Chronic HCV infection and inflammation:Clinical impact on hepatic and extra-hepatic manifestations

The liver has a central role in regulating inflammation by its capacity to secrete a number of proteins that control both local and systemic inflammatory responses. Chronic inflammation or an exaggerated inflammatory response can produce detrimental effects on target organs. Chronic hepatitis C virus(HCV) infection causes liver inflammation by complex and not yet well-understood molecular pathways, including direct viral effects and indirect mechanisms involving cytokine pathways,oxidative stress and steatosis induction. An increasing body of evidence recognizes the inflammatory response in chronic hepatitis C as pathogenically linked to the development of both liver-limited injury(fibrosis, cirrhosis and hepatocellular carcinoma) and extrahepatic HCV-related diseases(lymphoproliferative disease,atherosclerosis, cardiovascular and brain disease). Defining the complex mechanisms of HCV-induced inflammation could be crucial to determine the global impact of infection, to estimate progression of the disease, and to explore novel therapeutic approaches to avert HCVrelated diseases. This review focuses on HCV-related clinical conditions as a result of chronic liver and systemic inflammatory states.

Extra-hepatic manifestations associated with hepatitis E virus infection:a comprehensive review of the literature

Background and aims:Hepatitis E virus(HEV)infection is a significant public health problem that afflicts almost 20 million individuals annually and causes acute liver injury in 3.5 million,with approximately 56000 deaths.As with other viral hepatitides,extra-hepatic manifestations could represent an important aspect of this infection.The spectrum of these manifestations is still emerging.Acute pancreatitis and neurological,musculoskeletal,hematological,renal,and other immune-mediated manifestations have been described.The aim of this article is to comprehensively review the published literature of extra-hepatic manifestations associated with HEV infection.Data sources:We searched the PubMed database using the MeSH term“hepatitis E”and each of the extra-hepaticmanifestations associated with HEV infection.No language or date restrictions were set in these searches.Searches retrieving articles with non-A,non-B hepatitis were excluded.Additional articles were identified through the reference lists of included articles.Results:Several extra-hepatic manifestations associated with HEV infection have been published.The temporal association between some extra-hepatic manifestations and HEV infection and the exclusion of other possible etiologies suggests that HEV infection could have caused some of them.According to the available data,HEV infection appears to be strongly associated with acute pancreatitis,neurological disorders(with primarily dominant peripheral nerve involvement,most commonly manifested as Guillain-Barre´syndrome,followed by neuralgic amyotrophy),hematological diseases(hemolytic anemia due to glucose phosphate dehydrogenase deficiency,and severe thrombocytopenia),glomerulonephritis,and mixed cryoglobulinemia.More data are needed to clarify whether an association exists with musculoskeletal or other immunemediated manifestations.Conclusions:HEV infection should be considered in patients with acute pancreatitis,Guillain-Barre´syndrome,neuralgic amyotrophy,hemolytic anemia due to glucose phosphate dehydrogenase deficiency,severe thrombocytopenia,glomerulonephritis,and mixed cryoglobulinemia.Alternatively,signs and symptoms of these conditions should be sought in patients with acute or chronic HEV infection.More data are needed to confirm the role of HEV in other extra-hepatic disorders.

Clinical manifestations,diagnosis and long-term prognosis of adult autoimmune enteropathy:Experience from Peking Union Medical College Hospital

BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE patients.AIM To improve overall understanding of this disease’s diagnosis and prognosis.METHODS We retrospectively analyzed the clinical,endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023,whose diagnosis was based on the 2007 diagnostic criteria.RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea.The common endoscopic manifestations were edema,villous blunting and mucosal hyperemia in the duodenum and ileum.Villous blunting(100%),deep crypt lymphocytic infiltration(67%),apoptotic bodies(50%),and mild intraepithelial lymphocytosis(69%)were observed in the duodenal biopsies.Moreover,there were other remarkable abnormalities,including reduced or absent goblet cells(duodenum 94%,ileum 62%),reduced or absent Paneth cells(duodenum 94%,ileum 69%)and neutrophil infiltration(duodenum 100%,ileum 69%).Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies.All patients received glucocorticoid therapy as the initial medication,of which 14/16 patients achieved a clinical response in 5(IQR:3-20)days.Immunosuppressants were administered to 9 patients with indications of steroid dependence(6/9),steroid refractory status(2/9),or intensified maintenance medication(1/9).During the median of 20.5 months of followup,2 patients died from multiple organ failure,and 1 was diagnosed with non-Hodgkin’s lymphoma.The cumulative relapse-free survival rates were 62.5%,55.6%and 37.0%at 6 months,12 months and 48 months,respectively.CONCLUSION Certain histopathological findings,including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies,might be potential diagnostic criteria for adult AIE.The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications,which highlights the need for early diagnosis and novel medications.

