Extraintestinal manifestations in a large series of Italian inflammatory bowel disease patients

AIM: To investigate prevalence, type and time of onset of extraintestinal manifestations (EIMs) in a series of Italian inflammatory bowel disease (IBD) patients.

Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease

BACKGROUND Population of patients with inflammatory bowel disease(IBD)is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality.Growth-differentiation factor-15(GDF-15)is often overexpressed under stress conditions,such as inflammation,malignancies,heart failure,myocardial ischemia,and many others.AIM To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases.An additional aim was to determine possible associations between GDF-15 and multiple clinical,anthropometric and laboratory parameters in patients with IBD.METHODS This cross-sectional study included 90 adult patients diagnosed with IBD,encompassing both Crohn’s disease(CD)and ulcerative colitis(UC),and 67 healthy age-and sex-matched controls.All patients underwent an extensive workup,including colonoscopy with subsequent histopathological analysis.Disease activity was assessed by two independent gastroenterology consultants specialized in IBD,employing well-established clinical and endoscopic scoring systems.GDF-15 serum concentrations were determined following an overnight fasting,using electrochemiluminescence immunoassay.RESULTS In patients with IBD,serum GDF-15 concentrations were significantly higher in comparison to the healthy controls[800(512-1154)pg/mL vs 412(407-424)pg/mL,P<0.001],whereas no difference in GDF-15 was found between patients with CD and UC[807(554-1451)pg/mL vs 790(509-956)pg/mL,P=0.324].Moreover,multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age,sex,and C-reactive protein levels(P=0.016 and P=0.049,respectively).Finally,an association between GDF-15 and indices of anemia was established.Specifically,negative correlations were found between GDF-15 and serum iron levels(r=-0.248,P=0.021),as well as GDF-15 and hemoglobin(r=-0.351,P=0.021).Accordingly,in comparison to IBD patients with normal hemoglobin levels,GDF-15 serum levels were higher in patients with anemia(1256(502-2100)pg/mL vs 444(412-795)pg/mL,P<0.001).CONCLUSION For the first time,we demonstrated that serum concentrations of GDF-15 are elevated in patients with IBD in comparison to healthy controls,and the results imply that GDF-15 might be involved in IBD pathophysiology.Yet,it remains elusive whether GDF-15 could serve as a prognostic indicator in these patients.

Myocarditis as an extraintestinal manifestation of ulcerative colitis:A case report and review of the literature

BACKGROUND Although extraintestinal manifestations of inflammatory bowel disease(IBD) are well documented,myocarditis has only rarely been reported as an extraintestinal manifestation,and it can be fatal.The various clinical presentations and causes of myocarditis in IBD patients complicate making a correct and timely diagnosis.CASE SUMMARY Here we report a 15-year-old boy who presented with myocarditis as the initial presentation of a relapse of ulcerative colitis.In reviewing the literature for cases of myocarditis complicating IBD,we found 21 other cases,allowing us to expand our understanding of the clinical presentation,diagnosis,management,and outcomes of this rare condition.The most frequent diagnostic clues for myocarditis in IBD patients are dyspnea,chest pain,tachycardia,raised cardiac biomarkers,and abnormalities on trans-thoracic echocardiography.Additionally,we discuss the etiology of myocarditis in IBD patients,which include an extraintestinal manifestation,the adverse effects of mesalamine and infliximab,selenium deficiency,and infection,to help provide a framework for diagnosis and management.CONCLUSION Myocarditis as an extraintestinal manifestation of IBD can be life-threatening.Trans-thoracic echocardiogram and cardiac magnetic resonance may assist its diagnosis.

Extraintestinal manifestations and complications in inflammatory bowel diseases

Crohn＇s disease （CD） and ulcerative colitis （UC） are chronic inflammatory bowel diseases （IBD） that often involve organs other than those of the gastrointestinal tract. These nonintestinal affections are termed extraintestinal symptoms. Differentiating the true extraintestinal manifestations of inflammatory bowel diseases from secondary extraintestinal complications, caused by malnutrition, chronic inflammation or side effects of therapy, may be difficult. This review concentrates on frequency, clinical presentation and therapeutic implications of extraintestinal symptoms in inflammatory bowel diseases. If possible, extraintestinal manifestations are differentiated from extraintestinal complications. Special attention is given to the more recently described sites of involvement; i.e. thromboembolic events, osteoporosis, pulmonary involvement and affection of the central nervous system.

