation of CD. Case #2: 45-year-old female with SLE, nephrolithiasis, GERD, hypertension and ulcerative colitis (UC), initially on mesalamine, then vedolizumab, with clinical and endoscopic remission. Her SCr increased at the time of her UC diagnosis, and worsened over 6 months while on mesalamine, vedolizumab, PPI and losartan. Renal biopsy demonstrated acute and chronic TIN with eosinophils raising concern for an allergic/drug-induced injury. Nephrology concluded that her TIN was secondary to either UC or one of her medications. Case #3: 33-year-old male with UC transitioned to vedolizumab, having failed budesonide and mesalamine. He had latent TB and received 9 months of isoniazid. While on mesalamine, vedolizumab and PPI, he developed fever, chills and night sweats, with an acute rise in SCr, prompting discontinuation of meds. Three months later, still in remission and with improved SCr, he restarted vedolizumab. A year later he developed low-grade fever with elevated SCr, prompting discontinuation. Renal biopsy revealed acute and chronic TIN with severe interstitial fibrosis, tubular atrophy and focal global glomerulosclerosis. He started prednisone and remained off other IBD therapy for 6 months, but repeat colonoscopy revealed mild colitis. He restarted mesalamine, but again developed elevated SCr 2 months later. Repeat renal biopsy revealed TIN with less interstitial fibrosis and focal global glomerulosclerosis, and nephrology suggested his interstitial nephritis was likely secondary to UC over his medications. He started azathioprine with significant improvement in SCr and clinical remission of UC. In all three cases, neither nephrology consultation nor renal biopsy helped distinguish the etiology of renal injury, defaulting to either the IBD meds or an extra-intestinal manifestation of IBD, and not accounting for the acute inflammatory symptoms in two of the cases. While literature review reveals several cases that allege kidney injury as an extra-intestinal target of IBD serious doubts remain. TIN secondary to aminosalicylates is well-documented, but there are few reports of adalimumab-induced granulomatous TIN and only one report of vedolizumab-induced TIN. Each of our patients had well-controlled IBD and multiple confounding variables that could impact kidney function or cause TIN, including hypertension and multiple potential culprit medications, illustrating the dilemma of determining the etiology of renal injury in IBD patients.

Osteoporosis as an initial manifestation in a patient with Crohn's disease: A case report.

The present case report details a rare case of osteoporosis as the initial manifestation of Crohn's disease (CD). A 43-year-old male was referred to the Second Xiangya Hospital of Central South University (Changsha, China) for further examination of low back pain (LBP) without digestive symptoms. Bone mineral density (BMD) analysis indicated osteoporosis, particularly in the lumbar spine. Endoscopy revealed an inflamed and strictured ileocecal valve with less inflammation in the ascending, transverse colon, sigmoid colon and rectum, compatible with CD, which was in accordance with the appearance of an abdominal computed tomography scan. Duodenal-balloon enteroscopy indicated segmental ulceration and stricture in the jejunum, in accordance with CD. The patient was diagnosed with CD following examination. It was suspected that osteoporosis may be an extra-intestinal manifestation of CD. Steroids and biological agents were prescribed in sequence. LBP and BMD rapidly improved following treatment, and inflammatory markers returned to normal after 1.5 years of treatment. According to this case, osteoporosis with unknown causes should be considered as a possible sign of small intestinal CD.

Penile and Scrotal Swelling: An Underrecognized Presentation of Crohn's Disease.