Neurological Manifestations of Vitamin B12 Deficiency: About a Case

The authors report a case of deficient sensory neuropathy secondary to vitamin B12 deficiency, diagnosed in the neurology department of the Sino-Central African Friendship University Hospital in Bangui. The diagnosis was made possible by electroneuromyography which showed subclinical neurological damage associated with hematological damage (anemia). Through this observation, we recall the diagnostic criteria of the disease in a context of difficult medical practice. .

Rare extraintestinal manifestations of ulcerative colitis treated with dual biologic therapy:A case report

BACKGROUND Ulcerative colitis(UC)is an idiopathic,chronic inflammatory bowel disease(IBD)most often located in the rectum,but may involve the entire colon.Extra intestinal manifestations(EIMs)occur with varying frequency depending on the affected organ.The most common ones are musculoskeletal EIMs,affecting up to 33%-40%of IBD patients.These include,among others,inflammatory back pain,tendinitis,plantar fasciitis and arthritis.Only a few case reports in literature discuss Achilles tendinitis.CASE SUMMARY This report describes a patient with UC and Achilles tendinitis in whom after many unsuccessful attempts of treatment with sulfasalazine,mesalazine,glucocorticosteroids,infliximab and tofacitinib,a complete UC remission and resolution of Achilles tendinitis were achieved with the use of dual biologic therapy(DBT)-ustekinumab and adalimumab(ADA).CONCLUSION This case mentions rare EIMs of UC and suggests that DBT may be an alternative for patient with ulcerative colitis and EIMs.

Osteoarticular Manifestations of Pediatric Acute Lymphoblastic Leukemia: Study of an Observation and Review of the Literature

Introduction: Acute lymphoblastic leukemia (ALL) is a monoclonal hematological malignancy characterized by infiltration of the bone marrow by more than 20% of hematopoietic cells with blocked differentiation, called blasts, belonging to the lymphoblastic lineage of lymphoid nature (B or T lymphoblasts). Around 40% of childhood cancers are leukemias, and 85% of these are ALL. The first descriptions of osteoarticular involvement as an inaugural manifestation date back to 1913 with August Strauch. Our aim was to describe an isolated case of ALL with osteoarticular manifestations as an inaugural event supported by a review of the literature. Observation: A 14-year-old adolescent with no known pathological history was referred from pediatrics to investigate the etiology of a chronic peripheral polyarthritis that had been progressively evolving for about seven weeks. Clinically, he presented with chronic peripheral polyarthritis, polysynovitis, non-ankylosing deforming involving knees, shoulders, wrists, and proximal interphalangeals (PIP), and a leukemic facies (facial puffiness and periorbital erythema). Biological investigations revealed a non-specific inflammatory syndrome with a VS of 60 mm in the first hour and CRP increased to 45 mg/l (N ≤ 6 mg/l). The blood count showed hyperleukocytosis at 25,600/mm3 with lymphocyte predominance at 18,660/mm3, normocytic normochromic anemia with hemoglobin at 11 g/dl, and hyperplakettosis at 510,000/mm3. The blood smear showed 37% blasts confirmed on the medullogram, with more than 20% blastic invasion and a predominance of common B-type lymphocytes on immunophenotyping with negative Philadelphia. Immunological, renal, infectious, hepatic, lipid, and uricemia tests were normal. These clinical and paraclinical findings led to the diagnosis of B-type lymphocytic leukemia. The patient received multidrug therapy for induction, consolidation, and intensification. As part of the management of his osteoarticular disorders, infiltrations of the large painful joints were carried out with an adequate phosphocalcic intake. Conclusion: Leukemia is a diagnostic and therapeutic emergency, and osteoarticular damage may be the initial presentation.