Epidemiology and clinical course of Crohn's disease:Results from observational studies

The authors review the clinical outcome in patients with Crohn's disease(CD)based on studies describing the natural course of the disease.Population-based studies have demonstrated that the incidence rates and prevalence rates for CD have increased since the mid-1970s.The authors search for English language articles from 1980 until 2011.Geographical variations,incidence,prevalence,smoking habits,sex,mortality and medications are investigated.An increasing incidence and prevalence of CD have been found over the last three decades.The disease seems to be most common in northern Europe and North America,but is probably increasing also in Asia and Africa.Smoking is associated with an increased risk of developing CD.Age <40 at diagnosis,penetrating/stricturing complications,need for systemic steroids,and disease location in terminal ileum are factors associated with higher relapse rates.A slight predominance of women diagnosed with CD has been found.Ileocecal resection is the most commonly performed surgical procedure,and within the first five years after the diagnosis about one third of the patients have had intestinal surgery.Smoking is associated with a worse clinical course and withincreased risk of flare-ups.In most studies the overall mortality is comparable to the background population.To date,the most effective treatment options in acute flares are glucocorticosteroids and tumor necrosis factor(TNF)-α-blockers.Azathioprine/methotrexate and TNF-α-blockers are effective in maintaining remission.

Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases

AIM To investigate whether immune mediated diseases(IMD) are more frequent in patients with inflammatory bowel disease(IBD).METHODS In this population based registry study,a total of 47325 patients with IBD were alive and registered in the Danish National Patient Registry on December 16,2013. Controls were randomly selected from the Danish Civil Registration System(CRS) and matched for sex,age,and municipality. We used ICD 10 codes to identify the diagnoses of the included patients. The IBD population was divided into three subgroups: Ulcerative colitis(UC),Crohn's disease(CD) and Both the latter referring to those registered with both diagnoses. Subsequently,odds-ratios(OR) and 95%CI were obtained separately for each group and their respective controls. The use of Bonferoni post-test correction adjusted the significance level to P < 0.00125. P-values were estimated using Fisher's exact test.RESULTS There were significantly more women than men in the registry,and a greater percentage of comorbidity in the IBD groups(P < 0.05). Twenty different IMDs were all significantly more frequent in the IBD group. Sixteen were associated with UC versus twelve with CD. In both UC and CD ORs were significantly increased(P < 0.00125) for primary sclerosing cholangitis(PSC),celiac disease,type 1 diabetes(T1D),sarcoidosis,asthma,iridocyclitis,psoriasis,pyoderma gangrenosum,rheumatoid arthritis,and ankylosing spondylitis. Restricted to UC(P < 0.00125) were autoimmune hepatitis,primary biliary cholangitis,Grave's disease,polymyalgia rheumatica,temporal arteritis,and atrophic gastritis. Restricted to CD(P < 0.00125) were psoriatic arthritis and episcleritis. Restricted to women with UC(P < 0.00125) were atrophic gastritis,rheumatoid arthritis,temporal arteritis,and polymyalgia rheumatica. Restricted to women with CD were episcleritis,rheumatoid arthritis,and psoriatic arthritis. The only disease restricted to men(P < 0.00125) was sarcoidosis. CONCLUSION Immune mediated diseases were significantly more frequent in patients with IBD. Our results strengthen the hypothesis that some IMDs and IBD may have overlapping pathogenic pathways.

Oral manifestation in inflammatory bowel disease:A review

Inflammatory bowel diseases (IBDs), including Crohn&#x02019;s disease (CD) and ulcerative colitis, not only affect the intestinal tract but also have an extraintestinal involvement within the oral cavity. These oral manifestations may assist in the diagnosis and the monitoring of disease activity, whilst ignoring them may lead to an inaccurate diagnosis and useless and expensive workups. Indurated tag-like lesions, cobblestoning, and mucogingivitis are the most common specific oral findings encountered in CD cases. Aphthous stomatitis and pyostomatitis vegetans are among non-specific oral manifestations of IBD. In differential diagnosis, side effects of drugs, infections, nutritional deficiencies, and other inflammatory conditions should also be considered. Treatment usually involves managing the underlying intestinal disease. In severe cases with local symptoms, topical and/or systemic steroids and immunosuppressive drugs might be used.