Penile and scrotal swelling can occur as an extraintestinal manifestation of Crohn's disease (CD) and is thought to be an uncommon form of metastatic CD (MCD). Because of the rarity of this manifestation, much is unknown concerning the presentation, treatment, and response to therapy in children with genital MCD. Boys ages 1 to 17 years presenting with genital edema and a confirmed diagnosis or strong suspicion of CD who were evaluated at the Mayo Clinic between 1996 and 2014 were included for review. We sought to characterize the clinical and pathologic features of genital MCD and response to treatment in our cohort of patients. Eight patients with genital MCD were identified from our institution (mean age 11.4 yrs, range 7-16 yrs). Seven (88%) patients experienced cutaneous symptoms before a formal diagnosis of CD was made, and two of the seven had no adverse gastrointestinal symptoms at that time. Patients were prescribed an average of 3.4 medications (topical and systemic) for management of their gastrointestinal CD and MCD. Penile and scrotal swelling can occur as an extraintestinal manifestation of CD and is thought to be an uncommon form of MCD. In boys, genital swelling typically precedes intestinal CD. Treatment of the underlying CD with systemic medications was most helpful in this series. An evaluation for CD is necessary in all patients presenting with unexplained genital swelling.

Clinical Features and Extraintestinal Manifestations of Crohn Disease in Children.

PurposeThe aim of this study was to investigate the clinical features and extraintestinal manifestations (EIMs) of Crohn disease (CD) in Korean pediatric patients.MethodsThe medical records of 73 children diagnosed with CD were retrospectively reviewed. Data regarding baseline demographic and clinical characteristics, including CD phenotype at diagnosis based on the Montreal classification, and clinical features and course of EIMs were investigated.ResultsFifty-two (71.2%) of the patients were males. The mean age of the patients was 12.5 years. The mean follow-up period was 3.4 years. The disease location was ileal in 3 (4.1%) of the patients, colonic in 13 (17.8%), ileocolonic in 56 (76.7%). The clinical behavior was inflammatory in 62 (84.9%) of the patients, stricturing in 8 (11.0%), and penetrating in 3 (4.1%). Perianal abscesses or fistulas were found in 37 (50.7%) of the patients. EIMs observed during the study period were anal skin tag in 25 patients (34.2%), hypertransaminasemia in 20 (27.4%), peripheral arthritis in 2 (2.7%), erythema nodosum in 2 (2.7%), vulvitis in 1 (1.4%), uveitis in 1 (1.4%), and pulmonary thromboembolism in 1 (1.4%).ConclusionPerianal diseases and manifestations were present in more than half of Korean pediatric CD patients at diagnosis. Inspection of the anus should be mandatory in Korean children with suspicious CD, as perianal fistulas, abscesses, and anal skin tags may be the first clue to the diagnosis of CD.

Cutaneous Manifestations of Crohn Disease.

Awareness of the extraintestinal manifestations of Crohn disease is increasing in dermatology and gastroenterology, with enhanced identification of entities that range from granulomatous diseases recapitulating the underlying inflammatory bowel disease to reactive conditions and associated dermatoses. In this review, the underlying etiopathology of Crohn disease is discussed, and how this mirrors certain skin manifestations that present in a subset of patients is explored. The array of extraintestinal manifestations that do not share a similar pathology, but which are often seen in association with inflammatory bowel disease, is also discussed. Treatment and pathogenetic mechanisms, where available, are discussed.

The course of anaemia in children and adolescents with Crohn's disease included in a prospective registry.

The aim of this study is to determine the prevalence and evolution of anaemia in prospectively followed children and adolescents diagnosed with Crohn's disease (CD). The BELCRO registry (inclusion May 2008-April 2010), describing current clinical treatment practice of children diagnosed with CD, provided data on age, height, body mass index (BMI), paediatric Crohn's disease activity index (PCDAI), therapy and haemoglobin (Hb) at diagnosis 12 and 24 months follow-up. Anaemia was defined as Hb < -2 sd, while severe anaemia was defined as Hb < -4 sd. Patients were classified as child ≤13 and adolescent >13 years of age. Ninety-six were included, 13 dropped out due to insufficient Hb data (37 females/46 males; median age 13.3 years, range 2.2-17.8 years). At diagnosis, the median Hb sd was -2.66 (-8.4; 1.07) and was correlated with the PCDAI (p = 0.013). At diagnosis, 51/83 (61%) were anaemic and all had active disease. Hb z-score significantly improved (p < 0.0001) but 26/68 (38%) remained anaemic at 12 months and 29/76 (38%) at 24 months of follow-up. The correlation to the PCDAI disappeared. At 24 months, children were more likely to be anaemic. There was no difference in iron dose nor duration of iron supplements between children and adolescents. Iron treatment was more readily given to patients presenting with anaemia. Hb did not differ between patients with (n = 28) or without iron supplements. Half of the patients with persisting anaemia were given iron supplements, of which, only three were given intravenously. Anaemia remains an important extra-intestinal manifestation of CD in children. Physicians, lacking optimal treatment strategies, undertreat their patients.