Comparison of Oral Manifestations in Hospitalized COVID-19 Positive Patients and COVID-19 Negative Dental Outpatients. A Case Series Study and Literature Review

Background: The Coronavirus disease 2019 (COVID-19) is a respiratory infectious disease, also named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which can cause various systemic manifestations that pose a threat to human life. Oral lesions in patients with COVID-19 may appear during or after the illness and may or may not be a consequence of the viral infection. Objective: In this case series we compare the oral manifestations in hospitalized COVID-19 positive patients and COVID-19 negative dental outpatients. Methods: 60 hospitalized COVID-19 patients and 41 control patients, were examined for oral signs and symptoms. The controls were dental patients who visited the hospital for dental care without complaining of any problems related to the oral cavity itself. Results: We have observed a strong association between certain clinical findings and COVID-19, including alterations in taste (ageusia, dysgeusia, and hypogeusia), anosmia, hairy tongue, tongue imprints, red tongue, erythematous candidiasis, pseudomembranous candidiasis, and exfoliative cheilitis. A trend but not statistically significant association at the level of 5% was also noted for colored tongue, linea alba, and pale mucosa. On the contrary, fissured tongue and oral mucosa pigmentation were more frequent in the controls, statistically significant at the level of 5%. Conclusion: COVID-19 has been found to impact the oral cavity, resulting in various oral lesions that can be attributed to either the direct action of the virus or the patient’s immune response.

The relationship between the distribution of HBcAg in liver cells and the pathological manifestations of the liver in 429 HBeAg-positive chronic HBV-infected individuals

Background:The natural history of chronic HBV infection is typically characterized by four stages:the immune tolerance period,the immune clearance period,the immune control period,and the immune escape period.These stages are associated with the distribution of HBcAg in liver cells;however,this relationship remains a topic of broad debate within the field of liver disease.To objectively and quantitatively measure the intracellular distribution of HBcAg,this paper aims to design a method referred to as the“layered evaluation method”and to examine its validation.Methods:The distribution of HBcAg in liver cells is assessed using Image Pro Plus image processing software,along with calculations of cytoplasmic and nuclear positive staining rates.Results:The findings indicate that the highest proportion of patients exhibited a positive cytoplasmic expression rate ranging from 0-2.5%.More than 40% of the total sample was categorized within the 0-2.5% positive nuclear expression range.The HBcAg cytoplasmic positive staining rates were classified into five levels:a cytoplasmic HBcAg positive staining rate of less than 0.05% is designated as level 0,indicating negative expression;a staining rate between 0.05% and 5% is classified as level 1;a rate from 5% to less than 10% is classified as level 2;a rate from 10% to less than 20% is classified as level 3;and a nuclear positivity rate exceeding 20% is classified as level 4.Conclusion:The inflammatory activity grade in these patients was positively correlated with the cytoplasmic distribution of HBcAg.Furthermore,the nuclear distribution rate of HBcAg was significantly higher in the G3 group compared to the other groups.

Analysis of Manifestations of and Solutions to Chinglish

Chinglish often occurs in the process of English language acquisition.It’s necessary to clarify what Chinglish is and what the major features are.The paper elaborates five major manifestations of Chinglish in terms of phonological difference,lexical redundancy and word misuse,unreasonable sentence structure as well as semantic misuse,and then proposes solutions to Chinglish through improvement of linguistic competence,conversion of thinking modes and enhancement of the awareness of cultural factors.