Impact of COVID-19 pandemic on the neuropsychiatric status of Wilson’s disease

We have read with interest the Letter to the Editor by Drs.Zhuang and Zhong,who presented the clinical data of 68 patients with Wilson’s disease(WD)who were admitted to the hospital before and during the coronavirus disease 2019(COVID-19)pandemic,and appreciated their findings on hepatic and some extrahepatic manifestations.Nevertheless,given the strong impact of the pandemic on patients with neurological and psychiatric disorders,we would have expected a worsening of the psychiatric and/or neurological impairments in these patients.In contrast,according to the authors,these manifestations remained,somewhat unexpectedly,unchanged.This finding is in contrast with most of the current literature that highlights not only an increased incidence of mental health disorders in the general population but also an exacerbation of neurological and psychiatric symptoms in patients with chronic diseases,especially in those with pre-existing neuropsychiatric disorders,such as WD.Although the study was mainly focused on the hepatic features of WD patients taking anti-copper treatment,a generic and cumulative definition of neurological and psychiatric manifestations,as in this study,does not allow for further considerations.Future studies during and after the pandemic are necessary to clarify the real impact,either direct or indirect,of the COVID-19 pandemic on the neurological and psychiatric symptoms of WD patients.

A Fatal Case of Treatment-Related Adverse Effects in Granulomatosis with Polyangiitis (Wegener’s Granulomatosis)

Well-studied therapies have proven to be effective in treating Granulomatosis with polyangiitis (formerly Wegener’s granulomatosis) (GPA). There has been considerable improvement in survival of patients with GPA but treatment related morbidity and mortality remains still high, particularly in patients with renal disease. We describe a case of 64-year old woman with recent onset GPA, who responds well to the initial cyclophosphamide based therapy but latter develops a fatal stroke. Infectious complications should be considered in patients with GPA who are on adequate immunosuppression but develop symptoms that may mimic a relapse. Aggressive diagnostic interventions should be undertaken to discriminate between an infection and a relapse of GPA.

Ocular Manifestations in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is the most common autoimmune disease. Ocular manifestations of this autoimmune disease vary and are mainly keratoconjunctivitis sicca, episcleritis, scleritis and keratitis. Their appearance, as well as their severity are related to RA chronicity and resistance to therapy. The treatment consists of corticosteroids, NSAIDs and cytotoxic drugs, depending on the type of ocular manifestations and the patient’s response to treatment.

Sézary综合征1例报告及文献复习

目的归纳、分析S啨zary综合征的临床表现特征,提高对该病的诊疗水平。方法报告1例S啨zary综合征患者,并复习相关文献。结果患者男59岁,以全身皮肤潮红伴瘙痒为主要特征,外周血淋巴细胞达171.9×109/L,骨髓中异常淋巴细胞达33.5%,经大剂量糖皮质激素等治疗后缓解。1994年至今国内共报道11例S啨zary综合征患者,男性10例占90.9%,平均年龄56.9±19.1岁,以红皮病、剧痒为显著皮肤表现。结论S啨zary综合征是一种较罕见的T细胞淋巴瘤,多见于老年男性,早期皮肤损害显著但不典型,易被误诊为神经性皮炎、湿疹等。

炎症性肠病伴皮肤表现的临床与病理分析

目的 分析炎症性肠病(IBD)皮肤表现的临床及组织病理特点,为临床诊断提供指导。方法 回顾性分析2例IBD伴皮肤表现的临床及病理特点。结果 1例患者为克罗恩病合并皮肤表现,皮损表现为肛周红斑、溃疡,组织病理表现为真皮非干酪样非感染性肉芽肿,使用乌司奴单抗治疗后溃疡面积缩小。另1例为溃疡性结肠炎合并肠外表现,皮损表现为全身红斑、结节,小腿、臀部可见溃疡,组织病理表现为真皮中性粒细胞浸润,使用英夫利昔单抗治疗后皮损部分消退。结论 IBD合并皮肤表现具有不同的组织病理学特点。诊断时临床医生需结合临床表现及组织病理以免误诊漏诊。