Granulomatous Interstitial Nephritis as a Manifestation of Crohn Disease

Granulomatous interstitial nephritis is a rare extraintestinal manifestation of Crohn disease that has been described previously in 4 patients. We report a 23-year-old man with a history of Crohn disease since age 6 years who was admitted to the hospital for weight loss, fever, and bloody diarrhea in the midst of a recent flare up during the past 2 months. Investigations revealed anemia, high erythrocyte sedimentation rate, high C-reactive protein level, and an elevated serum creatinine level. Histopathologic examination of tissue specimens obtained at renal biopsy demonstrated granulomatous interstitial nephritis. Crohn disease needs to be in the differential diagnosis of granulomatous interstitial nephritis and can be a manifestation of drug allergy or the Crohn disease itself.

Capsule Endoscopy (CE) Can Improve Outcomes in Crohnʼs Disease: An Evaluation of Pre- and Post-treatment CE

Purpose: Capsule endoscopy has been demonstrated to be superior to standard endoscopic and radiographic modalities in diagnosing small bowel Crohn's disease (CD), especially for subtle mucosal lesions. However, its utility in tracking treatment response via mucosal healing has not been fully established. The aim of this study is to assess small bowel mucosal healing based on the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI, Dig Dis Sci (2008) 53:1933-27) after initiation or escalation of therapy.Table: Table. Change in CECDAI Pre- and Post-Treatment CEMethods: Retrospective review of CE in patients with suspected and known small bowel nonstricturing CD. CEs were read by two highly experienced readers who were not the managing IBD physicians at a tertiary referral center. Results: 2,190 capsule endoscopies were performed between October, 2001-October, 2012. One hundred fifty eight subjects underwent ≧ 2 capsule endoscopies during that time interval. Of those 158 subjects, 28 had known or suspected CD, for a total of 65 CE. Of those 28 subjects, 17 had known CD (60.7%), seven had suspected CD (25%), three had IBD-U (10.7%), and one had UC (3.6%). 7/11 (63.6%) with suspected CD or IBD-U were re-classified as CD and treated as such after pre-treatment CE. Indications for CE included abdominal pain (35%), extent of CD (20%), diarrhea (19%), growth failure (10%), anemia (8%), gastrointestinal bleed (4%), weight loss (2%), pouchitis (1%), and extraintestinal manifestations of CD (1%). The median age was 32 years old (range: 8-70), there were no capsule retentions, and 48/65 (73.8%) of capsules reached the cecum. The median time interval between pre- and post-treatment CE was 27 months (range: 1-81). CE results lead to escalation of therapy or switching of biologic agents in 15/28 (53.6%). There was a statistically significant difference in the CECDAI between the pre- and post-treatment CE (8.2 versus 4.1, p=0.0250.) However, there was no difference in pre- and post-treatment CRP (0.66 mg/dl vs 0.43 mg/dl, p=.21). Conclusion: CE was able to re-classify disease phenotype in >60% of those patients with suspected Crohn's disease or IBD-U, thereby potentially changing both the management and the natural outcome of small bowel Crohn's disease. More importantly, CE demonstrated mucosal healing in 70% of patients after escalation of therapy with a nonstricturing phenotype, positively changing disease outcomes and achieving a therapeutic goal. A prospective study is needed for confirmation. Disclosure - Neel K. Mann - Grant Support: Given Imaging.