Osteoarticular manifestations of human brucellosis:A review

Brucellosis is a common global zoonotic disease, which is responsible for a range of clinical manifestations. Fever, sweating and musculoskeletal pains are observed in most patients. The most frequent complication of brucellosis is osteoarticular involvement, with 10% to 85% of patients affected. The sacroiliac(up to 80%) and spinal joints(up to 54%) are the most common affected sites.Spondylitis and spondylodiscitis are the most frequent complications of brucellar spinal involvement. Peripheral arthritis, osteomyelitis, discitis, bursitis and tenosynovitis are other osteoarticular manifestations, but with a lower prevalence. Spinal brucellosis has two forms: focal and diffuse. Epidural abscess is a rare complication of spinal brucellosis but can lead to permanent neurological deficits or even death if not treated promptly. Spondylodiscitis is the most severe form of osteoarticular involvement by brucellosis, and can have single-or multifocal involvement. Early and appropriate diagnosis and treatment of the disease is important in order to have a successful management of the patients with osteoarticular brucellosis. Brucellosis should be considered as a differential diagnosis for sciatic and back pain, especially in endemic regions. Patients with septic arthritis living in endemic areas also need to be evaluated in terms of brucellosis. Physical examination, laboratory tests and imaging techniques are needed to diagnose the disease. Radiography, computed tomography, magnetic resonance imaging(MRI) and bone scintigraphy are imaging techniques for the diagnosis of osteoarticular brucellosis. MRI is helpful to differentiate between pyogenic spondylitis and brucellar spondylitis. Drug medications(antibiotics)and surgery are the only two options for the treatment and cure of osteoarticular brucellosis.

Scrub typhus:pathophysiology,clinical manifestations and prognosis

Scrub typhus is a zoonosis caused by the pathogen Orientia tsutsugamushi(O.tsvtsugamushi). The disease has significant prevalence in eastern and Southeast Asia.Usually presenting as an acute febrile illness,the diagnosis is often missed because of similarities with oilier tropical febrile infections.Many unusual manifestations are present,and these are described in this review,together with an outline of current knowledge of pathophysiology.Awareness of these unusual clinical manifestations will help the clinician to arrive at an early diagnosis,resulting in early administration of appropriate antibiotics.Prognostic indicators for severe disease have not yet been clearly established.

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.

Extrahepatic immune related manifestations in chronic hepatitis C virus infection

The association of chronic hepatitis C with immune related syndromes has been frequently reported.There is a great range of clinical manifestations affecting various systems and organs such as the skin,the kidneys,the central and peripheral nervous system,the musculoskeletal system and the endocrine glands.Despite the high prevalence of immune related syndromes in patients with chronic hepatitis C,the exact pathogenesis is not always clear.They have been often associated with mixed cryoglobulinemia,a common finding in chronic hepatitis C,cross reaction with viral antigens,or the direct effect of virus on the affected tissues.The aim of this review is to analyze the reported hepatitis C virus immune mediated syndromes,their prevalence and clinical manifestations and to discuss the most supported theories regarding their pathogenesis.

Hepatobiliary manifestations in inflammatory bowel disease: The gut,the drugs and the liver

Abnormal liver biochemical tests are present in up to30%of patients with inflammatory bowel disease(IBD),and therefore become a diagnostic challenge.Liver and biliary tract diseases are common extraintestinal manifestations for both Crohn’s disease and ulcerative colitis(UC),and typically do not correlate with intestinal activity.Primary sclerosing cholangitis(PSC)is the most common hepatobiliary manifestation of IBD,and is more prevalent in UC.Approximately 5%of patients with UC develop PSC,with the prevalence reaching up to 90%.Cholangiocarcinoma and colon cancer risks are increased in these patients.Less common disorders include autoimmune hepatitis/PSC overlap syndrome,IgG4-associated cholangiopathy,primary biliary cirrhosis,hepatic amyloidosis,granulomatous hepatitis,cholelithiasis,portal vein thrombosis,liver abscess,and non-alcoholic fatty liver disease.Hepatitis B reactivation during immunosuppressive therapy is a major concern,with screening and vaccination being recommended in serologically negative cases for patients with IBD.Reactivation prophylaxis with entecavir or tenofovir for 6to 12 mo after the end of immunosuppressive therapy is mandatory in patients showing as hepatitis B surface antigen(HBsAg)positive,independently from viral load.HBsAg negative and anti-HBc positive patients,with or without anti-HBs,should be closely monitored,measuring alanine aminotransferase and hepatitis B virus DNA within 12 mo after the end of therapy,and should be treated if the viral load increases.On the other hand,immunosuppressive therapy does not seem to promote reactivation of hepatitis C,and hepatitis C antiviral treatment does not influence IBD natural history either.Most of the drugs used for IBD treatment may induce hepatotoxicity,although the incidence of serious adverse events is low.Abnormalities in liver biochemical tests associated with aminosalicylates are uncommon and are usually not clinically relevant.Methotrexaterelated hepatotoxicity has been described in 14%of patients with IBD,in a dose-dependent manner.Liver biopsy is not routinely recommended.Biologics-related hepatotoxicity is rare,but has been shown most frequently in patients treated with infliximab.Thiopurines have been associated with veno-occlusive disease,regenerative nodular hyperplasia,and liver peliosis.Routine liver biochemical tests are recommended,especially during the first month of treatment.All these conditions should be considered in IBD patients with clinical or biochemical features suggestive of hepatobiliary involvement.Diagnosis and management of these disorders usually involve hepatologists and gastroenterologists due to its complexity.