Rasmussen综合征的临床过程及脑电图和神经影像学特征

目的:探讨Rasmussen综合征的临床过程及脑电图和神经影像学特征。方法:借助EEG、CT和MRI技术,进行临床观察和药物治疗及复习文献资料。结果:本组2例患儿均经过1～2年的临床随访,进行了必要的辅助检查和正规的抗癫痫治疗,临床确诊。起病年龄分别为2岁2月和6岁8月;以反复局灶性癫痫发作、慢性进行性部分性癫痫持续状态和一侧优势的全面性癫痫发作为主,伴进行性偏瘫和认知功能障碍和语言障碍(优势半球受累);EEG示持续性局灶慢活动异常伴后期棘慢波发放;MRI显示逐渐加重的局灶性高信号果影和脑萎缩;常规抗痫疗效差。结论:Rasmussen综合征是一种特殊类型的局灶性癫痫综合征,具有独特的临床表现以及脑电图和影像学特征,其病理生理和治疗措施具有研究价值。

以肝病症状为首发表现的成人Wilson病36例并文献复习

目的：对以肝病症状为首发表现的成人Wilson病的临床表现、实验室检查、诊断与治疗进行分析,旨在提高临床医师对本病的认识及避免延误诊断。方法：回顾分析2003年6月—2009年6月确诊的36例以肝病症状为首发表现的Wilson病患者的临床资料。结果：5例患者同时存在神经系统症状。最常见的肝病首发症状依次为腹胀、腹水（69%）,纳差（56%）,恶心、呕吐（50%）,少见症状为呕血、黑便（11%）,肝、脾肿大是最主要的体征;大多数患者肝功能异常;50%的患者发现角膜色素环;94%的患者血铜蓝蛋白〈0.2g.L-1。有30例早期延误诊断。所有患者采用低铜饮食,主要治疗药物为口服青霉胺（0.6~1.5g.d-1）,2例晚期肝病患者接受肝移植手术。结论：以肝病症状为首发表现的成人Wilson病常被延误诊断,其诊断仍依赖于临床表现结合角膜色素环及铜代谢异常的生化指标。

Maffucci’s综合征临床及病理分析

目的分析Maffucci’s综合征的临床病理特点,提高对该疾病的认识。方法对1例Maffucci’s综合征病例特点进行分析,并复习国内52例文献,分析其临床病理特点。结果该病发病率低,与性别无关,慢性起病,多见于青春期,无家族史;四肢皮下多发性血管瘤往往为其首发症状,骨软骨瘤好发于四肢长骨的干骺端,呈多发性,伴有关节肿胀、畸形及静脉石,恶变4例。X线示多发囊状膨胀性骨质破坏,病理表现为分化良好的肿瘤性软骨细胞及软骨基质组成。结论 Maffucci综合征是一种多发性内生性软骨瘤病伴有软组织血管瘤的慢性非遗传性疾病,罕见恶变。病变部位以四肢长骨为主,X线和病理检查是其有效的诊断手段,无特殊治疗方法,与胚胎时期软骨发育障碍有关,具体机制至今不清。

Crohn’s病的肠外表现特征及其临床意义

目的探讨Crohn’s病(CD)患者肠外表现的特点和临床意义。方法回顾性收集有肠外并发症表现的51例CD患者的临床资料,分析患者出现肠外并发症的特征表现,结合文献报道对比复习这些肠外并发症在Crohn’s的诊断和治疗中的意义。结果51例患者肠外表现依次为骨关节病变、口腔溃疡、肝胆病变、皮肤病变、眼部、代谢性骨病、血管闭塞等。出现一种肠外病变的29例,两种肠外病变的为13例,三种或以上病变的为9例。原发CD病灶的受累范围越广,其肠外表现的种类越多。结论肠外表现与Crohn’s病的累及部位与严重度有一定关系,肠外并发症对其原发Crohn’s病诊断和治疗均有一定的影响。