Chronic Inflammatory Demyelinating Polyradiculoneuropathy in a Patient with Crohn's Disease

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that is frequently accompanied by systemic complications. Neuropathologies have not been well investigated as extraintestinal manifestations of CD. We herein report the case of a 36-year-old man with CD who presented with progressive weakness and numbness. A neurological examination and the results of a nerve conduction study and a sural nerve biopsy led to a diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Plasma exchanges were initially effective; however, the effects gradually declined starting 10 days after the plasma exchange (PE). These results suggest that humoral factors may play an important role in CIDP associated with CD.

MRI of vulvar Crohn disease

Crohn disease is a chronic granulomatous inflammatory disorder that most commonly affects the gastrointestinal tract, particularly the distal small bowel and colon. While certain extraintestinal manifestations of Crohn disease are relatively common and well-known, others, such as metastatic cutaneous involvement, are quite rare and may be difficult to recognize, particularly in the pediatric population. This case report illustrates the magnetic resonance imaging (MRI) appearance of vulvar region cutaneous Crohn disease in an 11-year-old girl.

Chronic Pancreatitis an Extraintestinal Manifestation of Crohnʼs: Fact or Fiction?

Purpose: 32 year old male with history of pancreatitis, presents with 2 days of severe epigastric pain. Patient denied weight loss, night sweats, or bloody diarrhea. Medical history is significant for 2 bouts of acute pancreatitis 4 years ago, takes no medications and drinks 2 beers a month. On exam vitals were stable with epigastric tenderness. Labs: amylase 662U/L (0-137U/L), lipase 1395U/L (12-70 U/L), total bilirubin 0.3mg/dL (0.1-1.5 mg/dL), AST 13 IU/L (7-40IU/L), ALT 10 IU/L (7-40 IU/L), calcium 9.5 mg/dL (8.5-10.5 mg/dL), triglyceride 44 mg/dL (35-150 mg/dL), IgG subclasses 1-4 normal and WBC 11 K/uL (4.5-11.5 K/uL). CT: mild peripancreatic inflammatory stranding extending throughout the pancreas. Ultrasound: normal gallbladder without cholelithiasis or ductal dilatation and unremarkable pancreas. Patient was treated with narcotics and IV fluids. Hospital day #3 patient had worsening abdominal pain and distention. Patient was treated with nasogastric tube, followed by colonoscopy for decompression. Colonoscopy: scattered erythema, blunting of vascular pattern, and ulcers extending from cecum to descending colon; biopsies taken. Pathology: chronic active colitis with non-caseating granuloma without dysplasia; consistent with Crohn's disease (CD). EUS showed features suggestive of mild chronic pancreatitis. We report a case of pancreatitis as the initial presentation of CD. Pancreatitis is one of several known extraintestinal manifestations of CD and UC. The incidence of pancreatitis as a true extraintestinal manifestation has been a difficult task to prove, as it is rare and many of the drugs used to treat IBD may also cause pancreatitis. Barthet et al found a 1.2% incidence chronic pancreatitis by following all IBD patients over a 15 yr period at a group of French hospitals. Seyrig et al. similarly reported a 1.5% incidence. The previously reported studies may easily be underestimating the incidence in IBD, considering they only evaluated symptomatic patients. It has been reported that some cases of pancreatic involvement may indeed be asymptomatic in IBD. Generally in the natural history of IBD most extraintestinal manifestation occur after the diagnosis, however, a literature review proves that pancreatitis may precede the diagnosis of IBD. The mechanism of pancreatic involvement in IBD is unknown. It has been suggested that inflammatory involvement of the duodenal papilla may cause pancreatic obstruction, thereby leading to pancreatitis. However Barthet et al, reported only 1 periampullary involvement. Others have reported on intrapancreatic granulomatous inflammation. It is important that more research be conducted to understand the mechanism of injury to the pancreas in IBD.