Ocular manifestations of internal carotid artery dissection

Internal carotid artery dissection(ICAD) results from disruption of the intima of the arterial wall, and can lead to intrusion of blood into the arterial wall and form an intramural hematoma. The hematoma can compress the true lumen of the vessel, causing functional stenosis or occlusion. The classic triad signs of ICAD include pain in the ipsilateral neck, head and orbital regions; a(partial) Horner syndrome; and cerebral or retinal ischemia. However, not all ICAD patients present with this classic signs. In some cases, ocular manifestations are the initial(and sometimes the only) findings. We summarize the ocular manifestations associated with ICAD in 3 categories: visual symptoms, oculosympathetic palsy, and ocular motor nerve palsy.

Extraintestinal manifestations of inflammatory bowel disease:Do they influence treatment and outcome?

Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases that often involve organs other than those of the gastrointestinal tract. Immune-related extraintestinal manifestations (EIMs) are usually related to disease activity, but sometimes may take an independent course. Globally, about one third of patients develop these systemic manifestations. Phenotypic classification shows that certain subsets of patients are more susceptible to developing EIMs, which frequently occur simultaneously in the same patient overlapping joints, skin, mouth, and eyes. The clinical spectrum of these manifestations varies from mild transitory to very severe lesions, sometimes more incapacitating than the intestinal disease itself. The great majority of these EIMs accompany the activity of intestinal disease and patients run a higher risk of a severe clinical course. For most of the inflammatory EIMs, the primary therapeutic target remains the bowel. Early aggressive therapy can minimize severe complications and maintenance treatment has the potential to prevent some devastating consequences.

Smoking increases the risk of extraintestinal manifestations in Crohn's disease

AIM:To demonstrate a high prevalence of extraintestinal manifestations(EIMs)in a prospective populationbased cohort of inflammatory bowel disease(IBD)patients at first diagnosis as well as during the early course of the disease.METHODS:EIMs are common in patients with IBD.Data on the frequency of EIMs have mostly been assessed in patients from tertiary centers;however,data about the prevalence of EIMs at first diagnosis as well as factors influencing their incidence during the early course of disease from prospective population-based cohorts are scarce.We present data of patients of our population-based"Oberpfalz cohort"(Bavaria,Germany)from first diagnosis(up to 3 mo after first diagnosis)as well as during the early course of the disease.Possible risk factors were assessed by calculating the relative risk(RR)as well as using logistic regression analysis.RESULTS:In total,data of 257 newly diagnosed patients with IBD were evaluated[161 Crohn’s disease(CD),96 ulcerative colitis(UC)].Median duration of follow-up was 50 mo after first diagnosis.In 63.4%of all patients(n=163),an EIM was diagnosed at any point during the observation period.At first diagnosis,patients with CD had a significantly increased risk of an EIM[n=69(42.9%)]compared with UC patients[n=21(21.9%);P<0.001;RR=1.96;95%CI:1.30-2.98].Active smoking increased the risk of CD patients developing an EIM during the early course of the disease,but notably not of UC patients(P=0.046;RR=1.96;95%CI:1.01-3.79).In addition,using logistic regression analysis,the need for IBD-related surgery and a young age at first diagnosis were identified as risk factors for the development of an EIM in CD patients.No association with EIMs was found for the factors sex,localization of the disease and positive family history of IBD.In contrast,no key factors which increased the risk of development of an EIM could be identified in UC patients.CONCLUSION:We found a high prevalence of EIM in this cohort at first diagnosis and during the early course of the disease.In patients with CD,smoking,need for surgery and younger age at first diagnosis were risk factors for the development of an EIM.

Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment

The hepatitis E virus(HEV)is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s.Globally,it is one of the most frequent causes of acute viral hepatitis.The majority of HEV infections are asymptomatic and lead to the spontaneous clearance of the virus.Among the eight different genotypes identified to date,HEV genotype 1(HEV1),HEV2,HEV3,and HEV4 are the most frequent genotypes causing infections in humans.HEV1 and HEV2 are prevalent in developing regions and able to result in large-scale outbreaks originating from contaminated water supplies.They are also responsible for severe hepatitis in pregnant patients and infants.In contrast,HEV3 and HEV4 are zoonotic,and the transmission of these genotypes to humans occurs mainly through the fecal contamination of water and consumption of contaminated meat from infected animals.Their main reservoir is the pig,and they are mostly encountered in developed countries.The major risk groups for HEV infection and its ensuing adverse consequences are pregnant women,infants,older people,immunocompromised individuals,patients with underlying chronic liver diseases,and workers that come into close contact with HEV-infected animals.In the clinical perspective,HEV infections have diverse clinical manifestations including acute and self-limiting hepatitis,acute-on-chronic liver disease,chronic hepatitis,cirrhosis,and liver failure.Although HEV mainly results in acute selflimiting infection,chronic HEV infection may occur among immunocompromised patients(e.g.,solid-organ transplant recipients).Additionally,HEV-associated extrahepatic manifestations involving various organs have been reported in the last decade,although the causal link for many of them still needs to be proven.Ribavirin and interferon-alpha are the most widely used agents for the treatment of HEV infections with a certain level of success.However,ribavirin is contraindicated in pregnant patients,and interferon-alpha cannot be used in most transplant recipients.Therefore,there is an urgent need for novel antiviral compounds that are safe and effective particularly for patients having contraindications for ribavirin or interferon-alpha and infected by the ribavirinresistant HEV.In this review article,a literature search using PubMed and MEDLINE databases was performed,up to March 2020.Only the articles published in English were reviewed.

Rheumatologic manifestations of hepatic diseases

A possible link is suggested between hepatic diseases and rheumatic disease. Polyarthralgia and polyarthritis may be seen during the prodromal period of acute viral hepatitis, especially in hepatitis B virus (HBV). The symptoms of arthritis, mild, localized or generalized, mostly involve the small joints of hands. Joint symptoms frequently precede the onset of jaundice, no residual joint deformities. Circulating immune complexes are believed to play a causative role in the development of vasculitis and arthritis. Hemochromatosis is an antosomal recessive disorder of iron. About 43%-81% of patients with hemochromatosis have arthritis. The common extrahepatic manifestations of autoimmune hepatitis are arthralgia and skin rash. The reported prevalence of symptomatic inflammatory arthropathy in patients with primary biliary cirrhosis ranges from 4% to 50%. Skeletal involvement with Wilson's disease is common. Such patients may complain of pain and stiffness, mainly in the knee, wrist, or other large joints. Shwachman's syndrome is a disorder of pancreatic exocrine. Symmetric bone lesions have been reported in 10% to 15% of patients. They are involved predominantly at the femoral neck. Rheumatic symptoms are seen in one third of adult patients with cystic fibrosis and arthritis in 2.5% to 12% of patients. The arthritis caused by pancreatic panniculitis is usually symmetrical and involves the small joints of the hand, wrist, and feet, but may involve such larger joints as the elbow, ankle, and knee.

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.