Oral pathology in inflammatory bowel disease

The incidence of inflammatory bowel diseases (IBD) - Crohn&#x02019;s disease (CD) and ulcerative colitis (UC) - has been increasing on a global scale, and progressively, more gastroenterologists will be included in the diagnosis and treatment of IBD. Although IBD primarily affects the intestinal tract, extraintestinal manifestations of the disease are often apparent, including in the oral cavity, especially in CD. Specific oral manifestations in patients with CD are as follows: indurate mucosal tags, cobblestoning and mucogingivitis, deep linear ulcerations and lip swelling with vertical fissures. The most common non-specific manifestations, such as aphthous stomatitis and angular cheilitis, occur in both diseases, while pyostomatitis vegetans is more pronounced in patients with UC. Non-specific lesions in the oral cavity can also be the result of malnutrition and drugs. Malnutrition, followed by anemia and mineral and vitamin deficiency, affects the oral cavity and teeth. Furthermore, all of the drug classes that are applied to the treatment of inflammatory bowel diseases can lead to alterations in the oral cavity due to the direct toxic effects of the drugs on oral tissues, as well as indirect immunosuppressive effects with a risk of developing opportunistic infections or bone marrow suppression. There is a higher occurrence of malignant diseases in patients with IBD, which is related to the disease itself and to the IBD-related therapy with a possible oral pathology. Treatment of oral lesions includes treatment of the alterations in the oral cavity according to the etiology together with treatment of the primary intestinal disease, which requires adequate knowledge and a strong cooperation between gastroenterologists and specialists in oral medicine.

Sudden blindness in a child with Crohn's disease

Inflammatory bowel disease(IBD) is often associated with extraintestinal manifestations(EIMs) such as optic neuritis(ON),although this has been described in only a few adult patients so far,all of whom were affected with Crohn's disease(CD).Furthermore,ON and demyelinating diseases have been demonstrated to be more frequent in IBD patients than in control populations.In our current case report,we describe a child with active CD who developed sudden blindness due to bilateral ON that was not related to any known cause,and that promptly responded to a high dose of steroids.Investigations and a clinical follow-up have so far ruled out the development of demyelinating diseases in this patient.To our knowledge,this is the first report of ON in a pediatric patient with CD.Possible explanations for this case include an episodic EIM of an active bowel disease,an associated autoimmune disorder such as a recurrent isolated ON,the first manifestation of multiple sclerosis,or another demyelinating disease that could appear in a later follow-up.

Pancreatic disorders in inflammatory bowel disease

An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been recorded in patients with inflammatory bowel disease (IBD) compared to the general population. Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced, in some cases pancreatitis were defined as idiopathic, suggesting a direct pancreatic damage in IBD. Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn&rsquo;s disease and ulcerative colitis. This review will discuss the most common pancreatic diseases seen in patients with IBD.

Crohn's disease-related'gastrocnemius myalgia syndrome'successfully treated with infliximab:A case report

BACKGROUND Extra-intestinal manifestations in inflammatory bowel diseases(IBD)are frequent and involve virtually all organs.Conversely,the clinical characteristics and course of inflammatory myopathies in IBD remain poorly described and mostly related to orbital myositis.Moreover,alternative therapeutic strategies in non-responder patients to corticosteroid therapy must still be clarified.CASE SUMMARY A 33-year-old woman with a history of unclassified colitis presented with acute bilateral calf pain.On admission,her clinical and biological examinations were non-specific.However,magnetic resonance imaging showed bilateral inflammatory changes in gastrocnemius muscles suggestive of myositis.Muscle biopsy confirmed the diagnosis of myositis and demonstrated an inflammatory infiltrate mainly located in the perimysial compartment including lympho-plasmocytic cells with the formation of several granulomatous structures while the endomysium was relatively spared.The combined clinical,biological and histomyopathological findings were concordant with the diagnosis of‘gastrocnemius myalgia syndrome’(GMS),a rare disorder associated with Crohn’s disease(CD).Ileocolonoscopy confirmed CD diagnosis and systemic corticosteroids(CS)therapy was started,resulting in a rapid clinical improvement.During CS tapering,however,she experienced a relapse of GMS together with a severe active ileocolitis.Infliximab was started and allowed a sustained remission of both conditions at the latest follow-up(20 mo).CONCLUSION The GMS represent a rare CD-associated inflammatory myopathy for which anti-tumour necrosis factor-αtherapy might be considered as an effective therapeutic option.