Poster 208: Sudden Onset of Severely Debilitating Extraintestinal Manifestations of Crohn Disease: A Case Report

Poster 208: Sudden Onset of Severely Debilitating Extraintestinal Manifestations of Crohn Disease: A Case Report

Crohn Disease of the Esophagus: A Review of the Literature

Esophageal Crohn disease is a difficult disease both to diagnose and treat. The diagnosis is made in patients with other extraintestinal manifestations of Crohn disease in whom other esophageal pathology has been ruled out. This often requires integration of clinical, endoscopic, radiographic, and histologic findings. Despite its relative rarity, it does cause severe symptoms that are difficult to treat. Treatment requires careful integration of medical, endoscopic, and surgical techniques. This review aims to discuss the significant literature regarding diagnosis and treatment of this important manifestation of inflammatory bowel disease. There is additional discussion of the literature regarding the efficacy of newer medical and endoscopic therapies, including biologic agents and removable polymer stents.

Extraintestinal Manifestations of Inflammatory Bowel Disease

Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) have been reported to involve almost every organ system. This article focuses on the prevalence (where known) and clinical aspects of the more commonly described EIMs of Crohn disease (CD) and ulcerative colitis (UC). Because of limited data from pediatric populations, much of the information in this review is from adult reports. An important consideration is whether EIMs represent manifestations of the same pathogenetic mechanisms or distinctly different disease processes from the underlying IBD, possibly coincidental to the presence of IBD or as a consequence of the IBD or its treatment. EIMs may present before the onset of gastrointestinal symptoms, during the natural course of disease, and rarely may even follow colectomy in patients with UC. The prevalence of at least 1 EIM in recent population-based studies of patients with IBD ranges from 6% to 47% (1–4). Several reports from pediatric centers suggest a greater prevalence in younger patients. Grossman and DeBenedetti (5) reported that 68% of 41 children with IBD had EIMs, and a recent review of pediatric patients by Stawarski et al (6) reported that 50% with UC and 80% with CD had at least 1 EIM. In this review, we provide an overview of EIMs that have been reported to be associated with UC and CD, emphasizing the pediatric experience when such information is available. EIMs are subdivided into several categories: colitis related, specifically skin, eye, joint, and mouth, where the activity of the EIM parallels the activity of the underlying intestinal disease; hepatobiliary; impaired growth; EIMs secondary to complications of or as direct extensions of bowel disease, more frequently noted in patients with CD than with UC and including nephrolithiasis, obstructive uropathy, cholelithiasis, and pancreatitis; and EIMs that cannot be categorized clearly in one of the other groups, such as amyloidosis and cancer (7). EIMs involving vascular, hematological, pulmonary, cardiac, and neurological systems probably belong to this last group. Impaired growth, unique to the pediatric age group, may be an EIM potentially related to all of these categories. Iatrogenic EIMs, such as drug-induced bone marrow suppression and corticosteroid-associated myopathy, are not discussed (Table 1). TABLE 1 Extraintestinal manifestation of inflammatory bowel disease

Clinical manifestations of inflammatory bowel disease: East and West differences

Inflammatory bowel disease (IBD) is very common in developed countries, while it is relatively uncommon in Asian countries. However, the incidence of IBD has been increasing in some Asian countries in recent years. Most cases of ulcerative colitis (UC) in Asia are of the chronic relapsing type, run a milder course, and the fulminant type is rarely seen. There is no difference in clinical manifestations between Asian and developed countries. The incidence of Crohn's Disease (CD) is mainly in males in Asia, while it is mainly in females in developed countries. The clinical manifestations of CD are similar between both sets of countries. In China there are less fistulae and perianal diseases, and extraintestinal manifestations of CD are uncommon. In China, 5.6% of patients with UC have a family history, which is lower than 10-20% in developed countries. NOD2/CARD15 variants in the locus of 16q112 (IBD1) are significantly associated with the susceptibility of CD in developed countries, but NOD2/CARD15 variants have not been found in Asian CD patients.